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An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

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.

Wastewater surveillance can be used to track infectious diseases. A six-plex digital PCR assay is shown to provide information on four respiratory diseases at the same time, with data that have a high level of agreement with reported case numbers.

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

Mechanosensitive ion channels protect bacteria from a hypoosmotic shock. Here, Flegler et al. use electron microscopy to describe the gating transition of the MscS-like channel YnaI and a chimera generated from MscS and YnaI.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

A large language model designed for health monitoring provides personalized sleep and fitness predictions, insights and advice.

Two BCMA-targeted CAR T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved for the treatment of multiple myeloma (MM). Here the authors report distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in a realworld cohort of patients with MM.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Saur and colleagues perform a high-throughput combinatorial drug screen and identify a synergistic combination between nintedanib and trametinib that sensitizes mesenchymal PDAC to immune checkpoint blockade.

Lymphostatin is a large protein required for Escherichia coli virulence. Here, Griessmann et al. use electron cryo-microscopy to describe the structure of lymphostatin determined at different pH values, showing three conformations, six distinct domains, and long inter-domain linkers that occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains.

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.

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.

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.

Here the authors generate a capsid-like particle based vaccine candidate displaying the receptor-binding domain of the SARS-CoV-2 spike protein and show induction of neutralizing antibodies after intramuscular prime-boost immunization in mice.

Parks, Schneider et al. show that brain states like sleep and wake can be reliably detected from milliseconds of neural activity in local regions in mice. Regions can briefly switch states independently, coinciding with fleeting behavioral changes.

Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Rare mutations in the high requirement temperature protein A1 (HTRA1) cause cerebral vasculopathy. Here, authors establish mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the assembly and protease function of HTRA1.

In Gram-positive bacteria, arginine phosphorylation by the McsB kinase functions as a general post-translational marker for Clp-mediated proteolysis.

High-quality annotation of datasets is critical for machine-learning-based biomedical image analysis. However, a detailed examination of recent image competitions reveals a gap between annotators’ needs and quality of labelling instructions. It is also found that annotator performance can be substantially improved by providing exemplary images.

This study identifies candidate safeguard repressor transcription factors that repress alternate lineages in mature cell types and provides functional evidence that Prox1 performs such a function in hepatocytes during reprogramming, regeneration and in cancer.

JWST–NIRSpec spectroscopic confirmation of two luminous galaxies is presented, proving that luminous galaxies were already in place 300 million years after the Big Bang and are more common than what was expected before JWST.

A large-scale genomics study shows that the cell of origin and founding mutations determine disease subtype and lead to the expression of multiple haematopoietic lineage-defining antigens in mixed phenotype acute leukaemia.

The cellular RNA polymerase II C-terminal domain is known to support transcription of influenza virus mRNAs. Here, Krischuns et al. use cell-based and in vitro approaches to demonstrate that it also plays a role in replication of the viral genome.

Genetically encoded sensors have been developed and become versatile tools for imaging serotonin dynamics. Here, authors developed a family of serotonin (5-HT) sensors (sDarken), three variants with different affinities for 5-HT enable high spatiotemporal resolution of 5-HT dynamics.

Ectonucleotidases associated to regulatory T cells are known modulators in the inflammatory environment. Here the authors describe CD8 T cell-derived extracellular vesicles bearing CD73 and suggest they function as an additional intrinsic modulator of immune responses.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Wartewig et al. show that PDCD1 in T cell lymphoma restricts glycolytic energy and acetyl-CoA production. Inhibition of PD-1 signaling enforces ACLY activity and generates extramitochondrial acetyl-CoA for histone acetylation to enable AP-1 hyperactivation.

Multidomain RNA-binding proteins recognize specific target sequences through mechanisms that are not well understood. Here the authors present an integrated approach to define the RNA-binding specificity and RNP topology and apply it to the analysis of the prototypical multidomain RNA-binding protein IMP3.

The insatiable demands of the pharmaceutical industry are helping to drive labs into the automated world of industrial production lines. Tim Chapman joins the quest for speed.

Due to increasing disturbance of peatlands, Southeast Asian rivers are thought to play a major role in the transfer of CO₂to the atmosphere. Here, the authors present data collected from six Indonesian and Malaysian rivers and show that the region is not an outgassing hotspot as previously assumed.

The influenza virus genome replication complex comprises two viral polymerases and host factor ANP32. Structural studies reveal the complex architecture for influenzas A and B, demonstrate the chaperone role of ANP32 and explain polymerase mutations required for avian to human interspecies transmission.

The heparan sulfate proteoglycan-binding cytokine APRIL has a protective role against atherosclerotic disease.

Certain oxidative DNA lesions adopt altered conformational preferences that lead to mutations during replication. Biochemical and structural data reveal that for formamidopyrimidine lesions, tautomerization and altered base pair geometry in the DNA polymerase active site, rather than changes in glycosidic torsion angle, direct the mutagenicity of these lesions.

The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .