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Immunotherapy is used to treat melanoma, however patient responses vary widely highlighting the need for factors that can predict therapeutic success. Here, the authors show that MHC-II molecules expressed by tumour cells are positively correlated with a good response to therapy and overall patient survival.

Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.

A ‘mouse atlas’, comprising single-cell transcriptomic data from more than 100,000 cells from 20 organs and tissues, has been created as a resource for cell biology.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

The respiratory complex I (NADH:ubiquinone oxidoreductase) is a large redox-driven proton pump that initiates respiration in mitochondria. Here, the authors present the 3.0 Å cryo-EM structure of complex I from mouse heart mitochondria with the ubiquinone-analogue inhibitor piericidin A bound in the active site and with kinetic measurements and MD simulations they further show that this inhibitor acts competitively against the native ubiquinone-10 substrate.

Exploring the diversity of the wild progenitor of the wheat D subgenome allows for rapid trait discovery.

Nitrogen-containing compounds play an indispensable role in medicine, agriculture and materials, but alkylated derivatives especially in sterically congested environments, remain a challenge to prepare. Here, the authors report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines.

Multi-electron redox chemistry is important in transition-metal-mediated processes, but is rarely observed with uranium due to its propensity to undergo single-electron reactions. Now, uranium can use its electrons, coupled with those stored in redox-active ligands, to perform multi electron reduction of organoazides and form uranium tris(imido) derivatives.

Nanopore sensors have long analysis times when analytes are at low concentration and non-specific signals in complex media. Here the authors use antibody-modified magnetic nanoparticles to detect prostate-specific antigen at sub-femtomolar concentrations in blood.

An increase in wildfire extent and related greenhouse gas emissions can be linked to abrupt climatic changes during the last glacial period.

BRCA2 and its interactor HSF2BP are required for meiotic recombination. Here, the authors define the interaction structurally, revealing that a repeat in BRCA2 binds two HSF2BP units, increasing the affinity. This region is, however, not essential for mouse meiosis.

DNA methylation from cell-free DNA (cfDNA) can be profiled using whole genome bisulfite sequencing (WGBS). Here, the authors develop a computational method, FinaleMe, that predicts DNA methylation and tissues of-origin in cfDNA and validate its performance using paired deep and shallow-coverage whole-genome sequencing (WGS) and WGBS data.

Case report of an individual heterozygous for a rare RELN-COLBOS variant that confers resilience, via a gain-of-function mechanism, to Alzheimer’s disease.

A single-cell transcriptomic atlas across the lifespan of the mouse, denoted Tabula Muris Senis, provides molecular information about the hallmarks of ageing in a range of tissues and cell types.

Bacteroides fragilis toxin expression induces goblet cell and goblet-cell-associated passage development during the pre-weaning period in mice, enabling B. fragilis to access a privileged lamina propria niche and evade competition with gut lumen bacteria.

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.

Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility and low dynamics cause gene repression.

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.

The understanding of how a singlet exciton separates into triplet states in organic semiconductors is crucial to the design of efficient organic solar cells. Here, Lukmanet al. identify the role played by charge-transfer states during triplet formation through side-group engineering of pentacenes.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here, the authors model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical and applied urban settings.

Plant community responses to climate change tend to be lagged in forests, but could be faster in grasslands. Here, the authors integrate long-term experimental data with >1 million occurrence records for >300 species, finding grassland community shifts towards species associated with warmer and drier conditions at a pace that aligns with that of climate change.

Justin Rubio and colleagues report results of a genome-wide association study of multiple sclerosis using cases from Australia and New Zealand. Their findings confirm several published risk loci for MS and identify two new risk loci on chromosomes 12 and 20.

Despite observations from a hot-water-drilled access hole showing warm ocean waters beneath Thwaites Glacier Eastern Ice Shelf, the basal melt rate is strongly suppressed due to the low current speeds and strong density stratification.

