October 4, 2022
THE 2022 NOBEL PRIZE IN PHYSICS AWARDED TO QUANTUM TECHNOLOGY
The Nobel Prize in Physics 2022 is awarded to Alain Aspect, John F. Clauser and Anton Zeilinger “for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”. Their results have cleared the way for new technology based upon quantum information. Using groundbreaking experiments, Alain Aspect, John Clauser and Anton Zeilinger have demonstrated the potential to investigate and control particles that are in entangled states. What happens to one particle in an entangled pair determines what happens to the other, even if they are really too far apart to affect each other. The laureates’ development of experimental tools has laid the foundation for a new era of quantum technology.
October 3, 2022
The 2022 Nobel Prize in Physiology or Medicine awarded to Svante Pääbo
The Nobel Assembly at the Karolinska Institutet has decided to award the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution”. Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.
September 29, 2022
Automated solution-phase multiplicative synthesis of complex glycans
Carbohydrates play essential roles in nature, such as in cell–cell communication, cell growth and immunoresponse. However, the synthesis of structurally well-defined carbohydrates, especially large-sized glycans, is a challenging task. Yao et al. (Nature Synthesis, 2022) report an automated solution-phase multiplicative synthesis of complex glycans enabled by preactivation-based, multicomponent, one-pot glycosylation and continuous multiplying amplification. This was achieved by making a dual-mode automated solution-phase glycan synthesizer. Using this synthesizer, a library of oligosaccharides covering various glycoforms and glycosidic linkages was assembled rapidly, either in a general promoter-activation mode or in a light-induced-activation mode. The automated synthesis of a fully protected fondaparinux pentasaccharide (an anticoagulant) was realized on the gram scale. Furthermore, automated ten-component tandem reactions were performed, allowing the assembly of arabinans up to a 1,080-mer using this automated multiplicative synthesis strategy.
A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors
Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 104 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers (Dohlman et al. 2022; 185: P3807-3822. E12).
September 26, 2022
Unraveling the Mechanisms of the Apis mellifera Honeycomb Construction by 4D X-ray Microscopy
Honeycomb is one of nature’s best engineered structures. Even though it has inspired several modern engineering structures, an understanding of the process by which the hexagonal cells are formed in 3D space is lacking. Previous studies on the structure of the honeycomb are based on either 2D microscopy or by direct visual observations. As a result, several critical features of its microstructure and the precise mechanisms of its growth are not well understood. Using 4D X-ray microscopy, this study shows how individual and groups of honeycomb cells are formed. Cells grow additively from a corrugated central spine in a dynamic manner. The previously undocumented, corrugated spine contributes significantly to the comb’s robust mechanical properties in all three dimensions. As cells grow, honey bees create a “coping,” which this study shows to be the location where new wax material is deposited behind where compaction and densification take place. This is exemplified by pores in the wax observed at the coping and alternating rear junctions between the comb cells that arise from the additive building technique and the highly efficient cell packing methodology, respectively (Franklin et al. (Advanced Materials, 2022; Sep 2:e2202361).
The impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality
Epidemiological studies report the beneficial effects of habitual coffee consumption on incident arrhythmia, cardiovascular disease (CVD), and mortality. However, the impact of different coffee preparations on cardiovascular outcomes and survival is largely unknown. Decaffeinated, ground, and instant coffee, particularly at 2–3 cups/day, were associated with significant reductions in incident CVD and mortality. Ground and instant but not decaffeinated coffee was associated with reduced arrhythmia (Chieng et al. Eur J Prev Cardiol. 2022; Sep 27:zwac189).
September 12, 2022
Modern humans have greater neurogenesis in frontal neocortex than Neanderthals
Neanderthal brains were similar in size to those of modern humans but differed in shape. What we cannot tell from fossils is how Neanderthal brains might have differed in function or organization of brain layers such as the neocortex. Pinson et al. (Science 2022; 377(6611):eabl6422) have now analyzed the effect of a single amino acid change in the transketolase-like 1 (TKTL1) protein on production of basal radial glia, the workhorses that generate much of the neocortex. Modern humans differ from apes and Neanderthals by this single amino acid change. When placed in organoids or overexpressed in nonhuman brains, the human variant of TKTL1 drove more generation of neuroprogenitors than did the archaic variant. The authors suggest that the modern human has more neocortex to work with than the ancient Neanderthal did.
Exceeding 1.5°C global warming could trigger multiple climate tipping points
Climate tipping points are conditions beyond which changes in a part of the climate system become self-perpetuating. These changes may lead to abrupt, irreversible, and dangerous impacts with serious implications for humanity. Armstrong McKay et al. (Science 2022; 377: eabn7950) present an updated assessment of the most important climate tipping elements and their potential tipping points, including their temperature thresholds, time scales, and impacts. Their analysis indicates that even global warming of 1°C, a threshold that we already have passed, puts us at risk by triggering some tipping points. This finding provides a compelling reason to limit additional warming as much as possible.
The genomic history and global expansion of domestic donkeys
Donkeys have been important to humans for thousands of years, being the primary source of work and transport for many cultures. Unlike horses, little was known about the origin and domestication of donkeys. Todd et al. (Science 2022; 377: 1172-1180) sequenced the genomes of modern and ancient donkeys and found evidence of an eastern African origin over 7000 years ago, with subsequent isolation and divergence of lineages in Africa and Eurasia. They also reveal the imprint of desertification on divergence among groups and specifics about donkey breeding and husbandry, including selection for large size and the practice of inbreeding.
September 6, 2022
Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance
Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. Suez et al. (Cell 2022; 185: P3307-3328) assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.
Lignin-first biorefining of Nordic poplar to produce cellulose fibers could displace cotton production on agricultural lands
To meet the growing demand of food, materials, chemicals, and energy without crude oil or affecting the climate negatively is a major challenge for this century. By growing an engineered hybrid poplar on non-utilized marginal lands in Nordic climates, highly productive agricultural lands that today are used for cotton production can be reclaimed for food production. This is enabled by the production of wood-based fiber by using an emerging biomass fractionation technology. Besides increasing the capacity to produce food, other advantages comprise a reduced consumption of water and chemicals associated with cotton production. In addition, high yields of a lignin oil that is advantaged for production of biochemicals and biofuels are generated in the fractionation process. Adler et al. (Joule 2022; 6: P1845-1858) show that lignin-first biorefining of poplar can enable the production of dissolving cellulose pulp that can produce regenerated cellulose, which could substitute cotton. These results in turn indicate that agricultural land dedicated to cotton could be reclaimed for food production by extending poplar plantations to produce textile fibers. Based on climate-adapted poplar clones capable of growth on marginal lands in the Nordic region, they estimate an environmentally sustainable annual biomass production of ∼11 tonnes/ha. At scale, lignin-first biorefining of this poplar could annually generate 2.4 tonnes/ha of dissolving pulp for textiles and 1.1 m3 biofuels. Life cycle assessment indicates that, relative to cotton production, this approach could substantially reduce water consumption and identifies certain areas for further improvement. Overall, this work highlights a new value chain to reduce the environmental footprint of textiles, chemicals, and biofuels while enabling land reclamation and water savings from cotton back to food production.
September 2, 2022
Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation
Reduced gut microbial diversity after allogeneic stem cell transplantation has been associated with decreased survival, but the role of the gut microbiome after solid organ transplantation is not as well studied. Swarte and colleagues (Science Translational Medicine, 2022; 14: Issue 660) studied dysbiosis of the gut microbiome in a large cohort of individuals with end-stage liver or kidney disease before and after organ transplantation. Transplant recipients suffered from gut dysbiosis, with lower diversity and increased abundance of unhealthy species, virulence factors, and antibiotic resistance genes. Furthermore, immunosuppressive drug use was associated with dysbiosis, and increased dysbiosis was associated with increased mortality after transplantation. These results suggest that microbiome-targeted interventions could potentially affect outcomes after solid organ transplantation.
A microbial supply chain for production of the anti-cancer drug vinblastine
Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale. Zhang et al. (Nature, 2022) demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. The study showcases a very long biosynthetic pathway refactored into a microbial cell factory, including 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants, as well as deletions, knock-downs and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semisynthesis to vinblastine occurs. As the vinblastine pathway is one of the longest MIA biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and a virtually infinite number of new-to-nature analogues.
Gonadotropin-releasing hormone replacement rescues cognition in Down syndrome
Down syndrome (DS), the result of trisomy of chromosome 21, carries a suite of symptoms including intellectual disability and loss of olfaction. Manfredi-Lozano et al. (Science 2022; 377(6610):eabq4515) recognized a similarity between some of the DS symptoms and those seen in patients with a deficiency of gonadotropin-releasing hormone (GnRH). Indeed, analysis of a mouse model of DS showed deficits in GnRH expression. Interventions that restored physiological GnRH levels in the mouse DS model also improved cognitive deficits. In a preliminary clinical trial in patients affected by DS, pulsatile GnRH therapy improved cognition.
The human oxidation field
Hydroxyl radicals (OH) are highly reactive species that are responsible for the oxidation of most pollutant gases. Outdoors, OH radicals are formed primarily by the photolysis of ozone by short-wavelength sunlight, but that light is largely filtered out by glass windows, so what is the indoor OH radical environment like? Zannoni et al. (Science 2022; 377: 1071-1077) report that high concentrations of OH radicals were found when people were exposed to ozone in a climate-controlled chamber, and were a product of a reaction with the skin oil squalene. Their finding has implications for indoor air quality and ultimately for human health.
Insulin signaling in the long-lived reproductive caste of ants
A trade-off between reproduction and lifespan occurs across most living organisms. An exception is insects such as ants, in which reproductive activity is limited to one or a few “queens” that live much longer than nonreproductive “workers.” Studying a pseudo-queen state of the ant Harpegnathos saltator, Yan et al. (Science 2022; 377:1092-1099) found that the insulin and insulin-like growth factor signaling pathway was activated to promote reproduction, which also shortened life span. The authors propose that one branch of this pathway, mediated by the protein kinase Akt, is suppressed in the fat body and some ovarian tissues. Increased production of a protein that binds insulin-like molecules in the hemolymph might account for the difference that allowed the longer life span of the pseudo-queen.
August 18, 2022
Soybean photosynthesis and crop yield are improved by accelerating recovery from photoprotection
Crop leaves in full sunlight dissipate damaging excess absorbed light energy as heat. This protective dissipation continues after the leaf transitions to shade, reducing crop photosynthesis. A bioengineered acceleration of this adjustment increased photosynthetic efficiency and biomass in tobacco in the field. But could that also translate to increased yield in a food crop? De Souza et al. (Science 2022; 377: 851-854) bioengineered the same change into soybean. In replicated field trials, photosynthetic efficiency in fluctuating light was higher and seed yield in five independent transformation events increased by up to 33%. Despite increased seed quantity, seed protein and oil content were unaltered. This validates increasing photosynthetic efficiency as a much needed strategy toward sustainably increasing crop yield in support of future global food security.
The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery
Millions of patients have reported skipping therapeutic injections due to needle phobia or pain, which leads to poorer disease outcomes. Although simple and painless oral administration of protein therapeutics would circumvent patient hesitancy and suffering, it has not been possible because the intestine is not permeable to macromolecules, including protein. Lamson et al. (PNAS, 2022; 119 (33) e2207829119) demonstrate that the strawberry pigment pelargonidin reversibly permeabilizes the epithelial lining of the intestines and enables efficient oral protein delivery without inducing inflammation or tissue damage in mice.
Floating perovskite-Bismuth vanadate devices for scalable solar fuel production
Photoelectrochemical (PEC) artificial leaves hold the potential to lower the costs of sustainable solar fuel production by integrating light harvesting and catalysis within one compact device. However, current deposition techniques limit their scalability, whereas fragile and heavy bulk materials can affect their transport and deployment. Andrei et al. (Nature 2022; 608:518–522) demonstrate the fabrication of lightweight artificial leaves by employing thin, flexible substrates and carbonaceous protection layers. Lead halide perovskite photocathodes deposited onto indium tin oxide-coated polyethylene terephthalate achieved an activity of 4,266 µmol H2 g−1 h−1 using a platinum catalyst, whereas photocathodes with a molecular Co catalyst for CO2 reduction attained a high CO:H2 selectivity of 7.2 under lower (0.1 sun) irradiation. The corresponding lightweight perovskite-Bismuth vanadate PEC devices showed unassisted solar-to-fuel efficiencies of 0.58% (H2) and 0.053% (CO), respectively. Their potential for scalability is demonstrated by 100 cm2 stand-alone artificial leaves, which sustained a comparable performance and stability (of approximately 24 h) to their 1.7 cm2 counterparts. Bubbles formed under operation further enabled 30–100 mg cm−2 devices to float, while lightweight reactors facilitated gas collection during outdoor testing on a river. This leaf-like PEC device bridges the gulf in weight between traditional solar fuel approaches, showcasing activities per gram comparable to those of photocatalytic suspensions and plant leaves. The presented lightweight, floating systems may enable open-water applications, thus avoiding competition with land use.
August 12, 2022
Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts
Visual impairment from corneal stromal disease affects millions worldwide. Rafat et al. (Nature Biotechnology, 2022) describe a cell-free engineered corneal tissue, bioengineered porcine construct, double crosslinked (BPCDX) and a minimally invasive surgical method for its implantation. In a pilot feasibility study in India and Iran (clinicaltrials.gov no. NCT04653922), they implanted BPCDX in 20 advanced keratoconus subjects to reshape the native corneal stroma without removing existing tissue or using sutures. During 24 months of follow-up, no adverse event was observed. They document improvements in corneal thickness (mean increase of 209 ± 18 µm in India, 285 ± 99 µm in Iran), maximum keratometry (mean decrease of 13.9 ± 7.9 D in India and 11.2 ± 8.9 D in Iran) and visual acuity (to a mean contact-lens-corrected acuity of 20/26 in India and spectacle-corrected acuity of 20/58 in Iran). Fourteen of 14 initially blind subjects had a final mean best-corrected vision (spectacle or contact lens) of 20/36 and restored tolerance to contact lens wear. This work demonstrates restoration of vision using an approach that is potentially equally effective, safer, simpler and more broadly available than donor cornea transplantation.
August 10, 2022
Sponges sneeze mucus to shed particulate waste from their seawater inlet pores
Sponges, among the oldest extant multicellular organisms on Earth, play a key role in the cycling of nutrients in many aquatic ecosystems. They need to employ strategies to prevent clogging of their internal filter system by solid wastes, but self-cleaning mechanisms are largely unknown. It is commonly assumed that sponges remove solid waste with the outflowing water through distinct outflow openings (oscula). Komder et al. (Current Biology, 2022) present time-lapse video footage and analyses of sponge waste revealing a completely different mechanism of particle removal in the Caribbean tube sponge Aplysina archeri. This sponge actively moves particle-trapping mucus against the direction of its internal water flow and ejects it into the surrounding water from its seawater inlet pores (ostia) through periodic surface contractions that have been described earlier as “sneezing.” Visually, it appears as if the sponge is continuously streaming mucus-embedded particles and sneezes to shed this particulate waste, resulting in a notable flux of detritus that is actively consumed by sponge-associated fauna. The new data are used to estimate production of detritus for this abundant sponge on Caribbean coral reefs.
August 5, 2022
Teixobactin kills bacteria by a two-pronged attack on the cell envelope
Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance. Teixobactin represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan. Shukla et al. (Nature 2022; 608: 390–396) unraveled the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates.
Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion
High cholesterol is a major risk factor for cardiovascular disease. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. Human genetic studies have identified that the loss-of-function of Asialoglycoprotein receptor 1 (ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. Wang et al. (Nature 2022; 608: 413-420) find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing Liver X receptor alpha (LXRα). LXRα upregulates ATP Binding Cassette Subfamily A Member 1 (ABCA1) and ATP-cassette binding proteins G5 (ABCG5/G8), which promotes cholesterol transport to high-density lipoprotein and excretion to bile and feces, respectively. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. On the other hand, AMPK suppresses Sterol regulatory element-binding transcription factor 1 (SREBP1) that controls lipogenesis. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. Overall, targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels.
August 2, 2022
Development of synthetic embryo
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extra-embryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extra-embryonic compartments, remains unknown. Tarazi et al. (Cell 2022) adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting solely from naïve ESCs. This was achieved by co-aggregating non-transduced ESCs, with naïve ESCs transiently expressing Cdx2- and Gata4- to promote their priming towards trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos. The findings highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.
July 28, 2022
Bioadhesive ultrasound for long-term continuous imaging of diverse organs
Ultrasound is widely used for the noninvasive imaging of tissues and organs, but this method requires close contact between the transducer and the target area. This can make it difficult to acquire images over a long period of time, especially if the patient needs to be mobile. Wang et al. (Science 2022; 377: Issue 6605) describe a wearable ultrasound imaging device. A rigid piezoelectric probe array is bonded to the skin with an acoustically transparent hydrogel elastomer. In vivo testing showed that the device could be comfortably worn for 48 hours, and hooking the array up to a commercially available ultrasound platform allowed for continuous ultrasound images of the carotid artery, lung, and abdomen.
Pollinators of the sea: A discovery of animal-mediated fertilization in seaweed
Pollination by animals is a widespread and important symbiotic relationship that increases plants’ genetic diversity and fertilization success. Lavaut et al. (Science 2022; 377: Issue 6605) discovered that this relationship is not unique to plants; it is also found in the dioecious red alga Gracilaria gracilis. The isopod Idotea balthica carries the alga’s spermatia on its body, and experiments showed that isopods moving from a male to a female alga increased the alga’s fertilization. Transport of algal gametes by isopods could be an important mechanism for reproduction because the spermatia lack flagella and otherwise rely on water currents to transport them.
July 23, 2022
A transcriptional regulator that boosts grain yields and shortens the growth duration of rice
Rapid population growth, rising meat consumption, and the expanding use of crops for nonfood and nonfeed purposes increase the pressure on global food production. At the same time, the excessive use of nitrogen fertilizer to enhance agricultural production poses serious threats to both human health and the environment. To achieve the required yield increases and make agriculture more sustainable, intensified breeding and genetic engineering efforts are needed to obtain new crop varieties with higher photosynthetic capacity and improved nitrogen use efficiency (NUE). However, progress has been slow, largely due to the limited knowledge about regulator genes that potentially can coordinately optimize carbon assimilation and nitrogen utilization. Improvements in agricultural productivity could lessen the impact of agriculture on the environment and perhaps supply more food from less land. Working in rice, Wei et al. (Science 2022; 377, Issue 6604) identified a transcription factor, OsDREB1C that when overexpressed, has a variety of useful effects. The gene’s expression is induced by both light and low-nitrogen status, and it regulates photosynthetic capacity, nitrogen utilization, and flowering time. Overexpression of OsDREB1C not only boosts grain yields but also confers higher NUE and early flowering. The work demonstrates that by genetically modulating the expression of a single transcriptional regulator gene, substantial yield increases can be achieved while the growth duration of the crop is shortened. The existing natural allelic variation in OsDREB1C, the highly conserved function of the transcription factor in seed plants, and the ease with which its expression can be altered by genetic engineering suggest that this gene could be the target of future crop improvement strategies toward more efficient and more sustainable food production.
WHO declares monkeypox a public health emergency
The World Health Organization (WHO) has activated its highest alert level for the growing monkeypox outbreak, declaring the virus a public health emergency of international concern. WHO now views the outbreak as a significant enough threat to global health that a coordinated international response is required to prevent the virus from spreading further and potentially escalating into a pandemic.
July 21, 2022
Tirzepatide once weekly for the treatment of obesity
Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. In a 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight (Jastreboff et al. N Engl J Med 2022; 387: 205-216).
July 20, 2022
Rescue of autosomal dominant hearing loss by in vivo delivery of RNA base editor
Targeting disease-relevant transcripts using RNA editing holds promise for treating genetic diseases, without the risks associated with permanent changes induced by DNA alterations. Xiao et al. (Science Translational Medicine 2022; 14: Issue 654) evaluated the therapeutic potential of a Cas13-derived RNA base editor for correcting a hearing loss–causing mutation in the myosin VI (Myo6) transcript in a mouse model. The RNA base editor composed of a Cas13X variant and the RNA editing enzyme adenosine deaminase was delivered in the cochlea of mice using an adeno-associated virus (AAV). The treatment prevented hair cell loss and rescued auditory function in mice for up to 3 months after injection, suggesting that RNA editing might be effective for treating genetic disorders.
Competition for pollinators destabilizes plant coexistence
Mounting concern over the global decline of pollinators has fuelled calls for investigating their role in maintaining plant diversity. Theory predicts that competition for pollinators can stabilize interactions between plant species by providing opportunities for niche differentiation, while at the same time can drive competitive imbalances that favour exclusion. Johnson et al. (Nature 2022) empirically tested these contrasting effects by manipulating competition for pollinators in a way that predicts its long-term implications for plant coexistence. They subjected annual plant individuals situated across experimentally imposed gradients in neighbor density to either ambient insect pollination or a pollen supplementation treatment alleviating competition for pollinators. The vital rates of these individuals informed plant population dynamic models predicting the key theoretical metrics of species coexistence. Competition for pollinators generally destabilized the interactions between plant species, reducing the proportion of pairs expected to coexist. Interactions with pollinators also influenced the competitive imbalances between plant species, effects that are expected to strengthen with pollinator decline, potentially disrupting plant coexistence. Indeed, results from an experiment simulating pollinator decline showed that plant species experiencing greater reductions in floral visitation also suffered greater declines in population growth rate. The results reveal that competition for pollinators may weaken plant coexistence by destabilizing interactions and contributing to competitive imbalances, information critical for interpreting the impacts of pollinator decline.
July 15, 2022
Methanol biotransformation toward high-level production of fatty acid derivatives by engineering the industrial yeast Pichia pastoris
Methanol-based biomanufacturing is considered a promising way to achieve carbon neutrality. However, efficient methanol biotransformation toward chemical production is challenging. To address this challenge, Cai et al. (PNAS 2022; 119 (29) e2201711119) enhanced the precursor supply and coenzyme regeneration in Pichia pastoris, combined with reinforcing methanol assimilation, which resulted in significant improvements in fatty acid production. Furthermore, they offered an effective approach for rapidly constructing versatile cell factories that share common precursors. This study represents an important step forward in the rewiring of P. pastoris as industrialmicrobial cell factories for chemical production.
The gut metabolite indole-3 propionate promotes nerve regeneration and repair
The regenerative potential of mammalian peripheral nervous system neurons after injury is critically limited by their slow axonal regenerative rate. Regenerative ability is influenced by both injury-dependent and injury-independent mechanisms. Among the latter, environmental factors such as exercise and environmental enrichment have been shown to affect signaling pathways that promote axonal regeneration. Several of these pathways, including modifications in gene transcription and protein synthesis, mitochondrial metabolism and the release of neurotrophins, can be activated by intermittent fasting (IF). However, whether IF influences the axonal regenerative ability remains to be investigated. Serger et al. (Nature 2022; 607: 585–592) show that IF promotes axonal regeneration after sciatic nerve crush in mice through an unexpected mechanism that relies on the gram-positive gut microbiome and an increase in the gut bacteria-derived metabolite indole-3-propionic acid (IPA) in the serum. IPA production by Clostridium sporogenes is required for efficient axonal regeneration, and delivery of IPA after sciatic injury significantly enhances axonal regeneration, accelerating the recovery of sensory function. Mechanistically, RNA sequencing analysis from sciatic dorsal root ganglia suggested a role for neutrophil chemotaxis in the IPA-dependent regenerative phenotype, which was confirmed by inhibition of neutrophil chemotaxis. The results demonstrate the ability of a microbiome-derived metabolite, such as IPA, to facilitate regeneration and functional recovery of sensory axons through an immune-mediated mechanism.
Therapeutic functions of astrocytes to treat α-synuclein pathology in Parkinson’s disease
Intraneuronal inclusions of misfolded α-synuclein (α-syn) and prion-like spread of the pathologic α-syn contribute to progressive neuronal death in Parkinson’s disease (PD). Despite the pathologic significance, no efficient therapeutic intervention targeting α-synucleinopathy has been developed. Yang et al. (PNAS 2022; 119 (29) e2110746119) showed that astrocytes, especially those cultured from the ventral midbrain, substantially alleviate neuronal α-syn pathology by regulating a series of the proteostasis procedures associated with formation, transmission, disaggregation, and clearance of toxic α-syn aggregates in multiple in vitro and in vivo α-synucleinopathic models. Based on these findings, the therapeutic actions of astrocytes are proposed for use in relieving α-syn–mediated neuronal toxicity and in setting up a desirable cell-based therapy free from host-to-graft α-syn propagation in PD.
The impact of paleoclimatic changes on body size evolution in marine fishes
General rules are useful tools for understanding how organisms evolve. Cope’s rule (tendency to increase in size over evolutionary time) and Bergmann’s rule (tendency to grow to larger sizes in cooler climates) both relate to body size, an important factor that affects the biology, ecology, and physiology of organisms. These rules are well studied in endotherms but remain poorly understood among ectotherms. Troyer et al. (PNAS 2022; 119 (29) e2122486119) show that paleoclimatic changes strongly shaped the trajectory of body size evolution in tetraodontiform fishes. Their body size evolution is explained by both Cope’s and Bergmann’s rules, highlighting the impact of paleoclimatic changes on aquatic organisms, which rely on their environment for temperature regulation and are likely more susceptible than terrestrial vertebrates to climatic changes.
A highly photostable and bright green fluorescent protein
The low photostability of fluorescent proteins is a limiting factor in many applications of fluorescence microscopy. Hirano et al. (Nature Biotechnology 2022; 40:1132–1142) present StayGold, a green fluorescent protein (GFP) derived from the jellyfish Cytaeis uchidae. StayGold is over one order of magnitude more photostable than any currently available fluorescent protein and has a cellular brightness similar to mNeonGreen. They used StayGold to image the dynamics of the endoplasmic reticulum (ER) with high spatiotemporal resolution over several minutes using structured illumination microscopy (SIM) and observed substantially less photobleaching than with a GFP variant optimized for stability in the ER. Using StayGold fusions and SIM, they also imaged the dynamics of mitochondrial fusion and fission and mapped the viral spike proteins in fixed cells infected with severe acute respiratory syndrome coronavirus 2. As StayGold is a dimer, they created a tandem dimer version that allowed us to observe the dynamics of microtubules and the excitatory post-synaptic density in neurons. StayGold will substantially reduce the limitations imposed by photobleaching, especially in live cell or volumetric imaging.
July 10, 2022
Flint glass bottles cause white wine aroma identity degradation
Transparent packaging is increasingly used for foodstuffs, including wine, milk, beer, and juice. This choice is based on the marketing recommendation that consumers want to see the product before buying it, although scientists point out that light can damage food quality and nutritional value. Carlin et al. (PNAS 2022; 119 (29) e2121940119) revealed that light can dramatically damage the aroma profile and sensorial identity of varietal white wine in less than a week of shelf-life in flint glass bottles. They proposed a mechanism of the lightstrike off-odor development, which includes the decrease of the fruity and flowery aroma able to mask off-odors, the rapid loss of aroma enhancers, and the catalyzation of photodegradations. The authors are of the opinion that flint glass bottles should be avoided.
July 6 2022
Global collision-risk hotspots of marine traffic and the world’s largest fish, the whale shark
Marine traffic is increasing globally yet collisions with endangered megafauna such as whales, sea turtles, and planktivorous sharks go largely undetected or unreported. Collisions leading to mortality can have population-level consequences for endangered species. Hence, identifying simultaneous space use of megafauna and shipping throughout ranges may reveal as-yet-unknown spatial targets requiring conservation. However, global studies tracking megafauna and shipping occurrences are lacking. Womersley et al. (PNAS 2022; 119 (20) e2117440119) combine satellite-tracked movements of the whale shark, Rhincodon typus, and vessel activity to show that 92% of sharks’ horizontal space use and nearly 50% of vertical space use overlap with persistent large vessel (>300 gross tons) traffic. Collision-risk estimates correlated with reported whale shark mortality from ship strikes, indicating higher mortality in areas with greatest overlap. Hotspots of potential collision risk were evident in all major oceans, predominantly from overlap with cargo and tanker vessels, and were concentrated in gulf regions, where dense traffic co-occurred with seasonal shark movements. Nearly a third of whale shark hotspots overlapped with the highest collision-risk areas, with the last known locations of tracked sharks coinciding with busier shipping routes more often than expected. Depth-recording tags provided evidence for sinking, likely dead, whale sharks, suggesting substantial “cryptic” lethal ship strikes are possible, which could explain why whale shark population declines continue despite international protection and low fishing-induced mortality. Mitigation measures to reduce ship-strike risk should be considered to conserve this species and other ocean giants that are likely experiencing similar impacts from growing global vessel traffic.
June 26, 2022
Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Bademci et al. (PNAS 2022; 119 (26) e2204084119) report on DNA variants in MINAR2, encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities. MINAR2 is a recently annotated gene with limited functional understanding. The authors detected three MINAR2 variants in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The authors show that Minar2 is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein (Minar2tm1b/tm1b) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. The authors conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies.
Genes and evolutionary fates of the amanitin biosynthesis pathway in poisonous mushrooms
Why do unrelated poisonous mushrooms (Amanita, Galerina, and Lepiota) make the same deadly toxin, α-amanitin? One of the most effective and fast strategies for organisms to acquire new abilities is through horizontal gene transfer (HGT). With the help of genome sequencing and the finding of two genes for the amanitin biosynthetic pathway, Luo et al. (PNAS 2022; 119 (20) e2201113119) demonstrate that the pathway distribution resulted from HGT probably through an unknown ancestral fungal donor. In Amanita mushrooms, the pathway evolved, through a series of gene manipulations, to produce very high levels of toxins, generating “the deadliest mushroom known to mankind.”
New intranasal and injectable gene therapy for healthy life extension
As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. Jaijyan et al. (PNAS 2022; 119 (20) e2121499119) sought to determine whether the high-capacity cytomegalovirus vector (CMV) can be an effective and safe gene delivery method for two such protective factors: telomerase reverse transcriptase (TERT) and follistatin (FST). They found that the mouse cytomegalovirus (MCMV) carrying exogenous TERT or FST extended median lifespan by 41.4% and 32.5%, respectively. They report CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Specifically, this treatment significantly improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia. Further, telomere shortening associated with aging was ameliorated by TERT and mitochondrial structure deterioration was halted in both treatments. Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span.
Organic acids and glucose prime late-stage fungal biotrophy in maize
Some fungi depend on their living hosts for sustenance. The corn smut fungus Ustilago maydis can grow independently but depends on the host maize plant to reproduce. Kretschmer et al. (Science 376: 1187-1191) analyzed which host nutrients are required to support this obligate biotroph’s lifestyle. The fungus responds to a combination of nutrients, including organic acids such as malate, which maize uses as a substrate for C4 photosynthesis. Identification of dicarboxylate transporters showed that the ability of the fungus to draw these organic acids out of the host plant contributes to the pathogen’s virulence. With such nutrition ensured, the fungus can then move through its life cycle.
June 24, 2022
Tumor necrosis factor induces pathogenic mitochondrial reactive oxygen species in tuberculosis through reverse electron transport
Although tumor necrosis factor (TNF) acts an important tuberculosis (TB) resistance factor, too much of this cytokine can kill infected macrophages and allow mycobacteria to escape and grow uncontrolled in the extracellular space. Using a zebrafish model of TB infection, Roca et al. found that TNF induces reverse electron transport (RET) in mitochondrial complex I. This in turn drives the production of mitochondrial reactive oxygen species (mROS), causing macrophage necrosis. The complex I inhibitor metformin could be repurposed to inhibit TNF-induced mROS and necrosis in infected zebrafish and human macrophages, suggesting that this common antidiabetes drug may also be a useful adjunct therapy for TB (Roca et al. Science 2022; 376).
June 23, 2022
A centimeter-long bacterium with DNA contained in metabolically active, membrane-bound organelles
Cells of most bacterial species are around 2 micrometers in length, with some of the largest specimens reaching 750 micrometers. Using fluorescence, x-ray, and electron microscopy in conjunction with genome sequencing, Volland et al. (Science 376: 1453-1458) characterized Candidatus (Ca.) Thiomargarita magnifica, a bacterium that has an average cell length greater than 9000 micrometers and is visible to the naked eye. These cells grow orders of magnitude over theoretical limits for bacterial cell size, display unprecedented polyploidy of more than half a million copies of a very large genome, and undergo a dimorphic life cycle with asymmetric segregation of chromosomes into daughter cells. These features, along with compartmentalization of genomic material and ribosomes in translationally active organelles bound by bioenergetic membranes, indicate gain of complexity in the Thiomargarita lineage and challenge traditional concepts of bacterial cells.
June 22, 2022
The metastatic spread of cancer accelerates during sleep
The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumor cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumors or are shed as a consequence of mechanical insults. Diamantopoulo et al. (Nature 2022) observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, they demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, they find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumor cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers.
June 15, 2022
Lithiating magneto-ionics in a rechargeable battery
Magneto-ionics, real-time ionic control of magnetism in solid-state materials, promise ultralow-power memory, computing, and ultralow-field sensor technologies. The real-time ion intercalation is also the key state-of-charge feature in rechargeable batteries. Hu et al. (PNAS 2022; 119 (25) e2122866119) report that the reversible lithiation/delithiation in molecular magneto-ionic material, the cathode in a rechargeable lithium-ion battery, accurately monitors its real-time state of charge through a dynamic tunability of magnetic ordering. The electrochemical and magnetic studies confirm that the structural vacancy and hydrogen-bonding networks enable reversible lithiation and delithiation in the magnetic cathode. Coupling with microwave-excited spin wave at a low frequency (0.35 GHz) and a magnetic field of 100 Oe, we reveal a fast and reliable built-in magneto-ionic sensor monitoring state of charge in rechargeable batteries. The findings shown herein promise an integration of molecular magneto-ionic cathode and rechargeable batteries for real-time monitoring of state of charge.
Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain
To better understand the changes in the brain that support the transition from sporadic drinking to chronic alcohol abuse, Knabbe et al. (PNAS 2022; 119 (25) e2122477119) identified distinct effects of single ethanol exposure on a molecular, cellular, and behavioral level. Similar to learning and memory processes, the idea was to discover lasting changes that could mediate lasting ethanol reward memories. By imaging the brains of acutely exposed mice, they found that ethanol induced lasting changes in synaptic morphology, the axon initial segment, and mitochondrial trafficking. In Drosophila flies, specific knockdown of mitochondrial trafficking abolished positive ethanol reward memories. Together, the data suggest that a single ethanol exposure induces plastic changes which in turn could contribute to the basis of ethanol dependence.
Sialic acids on B cells are crucial for their survival and provide protection against apoptosis
Sialic acids (Sias) on the B cell membrane are involved in cell migration, in the control of the complement system and, as sialic acid–binding immunoglobulin-like lectin (Siglec) ligands, in the regulation of cellular signaling. Linder et al. (PNAS 2022; 119 (25) e2201129119) studied the role of sialoglycans on B cells in a mouse model with B cell–specific deletion of cytidine monophosphate sialic acid synthase (CMAS), the enzyme essential for the synthesis of sialoglycans. Surprisingly, these mice showed a severe B cell deficiency in secondary lymphoid organs. Additional depletion of the complement factor C3 rescued the phenotype only marginally, demonstrating a complement-independent mechanism. The B cell survival receptor BAFF receptor was not up-regulated, and levels of activated caspase 3 and processed caspase 8 were high in B cells of Cmas-deficient mice, indicating ongoing apoptosis. Overexpressed Bcl-2 could not rescue this phenotype, pointing to extrinsic apoptosis. These results show that sialoglycans on the B cell surface are crucial for B cell survival by counteracting several death-inducing pathways.
Hot and dry conditions predict shorter nestling telomeres in an endangered songbird
Heat waves are becoming more frequent, and we find that high air temperatures under dry conditions are associated with shorter telomere length in wild nestling purple-crowned fairy-wrens. Furthermore, impacts of heat exposure in nestlings may carry over into adulthood, as shorter early-life telomeres are associated with reduced lifetime fitness. Models using telomere data, fitness estimates, and climate change projections suggest that temperature-mediated telomere shortening could lead to population decline. However, the evolution of increased telomere length potentially counteracts these negative effects of warming and maintains population viability. For wildlife, increased early-life heat exposure from a warming climate may affect later life history with implications for population persistence and conservation (Eastwood et al. [PNAS 2022; 119 (25) e2122944119]).
June 11, 2022
Robust variation in infant gut microbiome assembly across a spectrum of lifestyles
Humans living an urbanized lifestyle in industrialized countries tend to have less diverse microbiota than people living more rural existences. Using fecal 16S ribosomal RNA sequencing, Olm et al. (Science 376: 1220-1223) found that after the first 6 months of life, the microbiome of infants living in contrasting environments diverged from Bifidobacteria-dominated assemblages. Deep metagenomic sequencing revealed that a large proportion of the bacterial species detected in samples from hunter-gatherer infants were new and were undetectable in samples from urbanized children. Gut microbiota diversity appears early in the lives of hunter-gatherer infants and is traceable to maternal transmission, with some influence from the local environment. The main driver for differences among gut microbiota originates in lifestyle rather than geography. It is suspected, but still enigmatic, that such differences in microbiota have functional implications for the health of developing children.
June 10, 2022
Organic acids and glucose prime late-stage fungal biotrophy in maize
Some fungi depend on their living hosts for sustenance. The corn smut fungus Ustilago maydis can grow independently but depends on the host maize plant to reproduce. Kretschmer et al. (Science 2022; 376:1187-1191) analyzed which host nutrients are required to support this obligate biotroph’s lifestyle. The fungus responds to a combination of nutrients, including organic acids such as malate, which maize uses as a substrate for C4 photosynthesis. Identification of dicarboxylate transporters showed that the ability of the fungus to draw these organic acids out of the host plant contributes to the pathogen’s virulence. With such nutrition ensured, the fungus can then move through its life cycle.
