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Savan and colleagues show that distinct isoforms of the RNA-binding protein ZAP function as an antiviral restriction factor or as an interferon-resolution factor, based on differences in their intracellular localization.

Arachnoid cuff exit points create openings in the arachnoid barrier enabling the drainage of cerebrospinal fluid and exchange of molecules and cells between the dura and the subarachnoid space, therefore physically connecting the brain and the dura.

The MAVEN spacecraft observed brightening in the Lyman-α line correlated with solar wind activity, which can be attributed to auroral activity by solar wind protons interacting with the Martian neutral hydrogen corona. Proton aurorae are normally seen at Earth only.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

While many tissues have been investigated for natural somatic mutations, human breast tissue has not been well studied. Here, the authors characterize somatic mutations in human breast tissue, finding effects of age and parity.

Unbiased chemical biology strategies for direct readout of small molecule protein interactomes provide advantages over target-focused approaches. Here, the authors describe the BioTAC system, a network-scale small molecule guided proximity labeling platform, to rapidly identify ligand-target interactomes.

When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months

Using cryo-electron microscopy, the authors describe the structure and function of a molecular motor powering both the Bacteroidetes type 9 protein secretion system and the associated gliding motility apparatus.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

In this study, Wrigth et al. use structural, medicinal chemistry, and behavioral approaches to examine how equilibrative nucleoside transporter subtype 1 (ENT1) exerts its functions; and their findings reveal ENT1 as a potential target for analgesia.

A new elpistostegalian from the Late Devonian period has been discovered that shows disparity in the group and represents a previously hidden ecological expansion, a secondary return to open water, near the origin of limbed vertebrates.

The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.

Nitrogen-containing compounds play an indispensable role in medicine, agriculture and materials, but alkylated derivatives especially in sterically congested environments, remain a challenge to prepare. Here, the authors report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines.

Mitotic errors promote chromosome fragmentation and rearrangements through chromothripsis. Here, the authors identify NHEJ as the primary DSB repair pathway underlying chromothripsis and investigate the kinetics of fragment reassembly across the cell cycle.

A first-in-patient trial of UB-312, an active immunotherapeutic for Parkinson’s disease, was well tolerated and elicited antibodies that engage misfolded α-synuclein.

Standard diagnostics are often not able to fully capture submicroscopic parasite dynamics after treatment with antimalarials. In this longitudinal analysis of molecular markers of malaria parasitemia in an Ugandan cohort, authors describe persistence of markers following antimalarial therapy with dynamic and complex multiclonal infections in the initial and post-treatment periods.

Optical pooled CRISPR screening is improved by combinatorial oligo hybridization for barcode detection.

This study shows that the brain can link action to value through neural population subspaces, balancing reliable binding of action to value and generalization to novel stimuli.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

 Prophage lysogeny-to-lysis transitions are controlled by regulatory modules consisting of transcription factors and partner small proteins that are activated through DNA-damage-independent pathways, including by quorum sensing, and these modules determine inter-prophage competition outcomes.

Long-range order is normally related to an entropy decrease. Yet, an increase in entropy in one part of a system can induce long-range order in another. A new form of such entropy-driven order is now demonstrated in an artificial spin-ice system.

Cryo-EM structures provide insight into how the antifolate methotrexate, a chemotherapy drug, is recognized by the reduced folate carrier.

Birds can adapt to temperature gradients by changing body size (Bergmann’s rule) or bill size (Allen’s rule), but many groups don’t conform to these patterns. Here the authors show that most bird families show subtle and complementary changes in bill and body size, while also being constrained by feeding ecology.

A deep convolutional neural network calculates liability scores for chronic obstructive pulmonary disease (COPD) from raw spirogram traces and noisy medical-record-based labels in the UK Biobank. Genome-wide analyses using these scores replicate known loci for lung function and identify 67 new disease loci.

Water resource development can have important downstream impacts on ecological functioning and affect socio-economic outcomes associated with marine fisheries. This study modelled the catchment-to-coast effects of reductions in freshwater flowing to estuaries in Australia.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Large sequences are integrated site specifically into the human genome without double-strand DNA cleavage.

Infection of African green monkeys with simian immunodeficiency virus is a potential model for HIV vaccine development. Here, Zhang et al. catalogue the immunoglobulin loci present in the genome of these animals, and experimentally study their B-cell response to the viral envelope protein.

l-cysteine is required for the growth of Lactobacillus iners, a vaginal microbiome species typically associated with adverse outcomes that lacks cysteine biosynthesis pathways and key uptake mechanisms present in other lactobacilli. Cystine uptake inhibitors can be used to suppress L. iners abundance in vitro in favour of L. crispatus, a species associated with favourable outcomes.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

IL-17a is an evolutionarily conserved cytokine with behavior-modulating roles in the central nervous system. Kipnis and colleagues characterize a population of meningeal γδ17 T cells that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

O’Shea and colleagues examine the three-dimensional chromatin architecture of the type 2 cytokine locus and how it differs between innate ILC2 cells and adaptive T_H2 lymphocytes.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The role of alternative splicing in pancreatic cancer (PDAC) development remains to be explored. Here, RBFOX2 is shown to regulate exon splicing events in transcripts encoding proteins involved in cytoskeletal remodelling programs and its downregulation promotes PDAC progression and liver metastasis.

Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.

Many viral proteins are thought to be unlikely candidates for drug discovery as they lack obvious drug binding sites. Here, the authors use computational approaches followed by experimental validation to identify a cryptic pocket within the Ebola virus protein VP35.

Kumar et al. show that under glucose-depleted conditions, neurons can use fatty acids as an alternative source of energy to support synaptic function.

Developing countries are experiencing huge rises in the incidence of type 2 diabetes mellitus (T2DM). In this Perspectives, Justin Echouffo-Tcheugui and Samuel Dagogo-Jack describe factors that underlie the rising prevalence of (T2DM), strategies to tackle the problem and discuss the difficulties that need to be overcome in order to implement solutions.

Here, in a sub-study of the MISAME-III randomized controlled trial, the authors show that maternal balanced energy-protein supplementation during pregnancy and lactation alters the maternal gut microbiome, leading to an enhanced infant carbohydrate metabolism, and identify microbial taxa with a potential role in mediating the effects.

Design of anomeric leaving groups with pendant H-bond acceptors results in a stereospecific chemical O-glycosylation with broad scope and applicability to automated synthesis.

While developmental phenotypes are often multigenic and involve environmental inputs, most research approaches involve perturbation of small numbers of genes. Here they use a synthetic evolution approach in Drosophila to show that adding extra copies of bicoid leads to rapid, system-wide phenotypic responses, potentiated by highly polygenic traits such as embryo size.