Hexa-acylated lipopolysaccharides from the gut microbiota are associated with efficacy in patients with cancer receiving anti-PD-1 and stimulate host immune activation for enhanced anti-tumour immunity in mouse models.

In a short-term study in which hearts from gene-edited pigs were transplanted into two recently deceased human recipients, the hearts were able to function for the duration of the study without signs of rejection and without evidence of pig virus transmission, encouraging further clinical study of cardiac xenotransplantation.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

In situ experiments have demonstrated chemotaxis of marine bacteria and archaea towards specific phytoplankton-derived dissolved organic matter, which leads to microscale partitioning of biogeochemical transformation in the ocean.

Serotonin inhibits adipose tissue thermogenesis. Here the authors show that obese mice housed in thermoneutrality have increased mast cell serotonin synthesis, and that inhibiting this pathway through deletion of mast cell Tph1 increases white adipose tissue browning and protects against diet-induced obesity, insulin resistance and liver steatosis.

Energetic constraints produce a fundamental tradeoff in starvation and recovery rates, impacting eco-evolutionary dynamics. Here, Yeakel et al. develop a nutritional state-structured model that predicts population size as a function of body mass known as Damuth’s law, and a mechanism for Cope’s rule, the evolutionary trend towards larger body mass.

Social learning through observing conspecifics can facilitate the acquisition of behaviors. Here, the authors show in Mongolian gerbils that auditory cortex is necessary for social learning of an auditory discrimination task, and that social exposure improves neuronal coding of auditory task cues.

New research examines disparities in renewable energy development on American Indian reservations relative to adjacent lands. Results highlight barriers contributing to these disparities and the scope for poverty alleviation, if eliminated, is quantified.

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.

The use of allosteric transcription factors (aTFs) as biosensors has been constrained by their limited natural ligand repertoire. Here, the authors report a method to screen large libraries of aTF variants to develop biosensors with altered specificities to non-native ligands.

Colitis is one of the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors. Here the authors show that a polygenic risk score for ulcerative colitis can predict immune checkpoint inhibitor-mediated colitis in patients with cancer.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

A new cryo-EM structure of the ~1 MDa Escherichia coli cellulose synthase macrocomplex reveals how cellulose biosynthesis and phosphoethanolamine (pEtN) modification are coupled to promote host-tissue adhesion.

Bacteriophage repressor proteins downregulate viral lytic gene expression. Herein, the authors present the X-ray crystal structure of a monomeric repressor that binds an asymmetric DNA sequence using two independent domains.

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.

ALS-linked mutations in FUS trigger defects within the nucleocytoplasmic transport pathway in human neurons and Drosophila. Aberrant interactions between FUS and nucleoporins are thought to underlie these defects.

Multimodal spatiotemporal transcriptomic resolution of palatal osteogenesis identifies previously unreported enriched genes in developing palate, paving the way toward viable diagnostic and therapeutic targets for cleft palate disorders.

Septoria tritici blotch (STB) is a devastating foliar disease affecting worldwide wheat production. Here, the authors report a cysteine-rich receptor-like kinase that can confer resistance to Zymoseptoria tritici, the pathogen that causes STB, and slow penetration and intercellular growth of the pathogen.

Harrington et al report their discovery of Nemacol, which is a small molecule inhibitor of the vesicular acetylcholine transporter (VAChT). VAChT loads synaptic vesicles with acetylcholine and is a key point of vulnerability in animals. Harrington et al show that Nemacol has nematode selectivity and potential utility against nematode parasites.

A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.

O’Shea and colleagues examine the three-dimensional chromatin architecture of the type 2 cytokine locus and how it differs between innate ILC2 cells and adaptive T_H2 lymphocytes.

Microorganisms are abundant in many environments and understanding their dispersal between ecosystems is important for ecology and conservation. These authors demonstrate that cyanobacterial populations are specific to hot or cold deserts and that gene flow between different populations does not occur.