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An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Cirrus cloud formation in the Northern Hemisphere is primarily triggered by mineral dust, according to global-scale dust observations and a cirrus-formation model.

Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis.

We present James Webb Space Telescope observations that detect the 3.3 μm polycyclic aromatic hydrocarbon feature in a galaxy observed less than 1.5 billion years after the Big Bang.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Barrachina et al. present an extensive lipidomic analysis at different stages of thrombopoiesis and, through in vitro and in vivo experiments, demonstrate that fatty acid uptake, largely dependent on the scavenger receptor CD36, and its regulation are essential for megakaryocyte maturation and platelet production.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

A mouse model of chronic COVID-19 facilitates the study of disease mechanisms and therapies.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

The atmospheric terminator region of WASP-39 b, a hot gas giant exoplanet, is inhomogeneous, despite past assumptions, with the evening terminator being hotter and thus probably clearer, and the morning terminator probably being cloudy and consequently cooler.

Environmental stressors have been associated with placental dysfunction and pregnancy complications. Here, the authors reveal gene expression changes in the mouse placenta exposed to arsenic at single-cell resolution and identify a potential therapeutic target to mitigate its harmful effects on pregnancy and fetal development.

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.

Efforts to apply targeted protein degradation for antibiotic development are limited by our understanding of prokaryotic protein degradation. Here, the authors establish a chemical-genetic platform and predictive model to determine the degradation potential of essential mycobacterial proteins.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Using a database of doubly labelled water energy expenditure measurements spanning more than 30 years, Speakman and colleagues show that total energy expenditure in humans has declined over time, while adjusted physical activity energy expenditure has increased over time.

Two malaria vaccines comprising Plasmodium falciparum sporozoites and treatment with either pyrimethamine or chloroquine induced durable protective responses against both the African vaccine strain and a heterologous South American strain of P. falciparum.

Biochemical techniques provide a detailed picture of how the catalytic core of the Tetrahymena ribozyme interacts with the surface of its helical substrate.

Routine sampling of pregnant women at first antenatal care (ANC) visits could be used for malaria surveillance. Here, the authors compare the genetic structure of Plasmodium falciparum parasite populations between samples from first ANC users and children from the community in Mozambique, and show that it can inform about changes in transmission beyond epidemiological data.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Plants frequently face trade-offs of growth and defence. One way for the switch is to produce defensive compounds from primary pathway intermediates. Here, the researchers characterized the biosynthetic pathway of an antibiotic diterpenoid in maize and revealed a crosstalk between maize secondary metabolism and gibberellin biosynthesis.

Matched Annotation from NCBI and EMBL-EBI (MANE) delivers joint transcript sets from Ensembl/GENCODE and RefSeq for standardizing variant reporting in clinical genomics and research.

Raf kinase activity is deregulated in cancers and is thought to promote tumor growth by inducing proliferation signaling through MEK/Erk. This report identifies a new role for c-Raf independent of MEK/Erk and relying on phosphorylation of Ser338. Phospho–C-Raf interacts with the mitotic kinases Aurora-A and Plk1, activating the latter to promote mitotic progression and increase cell division, and this pathway is a crucial mediator for the protumorigenic effect of c-Raf in vivo.

An array-based method can identify synthetic hydrogels that outperform Matrigel in screening for vascular-disruptor compounds and in supporting the expansion and pluripotency of human embryonic stem cells.

European river discharge observations suggest that catchments with similar flood generation processes produce similar extremes, enabling better predictability of megafloods using a continental scale perspective.

Constructing a reference genome for quinoa (Chenopodium quinoa) allows for genetic diversity during the evolution of sub-genomes in quinoa to be characterized and markers that may be used to develop sweet commercial varieties are identified.

Results from the LAVENDER phase 3 study demonstrate that trofinetide, a synthetic analog of glycine–proline–glutamate, provides significant therapeutic benefits in the core symptoms of Rett syndrome

Operating in space, NASA’s Deep Space Atomic Clock, a trapped-ion clock, is shown to have long-term stability and drift that are an order of magnitude better than current space clocks.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

Quantum supremacy is demonstrated using a programmable superconducting processor known as Sycamore, taking approximately 200 seconds to sample one instance of a quantum circuit a million times, which would take a state-of-the-art supercomputer around ten thousand years to compute.

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.

A tight-knit community and a cooperative spirit has helped San Diego to succeed. Eric Niiler checks out California's rising star.

A family of calcium-dependent protein kinases (CDPK) is present in apicomplexan parasites but not in animals, indicating their potential as targets for anti-parasitic drugs. Structural and functional studies on Toxoplasma gondii CDPK1 now reveal that this kinase is sensitive to a class of drugs called bumped kinase inhibitors, which can inhibit the parasite's growth and host cell invasion.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

In maize, a comprehensive set of approaches enabled the authors to analyse the biosynthetic pathway of the zealexin group of terpenoids and characterize the role of these antibiotic compounds in disease resistance.

Deep learning was used to map the crown sizes of each tree in the West African Sahara, Sahel and sub-humid zone using submetre-resolution satellite imagery, revealing a relatively high density of trees in arid areas.