Search

Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.

Neurons that respond emergently to illusory contours drive pattern completion in V1. Pattern completion in lower cortical areas may therefore mediate perceptual inference by selectively reinforcing activity patterns that match prior expectations.

Here the authors identify adenophages, a previously unknown macrophage population present in exocrine glands in mice and humans. These cells are dependent on ILC2-derived GM-CSF and support glandular homeostasis.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

Creating a new drug is a long and painstaking process, involving the skills and talents of numerous types of scientist, says Hannah Hoag. Each is vital to different stages of producing a drug that's both safe and effective. Drug development draws on various kinds of scientist.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Graphene is a single layer of carbon atoms whose high electron mobility offers potential for cheap, high-speed opto-electronic devices. Docherty et al.show that the terahertz frequency photoconductivity in graphene depends crucially on the type and density of environmental gas adsorbed.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Use of animals for testing early in the drug-development process aims to provide vital information to make new drugs safe and effective — and the process is being constantly refined. Hannah Hoag finds out what is involved.

Monoclonal antibodies and ligands targeting CD40 exhibit diverse agonistic and antitumor activities that are influenced by their design. Here, the authors identify mechanistic differences between clinically relevant anti-CD40 subclasses and CD40L, focusing on the dynamics and strengths of multi-bond formation at the single-molecule level.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Urban water crises, due to droughts and unsustainable water consumption, are becoming increasingly recurrent in metropolitan cities. This study shows the role of social inequalities in such crises, revealing the implications of water overconsumption by privileged social groups and individuals.

Mammalian recombination activating genes RAG1 and RAG2 are essential for the production and diversification of antibodies and T-cell receptors via V(D)J recombination in lymphocytes but are absent in simpler eukaryotes such as the yeast Saccharomyces cerevisiae. Here the authors integrate mouse RAG1/2 in S. cerevisiae and demonstrate the ability to create combinatorial diversity starting from a single genetic locus in vivo.

The molecular landscape of chromothriptic medulloblastoma remains to be characterised. Here, spatial transcriptomics analysis of 13 chromothriptic and non-chromothriptic medulloblastomas identifies distinct spatial composition patterns and cell communication networks in these tumours.

Neuromuscular junctions (NMJs) are denervated in amyotrophic lateral sclerosis (ALS) through unknown mechanisms. Here, the authors show immune cells infiltrating muscle of ALS patients and mouse models, driven by CCL2-CCR2, which can be blocked to protect NMJs.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Following the building principles of crown ethers for cation encapsulation, inverse crowns are rings of metals that bind anions. Now a redox-active inverse crown ether featuring Na⁺ cations and Mg⁰ has been shown to reduce epoxides, N₂O, S₈ or O₂ by combining anion complexation by the ring of metal cations with the reducing power of Mg⁰.

Nickel(II) dihalide precatalysts with bidentate nitrogen ligands are widely used in cross-coupling reactions, notably in combination with photosensitizers, forming catalytic systems that currently drive major conceptual and synthetic thrusts within organic chemistry. Here the authors show a general mechanism by which these precatalysts are converted to the reduced, catalytically active species, using a range of characterization and spectroscopic techniques.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

Here, the authors reveal variability in chromosome 21 gene overexpression among individuals with Down syndrome, identifying three distinct molecular subtypes. Each subtype exhibits unique biosignatures and immune profiles, offering new insights into the complex biology of Down syndrome.

The ubiquitin ligase, RNF168, promotes DNA break repair but must be regulated to prevent run-away ubiquitin signaling. Here, the authors identify a three-step post-translational cascade regulating RNF168 chromatin removal, acting to suppress excessive signaling and radiosensitivity.

An oral inulin allergen gel restores the microbiota of allergic mice and suppresses undesired immune responses to achieve allergen-specific oral tolerance, effectively overcoming food allergy.

