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The authors describe the mechanism of exo-endocytosis coupling at synapses. They find that actin forms a ring around the region of exocytosis. This ring conserves membrane area, allowing induction of inward membrane buckling following exocytosis.

A comparative analysis of Cryptosporidium genome sequences elucidates the evolutionary history of these parasites and highlights changes associated with its human adaptation.

The authors construct a time-calibrated phylogeny spanning >90% of spiny-rayed fishes to explore patterns of body shape disparity within acanthomorphs. They find a trend of steady accumulation of lineages from the Cenozoic, with an increase in morphological disparity following the Cretaceous–Palaeogene event, facilitating the radiation of diverse morphotypes that characterize acanthomorphs’ widespread ecological success today.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Stem cells exert their beneficial effects through secretion of regenerative factors. Here, the authors take the membranes and secreted factors from cardiac stem cells and generate a synthetic cell-mimicking microparticle, which, on injection in a mouse model of myocardial infarction, improves cardiac function.

High-energy electron scattering that can isolate pairs of nucleons in high-momentum configurations reveals a transition to spin-independent scalar forces at small separation distances, supporting the use of point-like nucleon models to describe dense nuclear systems.

The aggregation of the neuronal protein α-Synuclein is associated with the onset of Parkinson’s disease. Here the authors report a two-dimensional Fragment Assisted Structure-based technique to find antagonists of α-Synuclein aggregation and show its promise for identifying lead therapeutics for Parkinson’s disease.

The endoplasmic reticulum-localized adaptor STING regulates the innate immune response through its ability to sense DNA damage. Here the authors reveal that STING functions as a regulator of cellular ROS homeostasis and tumor cell susceptibility to reactive oxygen dependent, DNA damaging agents.

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. Here, the authors identify a bipartite Nuclear Localization Signal in the NF-κB p50/p65 heterodimer that is recognized with high affinity by importin α3.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

TDP43 proteinopathies are a devastating group of neurodegenerative disorders. Here the authors show that RNA-targeting CRISPR effector proteins can be used to mitigate TDP-43 pathology when targeting ataxin-2, a modifier of TDP-43-associated toxicity, and apply this to a mouse model.

Protein complexes containing RNA polymerase II and immature RNA are associated with active genes immediately after replication, suggesting that transmission of active transcriptional states to daughter cells may not require any additional epigenetic bookmarks.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Faecal carbon:nitrogen measurements and manipulation of nitrogen availability via diet and host secretions in a murine model suggest that intestinal nitrogen limitation occurs due to host absorption and microbial use, leading to benefits for specific taxa.

Electron scattering measurements are shown to reproduce only qualitatively state-of-the-art lepton–nucleus energy reconstruction models, indicating that improvements to these particle-interaction models are required to ensure the accuracy of future high-precision neutrino oscillation experiments.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung spheroid cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung spheroid cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem cells.

Randomised controlled experiments are the gold standard for scientific inference, but environmental and social scientists often rely on different study designs. Here the authors analyse the use of six common study designs in the fields of biodiversity conservation and social intervention, and quantify the biases in their estimates.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

A study identifies 41 consensus gene expression meta-programs that are coordinately upregulated in subpopulations of malignant cells across tumour types, providing a comprehensive picture of hallmarks of intratumour heterogeneity.

Coordination of cell wall assembly is critical for bacterial morphology and survival. Here, the authors show that activation of cell wall synthesis by the Rod complex is regulated by the structural dynamics of RodA-PBP2.

Offshore mariculture could promote food security and economic development while sparing wild fisheries. This model-based study finds that the Caribbean could produce over 40 million metric tons of cobia (Rachycentron canadum), about half as much as the current global wild fish catch, and in less than 1.5% of the study area.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

Nicole Soranzo and colleagues report a meta-analysis of genome-wide association datasets identifying 22 associations to 8 clinically relevant hematological traits. They also identify a long-range haplotype at 12q24 that includes variants associated with platelet counts as well as coronary artery disease and shows evidence of a selective sweep in Europeans.

Optical observations of Dimorphos, a satellite of the asteroid 65803 Didymos, before, during and after the impact of the DART spacecraft, from a network of citizen science telescopes across the world are reported.

Iterative expansion microscopy enables the use of confocal microscopes to uncover nanostructures in expanded yet otherwise intact tissues at a resolution of about 20 nm, as shown with the imaging of periodic amyloid nanoclusters in brain tissue.

Whether changes in atmospheric circulation over West Antarctica during the past few decades are part of a longer-term trend is unclear. Ice cores reveal a significant increase in the oxygen isotopes from precipitation over the past 50 years, but the anomaly cannot be distinguished from natural climate variability.

SBS leads to severe morbidity and mortality. Here, using a xenotransplantation model, the authors uncover the role of zinc transport pathways in intestinal adaptation in SBS, highlighting the potential of zinc supplementation as a therapeutic approach.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Deep learning algorithms perform as well as humans in identifying cells in tissue images.

Using 25 years of satellite chlorophyll a data, the authors demonstrate significant and widespread changes in the amplitude, timing, duration and seasonality of Southern Ocean phytoplankton blooms. Such changes threaten ecosystem services and can impact global climate by altering natural CO₂ uptake.

CAR T cells targeting PSMA and engineered to be resistant to immunosuppressive TGFβ signaling exhibit dose-dependent toxicity and expansion following infusion, with some transient antitumor activity, in patients with metastatic castration-resistant prostate cancer

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

Multitrait genome-wide analysis of glaucoma and related phenotypes identifies new risk loci and enables development of a polygenic risk score to predict disease susceptibility and key clinical outcomes.

Ultrasound-based technologies are emerging as promising noninvasive approaches to treat brain disorders. Researchers in Switzerland have shown that chronic pain can be alleviated through thermal ablation of thalamic tissue by high-intensity focused ultrasound.

Little is known about the interaction of different ecological factors in shaping adaptive evolution in natural habitats. This study found that plants evolved local adaption to different soils, but only when they interacted with aphid- herbivores and bumblebee-pollinators.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

From profiling the gene expression of five coral species exposed to Stony Coral Tissue Loss Disease (SCTLD), this study finds signatures of in situ degradation of Symbiodiniaceae experiencing photosystem dysfunction. These results indicate that Symbiodiniaceae may be the target of initial SCTLD infection, which subsequently induces host responses and tissue loss.

SNAIL promotes tumour metastasis through inducing epithelial to mesenchymal transition (EMT). Here the authors report that SNAIL bypasses senescence and regulates cell cycle progression to promote pancreatic carcinogenesis and this is independent of EMT induction.

The membrane-proximal external region of HIV-1 spike protein is a broadly neutralizing antibody target. Here, cryo-electron microscopy and molecular dynamics reveal spontaneous ectodomain tilting, a vulnerability exploitable for vaccine design.

UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.

Two-dimensional electronic spectroscopy reveals the existence of intermolecular conical intersections in molecular aggregates relevant for photovoltaics.

A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.

Impact models projections are used in integrated assessments of climate change. Here the authors test systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.