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Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Efficient learning is akin to goal-directed dimensionality reduction, in which relevant information is highlighted and irrelevant input is ignored. Here, the authors show that ventromedial prefrontal cortex uniquely supports such learning by compressing neural codes to represent goal-specific information.

Untreated, postconsumer-PET from 51 different thermoformed products can all be almost completely degraded by FAST-PETase in 1 week and PET can be resynthesized from the recovered monomers, demonstrating recycling at the industrial scale.

JWST observations of the Cosmic Gems arc resolve the light of an infant galaxy into five gravitationally bound star clusters located in a region smaller than 70 pc.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A strongly lensed galaxy at redshift z ≈ 6 is resolved into at least 15 star-forming clumps embedded in a rotating disk. Clump formation in this system, which is not predicted by cosmological zoom-in simulations, may be driven by disk instabilities with weak feedback, rather than past mergers.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Urban biodiversity is an unplanned species assemblage. Although promoting native biodiversity should be the primary goal, the built environment often contains optimal habitat for non-natives. With planning and research, we could use cities as semi-natural assurance colonies for endangered species.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

pgFARM (paired guide RNAs for alternative exon removal) is a CRISPR–Cas9-based approach to manipulate alternative splicing and identify functional roles for individual exons, including poison exons with essential and tumor-suppressor roles.

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.

Ossenkoppele, Coomans and colleagues analyzed the tau PET data of 12,048 individuals from 42 cohorts worldwide. They found that age, amyloid-β status, presence of an APOE ε4 allele and female sex are key contributors to tau PET positivity, which should aid clinical decision-making and trial designs.

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.

Dysregulation of alternative polyadenylation (APA) is associated with poor prognosis in cancer but its functional role is less clear. Here, the authors develop a CRISPR-Cas9- based screen to determine the effects of different APA events on melanoma growth in mouse models.

The preferential susceptibility of oncolytic viruses to certain antibiotics can be exploited to accelerate the engineering of oncolytic viruses expressing transgenes for immunomodulatory cytokines.

Mutations in genes involved in immune signalling and vesicle trafficking cause defects in the leaf microbiome of Arabidopsis thaliana that result in damage to leaf tissues, suggesting mechanisms by which terrestrial plants control the level and diversity of endophytic phyllosphere microbiota.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

White-tailed deer are a potential reservoir of SARS-CoV-2 variants.

Our current understanding of neurofibromatosis type 1 (NF1) is based on patients ascertained through phenotype-first approaches, which estimate a low prevalence at 1 in 3,000. Here, the authors leverage a genotype-first approach in multiple large patient cohorts to demonstrate an unexpectedly high prevalence (1 in 1,286) of NF1 pathogenic variants with distinct disease associations.

The authors identify Irf7 and associated interferon signaling as an important factor suppressing bone metastasis of breast cancers. Irf7 is lost in experimental metastasis and human bone metastastic tissue, and this fosters an immunosuppressive environment that facilitates metastasis. Manipulating this innate immune signaling pathway emerging from tumor cells by interferon administration had beneficial effects in mouse models by reducing bone metastasis and increasing survival time.

As part of the second phase of Human Microbiome Project, the Multi-Omic Microbiome Study: Pregnancy Initiative presents a community resource to help better understand how microbiome and host profiles change throughout pregnancy as well as to identify new opportunities for assessment of the risk of preterm birth.

Adoptive T-cell immunotherapy offers promise to patients who are resistant to standard anti-viral strategies. Here the authors describe clinical observations in patients with viral complications treated with adoptive immunotherapy over the last 15 years.

Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.

DICER1 is required for the maturation of miRNAs which regulate expression of thousands of genes. Here the authors show significantly reduced levels of DICER1in individuals having post-traumatic stress disorder and comorbid depression suggestive of a role in the molecular mechanism of the condition.

Rps genes are used to manage the major soybean pathogen Phytophthora sojae, which causes Phytophthora stem and root rot (PRR). Here, the authors show that widely used Rps genes are no longer effective for managing PRR in the United States, Canada and Argentina.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

This Perspective traces the evolution of fundamental and applied aspects of nanomotor research over the past 20 years, highlights current challenges and proposes design principles for developing the next generation of intelligent nanomotors.

RNA-based viruses can be engineered to express artificial microRNAs (amiRNAs). Here, the authors identify a candidate amiRNA that confers a replicative advantage to oncolytic viruses, enhancing their anticancer potency, and show that intercellular transfer of extracellular vesicles carrying the amiRNA promotes bystander killing of uninfected cancer cells.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

RIT1 mutations are mutually exclusive with other lung cancer drivers and lack targeted therapies. Here the authors examine genetic dependencies of mutant RIT1 with genome-wide CRISPR screens, revealing synergy between RIT1 and YAP1, and increased sensitivity to Aurora kinase inhibitors.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Competition is fierce in the microbial world, making evolutionary training and fitness essential for a microorganism to survive and thrive. To honour this spirit, in this Essay an expert panel has selected seven special events to make up the inaugural Microbial Olympics.

Smith and colleagues show that embryonic stem cell self-renewal does not rely on extrinsic instruction, and can be enabled by the elimination of factors that induce differentiation and by inhibition of glycogen synthase kinase 3. They interpret the data as showing the ground state of the embryonic stem cell in the absence of extrinsic instruction is self renewal.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.