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In this study, the authors show that during reward learning, transient loss of chloride transport enhances midbrain GABA network synchronization and dopamine signaling, changes essential for forming new reward-related memories.

Beneficial effects of fasting combined with endocrine therapy for oestrogen receptor-α-expressing breast cancers can be recapitulated using exogenous glucocorticoid receptor ligands instead of fasting to reduce harmful effects.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

Georeferencing translates textual location information, for instance, on herbarium specimen labels, into geographical coordinates, but traditional methods are labour intensive and costly. Large language models (LLMs), however, have the potential to facilitate the georeferencing of natural history collections. Under standardized testing, some available LLMs achieved a near-human level of accuracy quickly and affordably, such that their incorporation into current workflows will increase the efficiency of georeferencing.

Fresh basaltic glass preserved in a sample of volcanic breccia record a single eruptive event at the Alpha Ridge around 90 Ma, suggesting that parts of the ridge were emergent during the final stages of magmatism in the High Arctic Large Igneous Province, according to geochemical and geochronological analysis of the sample.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

The consequences of postprandial IL-1β surges in white adipose tissue are unknown. Here the authors show IL-1β regulates WAT remodelling by promoting adipogenesis and energy storage, which is blocked by chronic elevation of this cytokine (as in obesity).

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Endosomal recycling relies on SNX17 to transport membrane proteins via Retriever. Here, authors reveal the mechanisms of SNX17 autoinhibition and its interaction with Retriever, uncovering a broader family of factors with similar binding strategies.

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.

Joyce, Pascual et al. identify luminal progenitors as likely cells-of-origin in BRCA2-mutant breast cancer, exhibiting dysregulated proteostasis and translation, which may be therapeutically targeted via mTORC1 inhibition.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Spondyloarthropathies are characterized by a distinct pattern of inflammation at distinct anatomical sites and are associated with elevated expression of interleukin 23 (IL-23). Daniel Cua and his colleagues identify an IL-23–responsive CD4⁻CD8⁻ T cell population located within entheses. Systemic overexpression of IL-23 activates these cells and recapitulates aspects of the human disease in mice, and neutralization of IL-17 and IL-22 decreases pathology, suggesting new therapeutic targets for these disorders.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

A semiconductor chip, coupled to an ion-sensitive field effect transistor (ISFET) pH sensor, can amplify and quantitate DNA in real time without dyes, cameras and external heating devices.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

Mural progenitor cells are crucial for vascular stability. Here, the authors generate these cells from human pluripotent stem cells using NKX3.1 and show that they can mature into various mural cell types and contribute to blood vessel formation.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

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.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

Ken Ong and colleagues report meta-analysis of 32 genome-wide association studies for age at menarche. They identify 30 loci newly associated with age at menarche, including four that were previously associated with BMI.

This study reports that nuclear speckle constituents have two expression states in cancer correlating with patient survival and HIF-2α functional programs. HIF-2α mediates nuclear speckle association of key genes activated in renal cancer.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Monitoring COVID-19 vaccine uptake in those at risk of severe disease, such as people with mental illness, is important. Here, the authors use cohort and/or health registry data from five countries in northern Europe and investigate vaccine uptake by mental illness and treatment status.

Bacterial pathogens produce enterobactin, which suppresses microbiota-derived indole activation of Ahr in macrophages to inhibit bacterial clearance and increase the severity of bacterial sepsis.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.