Printed synaptic transistor–based electronic skin for robots to feel and learn
An electronic skin (e-skin) for the next generation of robots is expected to have biological skin-like multimodal sensing, signal encoding, and preprocessing. To this end, it is imperative to have high-quality, uniformly responding electronic devices distributed over large areas and capable of delivering synaptic behavior with long- and short-term memory. Liu et al. (Science Robotics 2022; 7: Issue 67) present an approach to realize synaptic transistors (12-by-14 array) using ZnO nanowires printed on flexible substrate with 100% yield and high uniformity. The presented devices show synaptic behavior under pulse stimuli, exhibiting excitatory (inhibitory) post-synaptic current, spiking rate-dependent plasticity, and short-term to long-term memory transition. The as-realized transistors demonstrate excellent bio-like synaptic behavior and show great potential for in-hardware learning. This is demonstrated through a prototype computational e-skin, comprising event-driven sensors, synaptic transistors, and spiking neurons that bestow biological skin-like haptic sensations to a robotic hand. With associative learning, the presented computational e-skin could gradually acquire a human body–like pain reflex. The learnt behavior could be strengthened through practice. Such a peripheral nervous system–like localized learning could substantially reduce the data latency and decrease the cognitive load on the robotic platform.
Early-life exposure to hardship increased risk tolerance and entrepreneurship in adulthood with gender differences
Many entrepreneurs credit their success to early hardship. Yi et al. (PNAS 2021; 119 (15) e2104033119) exploit geographical differences in the intensity of China’s Great Famine to investigate the effect of hardship during formative years on individual personality and engagement in business entrepreneurship. To exclude factors that might confound the relation between famine intensity and entrepreneurship, they model famine intensity by random weather shocks. They found robust evidence that individuals who experienced more hardship were subsequently more likely to become entrepreneurs (defined broadly as self-employed or business owners). Importantly, the increase in entrepreneurship was at least partly due to conditioning rather than selection. Regarding the behavioral mechanism, hardship was associated with greater risk tolerance among men and women but increased business ownership only among men. The gender differences were possibly due to the intricate relationship between a Chinese social norm—men focus more on market work, while women focus more on domestic work—and interspousal risk pooling associated with occupational choices. Scientifically, these findings contribute to a long-standing debate on whether entrepreneurship is due to nature or nurture, particularly how hardship conditions people to be entrepreneurial. The findings also highlight the importance of gender differences in shaping the effect of early-life experience on life cycle outcomes.
Circadian alignment of early onset caloric restriction promotes longevity in male mice
Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Animals fed a limited number of calories, just enough to avoid malnutrition, show extended health span and life span. However, they are so hungry that they eat those fewer calories in a limited period of time and consequently spend more time fasting than do animals for which access to food is not restricted. Acosta-Rodriguez et al. (Science 376: 1192-1202) therefore designed experiments in mice to control both caloric intake and the timing of their eating to see which factors were the most important. Caloric restriction extended life span as expected, but it worked best when feeding was restricted so that the animals fasted for at least 12 hours and when the period in which the animals ate corresponded to the active phase of their circadian cycle.
June 5, 2022
Robust variation in infant gut microbiome assembly across a spectrum of lifestyles
Humans living an urbanized lifestyle in industrialized countries tend to have less diverse microbiota than people living more rural existences. Using fecal 16S ribosomal RNA sequencing, Olm et al. found that after the first 6 months of life, the microbiome of infants living in contrasting environments diverged from Bifidobacteria-dominated assemblages. Deep metagenomic sequencing revealed that a large proportion of the bacterial species detected in samples from hunter-gatherer infants were new and were undetectable in samples from urbanized children. Gut microbiota diversity appears early in the lives of hunter-gatherer infants and is traceable to maternal transmission, with some influence from the local environment. The main driver for differences among gut microbiota originates in lifestyle rather than geography. It is suspected, but still enigmatic, that such differences in microbiota have functional implications for the health of developing children.
June 1, 2022
A tissue-like neurotransmitter sensor for the brain and gut
Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Li et al. (2022; Nature 606, 94–101) introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain–gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.
May 25, 2022
Biofortified tomatoes provide a new route to vitamin D sufficiency
Poor vitamin D status is a global health problem; insufficiency underpins higher risk of cancer, neurocognitive decline and all-cause mortality. Most foods contain little vitamin D and plants are very poor sources. Li et al. (Nature Plants, 2022) have engineered the accumulation of provitamin D3 in tomato by genome editing, modifying a duplicated section of phytosterol biosynthesis in Solanaceous plants, to provide a biofortified food with the added possibility of supplement production from waste material.
Scalable super hygroscopic polymer films for sustainable moisture harvesting in arid environments
Extracting ubiquitous atmospheric water is a sustainable strategy to enable decentralized access to safely managed water but remains challenging due to its limited daily water output at low relative humidity (≤30% RH). Guo et al. (2022) (Nature Communications 13: 2761) report super hygroscopic polymer films (SHPFs) composed of renewable biomasses and hygroscopic salt, exhibiting high water uptake of 0.64–0.96 g g−1 at 15–30% RH. Konjac glucomannan facilitates the highly porous structures with enlarged air-polymer interfaces for active moisture capture and water vapor transport. Thermoresponsive hydroxypropyl cellulose enables phase transition at a low temperature to assist the release of collected water via hydrophobic interactions. With rapid sorption-desorption kinetics, SHPFs operate 14–24 cycles per day in arid environments, equivalent to a water yield of 5.8–13.3 L kg−1. Synthesized via a simple casting method using sustainable raw materials, SHPFs highlight the potential for low-cost and scalable atmospheric water harvesting technology to mitigate the global water crisis.
Neuropathic pain caused by miswiring and abnormal end organ targeting
Nerve injury leads to chronic pain and exaggerated sensitivity to gentle touch (allodynia) as well as a loss of sensation in the areas in which injured and non-injured nerves come together. The mechanisms that disambiguate these mixed and paradoxical symptoms are unknown. Gangadharan et al. (Nature, 2022) longitudinally and non-invasively imaged genetically labelled populations of fibres that sense noxious stimuli (nociceptors) and gentle touch (low-threshold afferents) peripherally in the skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour in the same mice. Fully denervated areas of skin initially lost sensation, gradually recovered normal sensitivity and developed marked allodynia and aversion to gentle touch several months after injury. This reinnervation-induced neuropathic pain involved nociceptors that sprouted into denervated territories precisely reproducing the initial pattern of innervation, were guided by blood vessels and showed irregular terminal connectivity in the skin and lowered activation thresholds mimicking low-threshold afferents. By contrast, low-threshold afferents—which normally mediate touch sensation as well as allodynia in intact nerve territories after injury—did not reinnervate, leading to an aberrant innervation of tactile end organs such as Meissner corpuscles with nociceptors alone. Genetic ablation of nociceptors fully abrogated reinnervation allodynia. Their results thus reveal the emergence of a form of chronic neuropathic pain that is driven by structural plasticity, abnormal terminal connectivity and malfunction of nociceptors during reinnervation, and provide a mechanistic framework for the paradoxical sensory manifestations that are observed clinically and can impose a heavy burden on patients.
May 19, 2022
Portable Seawater Desalination System for Generating Drinkable Water in Remote Locations
A portable seawater desalination system would be highly desirable to solve water challenges in rural areas and disaster situations. While many reverse osmosis-based portable desalination systems are already available commercially, they are not adequate for providing reliable drinking water in remote locations due to the requirement of high-pressure pumping and repeated maintenance. Yoon et al. (Environ. Sci. Technol. 2022, 56: 6733–6743) demonstrate a field-deployable desalination system with multistage electromembrane processes, composed of two-stage ion concentration polarization and one-stage electrodialysis, to convert brackish water and seawater to drinkable water. A data-driven predictive model is used to optimize the multistage configuration, and the model predictions show good agreement with the experimental results. The portable system desalinates brackish water and seawater (2.5–45 g/L) into drinkable water (defined by WHO guideline), with the energy consumptions of 0.4–4 (brackish water) and 15.6–26.6 W h/L (seawater), respectively. In addition, the process can also reduce suspended solids by at least a factor of 10 from the source water, resulting in crystal clear water (<1 NTU) even from the source water with turbidity higher than 30 NTU (i.e., cloudy seawater by the tide). They built a fully integrated prototype (controller, pumps, and battery) packaged into a portable unit (42 × 33.5 × 19 cm3, 9.25 kg, and 0.33 L/h production rate) controlled by a smartphone, tested for battery-powered field operation. The demonstrated portable desalination system is unprecedented in size, efficiency, and operational flexibility. Therefore, it could address unique water challenges in remote, resource-limited regions of the world.
Diverse parentage relationships in paternal mouthbrooding fishes
While mouthbrooding is not an uncommon parental care strategy in fishes, paternal mouthbrooding only occurs in eight fish families and is little studied. The high cost of paternal mouthbrooding to the male implies a low risk of investment in another male’s offspring but genetic parentage patterns are poorly known for paternal mouthbrooders. Abecia et al. (2022; Biology Letters) used single-nucleotide polymorphism genetic data to investigate parentage relationships of broods of two mouthbrooders of northern Australian rivers, mouth almighty Glossamia aprion and blue catfish Neoarius graeffei. For N. graeffei, they found that the parentage pattern was largely monogamous with the brooder male as the sire. For G. aprion, the parentage pattern was more heterogeneous including observations of monogamous broods with the brooder male as the sire (73%), polygyny (13%), cuckoldry (6%) and a brood genetically unrelated to the brooder male (6%). Findings demonstrate the potential for complex interrelationships of male care, paternity confidence and mating behaviour in mouthbrooding fishes.
Foliar application of clay-delivered RNA interference for whitefly control
Whitefly (Bemisia tabaci) is a phloem-feeding global agricultural pest belonging to the order Hemiptera. Foliar application of double-stranded RNA (dsRNA) represents an attractive avenue for pest control; however, limited uptake and phloem availability of the dsRNA has restricted the development of RNA interference (RNAi)-based biopesticides against sap-sucking insects. Following high-throughput single and combinational target gene identification for additive effects, Jain et al. (2022; Nature Plants 8: 535–548) report that foliar application of dsRNA loaded onto layered double hydroxide (LDH), termed BioClay, can effectively disrupt multiple whitefly developmental stages in planta. Adjuvants were shown to enhance uptake and movement of foliar-applied dsRNA to vascular bundles and into the whitefly. Notably, delivering the dsRNA as a BioClay spray instead of as naked dsRNA improved protection against immature insect stages, demonstrating the platform’s potential to extend the benefits offered by RNA insecticides towards complete life cycle control of whitefly and potentially other pests.
Evidence that Indo-Pacific bottlenose dolphins self-medicate with invertebrates in coral reefs
Indo-Pacific bottlenose dolphins (Tursiops aduncus) have been observed queueing up in natural environments to rub particular body parts against selected corals (Rumphella aggregata, Sarcophyton sp.) and sponges (Ircinia sp.) in the Egyptian Northern Red Sea. It was hypothesized that the presence of bioactive metabolites accounts for this selective rubbing behavior. The three invertebrates preferentially accessed by the dolphins, collected and analyzed by hyphenated high-performance thin-layer chromatography contained seventeen active metabolites, providing evidence of potential self-medication. Repeated rubbing allows these active metabolites to come into contact with the skin of the dolphins, which in turn could help them achieve skin homeostasis and be useful for prophylaxis or auxiliary treatment against microbial infections. This interdisciplinary research in behavior, separation science, and effect-directed analysis highlighted the importance of particular invertebrates in coral reefs, the urgent need to protect coral reefs for dolphins and other species, and calls for further vertebrate-invertebrate interaction studies (Morlock et al. iScience, 2022).
May 12, 2022
Young cerebrospinal fluid rejuvenates the brain restores memory in aged mice
Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds. Iram et al. (Nature; 2022) discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. They further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, they identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. The authors screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.
High-resolution mapping of losses and gains of Earth’s tidal wetlands
Ecologically and economically important coastal wetlands are threatened by sea level rise and land use change. Murray et al. (Science 2022; 376: 744-749) used high-resolution satellite imagery to assess the global extent of tidal wetlands and changes in wetland extent and distribution over the past two decades. They found that although over 13,000 square kilometers of tidal wetland have recently been lost, much of this decreasing extent has been offset by the creation of new wetlands. The greatest losses and gains were in tidal flats, but mangrove ecosystems showed the largest net decline in area globally. Direct human impacts on wetlands, including land transformation and restoration, are detectable from satellite imagery and account for 27% of wetland losses and gains.
May 6, 2022
Conversion of oxybenzone sunscreen to phototoxic glucoside conjugates by sea anemones and corals
Coral reefs face many serious threats from human activity. Sunscreens can cause reef damage, and although the precise mechanisms involved are still under study, some localities have already phased out common components such as oxybenzone. Using a sea anemone as a model system, Vuckovic et al. Science 2022; 376:644-648 found that oxybenzone is modified within cells by attachment of glucose, turning it from a sunscreen into a potent photosensitizer. The glycoside conjugate is concentrated within the algal symbionts of anemones and corals, and bleached anemones are more susceptible to damage when exposed to ultraviolet light and oxybenzone, suggesting that the algae provide some protection to their hosts. These experiments add to the understanding of reef damage by sunscreens and may help to inform policy and new sunscreen development.
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection
Gastrointestinal symptoms and SARS-CoV-2 RNA shedding in feces point to the gastrointestinal tract as a possible site of infection in COVID-19. Researchers from Stanford University measured the dynamics of fecal viral RNA in patients with mild to moderate COVID-19 followed for 10 months post-diagnosis. Natarajan et al. (Med; 2022) found that fecal viral RNA shedding was correlated with gastrointestinal symptoms in patients who had cleared their respiratory infection. They also observed that fecal shedding can continue to 7 months post-diagnosis. In conjunction with recent related findings, this work presents compelling evidence of SARS-CoV-2 infection in the gastrointestinal tract and suggests a possible role for long-term infection of the gastrointestinal tract in syndromes such as “long COVID.”
May 1, 2022
Biological matrix composites from cultured plant cells
The development of novel degradable biocomposites can contribute to answering the increasing global demand for sustainable materials. Roumeli et al. (PNAS 2022; 119 (15) e2119523119) present a method to obtain self-bonded biocomposite materials from cultured plant cells. Subjecting cells to a cold-compression molding process creates hierarchical biocomposites that have stiffness and strength comparable to commodity plastics, while being 100% biodegradable in soil. Introducing fillers expands the attainable functionalities, demonstrating the versatility of the proposed platform. The use of fast-growing plant cells offers the benefits of short harvest time, zero biomass waste during processing, in situ manufacturing, and no arable land requirement. The approach allows the possibility of further tuning the final material properties by genetically engineering the processed cells.
Comparison of the Aroma Composition and Sensory Properties of Dark Chocolates Made with Moist Incubated and Fermented Cocoa Beans
In a previous investigation, “moist incubation” was described by Schluter et al. (J Agric Food Chem. 2022; 70(13):4057-4065) as a novel postharvest treatment for cocoa and the aroma composition of the resulting cocoa nibs was compared to unfermented and fermented cocoa nibs. For this treatment, unfermented and dried nibs are rehydrated with an aqueous solution containing lactic acid and ethanol to adjust the pH value and are subsequently incubated at 45 °C under aerobic conditions for 72 h before drying. The aim of the present study was to investigate the sensory properties and aroma composition of dark chocolates made of these materials after roasting. Therefore, gas chromatography-olfactometry (GC-O) in combination with aroma extract dilution analysis (AEDA), quantitation with isotopically labeled standards, odor activity value (OAV) determination, and sensory analysis were performed. The three different chocolates had distinct sensory and OAV profiles. The sensory profiles showed a higher intensity of fruity aroma notes and a lower intensity of bitterness and astringency in the chocolate made with the moist incubated cocoa, while the chocolate made of fermented cocoa reached higher scores in the roasty aroma notes. Furthermore, higher OAVs were determined for the Strecker aldehydes in the chocolate made of the moist incubated cocoa, whereas higher OAVs for the pyrazines and the acids were detected in the chocolate made of fermented cocoa. In contrast, the chocolate produced with the unfermented cocoa showed low cocoa specific aroma notes and high levels of astringency and bitterness. The detected differences reveal interesting insights into the influence of different postharvest treatments on the resulting aroma composition in the final chocolate. Furthermore, the alternative postharvest treatment was demonstrated to result in chocolates with a pleasant sensory profile.
Computer-designed repurposing of chemical wastes into drugs
As the chemical industry continues to produce considerable quantities of waste chemicals it is essential to devise ‘circular chemistry’ schemes to productively back-convert at least a portion of these unwanted materials into useful products. Despite substantial progress in the degradation of some classes of harmful chemicals, work on ‘closing the circle’—transforming waste substrates into valuable products—remains fragmented and focused on well known areas. Comprehensive analyses of which valuable products are synthesizable from diverse chemical wastes are difficult because even small sets of waste substrates can, within few steps, generate millions of putative products, each synthesizable by multiple routes forming densely connected networks. Tracing all such syntheses and selecting those that also meet criteria of process and ‘green’ chemistries is, arguably, beyond the cognition of human chemists. Wolos et al. (Nature 2022; 604: 668-676) show how computers equipped with broad synthetic knowledge can help address this challenge. Using the forward-synthesis Allchemy platform, they generated giant synthetic networks emanating from approximately 200 waste chemicals recycled on commercial scales, retrieve from these networks tens of thousands of routes leading to approximately 300 important drugs and agrochemicals, and algorithmically rank these syntheses according to the accepted metrics of sustainable chemistry. Several of these routes were validated by experiment, including an industrially realistic demonstration on a ‘pharmacy on demand’ flow-chemistry platform. Wide adoption of computerized waste-to-valuable algorithms can accelerate productive reuse of chemicals that would otherwise incur storage or disposal costs, or even pose environmental hazards.
April 28, 2022
Machine learning-aided engineering of hydrolases for PET depolymerization
Plastic waste poses an ecological challenge and enzymatic degradation offers one, potentially green and scalable, route for polyesters waste recycling. Poly(ethylene terephthalate) (PET) accounts for 12% of global solid waste, and a circular carbon economy for PET is theoretically attainable through rapid enzymatic depolymerization followed by repolymerization or conversion/valorization into other products. Application of PET hydrolases, however, has been hampered by their lack of robustness to pH and temperature ranges, slow reaction rates and inability to directly use untreated postconsumer plastics. Lu et al. (Nature 2022; 604: 662-667) use a structure-based, machine learning algorithm to engineer a robust and active PET hydrolase. The mutant and scaffold combination (FAST-PETase: functional, active, stable and tolerant PETase) contains five mutations compared to wild-type PETase (N233K/R224Q/S121E from prediction and D186H/R280A from scaffold) and shows superior PET-hydrolytic activity relative to both wild-type and engineered alternatives between 30 and 50 °C and a range of pH levels. They demonstrate that untreated, postconsumer-PET from 51 different thermoformed products can all be almost completely degraded by FAST-PETase in 1 week. FAST-PETase can also depolymerize untreated, amorphous portions of a commercial water bottle and an entire thermally pretreated water bottle at 50 ºC. Finally, they demonstrate a closed-loop PET recycling process by using FAST-PETase and resynthesizing PET from the recovered monomers. Collectively, the results demonstrate a viable route for enzymatic plastic recycling at the industrial scale.
Production of β-ketoadipic acid from glucose in Pseudomonas putida KT2440 for use in performance-advantaged nylons
Biomass-derived chemicals can offer unique chemical functionality relative to petroleum-derived building blocks. Rorrer et al. (Cell Report Physical Science 2022; 3: 100840) report that β-ketoadipic acid (βKA), a C6 diacid with a β-ketone group, can be used as a performance-advantaged replacement for adipic acid in a nylon-6,6 analog. Building on their previous efforts to produce shikimate-derived products from carbohydrates, Pseudomonas putida KT2440 is engineered to produce βKA from glucose, achieving a 26 g/L titer. Following purification, βKA imparts an increase of 69°C above the nylon-6,6 glass transition temperature and 20% reduced water permeability, equivalent to nylon-6,10. Molecular simulations predict that the enhanced thermal properties result from rigidity introduced by the β-ketone. Process analysis predicts that βKA can be produced for US$1.94/kg from sugars, requiring 63% less energy and emitting 43% less greenhouse gases than fossil-based adipic acid. Overall, the study illustrates the potential for βKA to serve as a useful building block for bio-based polymers.
Hypothalamic deep brain stimulation as a strategy to manage anxiety disorders
Anxiety disorders are among the most prevalent mental illnesses worldwide. Despite significant advances in their treatment, many patients remain treatment resistant. Thus, new treatment modalities and targets are much needed. Li et al. (PNAS 2022; 119 (16) e2113518119) developed a deep brain stimulation therapy that targets a recently identified anxiety center in the lateral hypothalamus. They show that this therapy rapidly silences anxiety-implicated neurons and immediately relieves diverse anxiety symptoms in a variety of stressful situations. This therapeutic effect occurs without acute or chronic side effects that are typical of many existing treatments, such as physical sedation or memory deficits. These findings identify a clinically applicable new therapeutic strategy for helping patients to manage treatment-resistant anxiety.
April 18, 2022
Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome
Bisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements—bisphenol S (BPS) and bisphenol F (BPF)—are coming into wider use with very few data about their biological activities. Winkler et al. (PNAS 2022; 119 (11) e2115308119) compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.
April 8, 2022
Assistive robots have the potential to support people with disabilities in a variety of activities of daily living, such as dressing. People who have completely lost their upper limb movement functionality may benefit from robot-assisted dressing, which involves complex deformable garment manipulation. Zhang and Demiris (Science Robotics 2022; 7 (65)) report a dressing pipeline intended for these people and experimentally validate it on a medical training manikin. The pipeline is composed of the robot grasping a hospital gown hung on a rail, fully unfolding the gown, navigating around a bed, and lifting up the user’s arms in sequence to finally dress the user. To automate this pipeline, the authors address two fundamental challenges: first, learning manipulation policies to bring the garment from an uncertain state into a configuration that facilitates robust dressing; second, transferring the deformable object manipulation policies learned in simulation to real world to leverage cost-effective data generation. They tackle the first challenge by proposing an active pre-grasp manipulation approach that learns to isolate the garment grasping area before grasping. The approach combines prehensile and nonprehensile actions and thus alleviates grasping-only behavioral uncertainties. For the second challenge, they bridge the sim-to-real gap of deformable object policy transfer by approximating the simulator to real-world garment physics. A contrastive neural network is introduced to compare pairs of real and simulated garment observations, measure their physical similarity, and account for simulator parameters inaccuracies. The proposed method enables a dual-arm robot to put back-opening hospital gowns onto a medical manikin with a success rate of more than 90%.
Spherical nucleic acids as an infectious disease vaccine platform
Using SARS-CoV-2 as a relevant case study for infectious disease, Teplensky et al. (PNAS 2022; 119 (14) e2119093119) investigate the structure–function relationships that dictate antiviral spherical nucleic acid (SNA) vaccine efficacy. They show that the SNA architecture can be rapidly employed to target COVID-19 through incorporation of the receptor-binding domain, and that the resulting vaccine potently activates human cells in vitro and mice in vivo. Furthermore, when challenged with a lethal viral infection, only mice treated with the SNA vaccine survived. Taken together, this work underscores the importance of rational vaccine design for infectious disease to yield vaccines that elicit more potent immune responses to effectively fight disease.
Blockage of mixed lineage kinase domain–like protein (MLKL) prevents myelin damage in experimental diabetic neuropathy
Demyelination is a pathological feature of diabetic neuropathy, a common and painful complication of diabetes, yet the mechanisms underlying diabetes-induced demyelination remain unclear. Guo et al. (PNAS 2022; 119 (14): e2121552119) show that targeting mixed lineage kinase domain–like protein (MLKL), a protein critical in necroptosis, using Schwann cell–specific genetic knockout, S441A single–amino acid knockin mutation, or pharmacological inhibition all blocked myelin sheath decompaction and prevented the decrease of nerve conduction velocity in streptozotocin-induced diabetic mice. The decompaction of the myelin sheaths of sural nerves was observed in biopsy samples from diabetic patients, and the MLKL-mediated myelin breakdown was activated in human diabetic neuropathy patients. The study establishes a direct myelin degradation–related role for MLKL in diabetic neuropathy and defines MLKL as a druggable target for developing agents to prevent or treat diabetic neuropathy.
March 29, 2022
In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Gurevich et al. (Nature Medicine 2022) evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts. Subsequently, a randomized, placebo-controlled, phase 1 and 2 clinical trial (NCT03536143) evaluated matched wounds from nine RDEB patients receiving topical B-VEC or placebo repeatedly over 12 weeks. No grade 2 or above B-VEC-related adverse events or vector shedding or tissue-bound skin immunoreactants were noted. HSV-1 and C7 antibodies sometimes presented at baseline or increased after B-VEC treatment without an apparent impact on safety or efficacy. Primary and secondary objectives of C7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure following B-VEC treatment were met. A patient-reported pain–severity secondary outcome was not assessed given the small proportion of wounds treated. A global assessment secondary endpoint was not pursued due to redundancy with regard to other endpoints. These studies show that B-VEC is an easily administered, safely tolerated, topical molecular corrective therapy promoting wound healing in patients with RDEB.
March 23, 2022
Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice
Immunotherapy has so far been of little use at treating highly aggressive pancreatic ductal adenocarcinoma (PDAC) due to its immunosuppressive tumor microenvironment. Selvanesan et al. (Sci Transl Med. 2022; 14(637):eabc1600) have solicited the help of Listeria monocytogenes to deliver highly immunogenic tetanus toxoid proteins directly into tumor cells. This delivery elicits an immune response, activating tetanus toxoid–specific memory T cells to kill tumor cells in mice. When combined with gemcitabine, advanced PDAC tumor burden and metastases were further reduced in mice, representing a promising new therapeutic strategy that needs further investigation in humans.
Recognition of natural objects by the archerfish
Recognition of individual objects and their categorization is a complex computational task. Nevertheless, visual systems can perform this task in a rapid and accurate manner. Humans and other animals can efficiently recognize objects despite countless variations in their projection on the retina due to different viewing angles, distance, illumination conditions and other parameters. To gain a better understanding of the recognition process in teleosts, Volotsky et al. (J Exp Biol. 2022; 225(3):jeb243237) explored it in archerfish, a species that hunts by shooting a jet of water at aerial targets and thus can benefit from ecologically relevant recognition of natural objects. The authors found that archerfish not only can categorize objects into relevant classes but also can do so for novel objects, and additionally they can recognize an individual object presented under different conditions. To understand the mechanisms underlying this capability, they developed a computational model based on object features and a machine learning classifier. The analysis of the model revealed that a small number of features was sufficient for categorization, and the fish were more sensitive to object contours than textures. They tested these predictions in additional behavioral experiments and validated them. The findings suggest the existence of a complex visual process in the archerfish visual system that enables object recognition and categorization.
March 15, 2022
Light exposure during sleep impairs cardiometabolic function
Ambient nighttime light exposure is implicated as a risk factor for adverse health outcomes, including cardiometabolic disease. However, the effects of nighttime light exposure during sleep on cardiometabolic outcomes and the related mechanisms are unclear. Mason et al. (PNAS 2022; 119 (12) e2113290119) showed that, in healthy adults, one night of moderate (100 lx) light exposure during sleep increases nighttime heart rate, decreases heart rate variability (higher sympathovagal balance), and increases next-morning insulin resistance when compared to sleep in a dimly lit (<3 lx) environment. Moreover, a positive relationship between higher sympathovagal balance and insulin levels suggests that sympathetic activation may play a role in the observed light-induced changes in insulin sensitivity.
Tryptophan depletion results in tryptophan-to-phenylalanine substitutants
Activated T cells secrete interferon-γ, which triggers intracellular tryptophan shortage by upregulating the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. IDO1 catabolizes tryptophan to generate metabolites along the kynurenine pathway to subvert T cell immunity. Pataskar et al. (Nature 2022; 603: 721–727) show that despite tryptophan depletion, in-frame protein synthesis continues across tryptophan codons. The authors identified tryptophan-to-phenylalanine codon reassignment (W>F) as the major event facilitating this process, and pinpointed tryptophanyl-tRNA synthetase (WARS1) as its source. They call these W>F peptides ‘substitutants’ to distinguish them from genetically encoded mutants. Using large-scale proteomics analyses, they demonstrate W>F substitutants to be highly abundant in multiple cancer types. W>F substitutants were enriched in tumours relative to matching adjacent normal tissues, and were associated with increased IDO1 expression, oncogenic signalling and the tumour-immune microenvironment. Functionally, W>F substitutants can impair protein activity, but also expand the landscape of antigens presented at the cell surface to activate T cell responses. Thus, substitutants are generated by an alternative decoding mechanism with potential effects on gene function and tumour immunoreactivity.
AVONET: morphological, ecological and geographical data for all birds
Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species-level information is complete. Tobias et al. (Ecology Letters 2022; 25(3):581-597) present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarized as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity.
March 11, 2022
Bacterioboat—a novel tool to increase the half-life period of the orally administered drug
The short half-life in the gastrointestinal tract necessitates an excess of drugs causing side effects of oral formulations. Kaur et al. (Science Advances 2022; 8: Issue 10) report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.
March 3, 2022
Sodium-enriched floral nectar increases pollinator visitation rate and diversity
Plants have evolved a variety of approaches to attract pollinators, including enriching their nectar with essential nutrients. Because sodium is an essential nutrient for pollinators, and sodium concentration in nectar can vary both within and among species, Finkelstein et al. (2022; Biology Letters) explored whether experimentally enriching floral nectar with sodium in five plant species would influence pollinator visitation and diversity. They found that the number of visits by pollinators increased on plants with sodium-enriched nectar, regardless of plant species, relative to plants receiving control nectar. Similarly, the number of species visiting plants with sodium-enriched nectar was twice that of controls. The findings suggest that sodium in floral nectar may play an important but unappreciated role in the ecology and evolution of plant–pollinator mutualisms.
Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants
Following a vegetarian diet has become increasingly popular and some evidence suggests that being vegetarian may be associated with a lower risk of cancer overall. However, for specific cancer sites, the evidence is limited. The aim was to assess the associations of vegetarian and non-vegetarian diets with risks of all cancer, colorectal cancer, postmenopausal breast cancer, and prostate cancer and to explore the role of potential mediators between these associations. Batling et al. (2022; BMC Medicine) conducted a prospective analysis of 472,377 UK Biobank participants who were free from cancer at recruitment. Participants were categorised into regular meat-eaters (n = 247,571), low meat-eaters (n = 205,385), fish-eaters (n = 10,696), and vegetarians (n = 8685) based on dietary questions completed at recruitment. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all cancer incidence and separate cancer sites across diet groups. After an average follow-up of 11.4 years, 54,961 incident cancers were identified, including 5882 colorectal, 7537 postmenopausal breast, and 9501 prostate cancers. Compared with regular meat-eaters, being a low meat-eater, fish-eater, or vegetarian were all associated with a lower risk of all cancer (HR: 0.98, 95% CI: 0.96–1.00; 0.90, 0.84–0.96; 0.86, 0.80–0.93, respectively). Being a low meat-eater was associated with a lower risk of colorectal cancer in comparison to regular meat-eaters (0.91, 0.86–0.96); however, there was heterogeneity in this association by sex (p = 0.007), with an inverse association across diet groups in men, but not in women. Vegetarian postmenopausal women had a lower risk of breast cancer (0.82, 0.68–0.99), which was attenuated and non-significant after adjusting for body mass index (BMI; 0.87, 0.72–1.05); in mediation analyses, BMI was found to possibly mediate the observed association. In men, being a fish-eater or a vegetarian was associated with a lower risk of prostate cancer (0.80, 0.65–0.99 and 0.69, 0.54–0.89, respectively). The lower risk of colorectal cancer in low meat-eaters is consistent with previous evidence suggesting an adverse impact of meat intake. The lower risk of postmenopausal breast cancer in vegetarian women may be explained by their lower BMI. It is not clear whether the other differences observed for all cancers and for prostate cancer reflect any causal relationships or are due to other factors such as residual confounding or differences in cancer detection.
March 2, 2022
Premature aging in mice with error-prone protein synthesis
The main source of error in gene expression is messenger RNA decoding by the ribosome. Translational accuracy has been suggested on a purely correlative basis to positively coincide with maximum possible life span among different rodent species, but causal evidence that translation errors accelerate aging in vivo and limit life span is lacking. Scherbakov et al. (2022; Science Advances 8: Issue 9) addressed this question experimentally by creating heterozygous knock-in mice that express the ribosomal ambiguity mutation RPS9 D95N, resulting in genome-wide error-prone translation. The authors show that Rps9 D95N knock-in mice exhibit reduced life span and a premature onset of numerous aging-related phenotypes, such as reduced weight, chest deformation, hunchback posture, poor fur condition, and urinary syndrome, together with lymphopenia, increased levels of reactive oxygen species–inflicted damage, accelerated age-related changes in DNA methylation, and telomere attrition. The data provide an experimental link between translational accuracy, life span, and aging-related phenotypes in mammals.
Mitochondria in cone photoreceptors act as microlenses to enhance photon delivery and confer directional sensitivity to light
Mammalian photoreceptors aggregate numerous mitochondria, organelles chiefly for energy production, in the ellipsoid region immediately adjacent to the light-sensitive outer segment to support the high metabolic demands of phototransduction. However, these complex, lipid-rich organelles are also poised to affect light passage into the outer segment. Ball et al. (2022; Science Advances 8: Issue 9) show, via live imaging and simulations, that despite this risk of light scattering or absorption, these tightly packed mitochondria “focus” light for entry into the outer segment and that mitochondrial remodeling affects such light concentration. This “microlens”-like feature of cone mitochondria delivers light with an angular dependence akin to the Stiles-Crawford effect (SCE), providing a simple explanation for this essential visual phenomenon that improves resolution. This new insight into the optical role of mitochondria is relevant for the interpretation of clinical ophthalmological imaging, lending support for the use of SCE as an early diagnostic tool in retinal disease.
Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells
Chromosome instability is a critical event in cancer progression. Histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Up-regulation of lncRNAs in many cancers correlates with poor prognosis and recurrence in patients. Arunkumar et al. (2022; Science Advances 8: Issue 9) report that transcription of 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the 8q24 chromatin landscape by H3.3 chaperone–mediated deposition of CENP-A–associated complexes. Furthermore, a transgene cassette carrying specific 8q24-derived lncRNA integrated into a naïve chromosome locus recruits CENP-A to the new location in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory at a fragile site in human cancer cells.
February 25, 2022
A unified genealogy of modern and ancient genomes
Hundreds of thousands of modern human genomes and thousands of ancient human genomes have been generated to date. However, different methods and data quality can make comparisons among them difficult. Furthermore, every human genome contains segments from ancestries of varying ages. Wohns et al. (2022; Science 375: Issue 6583) applied a tree recording method to ancient and modern human genomes to generate a unified human genealogy. This method allows for missing and erroneous data and uses ancient genomes to calibrate genomic coalescent times. This permits us to determine how our genomes have changed over time and between populations, informing upon the evolution of our species.
February 17, 2022
Latent heat thermophotovoltaic batteries
Latent heat thermophotovoltaic (LHTPV) batteries store electricity as latent heat at very high temperatures (>1,000°C) and convert this heat back to electricity on demand using thermophotovoltaics (TPVs). Datas et al. (2022; Joule 6: P418-443) discuss the techno-economics of LHTPV systems, focusing on parameters such as the round-trip efficiency, energy-to-power ratio, cost per energy and power capacities, and levelized cost of storage. The very low cost of the heat storage media (<4 €/kWh) results in optimal designs with high energy-to-power ratios, fitting long-duration storage (LDS) applications. Shorter-duration storage applications are also possible by increasing the overall round-trip conversion efficiency through cogeneration, that is, combined heat and power (CHP) generation. Results indicate that LHTPV systems can provide lower levelized cost of storage than Li-ion batteries in both LDS and CHP applications. Preliminary experimental results are provided to illustrate the real operation of a LHTPV system.
February 16, 2022
Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs
A major challenge in lung transplantation is the need for ABO blood group matching. To address this challenge, Wang et al. (2022. Sci Transl Med. 14(632):eabm7190) used two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, to convert blood group A lungs to blood group O lungs during ex vivo lung perfusion. The authors demonstrated successful removal of blood group A antigen with no overt changes in lung health. In an ex vivo simulation of transplantation, the authors showed reduced antibody and complement deposition, suggesting that this technique may reduce antibody-mediated injury in vivo. Together, these findings have the potential to improve fairness in lung allocation for transplantation.
The influence of iodine on the Antarctic stratospheric ozone hole
The role of chlorine and bromine in Antarctic stratospheric ozone depletion is well known. However, the contribution of iodine to the ozone hole chemistry has not been assessed, mainly due to the negligible amounts of iodine previously reported to enter the stratosphere. New measurements demonstrate that the injection of iodine to the lower stratosphere is higher than previously assumed. Based on these observations, Cuevas et al. (PNAS 2022; 119 (7): e2110864119) modeling work shows that iodine chemistry can enhance spring ozone loss at the lower part of the Antarctic ozone hole, and even dominate the halogen-mediated ozone loss during summer. Iodine can also alter, by several days, the timing of the seasonal formation and closure of the ozone hole.
February 15, 2022
Fear of predators in free-living wildlife reduces population growth over generations
Accurately evaluating the total impact of predators on prey population growth rates is fundamental to forecasting the consequences of predator conservation and management. That the fear (antipredator responses) predators inspire could contribute to this total impact has only relatively recently been recognized. Allen et al. (PNAS 2022; 119 (7) e2112404119) experimentally demonstrate that fear itself can impact prey population growth rates in free-living wildlife, extending to transgenerational impacts reducing population growth beyond the parental generation. They report how fear may contribute considerably to the total impact of predators and why this may be the norm in birds and mammals. The critical significance of our work lies in experimentally establishing that inferring the effects of predators using data on direct killing alone risks dramatically underestimating their total impact.
