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.