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This Commission aims to resolve the current dialysis policy challenges in Thailand and generate lessons for the global kidney community by drawing on empirical evidence, systems thinking and multidisciplinary expertise to generate policy goals and recommendations.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Oat consumption, particularly a short-term, high-dose oat diet, improves metabolic health in individuals with metabolic syndrome by increasing microbially produced phenolic metabolites, leading to lower blood cholesterol levels.

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.

Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England.

The authors describe the discovery of a series of potent non-competitive allosteric inhibitors of the ZIKV NS2B-NS3 protease, which exhibit antiviral activity in vitro and robust oral efficacy against ZIKV infections in a mouse model.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

In a case series of five patients with treatment-refractory antisynthetase syndrome and five patients with treatment-refractory systemic sclerosis, bispecific T cell engagers blinatumomab and teclistamab improved disease activity and were well tolerated.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

This study reveals diverse soil nematode community patterns across Atacama habitats, including dunes, high elevation mountains and fog oases. Latitude, rainfall and elevation were found to be associated with diversity and reproductive modes.

GATA6 maintains epithelial traits and limits EMT in pancreatic cancer. Combined MEK and HDAC inhibition restores GATA6+ tumor cells, boosting MHCI expression and CD8+ T cellmediated anti-tumor immunity.

Sepsis causes endothelial dysfunction that drives vascular failure and organ injury. Here the authors show that neutralizing truncated procalcitonin reduced pro-inflammatory activation and leakage in the endothelium, resulting in preserved organ integrity, improved clinical outcomes and predicted survival in septic mice.

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.

Contact matrices are used to describe social mixing patterns and inform mathematical models of disease transmission. Here, the authors evaluate the accuracy of synthetic contact matrices generated using mobility data compared to those derived empirically through surveys.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A large sulfur-bearing carbon ring molecule has been detected in space, 2,5-cyclohexadien-1-thione, using laboratory spectroscopy and a radio telescope. Found near the Galactic Centre, it opens the door to a new family of interstellar molecules.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Pender et al. evaluated depression and anxiety symptom trajectories in autistic adults receiving routine therapy in UK primary care.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

It remains elusive whether the T cell repertoire will cover all point mutations of a major epitope. The authors here show that COVID vaccine–induced CD8⁺ T cells detect most YLQ peptide variants except R5, but naïve T cells fill this gap by responding to R5 despite abundant WT-specific cells, ensuring broad coverage to prevent viral immune-escape.

Anti-tumor functions of low-avidity T cells are often suboptimal. Here the authors show that genetic disruption of TIGIT in TCR-engineered T cells enhances their anti-tumor activity against pancreatic and other gastrointestinal cancers by increasing TCR signal strength.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Behaviour changes, rather than vaccination or postinfection immunity, best explained the sudden decline of mpox cases among men who have sex with men during an outbreak in the Paris region in 2022, according to a network model and survey data.

This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

Nature's approach to biosynthesis often involves the rapid generation of advanced, enantiopure intermediates from simple starting materials. A new, highly efficient strategy adapts this approach, using organocascade catalysis to quickly construct a key intermediate that can be converted into several complex natural products.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Grazing affects plant diversity, but plant diversity in turn may modulate the effect of grazing on the plant community. This global analysis explores the association between plant species richness and plant cover resistance to grazing intensity in drylands.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Ventures focusing on gene therapy, adoptive T-cell therapy, protein homeostasis and the microbiome are among those selected by the editors in 2013's crop of startups.

Standard of care in patients with unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy followed by immunotherapy. Here, the authors report a phase II trial investigating induction chemo-immunotherapy (atezolizumab, carboplatin and paclitaxel) followed by concurrent chemoradiotherapy and immunotherapy maintenance in patients with stage III NSCLC.

The authors propose a Generalized Latent Equilibrium framework for fully local credit assignment in physical, dynamical neuronal networks such as the brain. By exploiting dendritic structure and prospective coding in cortical neurons, it enables an online approximation of backpropagation through space and time.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

Cell surface receptors perceive immunogenic elicitors, triggering downstream signalling via receptor-like cytoplasmic kinases such as BIK1. Here the authors define and use the phosphorylation motif of BIK1 to find novel substrate candidates.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.