February 10, 2022
Measuring biodiversity from DNA in the air
The crisis of declining biodiversity exceeds our current ability to monitor changes in ecosystems. Rapid terrestrial biomonitoring approaches are essential to quantify the causes and consequences of global change. Environmental DNA has revolutionized aquatic ecology, permitting population monitoring and remote diversity assessments matching or outperforming conventional methods of community sampling. Despite this model, similar methods have not been widely adopted in terrestrial ecosystems. Clare et al. (2022; Current Biology 32:693-700) demonstrate that DNA from terrestrial animals can be filtered, amplified, and then sequenced from air samples collected in natural settings representing a powerful tool for terrestrial ecology. They collected air samples at a zoological park, where spatially confined non-native species allowed us to track DNA sources. They show that DNA can be collected from air and used to identify species and their ecological interactions. Air samples contained DNA from 25 species of mammals and birds, including 17 known terrestrial resident zoo species. They also identified food items from air sampled in enclosures and detected taxa native to the local area, including the Eurasian hedgehog, endangered in the United Kingdom. The data demonstrate that airborne eDNA concentrates around recently inhabited areas but disperses away from sources, suggesting an ecology to airborne eDNA and the potential for sampling at a distance. The findings demonstrate the profound potential of air as a source of DNA for global terrestrial biomonitoring.
Fish waves as emergent collective antipredator behavior
The collective behavior of animals has attracted considerable attention in recent years, with many studies exploring how local interactions between individuals can give rise to global group properties. The functional aspects of collective behavior are less well studied, especially in the field, and relatively few studies have investigated the adaptive benefits of collective behavior in situations where prey are attacked by predators. This paucity of studies is unsurprising because predator-prey interactions in the field are difficult to observe. Furthermore, the focus in recent studies on predator-prey interactions has been on the collective behavior of the prey rather than on the behavior of the predator. Doran et al. (2022; Current Biology 32:708-714.e4) present a field study that investigated the anti-predator benefits of waves produced by fish at the water surface when diving down collectively in response to attacks of avian predators. Fish engaged in surface waves that were highly conspicuous, repetitive, and rhythmic involving many thousands of individuals for up to 2 min. Experimentally induced fish waves doubled the time birds waited until their next attack, therefore substantially reducing attack frequency. In one avian predator, capture probability, too, decreased with wave number and birds switched perches in response to wave displays more often than in control treatments, suggesting that they directed their attacks elsewhere. Taken together, these results support an anti-predator function of fish waves. The attack delay could be a result of a confusion effect or a consequence of waves acting as a perception advertisement, which requires further exploration.
Ants resort to majority concession to reach democratic consensus in the presence of a persistent minority
Social groups often need to overcome differences in individual interests and knowledge to reach consensus decisions. Rajendran et al. (Curr Biol. 2022 32(3):645-653.e8) combined experiments and modeling to study conflict resolution in emigrating ant colonies during binary nest selection. They find that cohesive emigration, without fragmentation, is achieved only by intermediate-sized colonies. They then imposed a conflict regarding the desired emigration target between colony subgroups. This is achieved using an automated selective gate system that manipulates the information accessible to each ant. Under this conflict, they find that individuals concede their potential benefit to promote social consensus. In particular, colonies resolve the conflict imposed by a persistent minority through “majority concession,” wherein a majority of ants that hold first-hand knowledge regarding the superior quality nest choose to reside in the inferior one. This outcome is unlikely in social groups of selfish individuals and emphasizes the importance of group cohesion in eusocial societies.
Caloric restriction in humans reveals immunometabolic regulators of health span
Moderately decreased food intake that does not cause malnutrition (caloric restriction) has beneficial effects on health span and life span in model organisms. Spadaro et al. (2022; Science 375: 671-677) examined measures of immune function in humans who restricted caloric intake by about 14% over 2 years and in mice under a more severe 40% restriction. Cellular analyses and transcriptional surveys showed marks of improved thymic function under caloric restriction. Expression of the gene encoding platelet activating factor acetylhydrolase (PLA2G7) was decreased in humans undergoing caloric restriction. Inactivation of the gene in mice decreased inflammation and improved markers of thymic function and some metabolic functions in aging mice. Thus, decreased expression of PLA2G7 might mediate some beneficial effects of caloric restriction.
February 9, 2022
Monocotyledonous plants graft at the embryonic root–shoot interface
Grafting is possible in both animals and plants. Although in animals the process requires surgery and is often associated with rejection of non-self, in plants grafting is widespread, and has been used since antiquity for crop improvement. However, in the monocotyledons, which represent the second largest group of terrestrial plants and include many staple crops, the absence of vascular cambium is thought to preclude grafting. Reeves et al (2022; Nature 602: 280–286) show that the embryonic hypocotyl allows intra- and inter-specific grafting in all three monocotyledon groups: the commelinids, lilioids and alismatids. They show functional graft unions through histology, application of exogenous fluorescent dyes, complementation assays for movement of endogenous hormones, and growth of plants to maturity. Expression profiling identifies genes that unify the molecular response associated with grafting in monocotyledons and dicotyledons, but also gene families that have not previously been associated with tissue union. Fusion of susceptible wheat scions to oat rootstocks confers resistance to the soil-borne pathogen Gaeumannomyces graminis. Collectively, these data overturn the consensus that monocotyledons cannot form graft unions, and identify the hypocotyl (mesocotyl in grasses) as a meristematic tissue that allows this process. The authors conclude that graft compatibility is a shared ability among seed-bearing plants.
Gigantic floating leaves occupy a large surface area at an economical material cost
The giant Amazonian waterlily (genus Victoria) produces the largest floating leaves in the plant kingdom. The leaves’ notable vasculature has inspired artists, engineers, and architects for centuries. Despite the aesthetic appeal and scale of this botanical enigma, little is known about the mechanics of these extraordinary leaves. For example, how do these leaves achieve gigantic proportions? Box et al. (2022; Science Advances 8: Issue 6) show that the geometric form of the leaf is structurally more efficient than those of other smaller species of waterlily. In particular, the spatially varying thickness and regular branching of the primary veins ensures the structural integrity necessary for extensive coverage of the water surface, enabling optimal light capture despite a relatively low leaf biomass. Leaf gigantism in waterlilies may have been driven by selection pressures favoring a large surface area at an economical material cost, for outcompeting other plants in fast-drying ephemeral pools.
Ebola virus persistence and disease recurrence in the brains of antibody-treated nonhuman primate survivors
Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, Liu et al. (2022; Science Translational Medicine 14: Issue 631) discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood–cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD.
February 8, 2022
The number of tree species on Earth
One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Gatti et al. (2022, PNAS 119 (6): e2115329119) based on global ground-sourced data, estimated the total tree species richness at global, continental, and biome levels. The results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness.
A 680,000-person megastudy of nudges to encourage vaccination in pharmacies
Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. Milkman et al. (2022; PNAS 119 (6): e2115126119) randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. They found that the reminder texts that they tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was “waiting for you.” Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy.
Airborne environmental DNA for terrestrial vertebrate community monitoring
Biodiversity monitoring at the community scale is a critical element of assessing and studying species distributions, ecology, diversity, and movements, and it is key to understanding and tracking environmental and anthropogenic effects on natural ecosystems. Vertebrates in terrestrial ecosystems are experiencing extinctions and declines in both population numbers and sizes due to increasing threats from human activities and environmental change. Terrestrial vertebrate monitoring using existing methods is generally costly and laborious, and although environmental DNA (eDNA) is becoming the tool of choice to assess biodiversity, few sample types effectively capture terrestrial vertebrate diversity. Lynggaard et al. (2022; Current Biology 32: P701-707) hypothesized that eDNA captured from air could allow straightforward collection and characterization of terrestrial vertebrate communities. They filtered air at three localities in the Copenhagen Zoo: a stable, outside between the outdoor enclosures, and in the Rainforest House. Through metabarcoding of airborne eDNA, they detected 49 vertebrate species spanning 26 orders and 37 families: 30 mammal, 13 bird, 4 fish, 1 amphibian, and 1 reptile species. These spanned animals kept at the zoo, species occurring in the zoo surroundings, and species used as feed in the zoo. The detected species comprise a range of taxonomic orders and families, sizes, behaviors, and abundances. They found shorter distance to the air sampling device and higher animal biomass to increase the probability of detection. The authors show that airborne eDNA can offer a fundamentally new way of studying and monitoring terrestrial communities.
February 3, 2022
Multiscale engineered artificial tooth enamel
Tooth enamel, renowned for its high stiffness, hardness, and viscoelasticity, is an ideal model for designing biomimetic materials, but accurate replication of complex hierarchical organization of high-performance biomaterials in scalable abiological composites is challenging. Zhao et al. (2022; Science 375: 551-556) engineered an enamel analog with the essential hierarchical structure at multiple scales through assembly of amorphous intergranular phase (AIP)–coated hydroxyapatite nanowires intertwined with polyvinyl alcohol. The nanocomposite simultaneously exhibited high stiffness, hardness, strength, viscoelasticity, and toughness, exceeding the properties of enamel and previously manufactured bulk enamel-inspired materials. The presence of AIP, polymer confinement, and strong interfacial adhesion are all needed for high mechanical performance. This multiscale design is suitable for scalable production of high-performance materials.
Reconfigurable perovskite nickelate electronics for artificial intelligence
Having all the core functionality required for neuromorphic computing in one type of a device could offer dramatic improvements to emerging computing architectures and brain-inspired hardware for artificial intelligence. Zhang et al. (Science 2022; 375: 533-539) showed that proton-doped perovskite neodymium nickelate (NdNiO3) could be reconfigured at room temperature by simple electrical pulses to generate the different functions of neuron, synapse, resistor, and capacitor. The authors designed a prototype experimental network that not only demonstrated electrical reconfiguration of the device, but also showed that such dynamic networks enabled a better approximation of the dataset for incremental learning scenarios compared with static networks.
February 2, 2022
Irreversible synthesis of an ultrastrong two-dimensional polymeric material
Polymers that extend covalently in two dimensions have attracted recent attention as a means of combining the mechanical strength and in-plane energy conduction of conventional two-dimensional (2D) materials with the low densities, synthetic processability and organic composition of their one-dimensional counterparts. Efforts so far have proven successful in forms that do not allow full realization of these properties, such as polymerization at flat interfaces or fixation of monomers in immobilized lattices. Another frequently employed synthetic approach is to introduce microscopic reversibility, at the cost of bond stability, to achieve 2D crystals after extensive error correction. Zeng et al. (2022; Nature 602:91-95) demonstrate a homogenous 2D irreversible polycondensation that results in a covalently bonded 2D polymeric material that is chemically stable and highly processable. Further processing yields highly oriented, free-standing films that have a 2D elastic modulus and yield strength of 12.7 ± 3.8 gigapascals and 488 ± 57 megapascals, respectively. This synthetic route provides opportunities for 2D materials in applications ranging from composite structures to barrier coating materials.
January 27, 2022
Nitrogen recycling via gut symbionts increases in ground squirrels over the hibernation season
Hibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. Regan et al. (2022) (Science 375: 460-463) reveal gut microbiome–mediated urea nitrogen recycling in hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Ureolytic gut microbes incorporate urea nitrogen into metabolites that are absorbed by the host, with the nitrogen reincorporated into the squirrel’s protein pool. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. These results reveal a functional role for the gut microbiome during hibernation and suggest mechanisms by which urea nitrogen recycling may contribute to protein balance in other monogastric animals.
Magnetic stop signs signal a European songbird’s arrival at the breeding site after migration
Although it is known that birds can return to their breeding grounds with exceptional precision, it has remained a mystery how they know when and where to stop migrating. Using nearly a century’s worth of Eurasian reed warbler (Acrocephalus scirpaceus) ringing recoveries, Wynn et al. (2022) (Science 375: 446-449) investigated whether fluctuations in Earth’s magnetic field predict variation in the sites to which birds return. Ringing recoveries suggest that magnetic inclination is learned before departure and is subsequently used as a uni-coordinate “stop sign” when relocating the natal or breeding site. However, many locations have the same inclination angle. Data from populations with different migratory directions indicate that birds solve this ambiguity by stopping at the first place where the right inclination is encountered on an inherited return vector.
Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis
Limb regeneration is a frontier in biomedical science. Identifying triggers of innate morphogenetic responses in vivo to induce the growth of healthy patterned tissue would address the needs of millions of patients, from diabetics to victims of trauma. Organisms such as Xenopus laevis—whose limited regenerative capacities in adulthood mirror those of humans—are important models with which to test interventions that can restore form and function. Murugan et al. (2022) (Science Advances 8, Issue 4) demonstrate long-term (18 months) regrowth, marked tissue repatterning, and functional restoration of an amputated X. laevis hindlimb following a 24-hour exposure to a multidrug, pro-regenerative treatment delivered by a wearable bioreactor. Regenerated tissues composed of skin, bone, vasculature, and nerves significantly exceeded the complexity and sensorimotor capacities of untreated and control animals’ hypomorphic spikes. RNA sequencing of early tissue buds revealed activation of developmental pathways such as Wnt/β-catenin, TGF-β, hedgehog, and Notch. These data demonstrate the successful “kickstarting” of endogenous regenerative pathways in a vertebrate model.
January 18, 2022
Conservation of magnetite biomineralization genes in all domains of life and implications for magnetic sensing
Animals use geomagnetic fields for navigational cues, yet the sensory mechanism underlying magnetic perception remains poorly understood. One idea is that geomagnetic fields are physically transduced by magnetite crystals contained inside specialized receptor cells, but evidence for intracellular, biogenic magnetite in eukaryotes is scant. Certain bacteria produce magnetite crystals inside intracellular compartments, representing the most ancient form of biomineralization known and having evolved prior to emergence of the crown group of eukaryotes, raising the question of whether magnetite biomineralization in eukaryotes and prokaryotes might share a common evolutionary history. Bellinger et al. (2022) (PNAS January 18, 2022 119 (3) e2108655119) discover that salmonid olfactory epithelium contains magnetite crystals arranged in compact clusters and determine that genes differentially expressed in magnetic olfactory cells, contrasted to nonmagnetic olfactory cells, share ancestry with an ancient prokaryote magnetite biomineralization system, consistent with exaptation for use in eukaryotic magnetoreception. They also show that 11 prokaryote biomineralization genes are universally present among a diverse set of eukaryote taxa and that nine of those genes are present within the Asgard clade of archaea Lokiarchaeota that affiliates with eukaryotes in phylogenomic analysis. Consistent with deep homology, they present an evolutionary genetics hypothesis for magnetite formation among eukaryotes to motivate convergent approaches for examining magnetite-based magnetoreception, molecular origins of matrix-associated biomineralization processes, and eukaryogenesis.
January 13, 2022
A vast icefish breeding colony discovered in the Antarctic
A breeding colony of notothenioid icefish (Neopagetopsis ionah, Nybelin 1947) of globally unprecedented extent has been discovered in the southern Weddell Sea, Antarctica. The colony was estimated to cover at least ∼240 km2 of the eastern flank of the Filchner Trough, comprised of fish nests at a density of 0.26 nests per square meter, representing an estimated total of ∼60 million active nests and associated fish biomass of >60,000 tonnes. The majority of nests were each occupied by 1 adult fish guarding 1,735 eggs. Bottom water temperatures measured across the nesting colony were up to 2°C warmer than the surrounding bottom waters, indicating a spatial correlation between the modified Warm Deep Water (mWDW) upflow onto the Weddell Shelf and the active nesting area. Historical and concurrently collected seal movement data indicate that this concentrated fish biomass may be utilized by predators such as Weddell seals (Leptonychotes weddellii, Lesson 1826). Numerous degraded fish carcasses within and near the nesting colony suggest that, in death as well as life, these fish provide input for local food webs and influence local biogeochemical processing. The area surveyed harbors the most spatially expansive continuous fish breeding colony discovered to date globally at any depth, as well as an exceptionally high Antarctic seafloor biomass. This discovery provides support for the establishment of a regional marine protected area in the Southern Ocean under the Convention on the Conservation of Antarctic Marine Living Resources (CCAMLR) umbrella [Purser et al. (2022). Current Biology].
January 12, 2022
Star formation near the Sun is driven by expansion of the Local Bubble
For decades we have known that the Sun lies within the Local Bubble, a cavity of low-density, high-temperature plasma surrounded by a shell of cold, neutral gas and dust. However, the precise shape and extent of this shell, the impetus and timescale for its formation and its relationship to nearby star formation have remained uncertain, largely due to low-resolution models of the local interstellar medium. Zuker et al. (2022) (Journal: Nature) report an analysis of the three-dimensional positions, shapes and motions of dense gas and young stars within 200 pc of the Sun, using new spatial and dynamical constraints. We find that nearly all of the star-forming complexes in the solar vicinity lie on the surface of the Local Bubble and that their young stars show outward expansion mainly perpendicular to the bubble’s surface. Tracebacks of these young stars’ motions support a picture in which the origin of the Local Bubble was a burst of stellar birth and then death (supernovae) taking place near the bubble’s centre beginning approximately 14 Myr ago. The expansion of the Local Bubble created by the supernovae swept up the ambient interstellar medium into an extended shell that has now fragmented and collapsed into the most prominent nearby molecular clouds, in turn providing robust observational support for the theory of supernova-driven star formation.
Cancer risk across mammals
Cancer is a ubiquitous disease of metazoans, predicted to disproportionately affect larger, long-lived organisms owing to their greater number of cell divisions, and thus increased probability of somatic mutations. While elevated cancer risk with larger body size and/or longevity has been documented within species, Peto’s paradox indicates the apparent lack of such an association among taxa. Yet, unequivocal empirical evidence for Peto’s paradox is lacking, stemming from the difficulty of estimating cancer risk in non-model species. Vincze et al. (2022) (Nature 601: 263–267) build and analyse a database on cancer-related mortality using data on adult zoo mammals (110,148 individuals, 191 species) and map age-controlled cancer mortality to the mammalian tree of life. They demonstrate the universality and high frequency of oncogenic phenomena in mammals and reveal substantial differences in cancer mortality across major mammalian orders. They show that the phylogenetic distribution of cancer mortality is associated with diet, with carnivorous mammals (especially mammal-consuming ones) facing the highest cancer-related mortality. Moreover, they provide unequivocal evidence for the body size and longevity components of Peto’s paradox by showing that cancer mortality risk is largely independent of both body mass and adult life expectancy across species. These results highlight the key role of life-history evolution in shaping cancer resistance and provide major advancements in the quest for natural anticancer defences.
Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits
More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Liu et al. (2022) (Science Translational Medicine 14: Issue 627) demonstrated that a biodegradable piezoelectric poly(L-lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. The PLLA scaffold under applied force or joint load generated a controllable piezoelectric charge, which promoted extracellular protein adsorption, facilitated cell migration or recruitment, induced endogenous TGF-β via calcium signaling pathway, and improved chondrogenesis and cartilage regeneration both in vitro and in vivo. Rabbits with critical-sized osteochondral defects receiving the piezoelectric scaffold and exercise treatment experienced hyaline-cartilage regeneration and completely healed cartilage with abundant chondrocytes and type II collagen after 1 to 2 months of exercise (2 to 3 months after surgery including 1 month of recovery before exercise), whereas rabbits treated with nonpiezoelectric scaffold and exercise treatment had unfilled defect and limited healing. The approach of combining biodegradable piezoelectric tissue scaffolds with controlled mechanical activation (via physical exercise) may therefore be useful for the treatment of osteoarthritis and is potentially applicable to regenerating other injured tissues.
Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma
Exacerbations of symptoms represent an unmet need for people with asthma. Bacterial dysbiosis and opportunistic bacterial infections have been observed in, and may contribute to, more severe asthma. However, the molecular mechanisms driving these exacerbations remain unclear. Headland et al. (2022) (Science Translational Medicine 14: Issue 627) show that bacterial lipopolysaccharide (LPS) induces oncostatin M (OSM) and that airway biopsies from patients with severe asthma present with an OSM-driven transcriptional profile. This profile correlates with activation of inflammatory and mucus-producing pathways. Using primary human lung tissue or human epithelial and mesenchymal cells, they demonstrate that OSM is necessary and sufficient to drive pathophysiological features observed in severe asthma after exposure to LPS or Klebsiella pneumoniae. These findings were further supported through blockade of OSM with an OSM-specific antibody. Single-cell RNA sequencing from human lung biopsies identified macrophages as a source of OSM. Additional studies using Osm-deficient murine macrophages demonstrated that macrophage-derived OSM translates LPS signals into asthma-associated pathologies. Together, these data provide rationale for inhibiting OSM to prevent bacterial-associated progression and exacerbation of severe asthma.
January 6, 2022
CAR T cells produced in vivo to treat cardiac injury
Cardiac fibrosis is the stiffening and scarring of heart tissue and can be fatal. Fibrosis affects millions of people with cardiac disease. Rurik et al. (2022) (Science 375: 91-96) designed an immunotherapy strategy to generate transient chimeric antigen receptor (CAR) T cells that can recognize the fibrotic cells in the heart. By injecting CD5-targeted lipid nanoparticles containing the messenger RNA (mRNA) instructions needed to reprogram T lymphocytes, the researchers were able to generate therapeutic CAR T cells entirely inside the body. Analysis of a mouse model of heart disease revealed that the approach was successful in reducing fibrosis and restoring cardiac function. The ability to produce CAR T cells in vivo using modified mRNA may have a number of therapeutic applications.
Chemically induced protein cage assembly with programmable opening and cargo release
Engineered protein cages are promising tools that can be customized for applications in medicine and nanotechnology. A major challenge is developing a straightforward strategy for endowing cages with bespoke, inducible disassembly. Such cages would allow release of encapsulated cargoes at desired timing and location. Stupka et al. (2022). Science Advances (8, Issue 1) achieve such programmable disassembly using protein cages, in which the subunits are held together by different molecular cross-linkers. This modular system enables cage disassembly to be controlled in a condition-dependent manner. Structural details of the resulting cages were determined using cryo–electron microscopy, which allowed observation of bridging cross-linkers at intended positions. Triggered disassembly was demonstrated by high-speed atomic force microscopy and subsequent cargo release using an encapsulated Förster resonance energy transfer pair whose signal depends on the quaternary structure of the cage.
All-in-one flexible supercapacitor with ultrastable performance under extreme load
Fiber-type solid-state supercapacitors are being widely investigated as stable power supply for next-generation wearable and flexible electronics. Integrating both high charge storage capability and superior mechanical properties into one fiber is crucial to realize fiber-type solid-state supercapacitors. In this study, Na et al (2022) (Science Advances 8: Issue 1) design a “jeweled necklace”–like hybrid composite fiber comprising double-walled carbon nanotube yarn and metal-organic frameworks (MOFs). Subsequent heat treatment transforms MOFs into MOF-derived carbon (MDC), thereby maximizing energy storage capability while retaining the superior mechanical properties. The hybrid fibers with tunable properties, including thickness and MDC loading amount, exhibit a high energy density of 7.54 milliwatt-hour per cubic centimeter at a power density of 190.94 milliwatt per cubic centimeter. The mechanical robustness of the hybrid fibers allows them to operate under various mechanical deformation conditions. Furthermore, it is demonstrated that the resulting superstrong fiber delivers sufficient power to switch on light-emitting diodes by itself while suspending 10-kilogram weight.
A versatile and robust cell purification system with an RNA-only circuit composed of microRNA-responsive ON and OFF switches
Human induced pluripotent stem cells (iPSCs) are promising cell resources for cell therapy and drug discovery. However, iPSC-derived differentiated cells are often heterogenous and need purification using a flow cytometer, which has high cost and time consumption for large-scale purification. MicroRNAs (miRNAs) can be used as cell selection markers, because their activity differs between cell types. Fujita et al. (2022) (Science Advances 8: Issue 1) show miRNA-responsive ON and OFF switch mRNAs for robust cell purification. The ON switch contains a miRNA-target sequence after the polyadenylate tail, triggering translational activation by sensing the target miRNA. By designing RNA-only circuits with miRNA-ON and -OFF switch mRNAs that encode a lethal ribonuclease, Barnase, and its inhibitor, Barstar, they efficiently purified specific cell types, including human iPSCs and differentiated cardiomyocytes, without flow cytometry. Synthetic mRNA circuits composed of ON and OFF switches provide a safe, versatile, and time-saving method to purify various cell types for biological and clinical applications.
December 23, 2021
Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response
The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al. (2021) (Science 374: 1632-1640) add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response.
An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19
The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al. (2021) (Science 374:1586-1593) report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats.
Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria
Antibiotic resistance is a pervasive and increasing problem. Zhao et al. (2021) (Science Translational Medicine 13, Issue 625) show that glutamine promotes increased influx and efficacy of a variety of antibiotics against multiple species of pathogenic Gram-negative bacteria. Mechanistically, glutamine promoted changes in nucleotide metabolism that led to the up-regulation of a two-component regulatory system, resulting in increased, nonspecific membrane permeability in bacteria having varied resistance mechanisms. Glutamine supplementation was also effective in mouse models of systemic or biofilm infection, suggesting a potential strategy to enhance antibiotic efficacy.
December 21, 2021
Combinations of slow-translating codon clusters can increase mRNA half-life in Saccharomyces cerevisiae
The rate of messenger RNA (mRNA) degradation influences the amount of protein produced from a gene. Ribosome queues at slow-translating codons promote mRNA degradation by recruiting ribosome-associated quality control machinery. The influence of multiple slow-codon clusters on mRNA half-lives is unknown, despite the majority of transcripts being composed of such clusters. Sharma et al. (2021) (PNAS 118: e2026362118) find that the slow-codon cluster nearest to the start codon is the primary determinant of mRNA half-life and that introducing a second slow-codon cluster near the start codon can increase mRNA half-life by suppressing ribosome queues at subsequent slow-codon clusters along the transcript. Thus, slow codon clusters have synergistic effects on mRNA half-lives, and their modeling approach provides a framework for understanding differential degradation rates between transcripts.
Bacteriophage self-counting in the presence of viral replication
Viral dormancy, in which the infected cell is not killed but rather becomes the long-term residence of the parasite, is a hallmark of viruses across kingdoms from bacteriophages to HIV. When and how viruses decide to opt for this lifestyle remains mysterious. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how the phage reliably counts infecting viral genomes even as their intracellular number increases because of replication. By combining theoretical modeling with single-cell measurements of viral copy number and gene expression, Yao et al. (2021) (PNAS 118 (51) e2104163118) find that instead of hindering lambda’s decision, replication facilitates it. In a nonreplicating mutant, viral gene expression simply scales with MOI rather than diverging into lytic (virulent) and lysogenic trajectories. A similar pattern is followed during early infection by wild-type phage. However, later in the infection, the modulation of viral replication by the decision genes amplifies the initially modest gene expression differences into divergent trajectories. Replication thus ensures the optimal decision—lysis upon single-phage infection and lysogeny at higher MOI.
Substantial accumulation of mercury in the deepest parts of the ocean and implications for the environmental mercury cycle
Mercury is a globally ubiquitous pollutant that is harmful to humans and animals. Most mercury entering the environment is released from anthropogenic sources and then stored for some period in soils and water bodies before potentially being remobilized, which greatly facilitates its global distribution. Although the ocean is recognized as the largest ultimate sink of mercury, the distribution and burial of mercury in deep ocean sediments remains largely unknown because of the difficulty in obtaining samples from these ecosystems. Liu et al (2021) (PNAS December 21, 2021 118 (51) e2102629118) found that although hadal trenches (the deepest parts of the oceans) occupy a very small portion (<0.5%) of the ocean area, they may receive a large amount of mercury and represent a disproportionately important, previously overlooked sink for mercury.
Health benefits of decreases in on-road transportation emissions in the United States from 2008 to 2017
Despite decades of reductions in vehicle emissions in the United States, their impacts remain large, and the offsetting effects of different factors on benefits achieved in recent years are not well understood. Choma et al. (2021) (PNAS 118 (51) e2107402118) assess benefits from 2008 to 2017 on a fine spatial resolution using the latest epidemiological evidence and emissions inventories. They find that regulation continues to yield large benefits: $270 (190 to 480) billion in 2017 from reduced PM2.5-attributable mortality and greenhouse gas emissions. Traffic-related PM2.5-attributable mortality would have been 2.4 times as large in 2017 if vehicles had still been emitting at 2008 levels, accounting for most benefits. Urban passenger light-duty vehicles have become increasingly important, and major health gains require more stringent policies to curb their emissions.
The hypothalamic link between arousal and sleep homeostasis in mice
Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep–wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state “quality”) and the functional significance thereof remains unexplored. Yamagata et al. (2021) (PNAS 118: e2101580118) show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep–wake states.
December 15, 2021
Tungsten-doped vanadium dioxide allows fabrications of windows that might be cooler in the summer and warmer in the winter
Radiative cooling materials spontaneously radiate long-wave infrared (LWIR) to the cold outer space, providing cooling power that is preferred in hot seasons. Radiative cooling has been widely explored for walls and roofs but rarely for windows, which are one of the least energy-efficient parts of buildings. Wang et al. (2021) (Science 374: 1501-1504) fabricated scalable smart windows using a solution process giving different emissivity at high and low temperatures to regulate radiative cooling automatically while maintaining luminous transparency and near-infrared (NIR) modulation. These passive and independent visible–NIR–LWIR regulated smart windows are capable of dynamic radiative cooling for self-adapting applications across different climate zones.
A nanopore-based approach is developed for reading individual peptides with sensitivity to single-amino-acid substitutions
Nanopore technology enables sensing of minute chemical changes at the single-molecule level by detecting differences in an ion current as molecules are drawn through a membrane-embedded pore. The sensitivity is sufficient to discriminate between nucleotide bases in nanopore sequencing, and other applications of this technology are promising. Brinkerhoff et al. (2021) (Science 374: 1509-1513) developed a nanopore-based, single-molecule approach in which a protein was sequentially scanned in single-amino-acid steps through the narrow construction of a nanopore, and ion currents were monitored to resolve differences in the amino acid sequence along the peptide backbone. The peptide reader was capable of reliably detecting single-amino-acid substitutions within individual peptides. An individual protein could be re-read many times, yielding very high read accuracy in variant identification. These proof-of-concept nanopore experiments constitute a promising basis for the development of a single-molecule protein sequencer.
RNA demethylation increases the yield and biomass of rice and potato plants in field trials
RNA N6-methyladenosine (m6A) modifications are essential in plants. Yu et al. (2021) (Nature Biotechnology 39:1581–1588) show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. They demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield.
Cholesterol-functionalized DNA/RNA heteroduplexes cross the blood–brain barrier and knock down genes in the rodent CNS
Achieving regulation of endogenous gene expression in the central nervous system (CNS) with antisense oligonucleotides (ASOs) administered systemically would facilitate the development of ASO-based therapies for neurological diseases. Nagata et al. (2021) (Nature Biotechnology 39:1529–1536) demonstrated that DNA/RNA heteroduplex oligonucleotides (HDOs) conjugated to cholesterol or α-tocopherol at the 5′ end of the RNA strand reach the CNS after subcutaneous or intravenous administration in mice and rats. The HDOs distribute throughout the brain, spinal cord and peripheral tissues and suppress the expression of four target genes by up to 90% in the CNS, whereas single-stranded ASOs conjugated to cholesterol have limited activity. Gene knockdown was observed in major CNS cell types and was greatest in neurons and microglial cells. Side effects, such as thrombocytopenia and focal brain necrosis, were limited by using subcutaneous delivery or by dividing intravenous injections. By crossing the blood–brain barrier more effectively, cholesterol-conjugated HDOs may overcome the limited efficacy of ASOs targeting the CNS without requiring intrathecal administration.
December 9, 2021
Pure tellurium can be used as a phase-change switching device for computer memory applications
Phase-change materials are attractive for computer memory and switching, in part due to their small size and fast switching speeds. However, competitive materials frequently have many elements, which decreases the switching reliability. Shen et al.(2021) (Science 374: 1390-1394) built a pure tellurium device that is capable of fast switching through a phase transformation. Unlike many other phase-change materials, the change in resistance happens because the tellurium melts during the switching process. The resulting device can be switched 100 million times before failure and is an appealing route for avoiding the issues from multi-element phase-change materials.
December 7, 2021
Sediment load determines the shape of rivers
Rivers carry and deposit sediment, thereby shaping most landscapes around us. In doing so, their malleable channels change shape to accommodate the sediment load. Popovic et al. (2021) (PNAS 118 (49) e2111215118) show how fluid stress, gravity, and the erratic trajectories of traveling grains combine together to determine the shape of a river. They find that the stress on the bed of a river cannot be significantly above the critical value for sediment motion, which bounds the intensity of sediment transport and, thus, forces the river to widen as its sediment load increases. Although the results relate directly only to experimental, laminar rivers, they likely also apply qualitatively to natural ones, potentially allowing to use the shape of a river as a proxy for its sediment discharge.
Tryptophan metabolism and bacterial commensals prevent fungal dysbiosis in Arabidopsis roots
In nature, roots of healthy plants are colonized by multikingdom microbial communities that include bacteria, fungi, and oomycetes. A key question is how plants control the assembly of these diverse microbes in roots to maintain host–microbe homeostasis and health. Using microbiota reconstitution experiments with a set of immunocompromised Arabidopsis thaliana mutants and a multikingdom synthetic microbial community (SynCom) representative of the natural A. thaliana root microbiota, Wolinska et al. (2021) (PNAS 118: e2111521118) observed that microbiota-mediated plant growth promotion was abolished in most of the tested immunocompromised mutants. Notably, more than 40% of between-genotype variation in these microbiota-induced growth differences was explained by fungal but not bacterial or oomycete load in roots. Extensive fungal overgrowth in roots and altered plant growth was evident at both vegetative and reproductive stages for a mutant impaired in the production of tryptophan-derived, specialized metabolites (cyp79b2/b3). Microbiota manipulation experiments with single- and multikingdom microbial SynComs further demonstrated that 1) the presence of fungi in the multikingdom SynCom was the direct cause of the dysbiotic phenotype in the cyp79b2/b3 mutant and 2) bacterial commensals and host tryptophan metabolism are both necessary to control fungal load, thereby promoting A. thaliana growth and survival. The results indicate that protective activities of bacterial root commensals are as critical as the host tryptophan metabolic pathway in preventing fungal dysbiosis in the A. thaliana root endosphere.
An ancient antimicrobial protein co-opted by a fungal plant pathogen for in planta mycobiome manipulation
Microbes secrete a diversity of molecules into their environment to mediate niche colonization. During host ingress, plant pathogenic microbes secrete effector proteins that facilitate disease development, many of which deregulate host immune responses. Snelders et al (2021) recently demonstrated that plant pathogens additionally exploit effectors with antibacterial activities to manipulate beneficial plant microbiota to promote host colonization. They show that the fungal pathogen Verticillium dahliae has co-opted an ancient antimicrobial protein, which likely served in microbial competition in terrestrial environments before land plants existed, as effector for the manipulation of fungal competitors during host colonization. The study demonstrate that pathogen effector repertoires comprise antifungal proteins and speculate that such effectors could be exploited for the development of antimycotics (Snelders et al. (2021) PNAS 118: e2110968118).
December 4, 2021
CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes
Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, Douglas et al. (2021) (Nature Communications 12: 6926) develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, the authors observe a degree of litter size compensation relative to control matings, indicating that their system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. The approach of harnessing the technological applications of CRISPR-Cas9 may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.
December 3 2021
Targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease
Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. A current goal in genomics is to identify genetic variation associated with actionable traits of clinical concern. Through exome sequencing of an Old Order Amish population, Montasser et al. (2021) (Science 374: 1221-1227) identified a genetic variant that results in an amino acid change in the beta-1,4-galactosyltransferase 1 protein and is correlated with lower levels of cardiovascular disease. Investigation of the mutant protein showed that it affects genes associated with low-density lipoprotein cholesterol (LDL-C), and mice engineered to express the mutant protein exhibited a 38% decrease in blood LDL-C levels. This study suggests that such genomic sequencing and analysis can link genotype to phenotype and identify potentially clinically actionable pathways to treat disease.
Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease
As tissue macrophages of the central nervous system (CNS), microglia constitute the pivotal immune cells of this organ. Microglial features are strongly dependent on environmental cues such as commensal microbiota. Gut bacteria are known to continuously modulate microglia maturation and function by the production of short-chain fatty acids (SCFAs). However, the precise mechanism of this crosstalk is unknown. Emy et al. (2021) (Cell Metabolism 33: 2260-2276) determined that the immature phenotype of microglia from germ-free (GF) mice is epigenetically imprinted by H3K4me3 and H3K9ac on metabolic genes associated with substantial functional alterations including increased mitochondrial mass and specific respiratory chain dysfunctions. They identified acetate as the essential microbiome-derived SCFA driving microglia maturation and regulating the homeostatic metabolic state, and further showed that it is able to modulate microglial phagocytosis and disease progression during neurodegeneration. These findings indicate that acetate is an essential bacteria-derived molecule driving metabolic pathways and functions of microglia during health and perturbation.
Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation
The retina is considered a window to the brain, and retinal degenerative diseases involve the same mechanisms as those of other neurodegenerative disorders. Neuronal degeneration is a complex process involving environmental stress, which can affect vulnerable neurons. High-fat diet–induced metabolic alterations may influence retinal homeostasis and exacerbate retinal degenerative diseases. This study provides evidence that short-term high-fat feeding promotes glucose intolerance, gut microbiome dysbiosis, retinal oxidative stress, and inflammation and accelerates the pathologic processes in retinal disease [Kutsyr et al. (2021). PNAS 118 (43): e2100566118].
The nematode Caenorhabditis elegans senses airborne sound
Unlike olfaction, taste, touch, vision, and proprioception, which are widespread across animal phyla, hearing is found only in vertebrates and some arthropods. The vast majority of invertebrate species are thus considered insensitive to sound. Iliff et al. (2021) (Neuron 109: P3633-3646) challenge this conventional view by showing that the earless nematode C. elegans senses airborne sound at frequencies reaching the kHz range. Sound vibrates C. elegans skin, which acts as a pressure-to-displacement transducer similar to vertebrate eardrum, activates sound-sensitive FLP/PVD neurons attached to the skin, and evokes phonotaxis behavior. We identified two nAChRs that transduce sound signals independently of ACh, revealing an unexpected function of nAChRs in mechanosensation. Thus, the ability to sense airborne sound is not restricted to vertebrates and arthropods as previously thought, and might have evolved multiple times independently in the animal kingdom, suggesting convergent evolution. Our studies also demonstrate that animals without ears may not be presumed to be sound insensitive.
