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Researchers reveal that TNF alpha unmasks a metabolic impairment in the enteric malate-aspartate shuttle. This dysfunction acts as a key pathological bridge linking intestinal inflammation to the neurodegeneration seen in Parkinson’s disease.

Enteroendocrine cells in the gut sense food to regulate feeding behavior. Here, the authors show in Drosophila L-glutamate reduces the frequency of calcium oscillations in enteroendocrine cells and decreases the release of NPF, thereby reducing the activation of a pair of anorexic enteric neurons.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

Skeletal muscle cells are multinucleate, and improper positioning of the nuclei contributes to muscle dysfunction.

Chronic lymphocytic leukemia is an indolent disease, and many patients succumb to infection rather than the direct effects of the disease. Here, the authors use medical records and machine learning to predict the patients that may be at risk of infection, which may enable a change in the course of their treatment.

Veiga-Fernandes and colleagues show that neuroepithelial interactions differentially control type 1 and type 2 enteric immunity via VIP–VIPR1 signaling.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

Riboswitches are allosteric RNA molecules that change conformation upon ligand binding to regulate downstream genes. Here, the authors use Restricted Boltzmann machines trained on natural sequences to design new riboswitch aptamer domains, and validate their functionality via chemical probing.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

An observational study of more than 13,000 healthcare workers shows that a prime–boost vaccine regimen of AstraZeneca ChAdOx1-S-nCoV-19 with Pfizer BNT162b2 provides enhanced protection against SARS-CoV-2 infection compared with two doses of BNT162b2.

On Titan, stratospheric polar clouds form each autumn from cooling and chemical changes, evolve in altitude and composition through winter, and then vanish in spring. A repeating cycle that shapes Titan’s climate and predicts the next cloud in 2027.

The interaction between MyD88 and ERK is necessary for RAS-dependent transformation and cancer cell survival. Here, the authors identify benzimidazole compound EI-52 as a disrupter of this interaction and demonstrate its therapeutic efficacy in tumours via ERK dysregulation and the induction of immunogenic cell death.

The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.

Phylogenomic and genetic analyses identify an ancestral module of genes expressed specifically in ciliated left–right organizer tissue and required for left–right axis specification in humans and certain vertebrates.

Monitoring of co-infections of SARS-CoV-2 variants is important to evaluate their clinical impact and the risk of emergence of recombinants. Here, the authors develop and validate a methodological pipeline to detect co-infections and apply it to samples from France in early 2022, when Delta and Omicron were co-circulating.

Adrenocortical carcinomas (ACC) are aggressive and often resistant to therapy. Here, the authors provide a single-nucleus transcriptomic atlas of ACCs and normal adrenal glands, finding ecotypes in steroid and microenvironment cells that are associated with clinical outcomes.

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development remains unknown. Here, the authors show that JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

The retina is known to strongly respond to omitted stimuli in periodic patterns. Here the authors propose that depressing inhibitory synapses shape the timing of such a response and are key to perform temporal pattern recognition in neural networks.

The authors combine field data with models of coastal geomorphology and bird behaviour and dynamics to understand the impact of sea-level rise on shorebird populations. They show that habitat quality is already declining and that the current focus on habitat quantity loss can underestimate threats.

The use and characterization of graphene quantum dots is limited by their pronounced tendency to form aggregates. Here, the authors synthesize rod-shaped motifs of nanographenes with up to 132 sp² carbon atoms that are fully individualized, which allows the precise description of their intrinsic photophysical properties.

Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.

Prior work has identified a male-only effective population size bottleneck 3-5000 years ago. While violent competition has been proposed as a cause, the authors here show that a segmentary patrilineal system with lineal fission provides a peaceful alternative explanation.

Applications of spontaneous symmetry breaking are hindered by unavoidable imperfections. Here, the authors reveal how a phase defect provides topological robustness to this process, enabling a bias free realization without fine tuning of parameters.

Felix Beuschlein, Martin Reincke and colleagues identify recurrent somatic mutations in ATP1A1 and ATP2B3 in aldosterone-producing adenomas with wild-type KCNJ5. The ATP1A1 and ATP2B3 mutations alter conserved residues and lead to impaired sodium, potassium and calcium ion homeostasis.

Oystercatchers are socially and sexually monogamous birds, but a new study reflects another side to their lifestyle. Occasionally, an usurping female will try to break up a pair, and, after fighting with the resident female, she may stay to form a polygynous trio. The male is mated by both females, and they cooperate to defend their territory and raise a brood. Although polygyny is very rare in oystercatchers, the authors suggest that both females benefit in terms of elevated social status.

Invariant natural killer T (NKT) cells are defined into subset based on transcription expression and cytokine production, but differences in the subset distributions of these cells are seen between inbred mouse strains. Here the authors show that CD1d mediated TCR signals along with intrinsic signals impact this strain specific difference in the composition of the NKT cell compartment.

Despite advances in cardioprotection, new therapeutic strategies precluding ischemia-reperfusion injury of patients are still needed. Here, the authors show that preventing serine 663 phosphorylation of SERCA2, significantly increases its activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca²⁺ overload.

Most morphological visualization platforms are not designed to share research data, or are limited to data visualization. Here the authors present MorphoNet, an open-source, web-based tool for interactive visualization and sharing of complex morphodynamic datasets, onto which users can project their own data.

A comparison of the evolutionary history and geographical spread of the antimicrobial-resistant pathogen Staphylococcus capitis in neonatal intensive care units indicates that acquisition of antibiotic resistance and increased competitiveness have led to the success of the NRCS-A S. capitis clone.

It is shown that the supply of fresh plant-derived carbon to deep soil layers stimulated the microbial mineralization of carbon that is thousands of years old, and is suggested that a lack of supply of fresh-carbon may prevent the decomposition of the organic carbon pool in deep soil layers in response to future changes in temperature.

To modulate gene expression, the glucocorticoid receptor binds to response elements (RE) that vary in sequence. Here, the authors show that RE sequences can modulate glucocorticoid receptor structure and activity, which might provide regulatory specificity towards individual target genes.

Multimodal label-free nonlinear microscopy and advanced image analysis map single-cell metabolism and myelin dynamics in live cerebellar tissue during demyelination, supporting research in neuroinflammation and neurodegeneration.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

Socially synchronized rhythms in shorebirds were assessed during biparental incubation under natural circumstances and were exceptionally diverse, often not following the 24-h day, whereby risk of predation, not starvation, determined some of the variation in incubation rhythms.