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Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

To maintain genome stability, the specialised reverse transcriptase telomerase processively adds telomeric DNA repeats to chromosome ends. Here the authors reported structures of human telomerase at three stages of telomeric repeat synthesis, providing key insights into its mechanism.

Peroxidases have long been considered to use ferryl heme intermediates (Fe(IV) = O) to catalyze oxidative chemistries. Here, Williams et al. find that ferric-oxyl (Fe^III–O^•–) excited states exist along the catalytic reaction coordinate of a peroxidase.

The authors report a highly diverse Middle Ordovician Burgess Shale-type fauna from Wales (UK) that compares with the Burgess Shale and Chengjiang biotas in palaeoenvironment and preservational style.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.

Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

This Perspective synthesizes insights from the past use of nature markets to identify design factors that are necessary if such markets are to achieve their environmental aims—although qualitative scoring of existing markets against these rules identifies pervasive gaps.

Using survey data from over 3 million individuals, Geldsetzer et al. present evidence for cardiovascular disease risk factors among individuals living in extreme poverty in low- and middle-income countries.

Protein motion in crowded environments governs cellular transport and reaction rates. Here, the authors use megahertz X-ray Photon Correlation Spectroscopy to reveal anomalous diffusion of ferritin, linking hydrodynamic and direct interactions to cage-trapping at microsecond time scales.

Myeloperoxidase, a highly expressed neutrophil protein, disassembles nucleosomes, facilitating neutrophil extracellular trap (NET) formation, and binds stably to NETs extracellularly.

Structural studies of 16 native yeast ribosomal small subunit processome structures provide insights into the mechanisms governing the transformation into a pre-40S particle.

In this study, the authors show that autophagy controls blood cell differentiation in a Drosophila model of hematopoiesis. Notch activation depends on the endocytic pathway and promotes crystal cell differentiation, while autophagy reduces Notch accumulation via lysosomal destruction in a nutrient-dependent manner.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

In cross-sectional and longitudinal analyses of 86,149 participants across 27 European countries, Amoruso, Hernandez and colleagues identify multilingualism as a protective factor against accelerated aging, using biobehavioral age gaps.

This Perspective examines the design of non-volatile memristive analogue in-memory computing tiles for deep neural network accelerators, considering the challenges and opportunities associated with designing the different components and providing projections for how technology scaling may impact key design elements.

Cryo-EM structures of cytb₆f with quinone bound in the Q_n site allow the identification of specific proton channels and reveal differences to known inhibitors. Nearby water channels imply a ‘piston-like’ mechanism during catalytic turnover.

Analyses of the exposomes of populations across 40 countries found global disparities in healthy aging attributed to diverse biological, socioeconomic and political factors, with accelerated aging seen in populations from Egypt, South Africa, and Latin American and Caribbean regions.

Brain age gaps (BAGs) highlight deviations from healthy brain aging, yet their biophysical underpinnings in aging and dementia are not well understood. Here, the authors use EEG connectivity and generative modeling across diverse populations to reveal that BAGs are influenced by geography, income, sex and education, with implications for understanding accelerated aging and dementia.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Cells can simultaneously produce structurally dissimilar ribosomes, suggesting functional specialization of distinct ribosome populations. Here, the authors show that distinct ribosomes cooperate rather than specialize in protein synthesis.

Multiomic brain tissue analysis identified sex-specific molecular changes in Amyotrophic lateral sclerosis (ALS), revealing subgroups within the disease and pointing to the MAPK pathway as an early disease mechanism and potential therapeutic target.

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.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Here the authors use drug susceptibility data from Plasmodium falciparum field isolates in a pharmacometric model to evaluate cabamiquine and pyronaridine efficacy, both individually and in combination. The combined treatment shows over 90% parasite reduction in most simulated cases, providing valuable guidance for clinical dose selection in real-world settings.

_{Household survey data is vital to health and development. The study describes and maps data quality in 35 African countries, finding that data quality varies and worsens with distance from towns, indicating a need for investment in data collection.}

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Quasi-elastic neutron scattering measurements show the existence of a body-centred cubic structure, similar to that of ice VII, where water molecules exhibit picosecond rotational dynamic and rapid orientational jumps characteristic of liquid water.

JWST has revealed many prolate, filamentary galaxies at z ≈ 3–8. Hydrodynamical simulations reproduce this trend only in warm or wave dark matter models, where smooth filamentary accretion dominates over the hierarchical fragmentation seen with cold dark matter.

Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.

Synaptic loss contributes to cognitive decline in Alzheimer’s disease, but its spatial distribution remains poorly understood. Here, the authors show that synaptic loss is partially shaped by network connectivity and modulated by phosphorylated tau.

Regulation of gene expression and splicing are thought to be tissue-specific. Here, the authors obtain genomic and transcriptomic data from putamen and substantia nigra of 117 neurologically healthy human brains and find that splicing eQTLs are enriched for neuron-specific regulatory information.

Aspartate in the tumour environment activates the N-methyl-d-aspartate receptor in cancer cells to induce cellular programmes that increase the aggressiveness of metastasis.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Substitution of food produce from declining wild fisheries with farmed species may exacerbate prevalent micronutrient deficiencies in regions such as the urban Peruvian Amazon, as well as negatively impact agricultural land use and greenhouse gas emissions.

Amyotrophic Lateral Sclerosis is characterized by TDP-43 proteinopathy in the brain. Here, the authors find TDP-43 aggregation might be mediated by the loss of Asparaginase-like 1, an enzyme that degrades detrimental isoaspartates and is downregulated by the endogenous retrovirus HML-2.

Small molecule machine learning aims to predict properties from molecular structures. Here, the authors introduce the myopic MCES distance and show that frequently used datasets fail to uniformly cover biomolecular structures, limiting resulting models.

Speleothem records from caves in Arctic Siberia allow for the reconstruction of multiannual air temperatures during the late Miocene (8.68±0.09 million years ago). These temperatures suggest that Eurasia was mostly permafrost-free during that time.

Predictive protein design and experiments are combined to develop anisotropic bifaceted protein nanomaterials using pseudosymmetric hetero-oligomeric building blocks.

The γ-TuRC plays a central role for nucleation of microtubules at the centrosome. Here, the authors dissect structural mechanisms for centrosomal recruitment and regulation of the γ-TuRC and identify a role for centriole-lumenal γ-TuRCs.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Scaffolding protein ankyrin-B, implicated in cardiometabolic syndrome, enables mitochondrial fission and flexibility of nutrient utilization under energetic stress in skeletal muscle to support energy production and optimal exercise capacity.

Here the authors perform the reconstruction and analysis of pathological ALys amyloid fibrils extracted from fat tissue from a patient carrying the D87G variant. They reveal an intact amyloid fibril with no evidence of proteolysis and four intact disulphide bonds.