Light-driven dynamic surface wrinkles for adaptive visible camouflage
Camouflage has broad applications in nature, engineering, and the military. This work demonstrated a feasible strategy for adaptive visible camouflage based on light-driven dynamic surface wrinkles. The multiwavelength light–driven dynamic surface wrinkles based on photothermal effect–induced thermal expansion of the substrate could tune the light scattering and the visibility of the film interference color. Consequently, the color captured by the observer could switch between the exposure state that is distinguished from the background and the camouflage state that is similar to the surroundings, demonstrating the adaptive camouflage. This system is simple to configure, easy to operate, versatile, and exhibits in situ dynamic characteristics without any external sensors and extra stimuli, which provided an alternative strategy for adaptive camouflage (Ma et al. 2021. PNAS 118 (48) e2114345118).
November 23, 2021
Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring
While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Rompala et al. (2021) (PNAS 118 (47) e2106115118) assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in utero environment reflected in the placental transcriptome. Children (∼3 to 6 y) were assessed for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing. Hair hormone analysis revealed increased cortisol levels in mCB children. In addition, mCB was associated with greater anxiety, aggression, and hyperactivity. Children with mCB also showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone. In the placenta, there was reduced expression of many genes involved in immune system function including type I interferon, neutrophil, and cytokine-signaling pathways. Finally, several of these mCB-linked immune genes organized into coexpression networks that correlated with child anxiety and hyperactivity. Overall, the findings reveal a relationship between mCB and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood.
November 19, 2021
Sniffing the human body volatile hexadecanal blocks aggression in men but triggers aggression in women
In terrestrial mammals, body volatiles can effectively trigger or block conspecific aggression. Mishor et al. (2021) (Science Advances 7, Issue 47) tested whether hexadecanal (HEX), a human body volatile implicated as a mammalian-wide social chemosignal, affects human aggression. Using validated behavioral paradigms, they observed a marked dissociation: Sniffing HEX blocked aggression in men but triggered aggression in women. Next, using functional brain imaging, they uncovered a pattern of brain activity mirroring behavior: In both men and women, HEX increased activity in the left angular gyrus, an area implicated in perception of social cues. HEX then modulated functional connectivity between the angular gyrus and a brain network implicated in social appraisal (temporal pole) and aggressive execution (amygdala and orbitofrontal cortex) in a sex-dependent manner consistent with behavior: increasing connectivity in men but decreasing connectivity in women. These findings implicate sex-specific social chemosignaling at the mechanistic heart of human aggressive behavior.
November 17, 2021
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians
Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases. Sato et al. (2021) (Nature 599: 458-464) show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, the authors identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, they found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.
mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent
Ixodes scapularis ticks transmit many pathogens that cause human disease, including Borrelia burgdorferi. Acquired resistance to I. scapularis due to repeated tick exposure has the potential to prevent tick-borne infectious diseases, and salivary proteins have been postulated to contribute to this process. Sajid et al. (2021) (Science Translational Medicine 13:620) examined the ability of lipid nanoparticle–containing nucleoside-modified mRNAs encoding 19 I. scapularis salivary proteins (19ISP) to enhance the recognition of a tick bite and diminish I. scapularis engorgement on a host and thereby prevent B. burgdorferi infection. Guinea pigs were immunized with a 19ISP mRNA vaccine and subsequently challenged with I. scapularis. Animals administered 19ISP developed erythema at the bite site shortly after ticks began to attach, and these ticks fed poorly, marked by early detachment and decreased engorgement weights. 19ISP immunization also impeded B. burgdorferi transmission in the guinea pigs. The effective induction of local redness early after I. scapularis attachment and the inability of the ticks to take a normal blood meal suggest that 19ISP may be used either alone or in conjunction with traditional pathogen-based vaccines for the prevention of Lyme disease, and potentially other tick-borne infections.
In-orbit demonstration of an iodine electric propulsion system
Propulsion is a critical subsystem of many spacecraft. For efficient propellant usage, electric propulsion systems based on the electrostatic acceleration of ions formed during electron impact ionization of a gas are particularly attractive. At present, xenon is used almost exclusively as an ionizable propellant for space propulsion. However, xenon is rare, it must be stored under high pressure and commercial production is expensive. Rafalskyi et al. (2021) (Nature 599: 411-415) demonstrate a propulsion system that uses iodine propellant and they present in-orbit results of this new technology. Diatomic iodine is stored as a solid and sublimated at low temperatures. A plasma is then produced with a radio-frequency inductive antenna, and they show that the ionization efficiency is enhanced compared with xenon. Both atomic and molecular iodine ions are accelerated by high-voltage grids to generate thrust, and a highly collimated beam can be produced with substantial iodine dissociation. The propulsion system has been successfully operated in space onboard a small satellite with manoeuvres confirmed using satellite tracking data. The authors anticipate that these results will accelerate the adoption of alternative propellants within the space industry and demonstrate the potential of iodine for a wide range of space missions. For example, iodine enables substantial system miniaturization and simplification, which provides small satellites and satellite constellations with new capabilities for deployment, collision avoidance, end-of-life disposal and space exploration.
The lungfish cocoon is a living tissue with antimicrobial functions
Terrestrialization is an extreme physiological adaptation by which African lungfish survive dry seasons. For months and up to several years, lungfish live inside a dry mucus cocoon that protects them from desiccation. Light and electron microscopy reveal that the lungfish cocoon is a living tissue that traps bacteria. Transcriptomic analyses identify a global state of inflammation in the terrestrialized lungfish skin characterized by granulocyte recruitment. Recruited granulocytes transmigrate into the cocoon where they release extracellular traps. In vivo DNase I surface spraying during terrestrialization results in dysbiosis, septicemia, skin wounds, and hemorrhages. Thus, lungfish have evolved unique immunological adaptations to protect their bodies from infection for extended periods of time while living on land. Trapping bacteria outside their bodies may benefit estivating vertebrates that undergo metabolic torpor (Heimroth et al. (2021). Science Advances 7:47).
November 16, 2021
Air pollution interacts with genetic risk to influence cortical networks implicated in depression
Air pollution is ubiquitous and may increase neuropsychiatric risk, including for depression. However, the neural underpinnings and whether this environmental risk acts independently or interactively with genetic risk mechanisms are not well understood. In healthy individuals exposed to significant air pollution, Li et al. (2021) (PNAS 118: e2109310118) find that combined high air pollution exposures and relatively high polygenic risk for depression disproportionately augmented stress-related effects on brain circuitry. The coexpression of depression-associated genes across the brain tracked corresponding brain connectivity, driven by individuals with higher polygenic risk and with higher exposures to air pollution. These findings add to the mechanistic understanding of brain processes implicated in how individuals with high genetic risk for depression may be particularly vulnerable to the brain effects of air pollution.
Thermodynamic feasibility of shipboard conversion of marine plastics to blue diesel for self-powered ocean cleanup
Plastic waste accumulating in the world’s oceans forms massive “plastic islands” in the oceanic gyres. Removing the plastic offers an opportunity to restore our oceans to a more pristine state. To clean the gyres, ships must collect and store the plastic before transporting it to port, often thousands of kilometers away. Instead, ocean plastic waste can be converted into fuel shipboard, for example, using hydrothermal liquefaction (HTL), which depolymerizes plastics at high temperature (300 °C to 550 °C) and high pressure (250 bar to 300 bar). The resulting depolymerization products, termed “blue diesel,” have the potential for self-powered cleanup (Belden et al. (2021) (PNAS 118: e2107250118).
Active math and grammar learning engages overlapping brain networks
Stillesjö et al. (2021) (PNAS 118:e2106520118) demonstrate common neurocognitive long-term memory effects of active learning that generalize over course subjects (mathematics and vocabulary) by the use of fMRI. One week after active learning, relative to more passive learning, performance and fronto-parietal brain activity was significantly higher during retesting, possibly related to the formation and reactivation of semantic representations. These observations indicate that active learning conditions stimulate common processes that become part of the representations and can be reactivated during retrieval to support performance. The findings are of broad interest and educational significance related to the emerging consensus of active learning as critical in promoting good long-term retention.
November 11, 2021
Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury
Artificial scaffolds that bear the peptide-signaling sequences of proteins for tissue regeneration often have limited effectiveness. Álvarez et al. (Science 2021; 374: 848-856) synthesized supramolecular peptide fibril scaffolds bearing two peptide sequences that promote nerve regeneration, one that reduces glial scarring and another that promotes blood vessel formation. In a mouse model of paralyzing human spinal cord injury, mutations in a tetrapeptide domain outside of the signaling regions improved recovery by promoting intense supramolecular motion within the fibrils. The mutation with the most intense dynamics resulted in corticospinal axon regrowth and myelination, functional revascularization, and motor neuron survival.
November 5, 2021
Profiling cellular diversity in sponges informs animal cell type and nervous system evolution
Sponges represent our distant animal relatives. They do not have a nervous system but do have a simple body for filter feeding. Surveying the cell types in the freshwater sponge Spongilla lacustris, Musser et al. (2021) (Science 374: 717-723) found that many genes important in synaptic communication are expressed in cells of the small digestive chambers. They found secretory machinery characteristic of the presynapse in small multipolar cells contacting all other cells and also the receptive apparatus of the postsynapse in the choanocytes that generate water flow and digest microbial food. These results suggest that the first directed communication in animals may have evolved to regulate feeding, serving as a starting point on the long path toward nervous system evolution.
Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection
Antimicrobial proteins (AMPs) are a frontline defense against pathogenic microorganisms at mucosal surfaces. These cationic molecules inactivate their targets primarily by disrupting cell walls and membranes. Hu et al. (2021) (Science 374) found that small proline-rich protein 2A (SPRR2A) is a bactericidal protein produced in the gut that targets Gram-positive bacteria and is phylogenetically distinct from all other known AMPs. SPRR2A production is selectively enhanced by type 2 cytokines such as interleukin-4 and -13 that are elicited by helminth infection. Mice lacking SPRR2A are unable to prevent intestinal bacteria from invading the intestinal barrier after helminths damage the intestinal epithelium. SPRR2A is thus a critical component of type 2 immunity that protects against the bacterial invasion and dissemination that follow helminth infection.
Abyssal Benthic Rover, an autonomous vehicle for long-term monitoring of deep-ocean processes
The deep-ocean carbon cycle is poorly quantified. An abyssal benthic rover was developed to make long time-series measurements of seafloor processes related to organic carbon remineralization and sequestration. Benthic Rover II (BR-II) is an autonomous dual-tracked vehicle that measures bottom water temperature and oxygen concentration, current velocity, and sediment community oxygen consumption (SCOC; respiration) (Smith et al. (2021) (Science Robotics 6). BR-II is programmed to transit with low surface-contact pressure across the seafloor, photograph bottom conditions, and stop regularly to occupy respirometer incubation sites, with deployment periods up to 1 year. Now, continuously operational at a 4000-m station in the northeast Pacific over 5 years, substantial weekly, seasonal, annual, and episodic events have been recorded, which are critical to assessing the deep-ocean carbon cycle. There was a significant increase in phytodetritus cover arriving on the seafloor from the overlying water column between 2015 and 2020 that was negatively correlated with bottom water dissolved oxygen concentration. Over the continuous 5-year monitoring period from November 2015 to November 2020, SCOC was positively correlated with phytodetritus cover and increased significantly from 2015 to 2020. These results show important influences of biological processes on the carbon cycle. The demonstrated success of BR-II now creates opportunities to expand the long-term monitoring of the deep sea to resolve the coupling of water column and benthic processes key to understanding the oceanic carbon cycle on a planet engulfed in a changing climate.
October 22, 2021
Lightweight, strong, moldable wood via cell wall engineering as a sustainable structural material
Wood is a sustainable structural material, but it cannot be easily shaped while maintaining its mechanical properties. Xiao et al. (2021). Science 374: 466-471 report a processing strategy that uses cell wall engineering to shape flat sheets of hardwood into versatile three-dimensional (3D) structures. After breaking down wood’s lignin component and closing the vessels and fibers by evaporating water, we partially re-swell the wood in a rapid water-shock process that selectively opens the vessels. This forms a distinct wrinkled cell wall structure that allows the material to be folded and molded into desired shapes. The resulting 3D-molded wood is six times stronger than the starting wood and comparable to widely used lightweight materials such as aluminum alloys. This approach widens wood’s potential as a structural material, with lower environmental impact for buildings and transportation applications.
Ivory poaching and the rapid evolution of tusklessness in African elephants
Understanding the evolutionary consequences of wildlife exploitation is increasingly important as harvesting becomes more efficient. Campbell-Staton et al. (2021) (Science 374: 483-487) examined the impacts of ivory poaching during the Mozambican Civil War (1977 to 1992) on the evolution of African savanna elephants (Loxodonta africana) in Gorongosa National Park. Poaching resulted in strong selection that favored tusklessness amid a rapid population decline. Survey data revealed tusk-inheritance patterns consistent with an X chromosome–linked dominant, male-lethal trait. Whole-genome scans implicated two candidate genes with known roles in mammalian tooth development (AMELX and MEP1a), including the formation of enamel, dentin, cementum, and the periodontium. One of these loci (AMELX) is associated with an X-linked dominant, male-lethal syndrome in humans that diminishes the growth of maxillary lateral incisors (homologous to elephant tusks). This study provides evidence for rapid, poaching-mediated selection for the loss of a prominent anatomical trait in a keystone species.
October 21, 2021
Silica fertilization improved wheat performance and increased phosphorus concentrations during drought at the field scale
Drought and the availability of mineable phosphorus minerals used for fertilization are two of the important issues agriculture is facing in the future. High phosphorus availability in soils is necessary to maintain high agricultural yields. Drought is one of the major threats for terrestrial ecosystem performance and crop production in future. Among the measures proposed to cope with the upcoming challenges of intensifying drought stress and to decrease the need for phosphorus fertilizer application is the fertilization with silica (Si). Schaller et al. (2021) (Scientific Reports 11: 20852) tested the importance of soil Si fertilization on wheat phosphorus concentration as well as wheat performance during drought at the field scale. Their data clearly showed a higher soil moisture for the Si fertilized plots. This higher soil moisture contributes to a better plant performance in terms of higher photosynthetic activity and later senescence as well as faster stomata responses ensuring higher productivity during drought periods. The plant phosphorus concentration was also higher in Si fertilized compared to control plots. Overall, Si fertilization or management of the soil Si pools seem to be a promising tool to maintain crop production under predicted longer and more serve droughts in the future and reduces phosphorus fertilizer requirements.
Why animals swirl and how they group
A possible solution is elucidated for the long-standing problem of the biological function of swirling motion, when a group of animals orbits a common center of the group. Nuzhin et al. (2021) (Scientific Reports 11: 20843) exploit the hypothesis that learning processes in the nervous system of animals may be modelled by reinforcement learning (RL) and apply it to explain the phenomenon. In contrast to hardly justified models of physical interactions between animals, the authors propose a small set of rules to be learned by the agents, which results in swirling. The rules are extremely simple and thus applicable to animals with very limited level of information processing. They demonstrate that swirling may be understood in terms of the escort behavior, when an individual animal tries to reside within a certain distance from the swarm center. Moreover, they reveal the biological function of swirling motion: a trained for swirling swarm is by orders of magnitude more resistant to external perturbations, than an untrained one. Using the approach the authors analyze another class of a coordinated motion of animals—a group locomotion in viscous fluid. On a model example they demonstrate that RL provides an optimal disposition of coherently moving animals with a minimal dissipation of energy.
Sake yeast induces the sleep-promoting effects under the stress-induced acute insomnia in mice
Sleep deprivation induces adverse effects on the health, productivity, and performance. The individuals who could not get enough sleep temporarily experience the symptoms of an induced acute insomnia. This study investigated the efficacy of sake yeast in treatment of acute insomnia in mice. The results of this study showed that sake yeast induced a significant dose-dependent wake reduction, a rapid eye movement (REM) and a non-REM (NREM) sleep enhancement during the first 6 h after the oral administration of sake yeast with locomotor activity and core body temperature decreases under the stressful environment in a new cage. In fact, the wake amounts at 3 h and 6 h were significantly reduced after the oral administration of sake yeast compared with the vehicle. The NREM sleep amounts at 3 h and 6 h significantly increased after the administration of sake yeast compared with the vehicle. The REM amount at 6 h significantly increased after the administration of sake yeast compared with the vehicle, but not at 3 h. The previous study suggested that the sleep-promoting effects of sake yeast could be referred from the activating effect of adenosine A2A receptor (A2AR). In summary, the sake yeast is an A2AR agonist and may induce sleep due to its stress-reducing and anti-anxiety properties. Nishimon et al. (2021). Scientific Reports 11: 20816.
Rapid and accurate electrochemical sensor for food allergen detection in complex foods
Food allergies are estimated to affect about 2–5% of adults and 6–8% of children, globally. Currently, the most effective strategy for food allergy management is stringent avoidance of the offending allergen. Unlike other major food allergens, soy is uniquely challenging to avoid due to its prevalence and insidiousness in a wide variety of foods, such as infant formulas. Sundhor et al. (2021) (Scientific Reports 11: 20831) demonstrated a simple, accurate, and consumer-friendly sensor using molecularly imprinted polymers (MIPs) for rapid detection of soy allergenic tracers in complex food matrices at clinically relevant levels. In this work, they build on these findings by subjecting MIP-based soy allergen sensors to test trials in 42 different food products, representing over 300 ingredients. Foods were selected based on their compositional complexity to capture a wide range of preparatory methods and processing conditions. In each case, the Allergy Amulet correctly reported on the presence or absence of soy allergen tracer in investigated samples and were subjected to immunoassay confirmatory analysis. The outcome of this research will help resolve persistent difficulties with commercial technologies in detecting allergenic tracers with minimal cross-interference in foods, and will give those with soy allergies the ability to easily, rapidly, and accurately identify and avoid foods with soy allergens.
October 19, 2021
No evidence for colonization of oral bacteria in the distal gut in healthy adults
The microbial communities in the mouth and colon are anatomically connected via the saliva. However, the extent to which oral microbes reach and successfully colonize the distal gut has been debated. To resolve this long-standing controversy, Rashidi et al. (2021) in the journal PNAS (118 (42) e2114152118) used exact amplicon sequence variants generated from concurrently collected saliva/stool microbiota in 66 healthy adults from two countries to show that, with one exception (Dialister invisus), the two niches are completely distinct. Thus, there is no evidence for colonization of oral bacteria in the distal gut. This defines the healthy state to which pathological states could be compared. Finding the same bacteria in the mouth and stool may warrant clinical investigation for an underlying pathology.
October 15, 2021
Physical disturbance by recovering sea otter populations increases eelgrass genetic diversity
Most knowledge regarding the role of predators is ecological in nature. Foster et al. (2021) in the journal Science (374: 333-336) report how disturbance generated by sea otters (Enhydra lutris) digging for infaunal prey in eelgrass (Zostera marina) meadows increases genetic diversity by promoting conditions for sexual reproduction of plants. Eelgrass allelic richness and genotypic diversity were, respectively, 30 and 6% higher in areas where recovering sea otter populations had been established for 20 to 30 years than in areas where they had been present <10 years or absent >100 years. The influence of sea otter occupancy on the aforementioned measures of genetic diversity was stronger than those of depth, temperature, latitude, or meadow size. The findings reveal an underappreciated evolutionary process by which megafauna may promote genetic diversity and ecological resilience.
October 8, 2021
Cellular mechanisms involved in adhesive fabrication in mussels
Mussels produce an exceptional proteinaceous adhesive so they can withstand waves and currents. To anchor in seashore habitats, mussels fabricate adhesive byssus fibers that are mechanically reinforced by protein-metal coordination mediated by 3,4-dihydroxyphenylalanine (DOPA). The mechanism by which metal ions are integrated during byssus formation remains unknown. Metal ions bound to modified tyrosine residues play an important role in reinforcing the adhesive. Priemel et al. (2021) (Science 374: 206-211) brought together a variety of spectroscopy and microscopy techniques to study the cellular mechanisms involved in adhesive fabrication in mussels. They found that metal ion–rich vesicles are secreted alongside vesicles containing the adhesive protein and mix in a microfluidic-like process within interconnected microchannels found in the lateral duct of the mussel foot to create porous, adhesive plaque filaments. These findings advance our understanding of metal use in biological materials with implications for next-generation metallopolymers and adhesives.
October 6, 2021
Nobel Prize in Chemistry 2021
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2021 to Benjamin List, Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany and David W.C. MacMillan, Princeton University, USA “for the development of asymmetric organocatalysis”.
October 5, 2021
Nobel Prize in Physics 2021
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2021 “for groundbreaking contributions to our understanding of complex physical systems” with one half jointly to Syukuro Manabe, Princeton University, USA and Klaus Hasselmann, Max Planck Institute for Meteorology, Hamburg, Germany “for the physical modelling of Earth’s climate, quantifying variability and reliably predicting global warming” and the other half to Giorgio Parisi, Sapienza University of Rome, Italy “for the discovery of the interplay of disorder and fluctuations in physical systems from atomic to planetary scales”.
October 4, 2021
Nobel Prize in Physiology and Medicine, 2021
The Nobel Assembly at the Karolinska Institutet decided to award the 2021 Nobel Prize in Physiology or Medicine jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch.
September 24, 2021
Cell-free chemoenzymatic starch synthesis from carbon dioxide
Many plants turn glucose from photosynthesis into polymers that form insoluble starch granules ideal for long-term energy storage in roots and seeds. Cai et al. (2021) (Science 373: 1523-1527) developed a hybrid system in which carbon dioxide is reduced to methanol by an inorganic catalyst and then converted by enzymes first to three and six carbon sugar units and then to polymeric starch. This artificial starch anabolic pathway relies on engineered recombinant enzymes from many different source organisms and can be tuned to produce amylose or amylopectin at excellent rates and efficiencies relative to other synthetic carbon fixation systems—and, depending on the metric used, even to field crops. This approach opens the way toward future chemo-biohybrid starch synthesis from CO2.
Bluefin tuna reveal global patterns of mercury pollution and bioavailability in the world’s oceans
Bluefin tuna (BFT), highly prized among consumers, accumulate high levels of mercury (Hg) as neurotoxic methylmercury (MeHg). However, how Hg bioaccumulation varies among globally distributed BFT populations is not understood. Tseng et al. (2021) (PNAS 118 (38) e2111205118) show mercury accumulation rates (MARs) in BFT are highest in the Mediterranean Sea and decrease as North Pacific Ocean > Indian Ocean > North Atlantic Ocean. Moreover, MARs increase in proportion to the concentrations of MeHg in regional seawater and zooplankton, linking MeHg accumulation in BFT to MeHg bioavailability at the base of each subbasin’s food web. Observed global patterns correspond to levels of Hg in each ocean subbasin; the Mediterranean, North Pacific, and Indian Oceans are subject to geogenic enrichment and anthropogenic contamination, while the North Atlantic Ocean is less so. MAR in BFT as a global pollution index reflects natural and human sources and global thermohaline circulation.
September 23, 2021
Bioaccumulation of therapeutic drugs by human gut bacteria
Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Klunemann et al. (2021) (Nature 597: 533-538) investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria–drug interactions, 29 of which had not to their knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth of the bacteria being affected. As a case in point, they studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. They find that duloxetine binds to several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. The authors further validated their findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegans to duloxetine. Together, the results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner.
Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks
Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic. Keita et al. (2021) (Nature 597: 539-543) used next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.
Three-dimensional electronic microfliers inspired by wind-dispersed seeds
Large, distributed collections of miniaturized, wireless electronic devices may form the basis of future systems for environmental monitoring, population surveillance, disease management and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and—inspired by wind-dispersed seeds— Kime et al. (2021; Nature 597: 503-510) examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. The authors demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.
Paths and timings of the peopling of Polynesia inferred from genomic networks
Polynesia was settled in a series of extraordinary voyages across an ocean spanning one third of the Earth, but the sequences of islands settled remain unknown and their timings disputed. Currently, several centuries separate the dates suggested by different archaeological surveys. Here, using genome-wide data from merely 430 modern individuals from 21 key Pacific island populations and novel ancestry-specific computational analyses, Ioannidis et al. (2021) in the journal Nature (597: 522-526) unravel the detailed genetic history of this vast, dispersed island network. The authors reconstruction of the branching Polynesian migration sequence reveals a serial founder expansion, characterized by directional loss of variants, that originated in Samoa and spread first through the Cook Islands (Rarotonga), then to the Society (Tōtaiete mā) Islands (11th century), the western Austral (Tuha’a Pae) Islands and Tuāmotu Archipelago (12th century), and finally to the widely separated, but genetically connected, megalithic statue-building cultures of the Marquesas (Te Henua ‘Enana) Islands in the north, Raivavae in the south, and Easter Island (Rapa Nui), the easternmost of the Polynesian islands, settled in approximately AD 1200 via Mangareva.
September 5, 2021
Chronic social isolation signals starvation and reduces sleep in Drosophila
Social isolation and loneliness have potent effects on public health. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Li et al. (2021) in the journal Nature (597:239–244) report that chronic, but not acute, social isolation reduces sleep in Drosophila. They used quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness.
September 2, 2021
Enlisting wild grass genes to combat nitrification in wheat farming
Globally, wheat farming is a major source of nitrogen pollution. Rapid generation of soil nitrates cause nitrogen leakage and damage ecosystems and human health. Subbarao et al. (2021). PNAS (118: e2101115118) reports that the 3NsbS chromosome arm in wild grass (Leymus racemosus) that controls root nitrification inhibitor production can be transferred into elite wheat cultivars, without disrupting the elite agronomic features. Biological nitrification inhibition (BNI)–enabled wheats can improve soil ammonium levels by slowing down its oxidation and generate significant synergistic benefits from assimilating dual nitrogen forms and improving adaptation to low nitrogen systems. Deploying BNI-enabled wheat on a significant proportion of current global wheat area (ca. 225 M ha) could be a powerful nature-based solution for reducing nitrogen fertilizer use and nitrogen losses while maintaining productivity.
September 1, 2021
Clock proteins and training modify exercise capacity in a daytime-dependent manner
Studies in mice and humans have revealed daytime variance in exercise performance, yet it is still unclear whether and how these daytime differences are regulated by the circadian clock. Adamovich et al. (2021) in the journal PNAS (118: e2101115118) show that exercise performance is circadian clock controlled and that specific clock proteins modify exercise capacity in a time-dependent manner, likely through differences in food consumption and liver glycogen stores. They also demonstrate that the time of day at which training is performed plays a role in improving exercise capacity. Their study suggests that exercise capacity is shaped by clock proteins and training in a daytime-dependent manner.
Monkeys exhibit a paradoxical decrease in performance in high-stakes scenarios
In high-stakes situations, people sometimes exhibit a frustrating phenomenon known as “choking under pressure.” Usually, we perform better when the potential payoff is larger. However, once potential rewards get too high, performance paradoxically decreases—we “choke.” Why do we choke under pressure? An animal model of choking would facilitate the investigation of its neural basis. However, it could be that choking is a uniquely human occurrence. To determine whether animals also choke, Smoulder et al. (2021) in the journal PNAS (118 (35) e2109643118) trained three rhesus monkeys to perform a difficult reaching task in which they knew in advance the amount of reward to be given upon successful completion. Like humans, monkeys performed worse when potential rewards were exceptionally valuable. Failures that occurred at the highest level of reward were due to overly cautious reaching, in line with the psychological theory that explicit monitoring of behavior leads to choking. Their results demonstrate that choking under pressure is not unique to humans, and thus, its neural basis might be conserved across species.
August 30, 2021
Chemical evidence for planetary ingestion in Sun-like stars
Stellar members of binary systems are formed from the same material, and therefore they should be chemically identical. However, recent studies have unveiled chemical differences between the two members of binary pairs composed of Sun-like stars. These chemically inhomogeneous binaries represent one of the most contradictory examples in stellar astrophysics and a source of tension between theory and observations. It is still unclear whether the abundance variations are the result of inhomogeneities in the protostellar gas clouds or are due to planet engulfment events that occurred after the stellar formation. The former scenario undermines the general belief that the chemical makeup of stars provides the fossil information of the environment in which they formed, whereas the second scenario would shed light on the possible evolutionary paths of planetary systems. Spina et al. (2021) in the journal Nature Astronomy provides compelling evidence in favor of the planet engulfment scenario. They also establish that planet engulfment events occur in Sun-like stars with a 20–35% probability. Therefore, an important fraction of planetary systems undergo very dynamical evolutionary paths that critically modify their architectures, unlike the calm Solar System. This study opens the possibility of using chemical abundances of stars to identify which ones are the most likely to host Solar System analogues.
August 20, 2021
Promoting potato as staple food can reduce the carbon–land–water impacts of crops in China
China has recently implemented a policy to promote potato as a national staple food and to close its large yield gaps with other countries. The carbon–land–water implications of this policy are examined in a paper by Liu et al. (2021) in the journal Nature Food (2:570–577) by compiling and analyzing detailed city-level life-cycle inventories of China’s staple crops. In general potato, despite relatively low yields, has lower greenhouse gas emissions and water demand than other staple crops (maize, wheat and rice) on a per-calorie basis, but substantial regional variation exists for each crop. Integrating potato as a staple in China to meet increases in food demand and close the yield gap has the potential to reduce the total carbon–land–water impacts of staple crops by 17–25% by 2030. However, an unsuccessful integration runs the risk of global burden-shifting if the policy, for example, reduced domestic rice production and led to increased rice imports. Potential synergies between food security and environmental sustainability in China can be created by the potato policy, but greater efforts are needed to promote potato across the entire food supply chain from production to consumption.
August 19, 2021
Dietary fructose improves intestinal cell survival and nutrient absorption
Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally. Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell. Although this pathway has been implicated in obesity and tumor promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Taylor et al. (2021) in the journal Nature show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival. Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumor growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumor growth by high-fructose corn syrup.
Chronic social isolation signals starvation and reduces sleep in Drosophila
Social isolation and loneliness have potent effects on public health. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Li et al. (2021) in the journal Nature report that chronic, but not acute, social isolation reduces sleep in Drosophila. The authors used quantitative behavioral analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness.
August 17, 2021
A polyyne toxin produced by an antagonistic bacterium blinds and lyses a Chlamydomonad alga
Algae are key contributors to global carbon fixation and form the basis of many food webs. In nature, their growth is often supported or suppressed by microorganisms. The bacterium Pseudomonas protegens Pf-5 arrests the growth of the green unicellular alga Chlamydomonas reinhardtii, deflagellates the alga by the cyclic lipopeptide orfamide A, and alters its morphology. Using a combination of Raman microspectroscopy, genome mining, and mutational analysis, Hotter et al. (2021) (PNAS 118 (33) e2107695118) discovered a polyyne toxin, protegencin, which is secreted by P. protegens, penetrates the algal cells, and causes destruction of the carotenoids of their primitive visual system, the eyespot. Together with secreted orfamide A, protegencin thus prevents the phototactic behavior of C. reinhardtii. A mutant of P. protegens deficient in protegencin production does not affect growth or eyespot carotenoids of C. reinhardtii. Protegencin acts in a direct and destructive way by lysing and killing the algal cells. The toxic effect of protegencin is also observed in an eyeless mutant and with the colony-forming Chlorophyte alga Gonium pectorale. These data reveal a two-pronged molecular strategy involving a cyclic lipopeptide and a conjugated tetrayne used by bacteria to attack select Chlamydomonad algae. In conjunction with the bloom-forming activity of several chlorophytes and the presence of the protegencin gene cluster in over 50 different Pseudomonas genomes these data are highly relevant to ecological interactions between Chlorophyte algae and Pseudomonadales bacteria.
Three-dimensional spider web construction and mechanics
Spiders are nature’s engineers that build lightweight and high-performance web architectures often several times their size and with very few supports. Spiders, silks, and webs have survived and prospered for millions of years, making them an evolutionary success. Learning how spiders used their silks and webs to adapt to environmental pressures have fascinated many fields of research such as biomedicine, biology, and engineering. Because of silk’s nanoscale size and the complex web architecture, little is known about the architecture and mechanics of three-dimensional (3D) spider webs during construction. Su et al. (2021) PNAS (118 (33) e2101296118) investigated the structure and mechanics for a Tidarren sisyphoides spider web at varying stages of construction. This is accomplished by imaging, modeling, and simulations throughout the web-building process to capture changes in the natural web geometry and the mechanical properties. They show that the foundation of the web geometry, strength, and functionality is created during the first 2 day of construction, after which the spider reinforces the existing network with limited expansion of the structure within the frame. A better understanding of the biological and mechanical performance of the 3D spider web under construction could inspire sustainable robust and resilient fiber networks, complex materials, structures, scaffolding, and self-assembly strategies for hierarchical structures and inspire additive manufacturing methods such as 3D printing as well as inspire artistic and architectural and engineering applications.
August 11, 2021
Biomimetic chameleon soft robot with artificial crypsis and disruptive coloration skin
Development of an artificial camouflage at a complete device level remains a vastly challenging task, especially under the aim of achieving more advanced and natural camouflage characteristics via high-resolution camouflage patterns. Kim et al. (2021) (Nature Communications 12: 4658) integrated a thermochromic liquid crystal layer with the vertically stacked, patterned silver nanowire heaters in a multilayer structure of a soft robot to overcome the limitations of the conventional lateral pixelated scheme through the superposition of the heater-induced temperature profiles. At the same time, the weaknesses of thermochromic camouflage schemes are resolved in this study by utilizing the temperature-dependent resistance of the silver nanowire network as the process variable of the active control system. Combined with the active control system and sensing units, the complete device chameleon model successfully retrieves the local background color and matches its surface color instantaneously with natural transition characteristics to be a competent option for a next-generation artificial camouflage.
August 10, 2021
A new carnivorous plant lineage (Triantha) with a unique sticky-inflorescence trap
Carnivorous plants consume animals for mineral nutrients that enhance growth and reproduction in nutrient-poor environments. Lin et al. (2021) report in the journal PNAS (118: e2022724118) that Triantha occidentalis (Tofieldiaceae) represents a previously overlooked carnivorous lineage that captures insects on sticky inflorescences. Field experiments, isotopic data, and mixing models demonstrate significant nitrogen transfer from prey to Triantha, with an estimated 64% of leaf nitrogen obtained from prey capture in previous years, comparable to levels inferred for the co-occurring round-leaved sundew, a recognized carnivore. Nitrogen obtained via carnivory is exported from the inflorescence and developing fruits and may ultimately be transferred to next year’s leaves. Glandular hairs on flowering stems secrete phosphatase, as seen in all carnivorous plants that directly digest prey. Triantha is unique among carnivorous plants in capturing prey solely with sticky traps adjacent to its flowers, contrary to theory. However, its glandular hairs capture only small insects, unlike the large bees and butterflies that act as pollinators, which may minimize the conflict between carnivory and pollination.
Volatile chemical product emissions enhance ozone and modulate urban chemistry
Decades of air quality improvements have substantially reduced the motor vehicle emissions of volatile organic compounds (VOCs). Today, volatile chemical products (VCPs) are responsible for half of the petrochemical VOCs emitted in major urban areas. Coggon et al. (2021) (PNAS 118: e2026653118) reports that VCP emissions are ubiquitous in US and European cities and scale with population density. They report significant VCP emissions for New York City (NYC), including a monoterpene flux of 14.7 to 24.4 kg ⋅ d−1 ⋅ km−2 from fragranced VCPs and other anthropogenic sources, which is comparable to that of a summertime forest. Photochemical modeling of an extreme heat event, with ozone well in excess of US standards, illustrates the significant impact of VCPs on air quality. In the most populated regions of NYC, ozone was sensitive to anthropogenic VOCs (AVOCs), even in the presence of biogenic sources. Within this VOC-sensitive regime, AVOCs contributed upwards of ∼20 ppb to maximum 8-h average ozone. VCPs accounted for more than 50% of this total AVOC contribution. Emissions from fragranced VCPs, including personal care and cleaning products, account for at least 50% of the ozone attributed to VCPs. The authors show that model simulations of ozone depend foremost on the magnitude of VCP emissions and that the addition of oxygenated VCP chemistry impacts simulations of key atmospheric oxidation products. NYC is a case study for developed megacities, and the impacts of VCPs on local ozone are likely similar for other major urban regions across North America or Europe.
August 9, 2021
Microbiota from young mice counteracts selective age-associated behavioral deficits
The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Boehme et al. (2021) (Nature Aging 1:666–676) conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. The results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.
August 6, 2021
Intelligent textiles with passive radiative cooling applications
Incorporating passive radiative cooling structures into personal thermal management technologies could effectively defend humans against intensifying global climate change. Zeng et al. (Science 2021; 373: 692-696) reports developing a multilayer metafabric composed of a titanium oxide polylactic acid composite laminated with a polytetrafluoroethylene layer. This combination creates a textile that has passive radiative cooling properties with good mechanical properties and scalability. The metafabrics can provide high emissivity (94.5%) in the atmospheric window and high reflectivity (92.4%) in the solar spectrum because of the hierarchical-morphology design of the randomly dispersed scatterers throughout the metafabric. Through scalable industrial textile manufacturing routes, their metafabrics exhibit desirable mechanical strength, waterproofness, and breathability for commercial clothing while maintaining efficient radiative cooling ability. Practical application tests demonstrated that a human body covered by the metafabric could be cooled ~4.8°C lower than one covered by commercial cotton fabric. The cost-effectiveness and high performance of our metafabrics present substantial advantages for intelligent garments, smart textiles, and passive radiative cooling applications.