Large quantum computers are likely to require methods of connecting devices by transmitting and absorbing photons. Entanglement between two superconducting qubit devices has now been established using a waveguide with tunable directionality.

The role of lateral inhibition for perception and neural computation remains unsolved. Del Rosario et al. show that distinct types of cortical interneurons in V1 drive lateral inhibition that causes subtraction or division of visual sensitivity.

Although molecular complexes can serve as well-defined model catalysts for CO₂ electroreduction, few compounds reduce CO₂ beyond two electrons. Now, hydrophobic molecular cobalt terpyridine complexes, containing perfluorinated alkyl side chains, have been shown to assemble at the gas–liquid–solid interface and to electrocatalytically reduce CO₂ to methane with high efficiencies.

Stably silenced genes with methylated CpG at the promoter are refractory to current CRISPR activation systems. Here the authors create a more robust activation system, TETact that recruits DNA-demethylating TET1 with transcriptional activators.

Recent barcoding technologies allow the reconstruction of a cell’s lineage tree while capturing paired transcriptomic data. Here, the authors present a statistical method to automatically detect gene expression patterns related to lineage progression.

Diener et al. present a method that allows the estimation of dietary intake from human stool by detecting food-derived DNA in faecal metagenomes.

Pollinator-driven evolution of floral traits is thought to be a major driver of angiosperm speciation and diversification. Here, the authors assemble the chromosome-scale genome of the sexually deceptive orchid Ophrys sphegodes and reveal insights into sexual deception and pollinator adaptation.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Sundowning in Alzheimer’s disease (AD) patients is characterized by agitation and aggression during their afternoon-to-evening transition and a phase delay in circadian rhythms. Here, the authors show that AD model mice develop a phase delay and increased aggression around their active-to-rest transition with Tau pathology in brainstem neurons that target the circadian system.

Tisza et al. carry out a sequencing-based analysis of wastewater samples from major cities, to detect and quantify hundreds of distinct pathogenic viruses, finding striking correlations between virus abundance and local clinical cases.

γδ T cells have potent effector functions through their production of IFN-γ or IL-17. Pennington and colleagues demonstrate that IFN-γ⁺ γδ T and IL-17⁺ γδ T cells have distinct metabolic requirements that can be independently targeted to elicit specific immune responses.

Identification of a hyperstable boronate enables automated lego-like synthesis to access a wider range of three-dimensionally complex small organic molecules rich in Csp³–C bonds. 

Electroreduction of CO₂ competes with the hydrogen evolution reaction; thus, controlling water’s activity to exclusively act as a proton donor is a desirable yet challenging goal. Now the behaviour of water in aprotic solvents is shown to depend on the solvent’s donor ability, which can modulate the hydrogen bond network and in turn promote the desired reactivity.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Arany and colleagues integrate metabolomics data, tissue RNA-sequencing data and proteomics data from explanted hearts of patients with end-stage heart failure to provide a comprehensive ‘multi-omic’ evaluation of the metabolic pathways affected by heart failure.

Antibodies that broadly inhibit influenza virus neuraminidase by binding to its active site could be therapeutic candidates, but circulating viruses have acquired a glycosylation site in that region. Here, the authors show that, while the S245N glycosylation site affects binding of tested monoclonal antibodies, protective activity in a mouse model is maintained.

Combining high-speed AFM, single molecule recognition force spectroscopy, and molecular dynamics simulations Zhu, Canena, Sikora et al. characterize the interaction dynamics of the trimeric spike protein of SARS-CoV-2 wt, and delta and omicron variants with its entry receptor ACE2. While delta variant increases avidity by multivalent binding to ACE2, omicron variant shows an extended binding lifetime.

A massive galaxy hosting an accreting supermassive black hole two billion years after the Big Bang shows fast neutral-gas outflows that are capable of stopping star formation by removing its fuel while the stars keep rotating in a disk.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.

Species are already on the move as waters warm. Conservation plans need to take this into account.