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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).

Storms cool the Southern Ocean surface in summer mainly by deepening the mixed layer, but increased air–sea turbulent fluxes reduce ocean heat loss and partly offset the cooling, according to glider observations, reanalyses and satellite data.

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.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Ventures focusing on gene therapy, adoptive T-cell therapy, protein homeostasis and the microbiome are among those selected by the editors in 2013's crop of startups.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Our annual survey highlights several academic startups developing immunotherapies as well as ventures focusing on microbiomes, proteostasis, integrin biology, nucleic acid delivery and subcellular imaging.

JWST/NIRSpec observations of the 49 Ceti debris disk reveal spatially resolved, fluorescently excited CO emission, indicating a secondary origin of the gas in debris disks (that is, from the collision of volatile-rich bodies).

The capture of helium by carbon to form oxygen is a key astrophysical reaction. The authors show that measuring this reaction using high-intensity photons and a Time Projection Chamber has significant advantages over conventional techniques, providing data with measured E1-E2 mixing angles that agree with quantum mechanical predictions.

The James Webb Space Telescope has detected water ice in the cold debris disk (analogous to the Kuiper belt) around the star HD 181327.

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.

Observed 730 Myr after the Big Bang, a little red dot is found to anchor an overdensity of eight galaxies and seems to be embedded in a massive host dark matter halo.

The warm Earth-sized planet LHS 475 b is validated and characterized with two transits observed by the JWST. The absence of evident spectroscopic features excludes a substantial hydrogen envelope and indicates that LHS 475 b has either little or no atmosphere or an optically thick cloud deck at high altitudes.

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.

The reported optical properties of organic hazes produced in water-rich exoplanet atmospheres differ from those in nitrogen-rich atmospheres. Such differences have a detectable effect on the spectra, impacting interpretation of JWST observations.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Two high-redshift post-starburst galaxies are in the process of quenching, although their quasars remain active, indicating the complex co-evolution between black hole activity and star formation.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

Simultaneous observations of TRAPPIST-1 b from JWST at 12.8 and 15 μm indicate that it is probably a bare rock with a mineral-rich surface. However, an alternative scenario with a CO₂-rich atmosphere and hazes could also explain the observations.

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.

How the necroptosis executioner, MLKL, converts to a killer form has been mysterious. Here, authors show RIPK3-mediated phosphorylation of human MLKL is the cue for pseudokinase domain dimerization before assembly of pro-necroptotic MLKL tetramers.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

A spectroscopic thermal phase curve of GJ 1214b obtained with the JWST in the mid-infrared is reported and a planet with a high metallicity atmosphere blanketed by thick and reflective clouds or haze is found.

While alternative splicing is known to drive oncogenesis and be a source of potential therapeutic targets, identifying such drivers on a genome-wide scale has proven difficult. Here, the authors present a computational approach to identify potential cancer-driver exons and evaluate applicability as therapeutic targets.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

_{Household survey data is vital to health and development. The study describes and maps data quality in 35 African countries, finding that data quality varies and worsens with distance from towns, indicating a need for investment in data collection.}

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

Laboratory experiments show that the inclusion of even small quantities of sulfur in the atmospheres of exoplanets at 800 K significantly increases photochemical complexity, both in the vapour and in the solid phase: many sulfur gas products are created (including potential biosignature gases) and the production of organic haze particles increases threefold.

Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

Storms dominate the subpolar Southern Ocean, where upwelling CO₂ drives outgassing that impacts global CO₂ budget, yet how storms modify this outgassing is unknown. Here, the authors present coupled atmosphere-ocean observations to show how storm-driven ocean mixing and circulation cause substantial CO₂ variability and outgassing.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.

Single-cell transcriptomic and phylogenetic analyses reveal new insights into the developmental origin and potential therapeutic targets for a particularly aggressive form of B-cell acute lymphoblastic leukemia in infants.

Here, the authors implement a genetic approach grouping fasting insulin-associated genetic variants based on their genetic and phenotypic similarities and highlight specific processes that decouple increased fasting insulin levels from T2D and cardiovascular risk, offering potential avenues for investigating process-specific pathways of disease risk.

With monogenetic neurodevelopmental disorders similar to autism serving as starting points for several drug discovery programs, smaller biotechs are now joining big pharma in pursuing therapies to tackle this perplexing condition. Sarah Webb reports.

Hibernation is a state of extreme metabolic and physiological plasticity occurring in conjunction with physical inactivity and prolonged fasting. Using in vivo tracing, Rice et al. reveal that nitrogen recycling staves off ammonia toxicity during hibernation in ground squirrels.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.