August 3, 2021
Signaling that reduces anxiety and fear
G protein–coupled receptors (GPCRs) are implicated in the regulation of fear and anxiety. GPCR signaling involves canonical G protein pathways but can also engage downstream kinases and effectors through scaffolding interactions mediated by β-arrestin. Ko et al. (Science Signaling 2021; 14: eaba0245) investigated whether β-arrestin signaling regulates anxiety-like and fear-related behavior in mice in response to activation of the GPCR δ-opioid receptor (δOR or DOR). Administration of β-arrestin–biased δOR agonists to mice revealed β-arrestin 2–dependent activation of extracellular signal–regulated kinases 1 and 2 (ERK1/2) in the dorsal hippocampus and amygdala and β-arrestin 1–dependent activation of ERK1/2 in the nucleus accumbens. In mice, β-arrestin–biased agonist treatment was associated with reduced anxiety-like and fear-related behaviors, with some overlapping and isoform-specific input. In contrast, applying a G protein–biased δOR agonist decreased ERK1/2 activity in all three regions as well as the dorsal striatum and was associated with increased fear-related behavior without effects on baseline anxiety. Their results indicate a complex picture of δOR neuromodulation in which β-arrestin 1– and 2–dependent ERK signaling in specific brain subregions suppresses behaviors associated with anxiety and fear and opposes the effects of G protein–biased signaling. Overall, the findings highlight the importance of noncanonical β-arrestin–dependent GPCR signaling in the regulation of these interrelated emotions.
July 30, 2021
Bumble bees show an induced preference for flowers when primed with caffeinated nectar and a target floral odor
Caffeine is a widely occurring plant defense chemical that occurs in the nectar of some plants, e.g., Coffea or Citrus spp., where it may influence pollinator behavior to enhance pollination. Honey bees fed caffeine form longer lasting olfactory memory associations, which could give plants with caffeinated nectar an adaptive advantage by inducing more visits to flowers. Caffeinated free-flying bees show enhanced learning performance and are more likely to revisit a caffeinated target feeder or artificial flower although it is not clear whether improved memory of the target cues or the perception of caffeine as a reward is the cause. Arnold et al. (2021) reports in the journal Current Biology that inexperienced bumble bees (Bombus terrestris) locate new food sources emitting a learned floral odor more consistently if they have been fed caffeine. In laboratory arena tests, they fed bees a caffeinated food alongside a floral odor blend (priming) and then used robotic experimental flowers to disentangle the effects of caffeine improving memory for learned food-associated cues versus caffeine as a reward. Inexperienced bees primed with caffeine made more initial visits to target robotic flowers emitting the target odor compared to control bees or those primed with odor alone. Caffeine-primed bees tended to improve their floral handling time faster. Although the effects of caffeine were short lived, they show that food-locating behaviors in free-flying bumble bees can be enhanced by caffeine provided in the nest. Consequently, there is potential to redesign commercial colonies to enhance bees’ forage focus or even bias bees to forage on a specific crop.
July 22, 2021
A small-molecule activator of the unfolded protein response eradicates human breast tumors
Metastatic estrogen receptor α (ERα)–positive breast cancer is presently incurable. Seeking to target these drug-resistant cancers, Boudreau et al. (2021) (Science Translational Medicine 1:eabf1383) report the discovery of a compound, called ErSO, that activates the anticipatory unfolded protein response (a-UPR) and induces rapid and selective necrosis of ERα-positive breast cancer cell lines in vitro. They then tested ErSO in vivo in several preclinical orthotopic and metastasis mouse models carrying different xenografts of human breast cancer lines or patient-derived breast tumors. In multiple orthotopic models, ErSO treatment given either orally or intraperitoneally for 14 to 21 days induced tumor regression without recurrence. In a cell line tail vein metastasis model, ErSO was also effective at inducing regression of most lung, bone, and liver metastases. ErSO treatment induced almost complete regression of brain metastases in mice carrying intracranial human breast cancer cell line xenografts. Tumors that did not undergo complete regression and regrew remained sensitive to retreatment with ErSO. ErSO was well tolerated in mice, rats, and dogs at doses above those needed for therapeutic responses and had little or no effect on normal ERα-expressing murine tissues. ErSO mediated its anticancer effects through activation of the a-UPR, suggesting that activation of a tumor protective pathway could induce tumor regression.
The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Murithi et al. (Science Translational Medicine 2021; 13: eabg6013) report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria.
July 21, 2021
A natively flexible 32-bit Arm microprocessor
Nearly 50 years ago, Intel created the world’s first commercially produced microprocessor—the 4004, a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 μm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention—that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Biggs et al. (2021) in the journal Nature (595:532–536) report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects.
July 20, 2021
Telomere dysfunction instigates inflammation in inflammatory bowel disease
Inflammatory bowel disease (IBD) is a chronic inflammatory condition driven by diverse genetic and non-genetic programs that converge to disrupt immune homeostasis in the intestine. We have reported that, in murine intestinal epithelium with telomere dysfunction, DNA damage-induced activation of ataxia-telangiectasia mutated (ATM) results in ATM-mediated phosphorylation and activation of the YAP1 transcriptional coactivator, which in turn up-regulates pro-IL-18, a pivotal immune regulator in IBD pathogenesis. Moreover, individuals with germline defects in telomere maintenance genes experience increased occurrence of intestinal inflammation and show activation of the ATM/YAP1/pro-IL-18 pathway in the intestinal epithelium. Chakravarti et al. (2021) in the journal PNAS (118 (29) e2024853118) reports determining the relevance of the ATM/YAP1/pro-IL-18 pathway as a potential driver of IBD, particularly older-onset IBD. Analysis of intestinal biopsy specimens and organoids from older-onset IBD patients documented the presence of telomere dysfunction and activation of the ATM/YAP1/precursor of interleukin 18 (pro-IL-18) pathway in the intestinal epithelium. Employing intestinal organoids from healthy individuals, they demonstrated that experimental induction of telomere dysfunction activates this inflammatory pathway. In organoid models from ulcerative colitis and Crohn’s disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production. Together, these findings support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease.
Inhalable nanocatchers for SARS-CoV-2 inhibition
The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)–like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, Zhang et al. (2021) reports in the journal PNAS (118 (29) e2102957118) designing hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, they developed an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of their formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, the inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.
July 16, 2021
Total protein, not amino acid composition, differs in plant-based versus omnivorous dietary patterns and determines metabolic health
Plant-based dietary patterns are associated with improved cardiometabolic health, but causal dietary components are unclear. Protein has been proposed to play a role, but the importance of protein quantity versus quality remains unknown. MacArthur et al. (2021(Cell Metabolism: https://doi.org/10.1016/j.cmet.2021.06.011) investigated the contributions of total protein amount, amino acid (AA) composition, and plant versus animal source. Analysis of total protein and AA composition of food items and dietary patterns revealed differences between individual food items, but few differences between AA profiles of vegan versus omnivorous dietary patterns. Effects of protein quantity, but not quality, on cardiometabolic health markers were observed in mice using semi-purified diets with crystalline AAs in plant versus animal-based ratios and naturally sourced diets with whole-food ingredients. The data show relatively little difference in protein quality between plant-based and omnivorous dietary patterns and that reduced total protein intake in plant-based dietary patterns may be a contributor to the benefits of plant-based diets.
July 15, 2021
A human apolipoprotein L with detergent-like activity kills intracellular pathogens
Most human cells, not just those belonging to the immune system, mount protective responses to infection when activated by the immune cytokine interferon-gamma (IFN-γ). How IFN-γ confers this function in nonimmune cells and tissues is poorly understood. Gaudet et al. (2021) in Science (373: Issue 6552, eabf8113) reports genome-scale CRISPR/Cas9 gene editing to identify apolipoprotein L-3 (APOL3) as an IFN-γ–induced bactericidal protein that protects human epithelium, endothelium, and fibroblasts against infection. APOL3 directly targets bacteria in the host cell cytosol and kills them by dissolving their anionic membranes into lipoprotein complexes. This work reveals a detergent-like mechanism enlisted during human cell-autonomous immunity to combat intracellular pathogens.
Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria
Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication. Moses et al. (2021) (New England Journal of Medicine; 385:217-227) implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, they recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. They used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. They applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them. They decoded sentences from the participant’s cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, they detected 98% of the attempts by the participant to produce individual words, and they classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period.
Generation of ovarian follicles from mouse pluripotent stem cells
Recent advances have enabled the generation of oocytes from pluripotent stem cells in vitro. However, these cells require a somatic environment to develop fully as reproductive cells. Yoshino et al. (2021) in the journal Science (373: eabe0237) applied what is known about differentiation processes in vivo to determine a culture condition to differentiate embryonic stem cells into gonadal somatic cell–like cells. When the embryonic stem cell–generated ovarian gonadal tissue was combined with early primordial germ cells or in vitro–derived primordial germ cell–like cells, germ cells developed into viable oocytes within the reconstituted follicles that could be fertilized and result in viable offspring. This system enables an alternative method for mouse gamete production and advances our understanding of mammalian reproduction and development.
SARS-CoV-2 amplifies the damaging senescent cell secretory state, and drugs that selectively clear senescent cells reduce mortality in infected aged mice
Cellular senescence is a state elicited in response to stress signals and is associated with a damaging secretory phenotype. The number of senescent cells increases with advanced age and this in turn drives age-related diseases. Camell et al. (2021) in the journal Science (373: eabe4832) show that senescent cells have an amplified inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This response is communicated to nonsenescent cells, suppressing viral defense mechanisms and increasing the expression of viral entry proteins. In old mice infected with a SARS-CoV-2–related virus, treatment with senolytics to reduce the senolytic cell burden reduced mortality and increased antiviral antibodies.
July 14, 2021
Snake venom–laden bioadhesive gel cross-linked by visible light
Bioadhesives reduce operation time and surgical complications. However, in the presence of blood, adhesion strength is often compromised. Inspired by the blood clotting activity of snake venom, Guo et al. (2021) in the journal Science Advances (7: eabf9635) report a visible light–induced blood-resistant hemostatic adhesive (HAD) containing gelatin methacryloyl and reptilase, which is a hemocoagulase (HC) extracted from Bothrops atrox. HAD leads to the activation and aggregation of platelets and efficiently transforms fibrinogen into fibrin to achieve rapid hemostasis and seal the tissue. Blood clotting time with HAD was about 45 s compared with 5 to 6 min without HAD. HAD instantaneously achieved hemostasis on liver incision (~45 s) and cut rat tail (~34 s) and reduced blood loss by 79 and 78%, respectively. HAD is also efficient in sealing severely injured liver and abdominal aorta. HAD has great potential to bridge injured tissues by combing hemostasis with adhesives.
July 13, 2021
Data storage using peptide sequences
Humankind is generating digital data at an exponential rate. These data are typically stored using electronic, magnetic or optical devices, which require large physical spaces and cannot last for a very long time. Chi et al. (2021) reports in the journal Nature Communications (12: 4242) the use of peptide sequences for data storage, which can be durable and of high storage density. With the selection of suitable constitutive amino acids, designs of address codes and error-correction schemes to protect the order and integrity of the stored data, optimization of the analytical protocol and development of a software to effectively recover peptide sequences from the tandem mass spectra, they demonstrated the feasibility of this method by successfully storing and retrieving a text file and the music file Silent Night with 40 and 511 18-mer peptides respectively. This method for the first time links data storage with the peptide synthesis industry and proteomics techniques, and is expected to stimulate the development of relevant fields.
Adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease
In utero base editing has the potential to correct disease-causing mutations before the onset of pathology. Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome) is a lysosomal storage disease (LSD) affecting multiple organs, often leading to early postnatal cardiopulmonary demise. Bose et al. (2021) in the journal Nature Communications (12: 4291) reports in utero adeno-associated virus serotype 9 (AAV9) delivery of an adenine base editor (ABE) targeting the Idua G→A (W392X) mutation in the animal models (mouse), corresponding to the common IDUA G→A (W402X) mutation in MPS-IH patients. They show efficient long-term W392X correction in hepatocytes and cardiomyocytes and low-level editing in the brain. In utero editing was associated with improved survival and amelioration of metabolic, musculoskeletal, and cardiac disease. This proof-of-concept study demonstrates the possibility of efficiently performing therapeutic base editing in multiple organs before birth via a clinically relevant delivery mechanism, highlighting the potential of this approach for MPS-IH and other genetic diseases.
A self-powered implantable and bioresorbable electrostimulation device for biofeedback bone fracture healing
Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Yao et al. (2021) in the journal PNAS (118 (28): e2100772118) present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. They demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.
July 10, 2021
Monsoon clouds, India
July 7, 2021
Dark wings increase the efficiency of seabird flight
Seabirds have evolved numerous adaptations that allow them to thrive under hostile conditions. Many seabirds share similar color patterns, often with dark wings, suggesting that their coloration might be adaptive. Interestingly, these darker wings become hotter when birds fly under high solar irradiance, and previous studies on aerofoils have provided evidence that aerofoil surface heating can affect the ratio between lift and drag, i.e. flight efficiency. However, whether this effect benefits birds remains unknown. Rogalla et al. (2021) reports in the Journal of Royal Society Interface phylogenetic analyses to show that strictly oceanic seabirds with a higher glide performance (optimized by reduced sink rates, i.e. the altitude lost over time) have evolved darker wings, potentially as an additional adaptation to improve flight. Using wind tunnel experiments, they showed that radiative heating of bird wings indeed improves their flight efficiency. These results illustrate that seabirds may have evolved wing pigmentation in part through selection for flight performance under extreme ocean conditions. They suggest that other bird clades, particularly long-distance migrants, might also benefit from this effect and therefore might show similar evolutionary trajectories. These findings may also serve as a guide for bioinspired innovations in aerospace and aviation, especially in low-speed regimes.
June 23, 2021
The cryptochrome 4 (CRY4) from the night-migratory European robin is magnetically sensitive and may aid in navigation
Night-migratory songbirds are remarkably proficient navigators. Flying alone and often over great distances, they use various directional cues including, crucially, a light-dependent magnetic compass. The mechanism of this compass has been suggested to rely on the quantum spin dynamics of photoinduced radical pairs in cryptochrome flavoproteins located in the retinas of the birds. Xu et al. (2021) reports in the journal Nature (594: 535–540) that the photochemistry of cryptochrome 4 (CRY4) from the night-migratory European robin (Erithacus rubecula) is magnetically sensitive in vitro, and more so than CRY4 from two non-migratory bird species, chicken (Gallus gallus) and pigeon (Columba livia). Site-specific mutations of ErCRY4 reveal the roles of four successive flavin–tryptophan radical pairs in generating magnetic field effects and in stabilizing potential signalling states in a way that could enable sensing and signalling functions to be independently optimized in night-migratory birds.
June 16, 2021
Development of beta-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease
Sickle cell disease (SCD) is the most common serious monogenic disease with 300,000 births annually worldwide. SCD is an autosomal recessive disease resulting from a single point mutation in codon six of the β-globin gene (HBB). Ex vivo β-globin gene correction in autologous patient-derived hematopoietic stem and progenitor cells (HSPCs) may potentially provide a curative treatment for SCD. Lattanzi et al. (2021) Science Translational Medicine 13(598): eabf2444 developed a CRISPR-Cas9 gene targeting strategy that uses high-fidelity Cas9 precomplexed with chemically modified guide RNAs to induce recombinant adeno-associated virus serotype 6 (rAAV6)–mediated HBB gene correction of the SCD-causing mutation in HSPCs. They further demonstrate the preclinical feasibility, efficacy, and toxicology of HBB gene correction in plerixafor-mobilized CD34+ cells from healthy and SCD patient donors (gcHBB-SCD). The authors achieved up to 60% HBB allelic correction in clinical-scale gcHBB-SCD manufacturing. After transplant into immunodeficient NSG mice, 20% gene correction was achieved with multilineage engraftment. The long-term safety, tumorigenicity, and toxicology study demonstrated no evidence of abnormal hematopoiesis, genotoxicity, or tumorigenicity from the engrafted gcHBB-SCD drug product. Together, these preclinical data support the safety, efficacy, and reproducibility of this gene correction strategy for initiation of a phase 1/2 clinical trial in patients with SCD.
June 15, 2021
Early life stress is associated with earlier emergence of permanent molars
Exposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either costly and difficult to collect, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. McDermott et al. (2021) PNAS 118 (24) e2105304118, evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a preregistered analysis they demonstrated that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). They replicate relationships between income and molar eruption in a population-representative dataset. These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.
June 10, 2021
Mosquitoes infected with the Wolbachia pipientis are less susceptible to dengue virus infection
A cluster-randomized trial involving releases of Wolbachia infected A. aegypti mosquitoes for the control of dengue was conducted in Yogyakarta, Indonesia (Utarini et al. 2021 N Engl J Med. 384:2177-2186). 12 geographic clusters was randomly assigned to receive deployments of Wolbachia -infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. Introgression of Wolbachia into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants.
June 9, 2021
Intensive human contact correlates with smaller brain in animals
Cattle are one of the most intensively bred domestic animals, providing humans with a multitude of products and uses. Using data from the fossil record, Balcarcel et al. (2021) report in the journal Proceedings of the Royal Society B report that their domestication, as for other taxa, has resulted in a reduction of their brain size. They not only conclude that Bos taurus (domestic cattle) have smaller brains than their wild ancestor, Bos primigenius (aurochs), but that brain size varies significantly by breed, with some having much smaller brains than others. Differences in husbandry practices between several breed categories align with a range of human engagement, which also aligns with the degree of selection for docility. Sampling 317 domestics from 71 breeds, they investigate if differences in brain size correlate with the intensity of human contact. A clear pattern emerges whereby a brain reduction gradient parallels a gradient in behavioural selection. Bullfighting cattle, which are bred for fighting and aggressive temperament, have much larger brains than dairy breeds, which are intensively selected for docility. The data add to a fundamental aspect of animal domestication theory: the interplay between basic features of the domestic environment—selection for docility, absence of predators and human provision of resources—seems to explain differences in brain size.
Inhaled nitrous oxide (laughing gas) for improving depression
About one-third of individuals suffering from depression are at risk for treatment resistance. Whereas inhaled 50% nitrous oxide has early antidepressant effects on individuals with treatment-resistant major depression (TRMD), adverse effects can occur at this concentration. Nagele et al. (2021) in the journal Science Translational Medicine 13:eabe1376, report the effects of a single 1-hour treatment with 25% nitrous oxide on depression symptoms in those with TRMD, finding that this lower concentration had comparable efficacy to 50% nitrous oxide over several weeks but was associated with significantly fewer adverse effects. These results highlight that lower concentrations of nitrous oxide may be a useful treatment for TRMD.
June 2, 2021
Thyroid hormones regulate the formation and environmental plasticity of white bars in clownfishes
Developmental plasticity is defined as the ability of an organism to adjust its development depending on environmental signals, thus producing alternative phenotypes precisely adjusted to the environment. Yet, the mechanisms underlying developmental plasticity are not fully understood. Salis et al. (2021) in the journal PNAS (118 (23) e2101634118) found that juvenile clownfish delay the development of their white bars during metamorphosis depending on the sea anemone species in which they are recruited. To understand this developmental plasticity, they investigated roles for thyroid hormones, the main hormones triggering metamorphosis in vertebrates. The authors found that thyroid hormones regulate white bar formation and that a shift in hormone levels, associated with ecological differences, results in divergent color patterns in different sea anemone species in which the young fish is recruited.
June 1, 2021
An aged immune system drives senescence and ageing of solid organs
Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly. To define the contribution of immune system ageing to organism ageing, Yousefzadeh et al. (2021) (Nature 594:100-105) selectively deleted Ercc1, which encodes a crucial DNA repair protein in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence in the immune system only. They show that Vav-iCre+/−;Ercc1−/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre+/−;Ercc1−/fl or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre+/−;Ercc1−/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.
May 25, 2021
Cyclone Yaas, India, May 25, 2021
May 14, 2021
Mammals can breathe through their intestine
Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Okabe et al. (2021) in the journal Clinical and Translational Resource and Technology Insights report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus). Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, they analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat. Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications
May 12, 2021
SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 pandemic. Coronaviruses developed varied mechanisms to repress host mRNA translation to allow the translation of viral mRNAs and concomitantly block the cellular innate immune response. Although different SARS-CoV-2 proteins are implicated in host expression shutoff, a comprehensive picture of the effects of SARS-CoV-2 infection on cellular gene expression is lacking. Finkel et al. (2021) published in the journal Nature combine RNA-sequencing, ribosome profiling and metabolic labeling of newly synthesized RNA, to comprehensively define the mechanisms that are utilized by SARS-CoV-2 to shutoff cellular protein synthesis. They show that infection leads to a global reduction in translation, but viral transcripts are not preferentially translated. Instead, they find that infection leads to accelerated degradation of cytosolic cellular mRNAs which facilitates viral takeover of the mRNA pool in infected cells. Moreover, they reveal that the translation of transcripts whose expression is induced in response to infection, including innate immune genes, is impaired. They demonstrate this impairment is likely mediated by inhibition of nuclear mRNA export, preventing newly transcribed cellular mRNAs from accessing ribosomes. Overall, the data uncover the multipronged strategy employed by SARS-CoV-2 to commandeer the translation machinery and to suppress host defenses.
April 23, 2021
Global groundwater wells at risk of running dry
Groundwater wells supply water to billions of people, but they can run dry when water tables decline. Jasechko and Perrone reports in the journal Science (2021; 372: 418-421) that 6 to 20% of wells are no more than 5 meters deeper than the water table, implying that millions of wells are at risk of running dry if groundwater levels decline by only a few meters. Further, newer wells are not being constructed deeper than older wells in some of the places experiencing significant groundwater level declines, suggesting that newer wells are at least as likely to run dry as older wells if groundwater levels continue to decline. Poor water quality in deep aquifers and the high costs of well construction limit the effectiveness of tapping deep groundwater to stave off the loss of access to water as wells run dry. The study was analyzed based on the construction records for ~39 million globally distributed wells.
April 21, 2021
Biohybrid soft robots with self-stimulating skeletons
Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers). The integration of biological components offers unique characteristics that artificial materials cannot precisely replicate, such as adaptability and response to external stimuli. Guix et al. (2021) reports in the journal Science Robotics (6: eabe7577) a skeletal muscle–based swimming biobot with a three-dimensional (3D)–printed serpentine spring skeleton that provides mechanical integrity and self-stimulation during the cell maturation process. The restoring force inherent to the spring system allows a dynamic skeleton compliance upon spontaneous muscle contraction, leading to a cyclic mechanical stimulation process that improves the muscle force output without external stimuli. Optimization of the 3D-printed skeletons is carried out by studying the geometrical stiffnesses of different designs via finite element analysis. Upon electrical actuation of the muscle tissue, two types of motion mechanisms are experimentally observed: directional swimming when the biobot is at the liquid-air interface and coasting motion when it is near the bottom surface. The integrated compliant skeleton provides both the mechanical self-stimulation and the required asymmetry for directional motion, displaying its maximum velocity at 5 hertz (800 micrometers per second, 3 body lengths per second). This skeletal muscle–based biohybrid swimmer attains speeds comparable with those of cardiac-based biohybrid robots and outperforms other muscle-based swimmers. The integration of serpentine-like structures in hybrid robotic systems allows self-stimulation processes that could lead to higher force outputs in current and future biomimetic robotic platforms.
April 13, 2021
Global warming is causing a more pronounced dip in marine species richness around the equator
The latitudinal gradient in species richness, with more species in the tropics and richness declining with latitude, is widely known and has been assumed to be stable over recent centuries. Chaudhary et al. (2021) (PNAS, 118 (15): e2015094118) analyzed data on 48,661 marine animal species since 1955, accounting for sampling variation, to assess whether the global latitudinal gradient in species richness is being impacted by climate change. The authors confirm recent studies that show a slight dip in species richness at the equator. Moreover, richness across latitudinal bands was sensitive to temperature, reaching a plateau or declining above a mean annual sea surface temperature of 20 °C for most taxa. In response, since the 1970s, species richness has declined at the equator relative to an increase at mid-latitudes and has shifted north in the northern hemisphere, particularly among pelagic species. This pattern is consistent with the hypothesis that climate change is impacting the latitudinal gradient in marine biodiversity at a global scale. The intensification of the dip in species richness at the equator, especially for pelagic species, suggests that it is already too warm there for some species to survive.
April 7, 2021
Discovery of a natural cyan blue: A unique food-sourced anthocyanin could replace synthetic brilliant blue
The color of food is critical to the food and beverage industries, as it influences many properties beyond eye-pleasing visuals including flavor, safety, and nutritional value. Blue is one of the rarest colors in nature’s food palette—especially a cyan blue—giving scientists few sources for natural blue food colorants. Finding a natural cyan blue dye equivalent to FD&C Blue No. 1 remains an industry-wide challenge and the subject of several research programs worldwide. Denish et al. (2021) Science Advances (7: eabe7871) used computational simulations and large-array spectroscopic techniques were used to determine the 3D chemical structure, color expression, and stability of this previously uncharacterized cyan blue anthocyanin-based colorant. Synthetic biology and computational protein design tools were leveraged to develop an enzymatic transformation of red cabbage anthocyanins into the desired anthocyanin. More broadly, this research demonstrates the power of a multidisciplinary strategy to solve a long-standing challenge in the food industry.
April 5, 2021
Processed foods drive intestinal barrier permeability and microvascular diseases
Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Snelson et al. (2021) report in the journal Science Advances (7:eabe4841) that in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a processed diet leads to innate immune complement activation and local kidney inflammation and injury via the potent proinflammatory effector molecule complement 5a (C5a). In a mouse model of diabetes, a high resistant starch fiber diet maintained gut barrier integrity and decreased severity of kidney injury via suppression of complement. These results demonstrate mechanisms by which processed foods cause inflammation that leads to chronic disease.
April 1, 2021
Toward net-zero sustainable aviation fuel with wet waste–derived volatile fatty acids
With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Huq et al. (2021) in the journal PNAS (118: e2023008118) reports SAF production from food waste–derived volatile fatty acids (VFA) by targeting normal paraffins for a near-term path to market and branched isoparaffins to increase the renewable content long term. Combining these distinct paraffin structures was shown to synergistically improve VFA-SAF flash point and viscosity to increase the renewable blend limit to 70%. Life cycle analysis shows the dramatic impact on the carbon footprint if food waste is diverted from landfills to produce VFA-SAF, highlighting the potential to meet jet fuel safety, operability, and environmental goals.
March 19, 2021
Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention
Rynearson et al. (2021) in the journal J Exp Med (218 (4): e20202560) reported developing a potent γ-secretase modulator (GSM) to circumvent problems associated with γ-secretase inhibitors (GSIs) and to potentially enable use in primary prevention of early-onset familial Alzheimer’s disease (EOFAD). Unlike GSIs, GSMs do not inhibit γ-secretase activity but rather allosterically modulate γ-secretase, reducing the net production of Aβ42 and to a lesser extent Aβ40, while concomitantly augmenting production of Aβ38 and Aβ37. This GSM demonstrated robust time- and dose-dependent efficacy in acute, subchronic, and chronic studies across multiple species, including primary and secondary prevention studies in a transgenic mouse model.
Hunger enhances food-odor attraction through a neuropeptide Y spotlight
Internal state controls olfaction through poorly understood mechanisms. Odors that represent food, mates, competitors and predators activate parallel neural circuits that may be flexibly shaped by physiological need to alter behavioral outcome. Horio and Liberles (2021) reported in the journal Nature (592: 262–266) identifying a neuronal mechanism by which hunger selectively promotes attraction to food odors over other olfactory cues. Optogenetic activation of hypothalamic agouti-related peptide (AGRP) neurons enhances attraction to food odors but not to pheromones, and branch-specific activation and inhibition reveal a key role for projections to the paraventricular thalamus. Mice that lack neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail to prefer food odors over pheromones after fasting, and hunger-dependent food-odor attraction is restored by cell-specific NPY rescue in AGRP neurons. Furthermore, acute NPY injection immediately rescues food-odor preference without additional training, indicating that NPY is required for reading olfactory circuits during behavioral expression rather than writing olfactory circuits during odor learning. Together, these findings show that food-odor-responsive neurons comprise an olfactory subcircuit that listens to hunger state through thalamic NPY release, and more generally, provide mechanistic insights into how internal state regulates behavior.
Mitochondrial copper depletion suppresses triple-negative breast cancer in mice
Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxic or ineffective for cancer treatment. Cui et al. report in the journal Nature Biotechnology (2021; 39: 357–367) a safe, mitochondria-targeted, copper-depleting nanoparticle (CDN) and test it against triple-negative breast cancer (TNBC). They show that CDNs decrease oxygen consumption and oxidative phosphorylation, cause a metabolic switch to glycolysis and reduce ATP production in TNBC cells. This energy deficiency, together with compromised mitochondrial membrane potential and elevated oxidative stress, results in apoptosis. CDNs should be less toxic than existing copper chelators because they favorably deprive copper in the mitochondria in cancer cells instead of systemic depletion. Indeed, they demonstrate low toxicity of CDNs in healthy mice. In three mouse models of TNBC, CDN administration inhibits tumor growth and substantially improves survival. The efficacy and safety of CDNs suggest the potential clinical relevance of this approach.
March 18, 2021
Sustainable polyethylene fabrics with engineered moisture transport for passive cooling
Polyethylene (PE) has emerged recently as a promising polymer for incorporation in wearable textiles owing to its high infrared transparency and tuneable visible opacity, which allows the human body to cool via thermal radiation, potentially saving energy on building refrigeration. Alberghini et al. (2021) in the journal Nature Sustainability (https://doi.org/10.1038/s41893-021-00688-5) reports that single-material PE fabrics may offer a sustainable, high-performance alternative to conventional textiles, extending beyond radiative cooling. PE fabrics exhibit ultra-light weight, low material cost and recyclability. Industrial materials sustainability (Higg) index calculations predict a low environmental footprint for PE fabrics in the production phase. They engineered PE fibres, yarns and fabrics to achieve efficient water wicking and fast-drying performance which, combined with their excellent stain resistance, offer promise in reducing energy and water consumption as well as the environmental footprint of PE textiles in their use phase. Unlike previously explored nanoporous PE materials, the high-performance PE fabrics in this study are made from fibres melt spun and woven on standard equipment used by the textile industry worldwide and do not require any chemical coatings. The authors further demonstrate that these PE fibres can be dry colored during fabrication, resulting in dramatic water savings without masking the PE molecular fingerprints scanned during the automated recycling process.
Microrobots for targeted therapeutic intervention
High-precision delivery of microrobots at the whole-body scale is of considerable importance for efforts toward targeted therapeutic intervention. However, vision-based control of microrobots, to deep and narrow spaces inside the body, remains a challenge. Wang et al. (2021) in the journal Science Robotics 6: eabd2813; report a soft and resilient magnetic cell microrobot with high biocompatibility that can interface with the human body and adapt to the complex surroundings while navigating inside the body. They achieve time-efficient delivery of soft microrobots using an integrated platform called endoscopy-assisted magnetic actuation with dual imaging system (EMADIS). EMADIS enables rapid deployment across multiple organ/tissue barriers at the whole-body scale and high-precision delivery of soft and biohybrid microrobots in real time to tiny regions with depth up to meter scale through natural orifice, which are commonly inaccessible and even invisible by conventional endoscope and medical robots. The precise delivery of magnetic stem cell spheroid microrobots (MSCSMs) by the EMADIS transesophageal into the bile duct with a total distance of about 100 centimeters can be completed within 8 minutes. The integration strategy offers a full clinical imaging technique–based therapeutic/intervention system, which broadens the accessibility of hitherto hard-to-access regions, by means of soft microrobots.
March 17, 2021
Legume–microbiome interactions unlock mineral nutrients in regrowing tropical forests
Legume trees form an abundant and functionally important component of tropical forests worldwide with N2-fixing symbioses linked to enhanced growth and recruitment in early secondary succession. However, it remains unclear how N2-fixers meet the high demands for inorganic nutrients imposed by rapid biomass accumulation on nutrient-poor tropical soils. Epihov et al. (2021) in the journal PNAS (118 (11) e2022241118) reports that N2-fixing trees in secondary Neotropical forests triggered twofold higher in situ weathering of fresh primary silicates compared to non-N2–fixing trees and induced locally enhanced nutrient cycling by the soil microbiome community. Shotgun metagenomic data from weathered minerals support the role of enhanced nitrogen and carbon cycling in increasing acidity and weathering. Metagenomic and marker gene analyses further revealed increased microbial potential beneath N2-fixers for anaerobic iron reduction, a process regulating the pool of phosphorus bound to iron-bearing soil minerals. The authors find that the Fe(III)-reducing gene pool in soil is dominated by acidophilic Acidobacteria, including a highly abundant genus of previously undescribed bacteria, Candidatus Acidoferrum, genus novus. The resulting dependence of the Fe-cycling gene pool to pH determines the high iron-reducing potential encoded in the metagenome of the more acidic soils of N2-fixers and their nonfixing neighbors. They infer that by promoting the activities of a specialized local microbiome through changes in soil pH and C:N ratios, N2-fixing trees can influence the wider biogeochemical functioning of tropical forest ecosystems in a manner that enhances their ability to assimilate and store atmospheric carbon.
Embryo-like structures generated from human pluripotent stem cells
Limited access to embryos has hampered the study of human embryogenesis and disorders that occur during early pregnancy. Human pluripotent stem cells provide an alternative means to study human development in a dish. Recent advances in partial embryo models derived from human pluripotent stem cells have enabled human development to be examined at early post-implantation stages. However, models of the pre-implantation human blastocyst are lacking. Starting from naive human pluripotent stem cells, Yu et al. (2021) Nature (https://doi.org/10.1038/s41586-021-03356-y) developed an effective three-dimensional culture strategy with successive lineage differentiation and self-organization to generate blastocyst-like structures in vitro. These structures—termrf ‘human blastoids’—resemble human blastocysts in terms of their morphology, size, cell number, and composition and allocation of different cell lineages. Single-cell RNA-sequencing analyses also reveal the transcriptomic similarity of blastoids to blastocysts. Human blastoids are amenable to embryonic and extra-embryonic stem cell derivation and can further develop into peri-implantation embryo-like structures in vitro. Using chemical perturbations, we show that specific isozymes of protein kinase C have a critical function in the formation of the blastoid cavity. Human blastoids provide a readily accessible, scalable, versatile and perturbable alternative to blastocysts for studying early human development, understanding early pregnancy loss and gaining insights into early developmental defects.
March 10, 2021
A large electronic display textile that is flexible, breathable and withstands repeated machine-washing is integrated with a keyboard and power supply to create a wearable, durable communication tool
Displays are basic building blocks of modern electronics. Integrating displays into textiles offers exciting opportunities for smart electronic textiles—the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices. Display textiles serve to bridge human–machine interactions, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating, sensing and supplying electricity have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Shi et al. (2021) reports in the journal Nature [591: 240-245] a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft–warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Their display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. They show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system’s potential within the ‘internet of things’ in various areas, including healthcare. The authors approach unifies the fabrication and function of electronic devices with textiles, and they expect that woven-fiber materials will shape the next generation of electronics.
Loss of furin cleavage site reduces SARS-CoV-2 pathogenesis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses. To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, Johnson et al. (2021) [Nature 591:293-299] generated a mutant SARS-CoV-2 that lacks the furin cleavage site (ΔPRRA). They report that replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the ΔPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Their results demonstrate a critical role for the furin cleavage site in infection with SARS-CoV-2 and highlight the importance of this site for evaluating the neutralization activities of antibodies.
March 5, 2021
Fewer butterflies seen by community scientists across the warming and drying landscapes of the American West
Uncertainty remains regarding the role of anthropogenic climate change in declining insect populations, partly because our understanding of biotic response to climate is often complicated by habitat loss and degradation among other compounding stressors. Forister et al. (2021) addressed this challenge by integrating expert and community scientist datasets that include decades of monitoring across more than 70 locations spanning the western United States. They report in the journal Science (371: 1042-1045) a 1.6% annual reduction in the number of individual butterflies observed over the past four decades, associated in particular with warming during fall months. The pervasive declines that they report advance our understanding of climate change impacts and suggest that a new approach is needed for butterfly conservation in the region, focused on suites of species with shared habitat or host associations.
March 3 2021
Self-powered soft robot in the Mariana Trench
The deep sea remains the largest unknown territory on Earth as it is difficult to explore. Owing to the extremely high pressure in the deep sea, rigid vessels and pressure-compensation systems are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths. Here, inspired by the structure of a deep-sea snailfish, Li et al. (2021) (Nature 59:66–71) develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, they decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot’s flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. The authors validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Their work highlights the potential of designing soft, lightweight devices for use in extreme conditions.
Asian Emissions Explain Much of the Arctic Black Carbon Events
Snow and sea ice are two of the most reflective surfaces occurring naturally on planet Earth. Light absorbing aerosols, such as wind blown black carbon, that stick to these pristine surfaces can make them less reflective, thus converting more sunlight into heat. The added heat leads to increased surface temperatures and is detrimental to the Arctic climate. There are few sources of light absorbing aerosols in the Arctic compared to the vast amounts of black carbon aerosols that are emitted closer to the equator. Backman et al. (2021) in the journal Geophysical Res. Letters 48: e2020GL091913, published an important pathway for light absorbing aerosols to enter the Arctic. Light absorbing aerosols that enter the Arctic through this pathway can then subsequently spread out throughout the Arctic. This pathway is shown to transport light absorbing airborne pollutants from the Indo‐Gangetic plane over Central Asia into the high Arctic in as little as 7 days in quantities that well exceed the background levels, thus highlighting the importance of this newly found pathway.
