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International trade of used vehicles lacks regulation on emissions standards. This study shows that vehicles exported from Great Britain generate substantially higher carbon and pollution emissions than scrapped or on-road vehicles.

Spatially defined molecular functionality serves as the foundation to construct unique chemical space to further advance discovery science. Herein the authors report a third functional feature of t-BuSF enabled by carbamoyl torsional strain-release that further expands the S(IV) and S(VI) chemical space.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

Development of a constraint model specifically for mitochondrial DNA and applied to data from the Genome Aggregation Database provides insights into which sites in the mitochondrial genome are important for health and disease.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering insights for targeted regenerative therapies.

Design of cysteine-targeting analogs of a reversible SETDB1 triple Tudor domain (3TD) ligand, UNC6535, led to UNC10013, a potent covalent ligand with high selectivity. UNC10013 demonstrated allosteric inhibition of SETDB1-mediated Akt methylation in cells, a promising approach to SETDB1 therapeutics.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

The yields of edited primary human lymphocytes can be increased substantially, with respect to those obtained via electroporation, by delivering a CRISPR ribonucleoprotein alongside an amphiphilic peptide identified via screening.

Geospatial modeling analyses in Malawi identified HIV treatment deserts, clusters of communities with either very low or high levels of access to HIV treatment services, reflecting extreme geographic misalignment of healthcare resource allocation.

A high-throughput mutation-scanning method for interrogating sequence variation in antimicrobial peptides facilitates the understanding of sequence–structure–function relationships affecting the membrane selectivity of antimicrobial peptides.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

The presynaptic release probability is a major determinant of synaptic transmission in brain. Here, the authors show that a trans-synaptic signaling complex comprising presynaptic Neurexin-3 and postsynaptic dystroglycan controls the release probability of diverse inhibitory synapses.

Venusian basaltic crust cannot be thicker than 20–65 km without either causing delamination and crustal recycling or melting and producing volcanic eruptions. The thickest the crust can be is ~65 km for a thermal gradient of 10 °C/km.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The authors report data from the emergency department AURORA study to characterize resilience in more detail than the absence of psychopathology after trauma.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Chu et al. develop a monthly-calibrated photoplethysmography pipeline that leverages an implicit HbA1c with PPG signals to non-invasively estimate fasting blood glucose across three diabetic cohorts. Improved accuracy is seen over prior approaches, as assessed by mean absolute relative differences and Parkes Error Grid analyses.

In this Viewpoint article, several experts discuss the microbial contributions to climate change and consider the effects of global warming, extreme weather and other consequences of climate change on microbial communities in the ocean and soil, host–microbiota interactions and the global burden of infectious diseases and ecosystem processes, and they explore open questions and research needs.

The Antarctic midge, Belgica antarctica, is the only insect endemic to Antarctica. Here, the authors sequence the B. antarcticagenome, the smallest insect genome yet reported, and suggest that genes involved in development, metabolism and stimuli response may have had a role in how this insect adapted to survive in such a harsh environment.

mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.

This study shows that Earth system models disagree on the spatial distribution of plant-induced precipitation changes but indicate that plant responses are as likely to decrease runoff as they are to increase it under rising CO₂.

Non-neutralizing antibodies against the nucleoprotein (NP) of Crimean-Congo hemorrhagic fever virus are protective against lethal challenge in mice. Here, the authors show that these anti-NP antibodies protect through the intracellular antibody receptor TRIM21 and that protection is independent of T cells.

It has been previously shown that combining immune checkpoint inhibitors with TGFβ blockade potentiates anti-tumor immune responses. Here the authors show that, in an immune excluded preclinical tumor model, combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8 + T cells.

Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.

Seizures can occur in autism spectrum disorders (ASD). Here, the authors report that mice lacking the ASD related Ank2 gene show abnormal behaviours, and juvenile seizure related death, through impaired Kv7 potassium channel function.

JWST observations of GRB 221009A reveal the associated supernova, confirming that the GRB resulted from the collapse of a rapidly rotating massive star. The lack of r-process emission suggests that these extreme events are not key sources of the heaviest elements.

The power of pangenomic graphs to improve genetic mapping is still unclear. Here, the authors demonstrate its value in identification of genetic variants associated with disease resistance traits in melon using PanPipes, a pangenome construction and low-coverage genotype-by-sequencing pipeline.

A study reports the development of a structural derivative of amphotericin B with broad antifungal activity in mice but without the renal toxicity associated with amphotericin B.

Two small-molecule drugs, risdiplam and branaplam, have been developed for treating spinal muscular atrophy. Here the authors develop quantitative modeling methods for the sequence-specific and concentration-dependent effects of these and other splice-modifying drugs.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Histone H2AX is a central regulator in DNA repair. Here, the authors show that the H2AX C-terminal linker mediates recruitment of 53BP1, a mechanism which evolved to function independently of the canonical phospho-ubiquitin axis important for DNA repair regulation.

This study shows that conserving approximately half of global land area through protection or sustainable management could provide 90% of ten of nature’s contributions to people and could meet representation targets for 26,709 species of mammals, birds, amphibians, and reptiles. This finding supports recent commitments to conserve at least 30% of global lands and waters by 2030.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

The role of solar and wind energy (SWE) in management of water-food-energy (WFE) nexus is largely neglected. Here the authors developed a trade-off frontier framework to quantify the water sustainability value of SWE and applied it in California, where they found that SWE penetration creates beneficial feedback for the WFE nexus by enhancing drought resilience and benefits groundwater sustainability over long run.

A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1.

A neuroimaging study using repeated transcranial magnetic stimulation on unmedicated patients with depression reveals a link between response in the subgenual anterior cingulate cortex and clinical improvement.

Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.

The functions of small nucleolar RNAs (snoRNAs) in cancer remain to be studied. Here the authors show that the snoRNA Snord67 promotes lymph node metastasis of breast cancer cells through guiding modifications of the spliceosome and regulating the splicing landscape.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease group with CAR T cells offering therapeutic success in otherwise hard-to-treat cases. Here, authors study the in vivo expansion and persistence of CAR T cells in the peripheral blood of successfully treated DLBCL patients, demonstrating that two different CD8+ precursor phenotypes in the initial cell product give rise to two independent waves of clonally expanded CAR T cells with distinct phenotypes in peripheral blood.

This study examines the history of North Atlantic deep-water masses, as recorded in marine sediments. Major lithological changes and increased rate of deposition reveal that stronger deep-ocean circulation initiated 3.6 million years ago.

veloVI enhances RNA velocity analysis with uncertainty quantification and extensibility by deep generative modeling of gene-specific transcriptional dynamics.

Cryo-EM structures of somatostatin 14- and octreotide-bound somatostatin receptor 2 reveal a flexible extracellular domain for recognizing different ligands and, together with functional assays, identify the basis of SSTR subtype selectivity.

The molecular organization of exocytic vesicles regulates their transport and fusion. Prasai, Taraska, and colleagues use correlative light and electron microscopy, along with 3D tomography and gold labeling, to directly map proteins on single exocytic organelles at the plasma membrane.

Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.