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Prior hypoglycemia alters the paracrine interaction between islet α and δ cells, leading to impaired counter-regulatory glucagon secretion through somatostatin hypersecretion, increasing the risk of recurrent hypoglycemia.

Interacting electrons in Hofstadter bands can form symmetry-broken topological states. These are now revealed in magic-angle twisted bilayer graphene, and their properties are influenced by non-uniform quantum geometry.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Diffusion models are reframed by developing a generative blood cell classifier that performs reliably in low-data regimes, adapts to domain shifts, detects anomalies with robustness and provides uncertainty estimates that surpass clinical expert benchmarks.

Twisted multilayer graphene structures composed of Bernal-stacked constituents are predicted to host flat moiré bands for several layer-number combinations. Here, the authors find an array of band insulators, correlated insulators, and topological states with notable similarities across different constructions.

We report signatures of a generalized version of the anomalous Hall crystal in twisted bilayer–trilayer graphene, whose formation is driven by the moiré potential.

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.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

A global multi-taxon extinction risk assessment of freshwater fauna for The IUCN Red List of Threatened Species finds one-quarter of species to be at high risk of extinction.

Mechanistic modelling of the effects of diurnal temperature variation on Plasmodium falciparum sporogony indicates this variation is important in the laboratory, but further validation is required to assess its effect in wild mosquitoes.

While organic agriculture has been found to outperform conventional methods on multiple sustainability measures, this Article examines the effects of farm size on agroecological practices and finds that as organic farms get larger, they exhibit more conventional traits.

Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Mutations in the Wnt co-receptor, LRP5, lead to skeletal diseases in humans. Matthew Warman and his colleagues have now developed mutant mice with tissue-specific alterations of Lrp5 expression and found that these mice phenocopy the human skeletal diseases. They also found that Lrp5 acts locally to affect bone homeostasis. Their data suggest that increasing LRP5 signaling in mature bone cells may be a strategy to treat osteoporosis.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Patagia—the mammalian gliding membrane—repeatedly originated through a process of convergent genomic evolution, whereby the regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species.

Caloric restriction (CR) can extend the organism life- and health-span. Here, the authors show that mild caloric restriction enhances insulin sensititivy to promote beta cell health and longevity, through an optimization of energy metabolism and homeostasis pathways.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

Regulatory T cells (T_reg cells) can destabilize in inflammatory environments. Sumida et al. show that β-catenin signaling perturbs T_reg cell function in patients with multiple sclerosis and under experimental high-salt conditions.

Cryoelectron microscopy structures elucidate how full-length, natural affinity T cell receptors selectively recognize a peptide MHC antigen expressed in cancer cells.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

Mislocalisation of tau occurs in several neurodegenerative diseases and is thought to contribute to synaptic function. The authors show that presynaptically, tau binds to synaptic vesicles via the N-terminus which contributes to synaptic dysfunction.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Observations from the JWST MIRI/LRS show the detection of SO₂ spectral features in the 5–12-μm transmission spectrum of the hot, Saturn-mass exoplanet WASP-39b, suggesting that photochemistry is a key process in high-temperature exoplanet atmospheres.

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.

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.

Caffeine may reduce cardiovascular disease risk, but the underlying mechanisms for these effects are incompletely understood. Here the authors report that caffeine inhibits the activation of the transcription factor SREBP2 to promote LDLc clearance through the PCSK9-LDLR axis.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Lavas erupted from volcanoes in the north of the Hawaiian volcanic island chain have a different geochemical signature from those in the south. Analysis of the geochemistry of lavas erupted in the Samoan and Marquesas volcanic chains reveals similar trends, implying that the lowermost mantle beneath the southern Pacific is isotopically enriched.

Diffraction-before-destruction of ultrashort X-ray pulses can visualize non-equilibrium processes at the nanoscale with sub-femtosecond precision. Here, the authors demonstrate how the brightness and the spatial resolution of such snapshots can be substantially increased despite ionization.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

In the study, the authors identify a protein excreted by the parasite Trichuris muris, p43, which can modulate IL-13 function, a key cytokine involved in host protection. These data suggest that p43 may be a novel therapeutic target for both whipworm infections and IL13 mediated pathologies.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

Many individual genetic risk loci associate with multiple diseases, but the molecular basis of these loci often remains unclear. Here, the authors provide a framework to reveal the genetic cross-disease associations at the PROCR vascular disease locus.

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

Single-nuclear transcriptomic and proteomic analyses identify molecular characteristics shared by multiple classes of congenital heart disease, including phenotypes associated with insulin resistance.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.