February 17, 2021
Electronics-free pneumatic circuits for controlling soft-legged robots
Pneumatically actuated soft robots have recently shown promise for their ability to adapt to their environment. Previously, these robots have been controlled with electromechanical components, such as valves and pumps that are typically bulky and expensive. Drotman et al. (2021) report in the journal Science Robotics an approach for controlling the gaits of soft-legged robots using simple pneumatic circuits without any electronic components. This approach produces locomotive gaits using ring oscillators composed of soft valves that generate oscillating signals analogous to biological central pattern generator neural circuits, which are acted upon by pneumatic logic components in response to sensor inputs. Their robot requires only a constant source of pressurized air to power both control and actuation systems. The authors demonstrate this approach by designing pneumatic control circuits to generate walking gaits for a soft-legged quadruped with three degrees of freedom per leg and to switch between gaits to control the direction of locomotion. In experiments, they controlled a basic walking gait using only three pneumatic memory elements (valves). With two oscillator circuits (seven valves), they were able to improve locomotion speed by 270%. Furthermore, with a pneumatic memory element they designed to mimic a double-pole double-throw switch, they demonstrated a control circuit that allowed the robot to select between gaits for omnidirectional locomotion and to respond to sensor input. This work represents a step toward fully autonomous, electronics-free walking robots for applications including low-cost robotics for entertainment and systems for operation in environments where electronics may not besuitable.
February 10, 2021
A stable antimicrobial peptide with dual functions of treating and preventing citrus Huanglongbing
Citrus Huanglongbing (HLB), caused by a vector-transmitted phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas), is the most devastating citrus disease worldwide. Currently, there are no effective strategies to prevent infection or to cure HLB-positive trees. HLB has caused billions of dollars in annual production losses, threatening the entire citrus industry. Despite extensive research efforts, there are still no effective management tools to treat HLB-positive trees or to prevent new infections. Current HLB management strategies include chemical application of insecticides and traditional heat-sensitive antibiotics, which pose threats to humans, animal health, and the environment, and likely generate drug resistant insects and microbes. Huang et al. (2021) reports in the journal PNAS (118: (6) e2019628118) identifying a novel class of stable antimicrobial peptides (SAMPs) from Australian finger lime and other HLB-tolerant citrus close relatives, which has dual functions of inhibiting CLas growth in HLB-positive trees and activating host immunity to prevent new infections. The SAMP from Microcitrus australiasica can rapidly kill Liberibacter crescens (Lcr), a culturable Liberibacter strain, and inhibit infections of CLas and CL. solanacearum in plants. In controlled greenhouse trials, SAMP not only effectively reduced CLas titer and disease symptoms in HLB-positive trees but also induced innate immunity to prevent and inhibit infections. Importantly, unlike antibiotics, SAMP is heat stable, making it better suited for field applications. Spray-applied SAMP was taken up by citrus leaves, stayed stable inside the plants for at least a week, and moved systemically through the vascular system where CLas is located. We further demonstrate that SAMP is most effective on α-proteobacteria and causes rapid cytosol leakage and cell lysis. The α-helix-2 domain of SAMP is sufficient to kill Lcr. Future field trials will help determine the efficacy of SAMP in controlling HLB and the ideal mode of application.
The long-term effects of war exposure on civic engagement
Recent studies document that exposure to civil war violence could increase postwar participation in social organizations. Yet, there is a lack of evidence on whether these effects persist over generations, the pathway of persistence, and whether they generalize to different types of conflict. Joan Barcelo in the journal PNAS (2021) (118 (6) e2015539118) address these gaps, drawing on a very detailed dataset on the conflict intensity in the Vietnam War and a representative survey in contemporary Vietnam that includes respondents’ migration history. Conflict-affected individuals tend to engage more in social organization and hold greater expressive values, at least 26 y after the individual’s exposure to the war. Further, the author find evidence that both persistence within individuals and community-wide transmission jointly account for the long-term increase of civic engagement.
Plant virus evolution under strong drought conditions results in a transition from parasitism to mutualism
Viruses are seen as selfish pathogens that harm their hosts to ensure their own survival. However, metagenomic studies are drawing a new picture in which viruses are present everywhere and not always associated to diseases. A classic observation in plant pathology is that the outcome of infection depends on environmental conditions. Gonzalez et al. (2021) reports in the journal PNAS (118 (6) e2020990118) that the relationship between a plant virus and its natural host can evolve from pathogenic to mutualistic under severe drought conditions. While viral strains evolved in normal watering conditions increased their virulence, drought-evolved viral strains confer plants with greater resistance to drought. The authors show that this transition to mutualism depends on a complex reorganization of hormone-induced signaling pathways and changes in gene expression.
February 3, 2021
How spiders hunt heavy prey: the tangle web as a pulley and spider’s lifting mechanics
The spiders of Theridiidae’s family display a peculiar behaviour when they hunt extremely large prey. They lift the quarry, making it unable to escape, by attaching pre-tensioned silk threads to it. Greco and Pugno (2021) in the Journal of Royal Society Interface (https://doi.org/10.1098/rsif.2020.0907) reports analyzing the lifting hunting mechanism and, in order to quantify the phenomenon, applied the lifting mechanics theory. The comparison between the experiments and the theory suggests that, during the process, spiders do not stretch the silk too much by keeping it in the linear elastic regime. The authors report further evidence for the strong role of silk in spiders’ evolution, especially how spiders can stretch and use it as an external tool to overcome their muscles’ limits and capture prey with large mass, e.g. 50 times the spider’s mass.
Do marmosets understand others’ conversations?
What information animals derive from eavesdropping on interactions between conspecifics, and whether they assign value to it, is difficult to assess because overt behavioral reactions are often lacking. An inside perspective of how observers perceive and process such interactions is thus paramount. Brugger et al. (2021) in the journal Science Advances (Vol. 7, no. 6, eabc8790) reports what happens in the mind of marmoset monkeys when they hear playbacks of positive or negative third-party vocal interactions, by combining thermography to assess physiological reactions and behavioral preference measures. The physiological reactions show that playbacks were perceived and processed holistically as interactions rather than as the sum of the separate elements. Subsequently, the animals preferred those individuals who had been simulated to engage in positive, cooperative vocal interactions during the playbacks. By using thermography to disentangle the mechanics of marmoset sociality, we thus find that marmosets eavesdrop on and socially evaluate vocal exchanges and use this information to distinguish between cooperative and noncooperative conspecifics.
January 29, 2021
Vocal dialect in naked mole rat is influenced by the queen
Naked mole-rats (Heterocephalus glaber) form some of the most cooperative groups in the animal kingdom, living in multigenerational colonies under the control of a single breeding queen. Yet how they maintain this highly organized social structure is unknown. Barker et al. (2021) in the journal Science (371: 503-507) show that the most common naked mole-rat vocalization, the soft chirp, is used to transmit information about group membership, creating distinctive colony dialects. Audio playback experiments demonstrate that individuals make preferential vocal responses to home colony dialects. Pups fostered in foreign colonies in early postnatal life learn the vocal dialect of their adoptive colonies, which suggests vertical transmission and flexibility of vocal signatures. Dialect integrity is partly controlled by the queen: Dialect cohesiveness decreases with queen loss and remerges only with the ascendance of a new queen.
January 26, 2021
Newborn mice form lasting memories of their mothers
Some of the most enduring social connections begin when infants first recognize their caregivers, memories that form the basis of many family relationships. It remains unknown whether these early social memories persist into adulthood in mice and, if so, which brain regions support them. Here we show that mice form memories of their mother within days after birth and that these memories persist into adulthood. Pups display greater interest in the mother than in an unfamiliar dam before weaning, after which this preference reverses. Inhibition of CA2 neurons in the pup temporarily blocks the ability to discriminate between the mother and an unfamiliar dam, whereas doing so in adulthood prevents the formation of short-term memories about conspecifics, as well as social discrimination related to long-term memories of the mother. These results suggest that the CA2 supports memories of the mother during infancy and adulthood with a developmental switch in social preference.
January 21, 2021
Restoring metabolism of myeloid cells reverses cognitive decline in ageing
Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer’s disease. Systemically, circulating pro-inflammatory factors can promote cognitive decline, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Minhas et al. (2021) in the journal Nature (590:122-128) reports that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Their study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.
January 20, 2021
A resonant squid-inspired robot unlocks biological propulsive efficiency
Elasticity has been linked to the remarkable propulsive efficiency of pulse-jet animals such as the squid and jellyfish, but reports that quantify the underlying dynamics or demonstrate its application in robotic systems are rare. This work identifies the pulse-jet propulsion mode used by these animals as a coupled mass-spring-mass oscillator, enabling the design of a flexible self-propelled robot. Bujard et al. (2021) Science Robotics (6: Issue 50, eabd2971) use this system to experimentally demonstrate that resonance greatly benefits pulse-jet swimming speed and efficiency, and the robot’s optimal cost of transport is found to match that of the most efficient biological swimmers in nature, such as the jellyfish Aurelia aurita. The robot also exhibits a preferred Strouhal number for efficient swimming, thereby bridging the gap between pulse-jet propulsion and established findings in efficient fish swimming. Extensions of the current robotic framework to larger amplitude oscillations could combine resonance effects with optimal vortex formation to further increase propulsive performance and potentially outperform biological swimmers altogether.
Enhanced SARS-CoV-2 neutralization by dimeric IgA
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of COVID-19. Although potent immunoglobulin G (IgG) antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might affect the initial viral spread and transmissibility from the mucosa. Wang et al. (2021) in the journal Science Translational Medicine (13: Issue 577, eabf1555) characterize the IgA response to SARS-CoV-2 in a cohort of 149 convalescent individuals after diagnosis with COVID-19. IgA responses in plasma generally correlated with IgG responses. Furthermore, clones of IgM-, IgG-, and IgA-producing B cells were derived from common progenitor cells. Plasma IgA monomers specific to SARS-CoV-2 proteins were demonstrated to be twofold less potent than IgG equivalents. However, IgA dimers, the primary form of antibody in the nasopharynx, were, on average, 15 times more potent than IgA monomers against the same target. Thus, dimeric IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.
The response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes
Domestic cats and other felids rub their faces and heads against catnip (Nepeta cataria) and silver vine (Actinidia polygama) and roll on the ground as a characteristic response. While this response is well known, its biological function and underlying mechanism remain undetermined. Uenoyama et al. (2021) reports in the journal Science Advances (7: eabd9135) found that the iridoid nepetalactol is the major component of silver vine that elicits this potent response in cats and other felids. Nepetalactol increased plasma β-endorphin levels in cats, while pharmacological inhibition of μ-opioid receptors suppressed the classic rubbing response. Rubbing behavior transfers nepetalactol onto the faces and heads of respondents where it repels the mosquito, Aedes albopictus. Thus, self-anointing behavior helps to protect cats against mosquito bites. The characteristic response of cats to nepetalactol via the μ-opioid system provides an important example of chemical pest defense using plant metabolites in nonhuman mammals.
January 13, 2021
Fish-inspired robot swarm
Many fish species gather by the thousands and swim in harmony with seemingly no effort. Large schools display a range of impressive collective behaviors, from simple shoaling to collective migration and from basic predator evasion to dynamic maneuvers such as bait balls and flash expansion. A wealth of experimental and theoretical work has shown that these complex three-dimensional (3D) behaviors can arise from visual observations of nearby neighbors, without explicit communication. By contrast, most underwater robot collectives rely on centralized, above-water, explicit communication and, as a result, exhibit limited coordination complexity. Berlinger et al. (2021) report in the journal Science Robotics (Vol. 6, Issue 50, eabd8668) 3D collective behaviors with a swarm of fish-inspired miniature underwater robots that use only implicit communication mediated through the production and sensing of blue light. They show that complex and dynamic 3D collective behaviors—synchrony, dispersion/aggregation, dynamic circle formation, and search-capture—can be achieved by sensing minimal, noisy impressions of neighbors, without any centralized intervention. The results provide insights into the power of implicit coordination and are of interest for future underwater robots that display collective capabilities on par with fish schools for applications such as environmental monitoring and search in coral reefs and coastal environments.
January 6, 2021
Control of bacteria with blue light and phytochemical carvacrol
Development of alternatives to antibiotics is one of the top priorities in the battle against multidrug-resistant (MDR) bacterial infections. Lu et al. (2021) in the journal Science Translational Medicine (13: eaba3571) report that two naturally occurring nonantibiotic modalities, blue light and phytochemical carvacrol, synergistically kill an array of bacteria including their planktonic forms, mature biofilms, and persisters, irrespective of their antibiotic susceptibility. Combination but not single treatment completely or substantially cured acute and established biofilm-associated Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus infections of full thickness murine third-degree burn wounds and rescued mice from lethal Pseudomonas aeruginosa skin wound infections. The combined therapy diminished bacterial colony-forming units as high as 7.5 log10 within 30 min and introduced few adverse events in the survival of cocultured mammalian cells, wound healing, or host DNA. Mechanistic studies revealed that carvacrol was photocatalytically oxidized into a series of photoreactive substrates that underwent photolysis or additional photosensitization reactions in response to the same blue light, forming two autoxidation cycles that interacted with each other resulting in robust generation of cytotoxic reactive oxygen species. This phototoxic reaction took place exclusively in bacteria, initiated by blue light excitation of endogenous porphyrin-like molecules abundantly produced in bacteria compared with mammalian cells. Moreover, no bacterial resistance developed to the combined treatment after 20 successive passages. This highly selective phototoxic reaction confers a unique strategy to combat the growing threat of MDR bacteria.
Therapeutic delivery of antibodies for the treatment of botulinum neurotoxins in the neurons
Botulism is a severe and potentially fatal disease characterized by muscle paralysis. The causing agent, botulinum neurotoxins (BoNTs), has the ability to enter motor neurons and to block neurotransmission. Members of BoNTs such as BoNT/A exhibit extremely long half-life within neurons, resulting in persistent paralysis for months, yet there are no therapeutics that can inhibit BoNTs once they enter neurons. In two independent studies, Miyashita et al. and McNutt et al. in the journal Science Translational Medicine (2021: Vol. 13, Issue 575) used nontoxic derivative of BoNT to deliver therapeutic antibodies against BoNTs in neurons. Miyashita et al. targeted BoNT/A and BoNT/B and reported therapeutic effects in mice. Using a similar approach targeting BoNT/A, McNutt et al. increased survival after lethal challenge in mice, guinea pigs, and monkeys. This approach provided a safe and effective treatment against BoNT intoxication and could be exploited for targeting other intracellular proteins in neurons.
January 4, 2021
Fiat Chrysler and PSA Peugeot merge to form Stellantis
Shareholders of the Italian-American Fiat Chrysler and French PSA Peugeot voted Monday to merge and create the world’s fourth-largest automobile company, Stellantis. Stellantis will be based in Amsterdam, The Netherlands. The name Stellantis will be used exclusively as a corporate brand, its brand names and logos will remain unchanged.
December 26, 2020
Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity
Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Ringel et al. (2020) reports in the journal Cell (183: 1848-1866) that high-fat diet (HFD)-induced obesity impairs CD8+ T cell function in the murine TME, accelerating tumor growth. They generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. The authors also found that tumor and CD8 + T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8 + T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8 + T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8 + T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy.
Nociceptive nerves regulate haematopoietic stem cell mobilization
Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow—often referred to as ‘niches’—that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves. Although sympathetic nerves are known to regulate the HSC niche, the contribution of nociceptive neurons in the bone marrow remains unclear. Gao et al. (2020) reports in the journal Nature that nociceptive nerves are required for enforced HSC mobilization and that they collaborate with sympathetic nerves to maintain HSCs in the bone marrow. Nociceptor neurons drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via the secretion of calcitonin gene-related peptide (CGRP). Unlike sympathetic nerves, which regulate HSCs indirectly via the niche, CGRP acts directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL) to promote egress by activating the Gαs/adenylyl cyclase/cAMP pathway. The ingestion of food containing capsaicin—a natural component of chili peppers that can trigger the activation of nociceptive neurons—significantly enhanced HSC mobilization in mice. Targeting the nociceptive nervous system could therefore represent a strategy to improve the yield of HSCs for stem cell-based therapeutic agents.
December 23, 2020
Xolography for linear volumetric 3D printing
The range of applications for additive manufacturing is expanding quickly, including mass production of athletic footwear parts, dental ceramics and aerospace components as well as fabrication of microfluidics, medical devices, and artificial organs. The light-induced additive manufacturing techniques used are particularly successful owing to their high spatial and temporal control, but such techniques still share the common motifs of pointwise or layered generation, as do stereolithography, laser powder bed fusion, and continuous liquid interface production and its successors. Volumetric 3D printing is the next step onward from sequential additive manufacturing methods. Regehly et al. (2020) reports in the journal Nature (588:620-624), where they introduce xolography, a dual colour technique using photoswitchable photoinitiators to induce local polymerization inside a confined monomer volume upon linear excitation by intersecting light beams of different wavelengths. They demonstrate this concept with a volumetric printer designed to generate three-dimensional objects with complex structural features as well as mechanical and optical functions. Compared to state-of-the-art volumetric printing methods, their technique has a resolution about ten times higher than computed axial lithography without feedback optimization, and a volume generation rate four to five orders of magnitude higher than two-photon photopolymerization. This technology could transform rapid volumetric production for objects at the nanoscopic to macroscopic length scales.
December 9, 2020
Honey bees use animal feces as a tool to defend colonies against group attack by giant hornets
Honey bees (genus Apis) are well known for the impressive suite of nest defenses they have evolved to protect their abundant stockpiles of food and the large colonies they sustain. In Asia, honey bees have evolved under tremendous predatory pressure from social wasps in the genus Vespa, the most formidable of which are the giant hornets that attack colonies in groups, kill adult defenders, and prey on brood. Mattila et al. (2020) report in the journal PLoS ONE (15(12): e0242668) for the first time an extraordinary collective defense used by Apis cerana against the giant hornet Vespa soror. In response to attack by V. soror, A. cerana workers foraged for and applied spots of animal feces around their nest entrances. Fecal spotting increased after colonies were exposed either to naturally occurring attacks or to chemicals that scout hornets use to target colonies for mass attack. Spotting continued for days after attacks ceased and occurred in response to V. soror, which frequently landed at and chewed on entrances to breach nests, but not Vespa velutina, a smaller hornet that rarely landed at entrances. Moderate to heavy fecal spotting suppressed attempts by V. soror to penetrate nests by lowering the incidence of multiple-hornet attacks and substantially reducing the likelihood of them approaching and chewing on entrances. The authors argue that A. cerana forages for animal feces because it has properties that repel this deadly predator from nest entrances, providing the first report of tool use by honey bees and the first evidence that they forage for solids that are not derived from plants. The study describes a remarkable weapon in the already sophisticated portfolio of defenses that honey bees have evolved in response to the predatory threats they face. It also highlights the strong selective pressure honey bees will encounter if giant hornets, recently detected in western North America, become established.
December 7, 2020
Why wild giant pandas frequently roll in horse manure
Until recently it was not understood why giant pandas frequently roll in horse manure. Pandas not only frequently sniffed and wallowed in fresh horse manure, but also actively rubbed the fecal matter all over their bodies. The frequency of horse manure rolling events was highly correlated with an ambient temperature lower than 15 °C. BCP/BCPO (beta-caryophyllene/caryophyllene oxide) in fresh horse manure was found to drive horse manure rolling behavior and attenuated the cold sensitivity of mice by directly targeting and inhibiting transient receptor potential melastatin 8 (TRPM8), an archetypical cold-activated ion channel of mammals. Therefore, horse manure containing BCP/BCPO likely bestows the wild giant pandas with cold tolerance at low ambient temperatures. Together, the study described an unusual behavior, identified BCP/BCPO as chemical inhibitors of TRPM8 ion channel, and provided a plausible chemistry-auxiliary mechanism, in which animals might actively seek and utilize potential chemical resources from their habitat for temperature acclimatization. (Zhou et al. (2020). PNAS. https://doi.org/10.1073/pnas.2004640117).
Communication hubs of cheetah are the source of a human–carnivore conflict and key to its solution
Human–wildlife conflicts occur worldwide. Although many nonlethal mitigation solutions are available, they rarely use the behavioral ecology of the conflict species to derive effective and long-lasting solutions. Melzheimer et al. (2020) report in the journal PNAS (https://doi.org/10.1073/pnas.2002487117) a long-term study with 106 GPS-collared free-ranging cheetahs (Acinonyx jubatus) to demonstrate how new insights into the socio-spatial organization of this species provide the key for such a solution. GPS-collared territory holders marked and defended communication hubs (CHs) in the core area of their territories. The CHs/territories were distributed in a regular pattern across the landscape such that they were not contiguous with each other but separated by a surrounding matrix. They were kept in this way by successive territory holders, thus maintaining this overdispersed distribution. The CHs were also visited by nonterritorial cheetah males and females for information exchange, thus forming hotspots of cheetah activity and presence. The authors hypothesized that the CHs pose an increased predation risk to young calves for cattle farmers in Namibia. In an experimental approach, farmers shifted cattle herds away from the CHs during the calving season. This drastically reduced their calf losses by cheetahs because cheetahs did not follow the herds but instead preyed on naturally occurring local wildlife prey in the CHs. This implies that in the cheetah system, there are “problem areas,” the CHs, rather than “problem individuals.” The incorporation of the behavioral ecology of conflict species opens promising areas to search for solutions in other conflict species with nonhomogenous space use.
Defect‐rich adhesive molybdenum disulfide/rgo vertical heterostructures with enhanced nanozyme activity for smart bacterial killing application
Nanomaterials with intrinsic enzyme‐like activities, namely “nanozymes,” are showing increasing potential as a new type of broad‐spectrum antibiotics. However, their feasibility is still far from satisfactory, due to their low catalytic activity, poor bacterial capturing capacity, and complicated material design. Wang et al. (2020) in the journal Advanced Materials (https://doi.org/10.1002/adma.202005423) reports facile synthesis of a defect‐rich adhesive molybdenum disulfide (MoS2)/rGO vertical heterostructure (VHS) through a one‐step microwave‐assisted hydrothermal method. This simple, convenient but effective method for rapid material synthesis enables extremely uniform and well‐dispersed MoS2/rGO VHS with abundant S and Mo vacancies and rough surface, for a performance approaching the requirements of practical application. It is demonstrated experimentally and theoretically that the as‐prepared MoS2/rGO VHS possesses defect and irradiation dual‐enhanced triple enzyme‐like activities (oxidase, peroxidase, and catalase) for promoting free‐radical generation, owing to much more active edge sites exposure. Meanwhile, the VHS‐achieved rough surface exhibits excellent capacity for bacterial capture, with elevated reactive oxygen species (ROS) destruction through local topological interactions. As a result, optimized efficacy against drug‐resistant Gram‐negative and Gram‐positive bacteria can be explored by such defect‐rich adhesive nanozymes, demonstrating a simple but powerful way to engineered nanozymes for alternative antibiotics.
December 3, 2020
A ubiquitous tire rubber–derived chemical induces acute mortality in coho salmon
In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), storm water exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, Tian et al. (2020) reports in the journal Science (eabd6951: DOI: 10.1126/science.abd6951) a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine) (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis of representative roadway runoff and storm water-impacted creeks of the U.S. West Coast indicated widespread occurrence of 6PPD-quinone (<0.3-19 μg/L) at toxic concentrations (LC50 of 0.8 ± 0.16 μg/L). These results reveal unanticipated risks of 6PPD antioxidants to an aquatic species and imply toxicological relevance for dissipated tire rubber residues.
Trawl and eDNA assessment of marine fish diversity, seasonality, and relative abundance
Environmental DNA (eDNA) technology potentially improves the monitoring of marine fish populations. Realizing this promise awaits better understanding of how eDNA relates to fish presence and abundance. Stoeckle et al. (2020) in the journal ICES Journal of Marine Science (fsaa225) evaluate performance by comparing bottom trawl catches to eDNA from concurrent water samples. In conjunction with New Jersey Ocean Trawl Survey, water samples were collected at surface and depth prior to tows at about one-fourth of Survey sites in January, June, August, and November 2019. eDNA fish diversity from 1 l was same as or higher than trawl fish diversity from 66 M litres swept by one tow. Most (70–87%) species detected by trawl in a given month were also detected by eDNA, and vice versa, including nearly all (92–100%) abundant species. Trawl and eDNA peak seasonal abundance agreed for ∼70% of fish species. In log-scale comparisons by month, eDNA species reads correlated with species biomass, and more strongly with an allometric index calculated from biomass. In this 1-year study, eDNA reporting largely concorded with monthly trawl estimates of marine fish species richness, composition, seasonality, and relative abundance. Piggybacking eDNA onto an existing survey provided a relatively low-cost approach to better understand eDNA for marine fish stock assessment.
December 2, 2020
Reprogramming to recover youthful epigenetic information and restore vision
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to DNA methylation patterns over time form the basis of ageing clocks, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity. Using the eye as a model CNS tissue, here Lu et al. (2020) reports in the journal Nature (588:124–129) show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo.
November 18, 2020
Magnetic spray transforms inanimate objects into millirobots for biomedical applications
Millirobots that can adapt to unstructured environments, operate in confined spaces, and interact with a diverse range of objects would be desirable for exploration and biomedical applications. The continued development of millirobots, however, requires simple and scalable fabrication techniques. Yang et al. (2020) in the journal Science Robotics (5: eabc8191) propose a minimalist approach to construct millirobots by coating inanimate objects with a composited agglutinate magnetic spray. Their approach enables a variety of one-dimensional (1D), 2D, or 3D objects to be covered with a thin magnetically drivable film (~100 to 250 micrometers in thickness). The film is thin enough to preserve the original size, morphology, and structure of the objects while providing actuation of up to hundreds of times its own weight. Under the actuation of a magnetic field, their millirobots are able to demonstrate a range of locomotive abilities: crawling, walking, and rolling. Moreover, they could reprogram and disintegrate the magnetic film on our millirobots on demand. They leverage these abilities to demonstrate biomedical applications, including catheter navigation and drug delivery.
November 5 2020
Inhibition of LTβR signaling activates regeneration in lung
Lymphotoxin β-receptor (LTβR) signaling promotes lymphoid neogenesis and the development of tertiary lymphoid structures which are associated with severe chronic inflammatory diseases that span several organ systems. How LTβR signaling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTβR blockade might be of therapeutic value have remained unclear. Conlon et al. (2020) in the journal Nature demonstrate increased expression of LTβR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signaling, and enriched LTβR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTβR signaling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTβR signaling dampened epithelial non-canonical activation of NF-κB, reduced TGFβ signaling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/β-catenin signaling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTβR signaling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.
September 23, 2020
Adolescents’ perceptions of family social status correlate with health and life chances: A twin difference longitudinal cohort study
Children from lower-income households are at increased risk for poor health, educational failure, and behavioral problems. This social gradient is one of the most reproduced findings in health and social science. How people view their position in social hierarchies also signals poor health. However, when adolescents’ views of their social position begin to independently relate to well-being is currently unknown. A co-twin design was leveraged to test whether adolescents with identical family backgrounds, but who viewed their family’s social status as higher than their same-aged and sex sibling, experienced better well-being in early and late adolescence. By late adolescence, perceptions of subjective family social status (SFSS) robustly correlated with multiple indicators of health and well-being, including depression; anxiety; conduct problems; marijuana use; optimism; not in education, employment, or training (NEET) status; and crime. Findings held controlling for objective socioeconomic status both statistically and by co-twin design after accounting for measures of childhood intelligence (IQ), negative affect, and prior mental health risk and when self-report, informant report, and administrative data were used. Little support was found for the biological embedding of adolescents’ perceptions of familial social status as indexed by inflammatory biomarkers or cognitive tests in late adolescence or for SFSS in early adolescence as a robust correlate of well-being or predictor of future problems. Future experimental studies are required to test whether altering adolescents’ subjective social status will lead to improved well-being and social mobility. (Rivenbank et al. (2020). PNAS 117: 23323-23328).
September 22, 2020
Neurotoxic peptides from the venom of the giant Australian stinging tree
Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. Gilding et al. (2020) in the journal Science Advances 6: eabb8828) reports that the venoms of Australian Dendrocnide species contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are miniproteins of 4 kilo dalton, whose 3D structure is stabilized in an inhibitory cystine knot motif, a characteristic shared with neurotoxins found in spider and cone snail venoms. The study provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure, and pharmacology.
September 21, 2020
Airbus introduces zero-emission commercial aircraft powered by hydrogen
Airbus has revealed three concepts for the world’s first zero-emission commercial aircraft which could enter service by 2035. These concepts each represent a different approach to achieving zero-emission flight, exploring various technology pathways and aerodynamic configurations in order to support the Company’s ambition of leading the way in the decarbonisation of the entire aviation industry.
All of these concepts rely on hydrogen as a primary power source – an option which Airbus believes holds exceptional promise as a clean aviation fuel and is likely to be a solution for aerospace and many other industries to meet their climate-neutral targets.
“This is a historic moment for the commercial aviation sector as a whole and we intend to play a leading role in the most important transition this industry has ever seen. The concepts we unveil today offer the world a glimpse of our ambition to drive a bold vision for the future of zero-emission flight,” said Guillaume Faury, Airbus CEO. “I strongly believe that the use of hydrogen – both in synthetic fuels and as a primary power source for commercial aircraft – has the potential to significantly reduce aviation’s climate impact.”
The three concepts – all codenamed “ZEROe” – for a first climate neutral zero-emission commercial aircraft include: A turbofan design (120-200 passengers) with a range of 2,000+ nautical miles, capable of operating transcontinentally and powered by a modified gas-turbine engine running on hydrogen, rather than jet fuel, through combustion. The liquid hydrogen will be stored and distributed via tanks located behind the rear pressure bulkhead.
A turboprop design (up to 100 passengers) using a turboprop engine instead of a turbofan and also powered by hydrogen combustion in modified gas-turbine engines, which would be capable of traveling more than 1,000 nautical miles, making it a perfect option for short-haul trips.
A “blended-wing body” design (up to 200 passengers) concept in which the wings merge with the main body of the aircraft with a range similar to that of the turbofan concept. The exceptionally wide fuselage opens up multiple options for hydrogen storage and distribution, and for cabin layout. “These concepts will help us explore and mature the design and layout of the world’s first climate-neutral, zero-emission commercial aircraft, which we aim to put into service by 2035,” said Guillaume Faury.
“The transition to hydrogen, as the primary power source for these concept planes, will require decisive action from the entire aviation ecosystem. Together with the support from government and industrial partners we can rise up to this challenge to scale-up renewable energy and hydrogen for the sustainable future of the aviation industry.” In order to tackle these challenges, airports will require significant hydrogen transport and refueling infrastructure to meet the needs of day-to-day operations. Support from governments will be key to meet these ambitious objectives with increased funding for research & technology, digitalisation, and mechanisms that encourage the use of sustainable fuels and the renewal of aircraft fleets to allow airlines to retire older, less environmentally friendly aircraft earlier.
September 19, 2020
Rain clouds over india (Sep. 19, 2020)
September 18, 2020
Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function
Associations between chronic kidney disease (CKD) and the gut microbiota have been postulated, yet questions remain about the underlying mechanisms. In humans, dietary protein increases gut bacterial production of hydrogen sulfide (H2S), indole, and indoxyl sulfate. The latter are uremic toxins, and H2S has diverse physiological functions, some of which are mediated by posttranslational modification. In a mouse model of CKD, Lobel et al. (2020), (Science 369: 1518) found that a high sulfur amino acid–containing diet resulted in posttranslationally modified microbial tryptophanase activity. This reduced uremic toxin–producing activity and ameliorated progression to CKD in the mice. Thus, diet can tune microbiota function to support healthy host physiology through posttranslational modification without altering microbial community composition.
Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. Mager et al. (2020) (Science 369: 1481) isolated three bacterial species—Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species—that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. They found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. The study identified a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.
Even the most optimistic scenario projects huge amounts of plastic pollution in the coming decades
Plastic pollution is a planetary threat, affecting nearly every marine and freshwater ecosystem globally. In response, multilevel mitigation strategies are being adopted but with a lack of quantitative assessment of how such strategies reduce plastic emissions. Borrelle et al. (2020) (Science 369: 1515-1518) assessed the impact of three broad management strategies, plastic waste reduction, waste management, and environmental recovery, at different levels of effort to estimate plastic emissions to 2030 for 173 countries. They estimate that 19 to 23 million metric tons, or 11%, of plastic waste generated globally in 2016 entered aquatic ecosystems. Considering the ambitious commitments currently set by governments, annual emissions may reach up to 53 million metric tons per year by 2030. To reduce emissions to a level well below this prediction, extraordinary efforts to transform the global plastics economy are needed.
September 16, 2020
Red blood cell (RBC) variation protects against severe malaria in the Dantu blood group
Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Kariuki et al. (2020) reports in the journal Nature the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). The authors find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC–parasite receptor–ligand interactions. By following invasion using video microscopy, they find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.
Cuscuta australis (dodder) parasite eavesdrops on the host plants’ signals to flower
In many plants, flowering is regulated by environmental cues, such as day length. Under flowering-inductive conditions, leaves synthesize and transmit FLOWERING LOCUS T (FT) protein to the shoot apex, where FT activates flowering. Dodder Cuscuta australis, which is a root- and leafless parasitic plant, however, very likely does not have fully functional FT genes, and it flowers only when the host plants flower. Shen et al. (2020) in the journal PNAS (117: 23125-23130) reports that host-synthesized FT protein is able to move into dodder stems, where FT physically interacts with dodder FD transcription factor, activating flowering of dodder. This specific manner of flowering allows dodder to synchronize its flowering time with that of the host plant, and this is likely a trait that is beneficial for dodder’s reproductive success.
September 10, 2020
Feeding-dependent tentacle development in the sea anemone Nematostella vectensis
In cnidarians, axial patterning is not restricted to embryogenesis but continues throughout a prolonged life history filled with unpredictable environmental changes. How this developmental capacity copes with fluctuations of food availability and whether it recapitulates embryonic mechanisms remain poorly understood. Ikmi et al. (2020) in the journal Nature Communications (11:4399) reports utilizing the tentacles of the sea anemone Nematostella vectensis as an experimental paradigm for developmental patterning across distinct life history stages. By analyzing over 1000 growing polyps, they find that tentacle progression is stereotyped and occurs in a feeding-dependent manner. Using a combination of genetic, cellular and molecular approaches, they demonstrate that the crosstalk between Target of Rapamycin (TOR) and Fibroblast growth factor receptor b (Fgfrb) signaling in ring muscles defines tentacle primordia in fed polyps. Interestingly, Fgfrb-dependent polarized growth is observed in polyp but not embryonic tentacle primordia. These findings show an unexpected plasticity of tentacle development, and link post-embryonic body patterning with food availability.
September 9, 2020
Age-induced accumulation of methylmalonic acid promotes tumour progression
The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing. Gomes et al. in the journal Nature (585:283-287) show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, the authors show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. They traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas.
To survive frigid nights, hummingbirds cool themselves to low temperatures
Torpor (physical inactivity) is thought to be particularly important for small animals occupying cold environments and with limited fat reserves to fuel metabolism, yet among birds deep torpor is both rare and variable in extent. Wolf et al. (2020) in the journal Biology Letters (https://doi.org/10.1098/rsbl.2020.0428) report torpor in hummingbirds at approximately 3800 meters above sea level in the tropical Andes by monitoring body temperature (Tb) in 26 individuals of six species held captive overnight and experiencing natural air temperature (Ta) patterns. All species used pronounced torpor, with a humming bird species, Metallura phoebe reaching a minimum Tb of 3.26°C, the lowest yet reported for any bird or non-hibernating mammal. The extent and duration of torpor varied among species, with overnight body mass (Mb) loss negatively correlated with both minimum Tb and bout duration. The authors found a significant phylogenetic signal for minimum Tb and overnight Mb loss, consistent with evolutionarily conserved thermoregulatory traits. Their findings suggest deep torpor is routine for high Andean hummingbirds.
September 8, 2020
Monsoon clouds over India
September 7, 2020
Politicians who are against lying have lower reelection rates, suggesting that honesty may not pay off in politics
Voters who would like to accurately evaluate the performance of politicians in office often rely on incomplete information and are uncertain whether politicians’ words can be trusted. Honesty is highly valued in politics because politicians who are averse to lying should in principle provide more trustworthy information. Despite the importance of honesty in politics, there is no scientific evidence on politicians’ lying aversion. Janezic and Gallego in the journal PNAS (117: 22002-22008) reported measuring preferences for truth-telling in a sample of 816 elected politicians and study observable characteristics associated with honesty. They find that, politicians who are against lying have lower reelection rates, suggesting that honesty may not pay off in politics.
September 4, 2020
Typhoon Haishen approaching East Asia
September 2, 2020
Biosynthesis of medicinal tropane alkaloids in yeast
Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization. Challenges in global supplies have resulted in frequent shortages of these drugs. Further vulnerabilities in supply chains have been revealed by events such as the Australian wildfires and the COVID-19 pandemic. Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval are needed. Srinivasan and Smolke in the journal Nature (Sept. 2020) reports engineereing baker’s yeast to produce the medicinal alkaloids hyoscyamine and scopolamine, starting from simple sugars and amino acids. They combined functional genomics to identify a missing pathway enzyme, protein engineering to enable the functional expression of an acyltransferase via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titres. Their integrated system positions more than twenty proteins adapted from yeast, bacteria, plants and animals across six sub-cellular locations to recapitulate the spatial organization of tropane alkaloid biosynthesis in plants. Microbial biosynthesis platforms can facilitate the discovery of tropane alkaloid derivatives as new therapeutic agents for neurological disease and, once scaled, enable robust and agile supply of these essential medicines.
August 29, 2020
Gut microorganisms act together to enhance inflammation in spinal cords
Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis) as well as human studies have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Miyauchi et al. (2020) in the journal Nature (585:102-106) report that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.
Copper-bottomed: electrochemically active bacteria exploit conductive sulphide networks for enhanced electrogeneity
Copper is toxic to bacteria, yeasts, and viruses they are rapidly killed on metallic copper surfaces. In a study reported in the journal Energy and Environmental Science, Beuth et al. (2020) demonstrate that anodic electroactive bacteria Geobacter sulfurreducens generate copper(I) and copper(II) sulphides when grown on copper electrodes. The insoluble copper sulphides form a conductive network within the biofilms, strongly enhancing the biofilm electrogeneity – i.e., the ability of the biofilm to produce electric currents. Compared to biofilms grown on graphite, the average relative current density of copper-based biofilms was 237%, with a maximum geometric current density of 1.59 ± 0.23 mA cm−2. An additional electrochemical CuS deposition prior to biofilm cultivation further increased the bioelectrocatalytic current generation to 2 mA cm−2. The chemical deposition of CuS onto graphite allowed cultivating biofilms with current densities 134% higher than at unmodified graphite. This approach – the chemical CuS deposition onto inexpensive electrode materials – thus represents a promising pathway for the development of scalable, high-performance electrode materials for microbial electrochemical technologies.
August 26, 2020
Electronically integrated, mass-manufactured, microscopic walking robots on a single four-inch wafer
Fifty years of Moore’s law scaling in microelectronics have brought remarkable opportunities for the rapidly evolving field of microscopic robotics. Electronic, magnetic and optical systems now offer an unprecedented combination of complexity, small size and low cost and could be readily appropriated for robots that are smaller than the resolution limit of human vision (less than a hundred micrometres). However, a major roadblock exists: there is no micrometre-scale actuator system that seamlessly integrates with semiconductor processing and responds to standard electronic control signals. Miskin et al. (2020) in the journal Nature (584: 557-561) reports overcoming this barrier by developing a new class of voltage-controllable electrochemical actuators that operate at low voltages (200 microvolts), low power (10 nanowatts) and are completely compatible with silicon processing. To demonstrate their potential, they develop lithographic fabrication-and-release protocols to prototype sub-hundred-micrometre walking robots. Every step in this process is performed in parallel, allowing us to produce over one million robots per four-inch wafer. These results are an important advance towards mass-manufactured, silicon-based, functional robots that are too small to be resolved by the naked eye.
New Guinea has the world’s richest island flora
New Guinea is the world’s largest tropical island and has fascinated naturalists for centuries. Home to some of the best-preserved ecosystems on the planet and to intact ecological gradients—from mangroves to tropical alpine grasslands—that are unmatched in the Asia-Pacific region, it is a globally recognized centre of biological and cultural diversity. So far, however, there has been no attempt to critically catalogue the entire vascular plant diversity of New Guinea. Camara-Leret et al. (2020) reports in the Journal Nature (584: 579–583) the first, expert-verified checklist of the vascular plants of mainland New Guinea and surrounding islands. The checklist includes 13,634 species (68% endemic), 1,742 genera and 264 families—suggesting that New Guinea is the most floristically diverse island in the world. Expert knowledge is essential for building checklists in the digital era: reliance on online taxonomic resources alone would have inflated species counts by 22%.
August 19, 2020
An insect-scale autonomous crawling robot driven by methanol
The creation of autonomous subgram microrobots capable of complex behaviors remains a grand challenge in robotics largely due to the lack of microactuators with high work densities and capable of using power sources with specific energies comparable to that of animal fat (38 megajoules per kilogram). Presently, the vast majority of microrobots are driven by electrically powered actuators; consequently, because of the low specific energies of batteries at small scales (below 1.8 megajoules per kilogram), almost all the subgram mobile robots capable of sustained operation remain tethered to external power sources through cables or electromagnetic fields. Yang et al. (2020) reported in the journal Science Robotics, RoBeetle, an 88-milligram insect-sized autonomous crawling robot powered by the catalytic combustion of methanol, a fuel with high specific energy (20 megajoules per kilogram). The design and physical realization of RoBeetle is the result of combining the notion of controllable NiTi-Pt–based catalytic artificial micromuscle with that of integrated millimeter-scale mechanical control mechanism (MCM). Through tethered experiments on several robotic prototypes and system characterization of the thermomechanical properties of their driving artificial muscles, they obtained the design parameters for the MCM that enabled RoBeetle to achieve autonomous crawling.
August 14, 2020
DNA vaccine protection against SARS-CoV-2 in rhesus macaques
The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. Yu et al. (2020). reports in the journal Science (369, 806-811) a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.
August 13, 2020
Soil carbon loss by warming in a tropical forest
Tropical soils contain one-third of the carbon stored in soils globally, so destabilization of soil organic matter caused by the warming predicted for tropical regions this century could accelerate climate change by releasing additional carbon dioxide (CO2) to the atmosphere. Theory predicts that warming should cause only modest carbon loss from tropical soils relative to those at higher latitudes, but there have been no warming experiments in tropical forests to test this. Nottingham et al. (2020) report in the journal Nature show experimental warming of a lowland tropical forest soil on Barro Colorado Island, Panama, caused an unexpectedly large increase in soil CO2 emissions. Two years of warming of the whole soil profile by four degrees Celsius increased CO2 emissions by 55 per cent compared to soils at ambient temperature. The additional CO2 originated from heterotrophic rather than autotrophic sources, and equated to a loss of 8.2 tonnes of carbon per hectare per year from the breakdown of soil organic matter. During this time, they detected no acclimation of respiration rates, no thermal compensation or change in the temperature sensitivity of enzyme activities, and no change in microbial carbon-use efficiency. These studies demonstrate that soil carbon in tropical forests is highly sensitive to warming, creating a potentially substantial positive feedback to climate change.
4-Vinylanisole is an aggregation pheromone in locusts
Recently locust attack is reported from Eastern Africa, Arabia all the way to India. Locust plagues threaten agricultural and food security. Aggregation pheromones have a crucial role in the transition of locusts from a solitary form to the devastating gregarious form and the formation of large-scale swarms. However, none of the candidate compounds reported meet all the criteria for a locust aggregation pheromone. Guo et al. (2020) report in the journal Nature that 4-vinylanisole (4VA) (also known as 4-methoxystyrene) is an aggregation pheromone of the migratory locust (Locusta migratoria). Both gregarious and solitary locusts are strongly attracted to 4VA, regardless of age and sex. Although it is emitted specifically by gregarious locusts, 4VA production can be triggered by aggregation of four to five solitary locusts. It elicits responses specifically from basiconic sensilla on locust antennae. The authors also identified OR35 as a specific olfactory receptor of 4VA. Knockout of OR35 using CRISPR–Cas9 markedly reduced the electrophysiological responses of the antennae and impaired 4VA behavioural attractiveness. Field trapping experiments verified the attractiveness of 4VA to experimental and wild populations. These findings identify a locust aggregation pheromone and provide insights for the development of novel control strategies for locusts.
August 12, 2020
Tunneling nanotube-like structures connect cells
Signaling between cells of the neurovascular unit, or neurovascular coupling, is essential to match local blood flow with neuronal activity. Pericytes interact with endothelial cells and extend processes that wrap capillaries, covering up to 90% of their surface area. Pericytes are candidates to regulate microcirculatory blood flow because they are strategically positioned along capillaries, contain contractile proteins and respond rapidly to neuronal stimulation but whether they synchronize microvascular dynamics and neurovascular coupling within a capillary network was unknown. Alarcon-Martinez et al. (2020) in the journal Nature identify nanotube-like processes that connect two bona fide pericytes on separate capillary systems, forming a functional network in the mouse retina, which they named interpericyte tunnelling nanotubes (IP-TNTs). The authors provide evidence that these (i) have an open-ended proximal side and a closed-ended terminal (end-foot) that connects with distal pericyte processes via gap junctions, (ii) carry organelles including mitochondria, which can travel along these processes, and (iii) serve as a conduit for intercellular Ca2+ waves, thus mediating communication between pericytes. Using two-photon microscope live imaging, they demonstrate that retinal pericytes rely on IP-TNTs to control local neurovascular coupling and coordinate light-evoked responses between adjacent capillaries. IP-TNT damage following ablation or ischaemia disrupts intercellular Ca2+ waves, impairing blood flow regulation and neurovascular coupling. Notably, pharmacological blockade of Ca2+ influx preserves IP-TNTs, rescues light-evoked capillary responses and restores blood flow after reperfusion. The study defines IP-TNTs and characterizes their critical role in regulating neurovascular coupling in the living retina under both physiological and pathological conditions.
August 7, 2020
Mechanism of steel deformation by your hair
Steels for sharp edges or tools typically have martensitic microstructures, high carbide contents, and various coatings to exhibit high hardness and wear resistance. Yet they become practically unusable upon cutting much softer materials such as human hair, cheese, or potatoes. Despite this being an everyday observation, the underlying physical micromechanisms are poorly understood because of the structural complexity of the interacting materials and the complex boundary conditions of their co-deformation. To unravel this complexity, Roscioli et al. (2020) (Science 369: 689-694) carried out interrupted tests and in situ electron microscopy cutting experiments with two micromechanical testing setups. A combination of out-of-plane bending, microstructural heterogeneity, and asperities—microscopic chips along the smooth edge—sometimes caused fracture to occur if the conditions lined up. This fracture originated at the hair-edge asperity interface and created chipping that dulled a blade faster than other processes.
August 6, 2020
Viburnum tinus fruits use lipids to produce metallic blue structural color
Viburnum tinus is an evergreen shrub that is native to the Mediterranean region but cultivated widely in Europe and around the world. It produces ripe metallic blue fruits throughout winter. Despite its limited fleshy pulp, its high lipid content makes it a valuable resource to the small birds that act as its seed-dispersers. Middleton et al. (2020) DOI:https://doi.org/10.1016/j.cub.2020.07.005 reports in the journal Current Biology that the metallic blue appearance of the fruits is produced by globular lipid inclusions arranged in a disordered multilayer structure. This structure is embedded in the cell walls of the epicarp and underlaid with a dark layer of anthocyanin pigments. The presence of such large, organized lipid aggregates in plant cell walls represents a new mechanism for structural coloration and may serve as an honest signal of nutritional content.
August 5, 2020
Marine heatwaves can drastically alter ocean ecosystems, with profound ecological and socioeconomic impacts
Marine heatwaves (MHWs)—discrete but prolonged periods of anomalously warm ocean temperatures—can drastically alter ocean ecosystems, with profound ecological and socioeconomic impacts. Considerable effort has been directed at understanding the patterns, drivers and trends of MHWs globally. Typically, MHWs are characterized on the basis of their intensity and persistence at a given location—an approach that is particularly relevant for corals and other sessile organisms that must endure increased temperatures. However, many ecologically and commercially important marine species respond to environmental disruptions by relocating to favorable habitats, and dramatic range shifts of mobile marine species are among the conspicuous impacts of MHWs. Whereas spatial temperature shifts have been studied extensively in the context of long-term warming trends, they are unaccounted for in existing global MHW analyses. Jacox et al. (2020) in the journal Nature (584:82–86) introduce thermal displacement as a metric that characterizes MHWs by the spatial shifts of surface temperature contours, instead of by local temperature anomalies, and use an observation-based global sea surface temperature dataset to calculate thermal displacements for all MHWs from 1982 to 2019. The authors show that thermal displacements during MHWs vary from tens to thousands of kilometres across the world’s oceans and do not correlate spatially with MHW intensity. Furthermore, short-term thermal displacements during MHWs are of comparable magnitude to century-scale shifts inferred from warming trends, although their global spatial patterns are very different. These results expand the understanding of MHWs and their potential impacts on marine species, revealing which regions are most susceptible to thermal displacement, and how such shifts may change under projected ocean warming. The findings also highlight the need for marine resource management to account for MHW-driven spatial shifts, which are of comparable scale to those associated with long-term climate change and are already happening.
August 5, 2020
Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19
Blood myeloid cells are known to be dysregulated in the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity, and whether markers of innate immunity discriminate high risk patients. Silvin et al. (2020) in the journal Cell (DOI:https://doi.org/10.1016/j.cell.2020.08.002) reported performing high dimensional flow cytometry and single cell RNA sequencing of COVID-19 patient peripheral blood cells and detected the disappearance of non-classical CD14LowCD16High monocytes, the accumulation of HLA-DRLow classical monocytes, and the release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immuno-suppressive profile accumulated as well in blood and lungs, suggesting emergency myelopoiesis. Thus, calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe COVID-19 form, suggesting a predictive value that deserves prospective evaluation.
August 1, 2020
Biosynthetic self-healing materials for soft machines
Self-healing materials are indispensable for soft actuators and robots that operate in dynamic and real-world environments, as these machines are vulnerable to mechanical damage. However, current self-healing materials have shortcomings that limit their practical application, such as low healing strength (below a megapascal) and long healing times (hours). Pena-Francesch et al. (2020) in the journal Nature Materials report introducing high-strength synthetic proteins that self-heal micro- and macro-scale mechanical damage within a second by local heating. These materials are optimized systematically to improve their hydrogen-bonded nanostructure and network morphology, with programmable healing properties (2–23 MPa strength after 1 s of healing) that surpass by several orders of magnitude those of other natural and synthetic soft materials. Such healing performance creates new opportunities for bioinspired materials design, and addresses current limitations in self-healing materials for soft robotics and personal protective equipment.
July 22, 2020
Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike
The SARS-CoV-2 pandemic rages on with devastating consequences on human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Liu et al. (2020) in the journal Nature (https://doi.org/10.1038/s41586-020-2571-7) report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.
July 20, 2020
Fasting-mimicking diet and hormone therapy reduce breast cancer
Approximately 75% of all breast cancers express the estrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit. Caffa et al. (2020) reports in the journal Nature (583:620-624) that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT–mTOR signalling. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving estrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to estrogen therapy in hormone-receptor-positive breast cancer.
July 5, 2020
Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Food and drug products contain diverse and abundant small-molecule additives called excipients with unclear impacts on human physiology, drug safety, and response. Zhou et al. (2020) reports in the journal PNAS (117: 16009-16018) the potential impact of these additives in intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 they identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R−N=N−R′) dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.
July 3, 2020
Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the central nervous system
Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Pan et al. (2020) in the journal PNAS (117: 15902-15910) using a lineage-tracking system, show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 days. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response. Notably, the extent of inflammatory cell infiltration was variable, dependent on anatomic location within the CNS, and without obvious correlation with numbers of surviving cells. They detected more demyelination in regions with larger numbers of T cells and microglia/macrophages compared to those with fewer infiltrating cells. Conversely, in regions with less inflammation, these previously infected OLs more rapidly extended processes, consistent with normal myelinating function. Together, these results show that OLs are inducers as well as targets of the host immune response and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination.
July 1, 2020
Experimental evidence of dispersal of fish eggs inside migratory waterfowl
Fish have somehow colonized isolated water bodies all over the world without human assistance. It has long been speculated that these colonization events are assisted by water birds, transporting fish eggs attached to their feet and feathers, yet empirical support for this is lacking. Recently, it was suggested that endozoochory (i.e., internal transport within the gut) might play a more important role, but only highly resistant diapause eggs of killifish have been found to survive passage through water bird guts. Lovas-Kiss et al. (2020). reports in the journal PNAS (117: 15397-15399) results of a controlled feeding experiment, where developing eggs of two cosmopolitan, invasive cyprinids (common carp, Prussian carp) were fed to captive mallards. Live embryos of both species were retrieved from fresh feces and survived beyond hatching. The study identifies an overlooked dispersal mechanism in fish, providing evidence for bird-mediated dispersal ability of soft-membraned eggs undergoing active development. Only 0.2% of ingested eggs survived gut passage, yet, given the abundance, diet, and movements of ducks in nature,the data has major implications for biodiversity conservation and invasion dynamics in freshwater ecosystems.
June 29, 2020
Multisystem Inflammatory Syndrome in Children with COVID-19
Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential multisystem inflammatory syndrome in children (MIS-C) in hospitalized patients younger than 21 years of age. Dufort et al (2020) NEJM (DOI: 10.1056/NEJMoa2021756) carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the case definition for MIS-C between March 1 and May 10, 2020. The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
June 25, 2020
Reversing a model of Parkinson’s disease with in situ converted nigral neurons
Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits. Qian et al. (2020) report in the journal Nature (582: 550-556) an efficient one-step conversion of isolated mouse and human astrocytes to functional neurons by depleting the RNA-binding protein PTB (also known as PTBP1). Applying this approach to the mouse brain, the authors demonstrate progressive conversion of astrocytes to new neurons that innervate into and repopulate endogenous neural circuits. Astrocytes from different brain regions are converted to different neuronal subtypes. Using a chemically induced model of Parkinson’s disease in mouse, the authors show conversion of midbrain astrocytes to dopaminergic neurons, which provide axons to reconstruct the nigrostriatal circuit. Notably, re-innervation of striatum is accompanied by restoration of dopamine levels and rescue of motor deficits. A similar reversal of disease phenotype is also accomplished by converting astrocytes to neurons using antisense oligonucleotides to transiently suppress PTB. These findings identify a potentially powerful and clinically feasible approach to treating neurodegeneration by replacing lost neurons.
June 23, 2020
Mentorship and protégé success in science and technology fields
Mentorship is arguably a scientist’s most significant collaborative relationship; yet of all collaborations, comparatively little research exists on the link between mentorship and protégé success. Ma et al. (2020) in the journal PNAS (117 (25) 14077-14083) reports genealogical data on nearly 40,000 scientists who published 1,167,518 papers in biomedicine, chemistry, math, or physics between 1960 and 2017 to investigate the relationship between mentorship and protégé achievement. The authors found groupings of mentors with similar records and reputations who attracted protégés of similar talents and expected levels of professional success. Successful mentors display skill in creating and communicating prizewinning research. Because the mentor’s ability for creating and communicating celebrated research existed before the prize’s conferment, protégés of future prizewinning mentors can be uniquely exposed to mentorship for conducting celebrated research. The authors describe that mentorship strongly predicts protégé success across diverse disciplines. Mentorship is associated with a 2×-to-4× rise in a protégé’s likelihood of prizewinning, National Academy of Science (NAS) induction, or superstardom relative to matched protégés. Mentorship is significantly associated with an increase in the probability of protégés pioneering their own research topics and being midcareer late bloomers. Contrary to conventional thought, protégés do not succeed most by following their mentors’ research topics but by studying original topics and coauthoring no more than a small fraction of papers with their mentors.
June 19, 2020
Making ultrastrong steel tough by grain-boundary delamination
Developing ultrahigh-strength steels that are ductile, fracture resistant, and cost effective would be attractive for a variety of structural applications. Liu et al. (2020) reports in the journal Science (368: 1347-1352) an improved fracture resistance in a steel with an ultrahigh yield strength of nearly 2 gigapascals that can be achieved by activating delamination toughening coupled with transformation-induced plasticity. Delamination toughening associated with intensive but controlled cracking at manganese-enriched prior-austenite grain boundaries normal to the primary fracture surface dramatically improves the overall fracture resistance. As a result, fracture under plane-strain conditions is automatically transformed into a series of fracture processes in “parallel” plane-stress conditions through the thickness. The steel is composed of less expensive elements, making it a potentially inexpensive material attractive for structural applications.
June 14, 2020
Transforming the spleen into a liver-like organ in vivo
Regenerating human organs remains an unmet medical challenge. Suitable transplants are scarce, while engineered tissues have a long way to go toward clinical use. Wang et al. (2020) in the journal Science Advances (Vol. 6, no. 24, eaaz9974) demonstrate a different strategy that successfully transformed an existing, functionally dispensable organ to regenerate another functionally vital one in the body. Specifically, the authors injected a tumor extract into the mouse spleen to remodel its tissue structure into an immunosuppressive and proregenerative microenvironment. They implanted autologous, allogeneic, or xenogeneic liver cells (either primary or immortalized), which survived and proliferated in the remodeled spleen, without exerting adverse responses. Notably, the allografted primary liver cells exerted typical hepatic functions to rescue the host mice from severe liver damages including 90% hepatectomy. Their approach shows its competence in overcoming the key challenges in tissue regeneration, including insufficient transplants, immune rejection, and poor vascularization. It may be ready for translation into new therapies to regenerate large, complex human tissue/organs.
June 13, 2020
Conditional cash transfers to alleviate poverty also reduced deforestation in Indonesia
Solutions to poverty and ecosystem degradation are often framed as conflicting. It is not known whether Indonesia’s national anti-poverty program, which transfers cash to hundreds of thousands of poor households, reduced deforestation as a side benefit. Although the program has no direct link to conservation, Ferraro and Simorangkir in the journal Science Advances (Vol. 6, no. 24, eaaz1298) estimate that it reduced tree cover loss in villages by 30% (95% confidence interval, 10 to 50%). About half of the avoided losses were in primary forests, and reductions were larger when participation density was higher. The economic value of the avoided carbon emissions alone compares favorably to program implementation costs. The program’s environmental impact appears to be mediated through channels widely available in developing nations: consumption smoothing, whereby cash substitutes for deforestation as a form of insurance, and consumption substitution, whereby market-purchased goods substitute for deforestation-sourced goods. The results imply that anti-poverty programs targeted at the very poor can help achieve global environmental goals under certain conditions.
June 10, 2020
Noninvasive, wearable, and tunable electromagnetic multisensing system for continuous glucose monitoring
Painless, needle-free, and continuous glucose monitoring sensors are needed to enhance the life quality of diabetic patients. Hanna et al. (2020) reports in the journal Science Advances (Vol. 6, no. 24, eaba5320) reports a first-of-its-kind, highly sensitive, noninvasive continuous glycemic monitoring wearable multisensor system. The proposed sensors are validated on serum, animal tissues, and animal models of diabetes and in a clinical setting. The noninvasive measurement results during human trials reported high correlation (>0.9) between the system’s physical parameters and blood glucose levels, without any time lag. The accurate real-time responses of the sensors are attributed to their unique vasculature anatomy–inspired tunable electromagnetic topologies. These wearable apparels wirelessly sense hypo- to hyperglycemic variations with high fidelity. These components are designed to simultaneously target multiple body locations, which opens the door for the development of a closed-loop artificial pancreas.
June 4, 2020
Oncometabolites suppress DNA repair by disrupting local chromatin signaling
Deregulation of metabolism and disruption of genome integrity are hallmarks of cancer. Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 genes, or germline mutations in the fumarate hydratase and succinate dehydrogenase genes, respectively. Recent work has made an unexpected connection between these metabolites and DNA repair by showing that they suppress the pathway of homology-dependent repair (HDR) and confer an exquisite sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials. However, the mechanism by which these oncometabolites inhibit HDR remains poorly understood. Sulkowski et al. (2020) reports in the journal Nature the pathway by which these metabolites disrupt DNA repair. They show that oncometabolite-induced inhibition of the lysine demethylase results in aberrant hypermethylation of histone 3 lysine 9 (H3K9) at loci surrounding DNA breaks, masking a local H3K9 trimethylation signal that is essential for the proper execution of HDR. Consequently, recruitment of TIP60 and ATM, two key proximal HDR factors, is substantially impaired at DNA breaks, with reduced end resection and diminished recruitment of downstream repair factors. These findings provide a mechanistic basis for oncometabolite-induced HDR suppression and may guide effective strategies to exploit these defects for therapeutic gain.
June 3, 2020
Hair-bearing human skin generated entirely from pluripotent stem cells
The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain. Reconstructing hair bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met. Lee et al. (2020) in the journal Nature (https://doi.org/10.1038/s41586-020-2352-3) report an organoid culture system that generates complex skin from human pluripotent stem cells. They used stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4–5 months, the authors observed the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. The authors also showed that skin organoids form planar hair-bearing skin when grafted onto nude mice. The data demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. The skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
June 2, 2020
Design of robust super hydrophobic surfaces
The ability of super hydrophobic surfaces to stay dry, self-clean and avoid biofouling is attractive for applications in biotechnology, medicine and heat transfer. Water droplets that contact these surfaces must have large apparent contact angles (greater than 150 degrees) and small roll-off angles (less than 10 degrees). This can be realized for surfaces that have low-surface-energy chemistry and micro- or nanoscale surface roughness, minimizing contact between the liquid and the solid surface. However, rough surfaces—for which only a small fraction of the overall area is in contact with the liquid—experience high local pressures under mechanical load, making them fragile and highly susceptible to abrasion. Additionally, abrasion exposes underlying materials and may change the local nature of the surface from hydrophobic to hydrophilic, resulting in the pinning of water droplets to the surface. It has therefore been assumed that mechanical robustness and water repellency are mutually exclusive surface properties. Wang et al (2020) in the journal Nature (582: 55–59) show that robust super hydrophobicity can be realized by structuring surfaces at two different length scales, with a nanostructure design to provide water repellency and a microstructure design to provide durability. The microstructure is an interconnected surface frame containing ‘pockets’ that house highly water-repellent and mechanically fragile nanostructures. This surface frame acts as ‘armour’, preventing the removal of the nanostructures by abradants that are larger than the frame size. They applied this strategy to various substrates—including silicon, ceramic, metal and transparent glass—and show that the water repellency of the resulting superhydrophobic surfaces is preserved even after abrasion by sandpaper and by a sharp steel blade. The authors suggest that this transparent, mechanically robust, self-cleaning glass could help to negate the dust-contamination issue that leads to a loss of efficiency in solar cells.
May 21, 2020
Bumble bees damage plant leaves and accelerate flower production when pollen is scarce
Bumble bees rely heavily on pollen resources for essential nutrients as they build their summer colonies. Pashalidou et al. (2020) reports (368: 881-884) in the journal Science that bees may have strategies to cope with irregular seasonal flowering. When faced with a shortage of pollen, bumble bees actively damaged plant leaves in a characteristic way, and this behavior resulted in earlier flowering by as much as 30 days. Laboratory studies revealed that leaf-damaging behavior is strongly influenced by pollen availability and that bee-damaged plants flower significantly earlier than undamaged or mechanically damaged controls. Subsequent outdoor experiments showed that the intensity of damage inflicted varies with local flower availability; furthermore, workers from wild colonies of two additional bumble bee species were also observed to damage plant leaves. These findings elucidate a feature of bumble bee worker behavior that can influence the local availability of floral resources.
May 11, 2020
Cultured macrophages transfer surplus cholesterol into adjacent cells in the absence of serum or high-density lipoproteins
By ingesting dying cells and other cellular debris, macrophages accumulate cholesterol. Some of the cholesterol is esterified and stored in cytosolic lipid droplets, mitigating the toxicity from free cholesterol. Eventually, however, macrophages must unload surplus cholesterol—a process often referred to as “cholesterol efflux.” Cholesterol efflux is an important physiologic process because it would be expected to retard the formation of cholesterol-rich macrophage foam cells in atherosclerotic plaques. Most studies of cholesterol efflux have focused on the ability of ABC transporters to export cholesterol onto high-density lipoproteins. The current study examines another mechanism. He et al. (2020) in the journal PNAS (117: 10476-10483) reports that macrophages unload cholesterol directly into adjacent smooth muscle cells. This mechanism is potentially relevant to cholesterol efflux by tissue macrophages.
May 9, 2020
Aerodynamic imaging by mosquitoes inspires a surface detector for autonomous flying vehicles
Some flying animals use active sensing to perceive and avoid obstacles. Nocturnal mosquitoes exhibit a behavioral response to divert away from surfaces when vision is unavailable, indicating a short-range, mechanosensory collision-avoidance mechanism. Nakata et al. (2020) reports in Science (368: 634-637) reports that this behavior is mediated by perceiving modulations of their self-induced airflow patterns as they enter a ground or wall effect. The authors used computational fluid dynamics simulations of low-altitude and near-wall flights based on in vivo high-speed kinematic measurements to quantify changes in the self-generated pressure and velocity cues at the sensitive mechanosensory antennae. They validated the principle that encoding aerodynamic information can enable collision avoidance by developing a quadcopter with a sensory system inspired by the mosquito. Such low-power sensing systems have major potential for future use in safer rotorcraft control systems.
May 8, 2020
Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for snakebite
Snakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Albulescu et al. (2020) reports in the journal Science Translational Medicine (12: eaay8314) the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a “challenge and treat” model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. The study demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.
May 7, 2020
Aerodynamic imaging by mosquitoes inspires a surface detector for autonomous flying vehicles
Although sonar or lidar are used by autonomous vehicles to detect nearby objects, these approaches incur significant equipment and signal-processing costs. Nakata et al. (2020) report in the journal Science (Vol. 368, Issue 6491, pp. 634-637) show that nocturnal mosquitoes exhibit a behavioral response to divert away from surfaces when vision is unavailable, indicating a short-range, mechanosensory collision-avoidance mechanism. We suggest that this behavior is mediated by perceiving modulations of their self-induced airflow patterns as they enter a ground or wall effect. The authors used computational fluid dynamics simulations of low-altitude and near-wall flights based on in vivo high-speed kinematic measurements to quantify changes in the self-generated pressure and velocity cues at the sensitive mechanosensory antennae. They further validated the principle that encoding aerodynamic information can enable collision avoidance by developing a quadcopter with a sensory system inspired by the mosquito. Such low-power sensing systems have major potential for future use in safer rotorcraft control systems.
May 3, 2020
Mechanism of water extraction from gypsum rock by desert colonizing microorganisms
Microorganisms, in the most hyperarid deserts around the world, inhabit the inside of rocks as a survival strategy. Water is essential for life, and the ability of a rock substrate to retain water is essential for its habitability. Huang et al. (2020) reports in PNAS (117: 10681-10687) that the microorganisms can extract water of crystallization from the rock, inducing a phase transformation from gypsum (CaSO4·2H2O) to anhydrite (CaSO4). To investigate and validate the water extraction and phase transformation mechanisms found in the natural geological environment, the authors cultivated a cyanobacterium isolate on gypsum rock samples under controlled conditions. They found that the cyanobacteria attached onto high surface energy crystal planes of gypsum samples generate a thin biofilm that induced mineral dissolution accompanied by water extraction. This process led to a phase transformation to an anhydrous calcium sulfate, anhydrite, which was formed via re-precipitation and subsequent attachment and alignment of nanocrystals. The data of this work not only shed light on how microorganisms can obtain water under severe xeric conditions but also provide strategies for advanced water storage methods.
May 1, 2020
Interleukin-13 drives metabolic conditioning of muscle to endurance exercise
Interleukin-13 (IL-13) is a cytokine secreted by T cells, innate lymphoid cells (ILC2s), and granulocytes. It acts as a central mediator in allergy and antihelminth defense with various effects. Knudsen et al. (2020) in the journal Science Vol. 368, Issue 6490, eaat3987 , report a distinct role for IL-13 in exercise and metabolism. Animals subjected to endurance training showed increases in circulating IL-13, which correlated with ILC2 expansion in the muscles. By contrast, exercise-induced increases in muscle fatty acid utilization and mitochondrial biogenesis were erased when animals lacked IL-13. Activation of signaling pathways downstream of the muscle IL-13 receptor was key to this effect. Intramuscular injection of adenoviral IL-13 could recapitulate exercise-induced metabolic reprogramming. This signaling pathway may have evolved to combat the metabolic stresses of parasite infection.
April 29, 2020
The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter of Prokaryotes
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses Thomas (2020) (Preprints, 2020040512) (doi: 10.20944/preprints202004.0512.v2), determined the structure and potential function of the M protein. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of sugar transporter-like structure in viruses is unknown. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. It could be hypothesized that the semiSWEET sugar transporters could be used in multiple pathways that may aid in the rapid proliferation and replication of the virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.
April 18, 2020
Emerging North American megadrought induced by human activity
Global warming has pushed what would have been a moderate drought in southwestern North America into megadrought territory. Williams et al. (2020) in the journal Science (368:314-318) used a combination of hydrological modeling and tree-ring reconstructions of summer soil moisture to show that the period from 2000 to 2018 was the driest 19-year span since the late 1500s and the second driest since 800 AD. The changes in temperature, relative humidity, and precipitation can be correlated to human activity. This appears to be just the beginning of a more extreme trend toward megadrought as global warming continues.
April 14, 2020
Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury
Spasticity, one of the most frequent comorbidities of spinal cord injury (SCI), disrupts motor recovery and quality of life. Despite major progress in neurorehabilitative and pharmacological approaches, therapeutic strategies for treating spasticity are lacking. Marcantoni et al. (2020) in the journal Science Translational Medicine (12: eaay0167) reports in a mouse model of chronic SCI that treatment with nimodipine—an L-type calcium channel blocker already approved from the European Medicine Agency and from the U.S. Food and Drug Administration—starting in the acute phase of SCI completely prevents the development of spasticity measured as increased muscle tone and spontaneous spasms. The aberrant muscle activities associated with spasticity remain inhibited even after termination of the treatment. Constitutive and conditional silencing of the L-type calcium channel CaV1.3 in neuronal subtypes demonstrated that this channel mediated the preventive effect of nimodipine on spasticity after SCI. This study identifies a treatment protocol and suggests that targeting CaV1.3 could prevent spasticity after SCI.
April 9, 2020
Dendritic cell–derived hepcidin sequesters iron from the microbiota to promote intestine healing
Anemia due to bleeding and altered iron distribution is a frequent complication of disorders such as inflammatory bowel disease. Bessman et al. (2020) in the journal Science (368:186-189) reports that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, the authors identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.
April 2, 2020
Susceptibility of cats and dogs to SARS-coronavirus-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019. Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; with report of intermediate animal sources of the virus as pangolin. Chen (2020) has reported in the preprint server, Biorxive the susceptibility of ferrets and other animals in close contact with humans to SARS-CoV-2. He reports that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but efficiently in ferrets and cats. The virus transmits in cats via respiratory droplets. The study provides important insights into the animal reservoirs of SARS-CoV-2 and animal management for COVID-19 control.
March 28, 2020
Pangolins may be intermediate hosts in the emergence of novel coronaviruses
The ongoing outbreak of viral pneumonia all over the world is associated with a novel coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for SARS-CoV-2, the identity of any intermediate host that might have facilitated transfer to humans is unknown. Lam et al. (2020) in Nature report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity to SARS-CoV-2 in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of novel coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
March 23, 2020
High-salt diet increase infections due to reduced capacity of neutrophils to kill ingested bacteria
A diet rich in salt poses various health risks. A high-salt diet (HSD) can stimulate immunity through the nuclear factor of activated T cells 5 (Nfat5)–signaling pathway, especially in the skin, where sodium is stored. The kidney medulla also accumulates sodium to build an osmotic gradient for water conservation.
Jobin et al. (2020) reports in the journal Science Translation Medicine the effect of an HSD on the immune defense against uropathogenic E. coli–induced pyelonephritis, the most common kidney infection. Pyelonephritis enhanced in mice on an HSD by different mechanisms. First, on an HSD, sodium must be excreted; therefore, the kidney used urea instead to build the osmotic gradient. However, in contrast to sodium, urea suppressed the antibacterial functionality of neutrophils, the principal immune effectors against pyelonephritis. Second, the body excretes sodium by lowering mineralocorticoid production via suppressing aldosterone synthase. This caused an accumulation of aldosterone precursors with glucocorticoid functionality, which abolished the diurnal adrenocorticotropic hormone–driven glucocorticoid rhythm and compromised neutrophil development and antibacterial functionality systemically. Consistently, under an HSD, systemic Listeria monocytogenes infection was also aggravated in a glucocorticoid-dependent manner. Healthy humans consuming an HSD for 1 week showed hyperglucocorticoidism and impaired antibacterial neutrophil function. These findings argue against high-salt consumption during bacterial infections.
Cryo-electron microscopy structure of the SARS-CoV-2 spike
The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. To facilitate medical countermeasure development, Wrapp et al. (2020) report in the journal Science (367:1260-1263) the cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. The authors also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. They also tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
March 10, 2020
The pneumonia outbreak associated with the coronavirus (SARS-CoV-2) is probably of bat origin
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is a pandemic since its origin in China in December 2019. There are many theories on where the virus originated. Zhou et al. (2020) in the journal Nature (579: 270–273) report the identification and characterization of the coronavirus (2019-nCoV), which caused the epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, has 200,000 infections and 8000 deaths until 10 March 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, the authors show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, the authors confirm that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
March 9, 2020
Oil and gas companies invest in legislators that vote against the environment
The role of money in politics has long been a focus of research in political science. One explanation for campaign contributions to Congress is to buy influence. That is, companies contribute to the campaigns of those running for Congress with the expectation that those candidates, if elected, will vote in ways aligned with the interests of the companies.
The influence of money in politics has taken on new importance in the United States with the Citizens United versus Federal Election Commission Supreme Court decision in 2010. With the Citizens United decision, the court ruled that the First Amendment to the US Constitution protects independent spending for political communications by for-profit corporations, nonprofit corporations, and labor unions. Large corporations have taken full advantage of this “money as speech” court decision.
Using 28 years of campaign contribution data, Goldberg et al. (2020) in the journal PNAS (117:5111) reports that more a given member of Congress votes against environmental policies, the more contributions they receive from oil and gas companies supporting their reelection. Oil and gas companies contributed more than $84 million to candidates running for the US Congress in 2018. This is more than a twofold increase since the Citizens United decision in 2010, when oil and gas companies contributed approximately $35 million to candidates. While the absolute value of these contributions may seem relatively small, the doubling is noteworthy because it occurred in conjunction with the allowance of unlimited election spending by corporations and labor unions through the establishment of “independent expenditure-only committees,” or Super PACs. Thus, it is important to investigate how this money may influence legislators’ voting behavior on environmental issues.
March 3, 2020
Bisphenol A and bisphenol S used in plastic manufacturing disrupts placenta and effects the placenta–brain axis
BPA (Bisphenol A) is a precursor of plastics including polycarbonates, epoxy resins and polysulfones. BPA-based plastic is clear and tough, and is made into a variety of common consumer goods, such as plastic bottles including water bottles, food storage containers baby bottles, sports equipment, CDs, and DVDs. Epoxy resins derived from BPA are used to line water pipes, as coatings on the inside of many food and beverage cans and in the manufacture of thermal paper used in sales receipts.
BPA is similar to the hormone estrogen. BPA bind to both the nuclear estrogen receptors and mimics the hormone. The mammalian placenta is a target for BPA. Consumer unease with BPA has led to manufacture of substitutes, such as bisphenol S (BPS). Mao et al. (2020) in the journal PNAS (117: 4642-4652) reported using a multiomics approach to study effects of developmental exposure to BPA and BPS on midgestational mouse placenta. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin concentrations, and lowered serotonin GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. The data imply that in rodents there could be associated effects on the placental–fetal brain axis. The authors conclude that BPS should be regarded as hazardous as BPA.
February 29, 2020
Bacteriophages could contribute to the bacterial community changes observed in child stunting
Malnutrition is a major health concern in low- and middle-income countries and the leading cause of death in children younger than 5 years. Stunting, a severe and multigenerational growth impairment, globally affects 22% of children under the age of 5 years. The largest concentration of our microbiome occupies the gut. The gut microbiota plays essential roles in host metabolism, immune modulation, and colonization resistance to pathogens. Shifts in gut bacterial composition have been associated with increasing numbers of diseases including inflammatory bowel diseases (IBD), allergies, diabetes, and obesity.
Stunted children have altered gut bacterial communities with higher proportions of Proteobacteria, a phylum with several known human pathogens. Stunted children also harbor an altered gut microbiota, with increased prevalence of Enterobacteriaceae, which may further contribute to their impaired growth and nutritional deficiencies. Indeed, the local inflammation caused by overgrowth of Enterobacteriaceae has been shown to lead to impaired digestive and absorptive functions of the gut, all linked to stunting. Stunted children have an immature gut microbiota relative to their non-stunted age-matched counterparts.
Despite the links between an altered gut microbiota and stunting, the role of bacteriophages, highly abundant bacterial viruses, is unknown. The role of gut phage communities in child stunting remains largely unexplored. Phages are bacterial viruses that are key to the maintenance and function of many ecosystems by supplying bacteria with genes involved in host adaptation, toxin production, and metabolism. Phages control bacterial diversity and abundance and can modify the O-antigen component of lipopolysaccharide (LPS) in gram-negative bacteria, which is particularly relevant to intestinal inflammation. In the gut, phages are abundant, with a phage-to-bacteria ratio close to 1:1 based on sequencing data. Phage communities are distinct between individuals and stable over time compared with gut bacterial ones. Recently, changes in the diversity and abundance of phages have been associated with many diseases such as IBD, diabetes, malnutrition, AIDS, and Parkinson’s disease, highlighting their potential role in human health.
Mirzaei et al. (2020) in the journal Cell Host and Microbiome (27: 199-212) reports whole community bacteria-phage population dynamics from stunted and non-stunted, otherwise clinically healthy, children from Dhaka, Bangladesh. Despite the significant progress in tackling malnutrition, Bangladesh still has one of the highest rates of child stunting in the world, affecting an average of 36.1% of children younger than 5 years. The authors report that these children harbor distinct gut bacteriophages relative to their non-stunted counterparts. In vitro, these gut bacteriophages are infectious and can regulate bacterial abundance and composition in an age-specific manner, highlighting their possible role in the pathophysiology of child stunting. Specifically, Proteobacteria from non-stunted children increased in the presence of phages from younger stunted children, suggesting that phages could contribute to the bacterial community changes observed in child stunting.
February 27, 2020
High dose vitamin C promotes cancer immunotherapy
Vitamin C plays an important role in a number of bodily functions including the production of collagen, L-carnitine, and some neurotransmitters. Collagen, which vitamin C helps produce, is the main component of connective tissue and the most abundant protein in mammals. Between 1 and 2% of muscle tissue is collagen. Wounds, cuts, and grazes may heal faster in people with a higher intake of vitamin C than is usually available from their food. This may be because vitamin C contributes to collagen production. In addition, people with adequate levels of vitamin C are thought to be better able to fight off infections compared to people with vitamin C deficiency. Vitamin C may also help prevent acute respiratory infections, especially in people with malnutrition and those who are physically stressed.
The role of vitamin C as an antioxidant also helps repair tissue and reduce damage from inflammation and oxidation. Vitamin C helps metabolize proteins and its antioxidant activity may reduce the risk of some cancers. Vitamin C is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its anti-tumoral efficacy. In addition, whether and how vitamin C modulates anticancer immune responses is mostly unknown.
Magri et al. (2020) in the journal Science Translational Medicine (12: eaay8707) reports that a fully competent immune system is required to maximize the antiproliferative effect of vitamin C in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose vitamin C modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell–dependent manner. Vitamin C not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of vitamin C and ICT can be curative in models of mismatch repair–deficient tumors with high mutational burden. The authors study provides a rationale for clinical trials combining ICT with high doses of vitamin C.
February 26, 2020
Timing of fungal spore release influence survival during atmospheric transport
Fungi are so widespread and numerous that they make up a large proportion of the biomass in any given ecosystem. Fungi play an important role in energy cycling within, and between, ecosystems. Fungi play a very important part in the decomposition process, because they can break down tough organic materials, such as cellulose and lignin, which invertebrates find difficult to digest. Fungi release digestive enzymes that are used to metabolize complex organic compounds into soluble nutrients, such as simple sugars, nitrates and phosphates.
Fungi disperse spores to move across landscapes and spore liberation takes different patterns. Many species release spores intermittently; others release spores at specific times of day. It is clearly not understood whether timing of release of spores influence the survival of the spores during atmospheric transport.
Oneto et al. (2020) in the journal PNAS (https://doi.org/10.1073/pnas.1913752117) reports using state-of-the-art numerical simulations of atmospheric transport and meteorological data to follow the trajectory of many spores in the atmosphere at different times of day, seasons, and locations across North America. The authors report that spores released during the day fly for several days, whereas spores released at night return to ground within a few hours. Differences are caused by intense turbulence during the day and weak turbulence at night. The pattern is widespread but its reliability varies; for example, day/night patterns are stronger in southern regions. Species with short-lived spores reproducing where there is strong turbulence during the day, for example in Mexico, maximize survival by releasing spores at night. The study suggest the timing of spore liberation may be finely tuned to maximize fitness during atmospheric transport.
February 21, 2020
Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with Vaping
E-cigarettes are devices that heat a liquid into an aerosol that the user inhales. The liquid usually has nicotine and flavoring in it, and other additives. The nicotine in e-cigarettes and regular cigarettes is addictive. E-cigarettes were introduced as an alternate to regular cigarettes. E-cigarettes (the device associated with vaping) heat nicotine (extracted from tobacco), flavorings and other chemicals to create a water vapor that you inhale. Regular tobacco cigarettes contain 7,000 chemicals, many of which are toxic. It is not known what chemicals are in e-cigarettes.
Recent reports point to the harmful effects of vaping on young adults. Lung injuries and deaths are reported associated with vaping. As of January 2020, the Centers for Disease Control and Prevention (CDC) confirmed 60 deaths associated with vaping. The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use–associated lung injury (EVALI) have not been established.
Blount et al. (2020) in the journal New England Journal of Medicine (382:697-705) reports the analyses of the bronchoalveolar-lavage (BAL) fluid from patients with EVALI. Vitamin E acetate was associated with EVALI in a sample of 51 patients in 16 states across the United States. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid.
February 17, 2020
Harvesting energy from humid atmosphere
The energy needs are increasing due to increase in portable devices and hence there is a demand for renewable clean energy. Harvesting energy from the environment offers the promise of clean power for self-sustained systems. Known technologies—such as solar cells, thermoelectric devices and mechanical generators—have specific environmental requirements that restrict where they can be deployed and limit their potential for continuous energy production. The vast atmospheric moisture offers an alternative. However, existing moisture-based energy-harvesting technologies can produce only intermittent, brief (shorter than 50 seconds) bursts of power in the ambient environment, owing to the lack of a sustained conversion mechanism.
Liu et al. reports in the journal Nature (2020) that thin-film devices made from nanometer-scale protein wires harvested from the microorganism Geobacter sulfurreducens can generate continuous electric power in the ambient environment. The device produces a sustained voltage of around 0.5 volts across a 7-micrometre-thick film, with a current density of around 17 microamperes per square centimeter. The authors find the driving force behind this energy generation to be a self-maintained moisture gradient that forms within the film when the film is exposed to the humidity that is naturally present in air. Connecting several devices linearly scales up the voltage and current to power electronics. The study demonstrates the feasibility of a continuous energy-harvesting strategy that is less restricted by location or environmental conditions than other sustainable approaches.
February 14, 2020
Tropical snake diversity collapses after widespread amphibian loss
Biodiversity is declining at unprecedented rates worldwide. The global pandemic chytridiomycosis caused by the amphibian fungal pathogen Batrachochytrium dendrobatidis has decimated frog populations around the world. This decline has been called out as a potential catastrophe for amphibian species. What has been less explored are the impacts of amphibian declines on other members of their ecological communities. Using survey data collected over 13 years, Zipkin et al. (2020) in the journal Science (367:814-816) looked at diversity and body condition of a tropical snake community heavily affected by chytridiomycosis. After mass mortality of amphibians, the snake community contained fewer species and was more homogeneous across the study site, with several species in poorer body condition, despite no other systematic changes in the environment. The demise of the snake community after amphibian loss demonstrates the repercussive and often unnoticed consequences of the biodiversity crisis and calls attention to the invisible declines of rare and data-deficient species.
Global ecosystem thresholds driven by aridity
Aridity, which is increasing worldwide because of climate change, affects the structure and functioning of dryland ecosystems. Whether aridification leads to gradual (versus abrupt) and systemic (versus specific) ecosystem changes is largely unknown. Berdugo et al. (2020) in the journal Science (367: 787-790) investigated how 20 structural and functional ecosystem attributes respond to aridity in global drylands. Aridification led to systemic and abrupt changes in multiple ecosystem attributes. These changes occurred sequentially in three phases characterized by abrupt decays in plant productivity, soil fertility, and plant cover and richness, culminating with a shift to low-cover ecosystems that are nutrient- and species-poor at high aridity values. More than 20% of the terrestrial surface will cross one or several of these thresholds by 2100, which calls for immediate actions to minimize the negative impacts of aridification that can potentially lead to widespread land degradation and desertification worldwide.
February 12, 2020
B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke
Neuroinflammation occurs immediately after stroke onset, but whether neuroinflammation occurs in remote regions of the brain supporting functional recovery remains unknown. Ortega et al (2020) in the journal PNAS (https://doi.org/10.1073/pnas.1913292117) reports using advanced imaging to quantify whole-brain B cells in the capillaries. The authors identified bilateral B cell in the remote regions, outside of the injury, that support motor and cognitive recovery in animal models. Poststroke depletion of B cells confirms a positive role in neurogenesis, neuronal survival, and recovery of motor coordination, spatial learning, and anxiety. B cell depletion in animal models demonstrated delayed motor recovery, impaired spatial memory, and increased anxiety. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. B cell diapedesis occurring in areas remote to the infarct mediate motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.
More than 80% of stroke survivors have long-term disability uniquely affected by age and lifestyle factors. Thus, identifying beneficial neuroinflammation during long-term recovery increases the opportunity of therapeutic interventions to support functional recovery.
February 10, 2020
Helicobacter pylori eradication treatment reduces the risk of gastric cancer
Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.
Choi et al. (2020) in the journal New England Journal of Medicine (382: 427-436) reports that among persons with H. pylori infection who has a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer.
February 4, 2020
The 2019 coronavirus may have had its origin in bats
The 2019 novel coronavirus (2019-nCoV) is a threat to the entire planet. As yet, it is not known the origin of the virus. Zhou et al. (2020) in the journal Nature report the identification and characterization of 2019-nCoV which caused an epidemic of acute respiratory syndrome in humans that started in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, the authors confirmed that the novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.
January 31, 2020
Transmission of 2019 coronavirus (nCoV) Infection from an Asymptomatic Contact
The novel coronavirus (2019-nCoV) that originated in Wuhan, China, is a concern as the virus is spreading around the world. The disease caused by the virus is causing severe economic and emotional distress all over the world. Since its identification in late December 2019, the number of cases in China and other countries is on the rise. Rothe et al. (2020) reports in the clinical journal New England Journal of Medicine (DOI: 10.1056/NEJMc2001468) that the coronavirus could be transmitted from asymptomatic person to a healthy person.
January 28, 2020
Any matter containing carbon could be converted into graphene
With atom-thin sheets of carbon atoms arranged like chicken wire, graphene is stronger than steel, conducts electricity and heat better than copper, and can serve as an impermeable barrier preventing metals from rusting. Current strategies to make graphene at industrial scale is expensive.
Most bulk-scale graphene is produced by a top-down approach, exfoliating graphite, which often requires large amounts of solvent with high-energy mixing, shearing, sonication or electrochemical treatment. Although chemical oxidation of graphite to graphene oxide promotes exfoliation, it requires harsh oxidants and leaves the graphene with a defective perforated structure after the subsequent reduction step. Bottom-up synthesis of high-quality graphene is often restricted to ultrasmall amounts if performed by chemical vapour deposition or advanced synthetic organic methods, or it provides a defect-ridden structure if carried out in bulk solution.
Luong et al. (2020) in the journal Nature report that flash Joule heating of inexpensive carbon sources—such as coal, petroleum coke, carbon black, discarded food, rubber tyres and mixed plastic waste—can afford gram-scale quantities of graphene in less than one second. The product, named flash graphene (FG) after the process used to produce it, shows turbostratic arrangement (that is, little order) between the stacked graphene layers. FG synthesis uses no furnace and no solvents or reactive gases. Yields depend on the carbon content of the source; when using a high-carbon source, such as carbon black, anthracitic coal or calcined coke, yields can range from 80 to 90 per cent with carbon purity greater than 99 per cent. No purification steps are necessary. The electric energy cost for FG synthesis is only about 7.2 kilojoules per gram, which could render FG suitable for use in bulk composites of plastic, metals, plywood, concrete and other building materials.
January 23, 2020
How stress turns hair white
Rapid greying of hairis often assumed to be caused by stress. The relative contributions of ageing, genetic factors and stress to greying are not known – due to a lack of mechanistic understanding of the process.
Hair color is determined by cells called melanocytes, which produce different combinations of light-absorbing melanin pigments. Melanocytes are derived from melanocyte stem cells (MeSCs), which are located in a part of the hair follicle called the bulge. The normal hair cycle is divided into three stages: hair-follicle regeneration (anagen), degeneration (catagen) and rest (telogen). Melanocyte production begins early in the anagen phase. As people age, the pool of MeSCs is gradually depleted — and so pigmented hair becomes ‘salt and pepper’ colored, and then turns to grey and finally to white after a complete loss of pigment in all hair follicles.
Zhang et al. (2020)in the journal Nature reported the role of stress in the greying process in mice. The authors report that acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. The study demonstrated that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.
January 22, 2020
Global-scale human impact on delta morphology has led to net land area gain
River deltas are created by deposition of sediment that is carried by a river as the flow leaves its mouth and enters slower-moving or stagnant water. Due to their rich soils and convenient positions for trade and transport, many deltas have become hotspots of socio-economic development. River deltas rank among the most economically and ecologically valuable environments on Earth. Even in the absence of sea-level rise, deltas are increasingly vulnerable to coastal hazards as declining sediment supply and climate change alter their sediment budget, affecting delta morphology and possibly leading to erosion.
Nienhuis et al. (2020) in the journal Nature (577:514–518) reports that human activity has led to net increase in delta land area. The author’s model estimates delta morphology on the basis of a quantitative characterization of three main drivers that shape deltas. These are: sediment delivered by the river; wave action that redistributes sediment along the coast; and sediment transported into or out of the delta by tidal flows. The relative influences of these drivers were used to determine two key morphological metrics; namely, the protrusion of the delta into the sea and the shape of the river channel.
The morphology of deltas all over the world has been affected by river damming and deforestation. Over the past 30 years, despite sea-level rise, deltas globally have experienced a net land gain of 55 square kilometres per year. Humans are a considerable driver of these net land gains – 25 per cent of delta growth can be attributed to deforestation-induced increases in fluvial sediment supply. However for some delta regions, river damming has resulted in a severe (more than 50 per cent) reduction in anthropogenic sediment flux, forcing a collective loss of 15 square kilometres per year of deltaic land. Not all deltas lose land in response to river damming: deltas transitioning towards tide dominance are currently gaining land, probably through channel infilling.
The study also reveals notable regional patterns. The Arctic river deltas have seen almost no change in morphology. Sediment delivery by rivers in North America has fallen overall, leading to large land losses – especially in the Mississippi delta. The largest land gains are in eastern South America and in south, southeast and east Asia, where soil erosion due to deforestation has caused a net growth in delta areas, despite the construction of sizeable dams in these regions. With expected accelerated sea-level rise, however, recent land gains are unlikely to be sustained throughout the twenty-first century.
January 21, 2020
Ozone depleting gases influence extreme Arctic warming
The Arctic is warming at more than twice the average rate of the rest of the planet – a phenomenon known as Arctic amplification – and it is losing sea ice rapidly.
Ozone-depleting substances, including chlorofluorocarbons (CFCs), are known to warm the atmosphere more efficiently than carbon dioxide. However, most of the research on these chemicals has focused on their effects on the planet’s protective ozone layer – especially over the Southern hemisphere, where they are responsible for the formation of the Antarctic ozone hole.
Polvani et al. (2020) in the journal Nature Climate Change (https://doi.org/10.1038/s41558-019-0677-4) reports that when ozone depleting substances (ODS) are kept fixed, forced Arctic surface warming and forced sea-ice loss are only half as large as when ODS are allowed to increase. They also demonstrated that the large impact of ODS on the Arctic occurs primarily via direct radiative warming, not via ozone depletion. Their findings reveal a substantial contribution of ODS to recent Arctic warming, and highlight the importance of the Montreal Protocol as a major climate change-mitigation treaty. The Montreal Protocol (ratified in 1987) is a treaty to protect the ozone layer by phasing out the production of substances that are responsible for ozone depletion.
January 16, 2020
Use of bacteria in building construction
Building materials using sand, cement or other binders have been employed for construction purposes for a long time. Recent innovations in construction includes the use of 3D printing technology for construction.
Living building materials (LBM) is a new concept wherein microorganisms (eg. bacteria) are used in the manufacture of building materials based on the principle of biomineralization. Biomineralization is the chemical alteration of an environment by microbial activity that results in the precipitation of minerals. Microbially induced calcite precipitation (MICP) refers to the formation of calcium carbonate from a supersaturated solution due to the presence of their microbial cells and biochemical activities. During MICP, organisms are able to secrete one or more metabolic products (carbonate) that react with ions (calcium) in the environment resulting in the subsequent precipitation of minerals. The enzyme urease induce carbonate precipitation in the microorganisms. Some bacterial species like Sporosarcina pasteurii has high level of urease that induce calcite precipitation.
MICP is utilized for soil stabilization, in situ concrete crack repair, fracture sealing of oil and gas wells, bioremediation of metals, and mitigating leakage from geologically sequestered carbon dioxide (CO2). During MICP, the metabolic activity of microorganisms increases the saturation state local to the bacterial cell and promotes calcium carbonate precipitation.
Heveran and coworkers in the journal Matter (2020) (https://doi.org/10.1016/j.matt.2019.11.016) reports LBMs created by inoculating an inert structural sand-hydrogel scaffold with Synechococcus sp., a photosynthetic cyanobacterium. The scaffold provided structural support for Synechococcus, which toughened the hydrogel matrix via calcium carbonate biomineralization resulting in the formation of solid bricks.
When half of a brick is placed in a mold with more of the gel and sand, the bacteria from that half will migrate and colonize the new material, eventually forming another brick. Ultimately, one parent brick – that is initially divided – can be used to produce up to eight more bricks.
Although this technology is in its nascence, potential applications of LBMs range from temporary civil and military structures to paving, façades, and other light-duty load-bearing materials. LBMs are not intended to broadly replace cementitious materials, but instead represent a new class of materials in which structural function is complemented by biological functionalities.
January 14, 2020
Engineered banana lectin, a carbohydrate binding protein, could protect against influenza virus infection
Flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs. It can cause mild to severe illness, and at times can lead to death. Many strains of the influenza virus exist. They are constantly mutating and changing. The best way to prevent flu is by getting a flu vaccine each year. The Centers for Disease Control and Prevention (CDC) estimates that influenza has resulted in between 9 million – 45 million illnesses, between 140,000 – 810,000 hospitalizations and between 12,000 – 61,000 deaths annually since 2010. Flu can directly lead to death when the virus triggers severe inflammation in the lungs. When this happens, it can cause rapid respiratory failure because your lungs can’t transport enough oxygen into the rest of your body. There is a pressing need for new anti-influenza therapeutic agents as current therapies are not very effective.
Lectins are carbohydrate binding proteins and found in several foods including beans, banana, cereals, etc. Coves-Datson and colleagues report in the journal PNAS (2020) (https://doi.org/10.1073/pnas.1915152117) that a molecularly engineered banana lectin has broad-spectrum activity against all influenza strains tested, including drug-resistant and currently circulating strains; is safe upon repeated administration in animal models; and, moreover, is efficacious at treating lethal influenza infection via clinically pertinent routes of administration. The authors demonstrate that the lectin binds to the viral hemagglutinin glycoprotein and exerts its primary antiviral effect via inhibition of an early stage of the viral life cycle, viral membrane fusion to the host endosomal membrane. The studies indicate that this engineered lectin, which has a mechanism of action quite distinct from the presently available agents, has potential as an anti-influenza agent.
January 10, 2020
Some species of parrots voluntarily help each other to obtain food rewards
Altruism is the belief that the well-being of others is equally, if not more, important than the well-being or survival of the self. Altruism involves selfless acts or undertakings that put the welfare of others before one’s own. Helping others to obtain benefits, even at a cost to oneself, poses an evolutionary puzzle. Kin selection may explain such “selfless” acts among relatives, only reciprocity (paying back received favors) entails fitness benefits for unrelated individuals. Experimental evidence for both prosocial helping (providing voluntary assistance for achieving an action-based goal) and reciprocity has been reported in a few mammals, including bonobos and orangutans, but no avian species. Brucks et al. in the journal Current Biology (DOI:https://doi.org/10.1016/j.cub.2019.11.030) reports testing two parrot species in an instrumental-helping paradigm involving “token transfer.” Here, actors could provide tokens to their neighbor, who could exchange them with an experimenter for food. The authors found that African grey parrots voluntarily and spontaneously transferred tokens to conspecific partners, whereas significantly fewer transfers occurred in the control conditions. Blue-headed macaws, in contrast, transferred hardly any tokens. Species differences in social tolerance might explain this discrepancy. These findings show that instrumental helping based on a prosocial attitude, accompanied but potentially not sustained by reciprocity, is present in parrots, suggesting that this capacity evolved convergently in this avian group and mammals.
January 4, 2020
Residential neighborhood green space is associated with reduced risk of cardiovascular disease
Diseases of the heart and circulatory system (cardiovascular disease or CVD) are the biggest cause of death globally. According to a substantial body of evidence, people have better physical and mental health in areas of green space–natural areas or urban vegetation.
Green spaces such as parks and sports fields as well as woods and natural meadows, wetlands or other ecosystems, represent a fundamental component of any urban ecosystem. Green urban areas facilitate physical activity and relaxation, and form a refuge from noise. Trees produce oxygen, and help filter out harmful air pollution, including airborne particulate matter.
Dalton and Jones (2020) in the journal PLoS ONE (15(1): e0226524) reports the importance of green space in reducing cardiovascular risk. There is a statistically significant decrease in mortality for people living in greener areas. Greener home neighborhoods may protect against risk of cardiovascular disease even after accounting for socioeconomic status (SES), whilst the mechanism does not appear to be strongly associated with physical activity. Exposure to green space may be protective against incident CVD in older adults. Participants living in the greenest locations had a 7% lower relative risk of developing CVD at follow-up when compared to those living in the least green areas, after adjustment for potential confounding by age, sex, body mass index, prevalent diabetes and SES.
The causes of the association between green space exposure and incident CVD remain largely unexplained, despite a growing body of work in this field. Likely explanations include physiological and psychological benefits of seeing green space, including stress reduction and restoration; the role of green space in creating a sense of attachment to place and community, and reduced isolation and increased social ties; the advantages of exposure to nature for immunological regulation; and, albeit with less evidence, the ‘biogenics’ hypothesis, that natural toxins and compounds can reduce unhealthy cell activity in humans, and reduce the incidence of disease.
December 31, 2019
Steering carbon dioxide electroreduction toward ethanol production
Carbon dioxide (CO2) is an important greenhouse gas, which is released through human activities such as deforestation and burning fossil fuels. When the carbon dioxide concentration goes up, temperature goes up. Similarly, when the carbon dioxide concentration goes down, temperature goes down.
Scientists have considered various strategies to store CO2. Carbon capture and storage (CCS) is a process whereby CO2 is “captured” from the air and then transported to a storage site – which could be, for example, a depleted oil or gas field or a deep rock reservoir beneath the sea. Though the technologies are currently restricted to a few small pilot projects, many view its large-scale development as an essential step to limiting the effects of future climate change.
Electrochemical reduction of CO2 can convert CO2 emission back to value-added fuels and chemicals and store renewable electricity. Reducing CO2 to multi-carbon products has attracted great interest because of their higher energy densities and associated economic values. Liu et al (2019) reports in the journal PNAS (116: 26353-26358) a strategy for steering CO2 electroreduction toward ethanol production by exploiting a surface-bound Ruthenium (Ru) polypyridyl carbene catalyst on an N-doped porous carbon electrode. The authors show the synergistic effects of Ru polypyridyl carbene for CO intermediate production with a porous carbon for C–C coupling that could boost ethanol production at relatively low over potentials. The strategy provides insights on how to improve selectivity and efficiency for CO2 reduction toward multi-carbon products.
December 30, 2019
Decline in prey body size due to resurgence of an apex marine predator
In coastal waters of the northeast Pacific Ocean, marine mammals have increased in abundance over the past 50 years, including fish-eating killer whales that feed primarily on Chinook salmon. Chinook salmon, a species of high cultural and economic value, have exhibited marked declines in average size and age throughout most of their North American range during this time.
Chinook salmon (Oncorhynchus tshawytscha) hatch and rear in freshwater, subsequently migrate to sea to spend 1 to 5 years in the ocean, and finally return to their native rivers to spawn once and then die. In the ocean, these fish often migrate thousands of kilometers and are widely distributed along the west coast of North America, the Gulf of Alaska, and farther west along the Aleutian Islands and into the Bering Sea. In most populations, fish now mature at younger ages, and while the size of younger fish has been stable or increasing, older fish that return to spawn after several years in the ocean are increasingly smaller. The trend toward smaller and younger fish is a pressing concern because Chinook salmon are valuable to commercial, recreational, and subsistence fisheries, and because large fish contribute disproportionally to reproduction.
The successful implementation of the 1972 US Marine Mammal Protection Act had increased the recovery of marine mammal predators. Killer whales (Orcinus orca) are the ocean’s ultimate apex predator and are widely distributed throughout the world’s oceans. Resident killer whales, which primarily occupy coastal waters, have nearly tripled in abundance in the northeast Pacific Ocean since the early 1970s. Their diets are dominated by salmon, especially Chinook salmon, which have the highest energy content of any salmon, and the whales selectively prey on the largest Chinook salmon. Estimates suggest that killer whales consume over 2.5 million adult Chinook salmon every year; these consumption levels by killer whales now exceed the combined annual removals of Chinook salmon by commercial, recreational, and subsistence fisheries.
Ohlberger et al. (2019), reports in the journal PNAS (116: 26682-26689) that fish-eating killer whales are currently having a larger effect than fisheries on phenotypic traits and life-history characteristics of Chinook salmon. The widespread declines in the body size of Chinook salmon over the past 50 years can be explained by intensified predation by growing populations of resident killer whales that selectively feed on large Chinook salmon, thus revealing a potential conflict between salmon fisheries and marine mammal conservation objectives. Further, the direct removal of large maturing fish, primarily via predation, has a larger effect on prey body size than evolutionary changes resulting from selection for faster growth and earlier maturation.
Camponotus ants feed on vertebrate urine to extract nitrogen
Ants eat a variety of food ranging from seeds, fruits, nectar, fungi, invertebrates to flesh of vertebrates. However, the environment influences the feeding habit of organisms including ants.
Petit et al. (2019) in the journal Austral Ecology (https://doi.org/10.1111/aec.12840) has reported the feeding behavior of the Camponotous ants at Kangaroo islands, a resource poor island in Australia. The ants have preference for animal urine. The researchers wondered whether why the ants preferred urine to other food resources. They baited ants with liquid stains of urine (human and kangaroo), urea in water (2.5%. 3.5%, 7.0%, 10.0%) and sucrose in water (20% and 40%) poured directly on the ground, as well as hard baits in plots drawn on sandy soil. Ants were most numerous on 10% urea, followed by 7% urea, 3.5% urea, urine (which contains ~2.5% urea) and 2.5% urea; sucrose was less attractive to them than equimolar urea bait. Ants were attracted to human, kangaroo, and unidentified urine, and they collected bird guano (rich in nitrogen). The remarkable ability of the Camponotous ants to extract nitrogen from dry sand over weeks explains partly its success on sandy soils. Foraging on urine may be an important strategy to address nitrogen limitation on sandy soils and exploit commensally niches in which hosts are kangaroos, wallabies and other vertebrates.
December 28, 2019
How does large humpback whales capture highly maneuverable fish
Predator–prey relationships have been likened to an evolutionary arms race—the prey become more difficult to capture and eat, while the predators perfect their abilities to catch and kill their prey. Just how strong these selective forces are probably depends on the strength of the interactions between the predators and their prey.
The humpback whales are around 15 meters long and weigh around 30 tons and are the largest of the rorqual species of whales. The humpback whales feed in the polar waters and migrate to the tropical and sub-tropical waters to breed and give birth. The diet consists of krill and small fish. But how does species such as humpback whale capture forage fish at speeds that barely exceed their prey where highly maneuverable fish could easily escape. Cade et al. (2019) reports in the journal PNAS (https://doi.org/10.1073/pnas.1911099116) that humpback whales delay the expansion of their jaws until very close to schools of anchovies, and it is only at this point that the prey react, when it is too late for a substantial portion of them to escape. This suggests that escape responses of these schooling fish, which have evolved under pressure from single-prey feeding predators for millions of years before the advent of lunge feeding, are not tuned sufficiently to respond to predators that can engulf entire schools, allowing humpback whales flexibility in prey choice.
December 27, 2019
Serotonin modulates walking in the fruit fly, Drosophila
People with neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease have walking difficulties. When these difficulties occur, patients walk with slow and irregular steps and find it hard to negotiate turns, climb onto a stepping stool, avoid obstacles in their path.
Howard et al. (2019) in the journal Current Biology (29:P4218-4230) reports that that the serotonergic system in the fruit fly, Drosophila melanogaster, can modulate walking speed in a variety of contexts and also change how flies respond to sudden changes in the environment. These multifaceted roles of serotonin in locomotion are differentially mediated by a family of serotonergic receptors with distinct activities and expression patterns.
Serotonin, a neurotransmitter is predominantly synthesized in the intestine (not in the brain). It is estimated that 90 percent of the body’s serotonin is made in the digestive tract. Serotonin is synthesized by specialized cells in the intestine mediated by the host microbes. Diet influences the rate of serotonin synthesis. A diet rich in the amino acid tryptophan may increase serotonin levels. It is not known if serotonin influences locomotion in humans. Future studies will determine whether serotonin levels could influence locomotion in neurodegenerative diseases.
December 24, 2019
Sleep fragmentation is accompanied by accelerated microglial aging and cognitive impairment in Alzheimer’s disease
People are living longer than the previous generation all over the world. However, the quality of life is declining with old age. Cognitive impairment and dementia constitute a growing public health concern. The global prevalence of dementia is estimated at 35.6 million individuals and is predicted to nearly double in 20 years.
Modern lifestyle and behavior have led to poor quality sleep patterns. Sleep disruption may contribute to cognitive impairment and dementia in older adults. In experimental studies, sleep deprivation is associated with altered expression of genes associated with inflammation and altered immune function. Immune dysregulation may, in turn, contribute to cognition-related disease processes, including Alzheimer’s disease (AD).
Sleep disruption may contribute to cognitive impairment through an immune mechanism. The nervous system comprises a remarkably diverse and complex network of different cell types, which must communicate with one another with speed, reliability, and precision. Microglia, the resident innate immune cells of the central nervous system, may play an important role in AD. It has been shown in animal models that chronic sleep restriction or deprivation can alter the immune signaling in a way known to trigger changes in microglial function and can lead to morphologic microglial activation and inhibiting this can improve cognition.
Kaneshwaran et al. (2019) in the journal Science Advances (5: eaax7331) reports that greater sleep fragmentation was associated with higher neocortical expression of genes characteristic of aged microglia, and a higher proportion of morphologically activated microglia, independent of chronological age- and dementia-related neuropathologies. Thus, sleep fragmentation is accompanied by accelerated microglial aging and activation, which may partially underlie its association with cognitive impairment.
December 19, 2019
New classes of antibiotics to treat Gram-negative bacteria
Bacteria are classified as Gram-positive and Gram-negative based on the ability to bid Gram stain. Gram-negative bacteria has a more complex cell membrane compared to the Gram-positive counterpart and hence resistant to several antibiotics. There are several Gram-negative bacteria that are pathogenic that are harmful to humans. E. coli, Klebsiella, Neisseria, Pseudomonas, etc., are examples of Gram-negative bacteria that cause illnesses.
The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens. The last class of antibiotics that acted against Gram-negative bacteria was developed in the 1960s.
Imai et al. (2019) reports in the Journal Nature 576:459-464 a new antibiotic named darobactin, which was obtained from the Gram-negative bacteria, Photorhabdus. Photorhabdus is a genus of bioluminescent bacilli that lives symbiotically within entomopathogenic nematodes. Photorhabdus is known to be pathogenic to a wide range of insects and has been used as a biopesticide in agriculture.
Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against Gram-negative pathogens and was tested in cell culture and in animal models of infection. The authors demonstrated that the bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics.
In the same issue of the journal Nature, Luther et al. (2019) 576: 452-458 describe a class of synthetic antibiotics inspired by scaffolds derived from natural products. These chimeric antibiotics contain a β-hairpin peptide macrocycle linked to the macrocycle found in the polymyxin and colistin family of natural products. They are bactericidal and have a mechanism of action that involves binding to both lipopolysaccharide and the main component (BamA) of the β-barrel folding complex (BAM) that is required for the folding and insertion of β-barrel proteins into the outer membrane of Gram-negative bacteria. These antibiotics protected against Gram-negative pathogenic bacteria.
December 11, 2019
Monocrop cannot sustain the long-term nutritional health of bee colonies; but integrating biodiversity into the landscape provides relief to nutritional stress.
Honey bees are responsible for providing the food security of man. The honey bees not only pollinate flowers, but also provide us with honey, bees wax, etc.
Climate change, over use of pesticides and insecticides, bacterial and fungal diseases has an impact on the bee population. In recent years, it is known that the agriculture land use patterns impact the health of honey bees.
An ever-increasing demand for food and biofuels following human population expansion requires more land be dedicated to agricultural production. Global land use has shifted to meet this demand, with natural areas and smaller-scale agricultural enterprises transformed into high-yielding monocultures. Monocultures can have substantial negative environmental effects on soil, water, and air quality, and when coupled with the removal of native, non-crop habitat, this form of agriculture is associated with declines in pollinator populations.
Dolezal et al. in the journal PNAS (2019; 116 (50): 25147-25155) reported the impact of soybean or corn monoculture on the wellness of honey bee population. The authors report that a brief burst of colony growth during soybean bloom, is followed by a longer period of forage scarcity, resulting in decline in several aspects of honey bee health at both colony and individual levels. This decline is reversible when honey bees have access to native, perennial plants (i.e., prairie). The authors conclude that a sustainable pollinator management in landscapes dominated by monocultures can be achieved through reintegration of native biodiversity.
December 5, 2019
Are you tired seeing no improvements in the glucose levels even after regular exercise – blame your microbiome
Metabolic syndrome is a collection of disease risk factors that increase your chance of developing heart disease, stroke, and diabetes. The condition is also known by other names including Syndrome X, insulin resistance syndrome, and dysmetabolic syndrome. More than 1 in 5 Americans has metabolic syndrome. The number of people with metabolic syndrome increases with age, affecting more than 40% of people in their 60s and 70s.
The exact cause of metabolic syndrome is not known. Many features of the metabolic syndrome are associated with insulin resistance. Insulin resistance means that the body does not use insulin efficiently to lower glucose and triglyceride levels. A combination of genetic and lifestyle factors may result in insulin resistance. Lifestyle factors include dietary habits, activity and interrupted sleep patterns.
Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Liu and team reported in the journal Cell Metabolism (https://doi.org/10.1016/j.cmet.2019.11.001) that exercise induced changes in the host gut microbiome (all the microbiota of your body’s gut) and it correlated to improvements in glucose homeostasis and insulin sensitivity. The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.
December 3, 2019
Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
Inuit are the indigenous people inhabiting the arctic regions of Canada, Greenland and Alaska. Domestic dogs have been central to life of the Intuits in the North American Arctic for thousands of years. Aside from this initial peopling of the Americas, the North American Arctic has experienced additional human migration episodes of genetically distinct populations, which were accompanied by potentially distinct dog populations. Investigating whether or not these new groups brought genetically differentiated dog populations with them into the North American Arctic, and the relationship between these dogs and those already present in the region, is crucial for understanding the history of dogs in the Americas.
Recent genetic analyses indicate that the earliest dogs found in the Americas belonged to a now extinct lineage of Arctic dog that was introduced from Eurasia at least 10,000 years ago. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown.
The Inuit emergence in Alaska beginning approximately 2000 years ago brought large-scale changes in life style, subsistence practices and material culture to the North American Arctic. Their subsequent expansion translocated this culture out of Alaska eastward to Greenland, and along the coast of subarctic Eastern Canada around 1000 years ago. The rapid expansion of the Inuit is attributed in part to their exploitation of advanced transportation technologies, including the development and widespread usage of the umiak and kayak for sea travel, and the dog sledge for use on land and ice.
Ameen et al. recently reported in the journal Proceedings of the Royal Society B (2019) (https://doi.org/10.1098/rspb.2019.1929) that the Inuit dogs are distinct from the earlier dogs of the Arctic. The authors analyzed themitochondrial DNA and geometric morphometric data of skull and dental elements of North American Arctic dogs and wolves spanning over 4500 years. Their analyses revealed that dogs from Inuit sites dating more than 2000 years ago possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. The authors are of the opinion that the Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 years ago.