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The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

Engineering a mutant-specific customized base editor precisely corrects a mutation while minimizing bystander edits, leading to substantial phenotypic recovery in mouse models of multisystemic smooth muscle dysfunction syndrome.

Ancient sedimentary DNA evidence shows that large blooms of the haptophyte algae Phaeocystis antarctica enhanced marine carbon uptake during the Antarctic Cold Reversal.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Klebanoff and colleagues report that survival and persistence of CAR-T and CAR-NK cells are regulated by a FAS ligand–FAS autoregulatory circuit, showing that disabling FAS signaling enhances their antitumor efficacy in preclinical models.

In schistosomiasis-endemic regions, the cyclical nature of infection and treatment complicates understanding of host immune responses. Repeated controlled human Schistosoma mansoni infection, designed to reflect the reinfection cycles common in endemic areas, shows that repeated exposure induces mixed worm-specific CD4⁺ T cell responses similar to those seen in endemic infection.

Identifying DNA lesions is key to assessing mutagenic activity. Here, the authors develop STEEL-seq, a method that maps single-stranded DNA breaks (SSBs) using a custom error-prone DNA polymerase. This approach reveals SSB enrichment near active promoters in the human genome.

The lysosomal enzyme beta-glucocerebrosidase is a key player and promising therapeutic target in Parkinson’s disease. Here, Dobert et al. leveraged cryo-EM to solve the protein structure of the enzyme in complex with its lysosomal transporter LIMP-2.

Explaining species richness patterns is a key question in ecology. Peterset al. sample diverse plant and animal groups across elevation on Mt. Kilimanjaro to show that, while disparate factors drive distributions of individual taxa, diversity overall decreases with elevation, mostly driven by effects of temperature.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

Time-resolved wide-angle X-ray scattering (TR-WAXS) using synchrotron radiation can be used to observe dynamic protein structural changes with nanosecond time resolution in solution, complementing time-resolved optical spectroscopy and Laue crystallography methods.

A randomized, double-blind, placebo-controlled phase 1b study evaluated the safety of the anti-oligomeric PRI-002 in 19 MCI or mild AD patients after 28 d of treatment. Overall, PRI-002 was well tolerated. While no biomarker changes or ARIA were detected, memory improved in the PRI-002 group.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

The authors measure numerous ecosystem functions across an elevational gradient on Mt Kilimanjaro and find that species richness impacts function more than species turnover across sites. They also show that variation in species richness impacts ecosystem functioning more strongly at the landscape scale than at the local scale.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

A ruthenium complex bearing a chemically and redox-non-innocent tetradentate diolefin diazadiene ligand is shown to be an efficient homogeneous catalyst for the conversion of a 1:1 mixture of methanol and water to hydrogen and carbon dioxide. Development of this process is an important step in the production of hydrogen for use as a fuel from biomass.

Hookworm infection remains a threat to public health where economic factors restrict treatment and lack of effective vaccination have limited successful therapeutic control which results in reinfection in endemic areas. Here the authors use a controlled human hookworm infection model and use high dimensional single cell profiling to show that plasmacytoid dendritic cells and regulatory T cells profiles that resemble those seen during natural infections in endemic areas.

Borna disease virus 1 (BoDV-1) is a zoonotic pathogen endemic in bicoloured white-toothed shrews in Central Europe that can cause fatal encephalitis in humans and other mammals. Here, the authors investigate the molecular epidemiology and phylogeography of BoDV-1 using newly collected and archived samples.

Using a curated dataset of 2,400 cases and a framework to simulate a realistic clinical setting, current large language models are shown to incur substantial pitfalls when used for autonomous clinical decision-making.

Neurodegenerative diseases are linked to changes in the immune system and inflammation. Here, the authors studied immune cells from healthy individuals and neurodegenerative diseases and identified sex-specific disease-associated changes.

Quantum error correction is essential for reliable quantum computing, but no single code supports all required fault-tolerant gates. The demonstration of switching between two codes now enables universal quantum computation with reduced overhead.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

Gelabert et al. examine genomic and archaeological data from Europe’s earliest farming communities in Central Europe (5500–5000 bce). They find differentiated genetic networks but no evidence of unequal access to resources linked to sex or kin.

The soft-grainy microstructure of cooked egg yolk is the result of a series of out of equilibrium processes of its protein-lipid contents. Here, the authors develop a time-temperature phase diagram that shows the coupling of the nanoscale processes that result in the grainy-gel microstructure of cooked egg yolk.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

A gene therapy phase 1 trial in patients with β-thalassemia shows transplantation of autologous CD34⁺ cells transduced with a lentiviral globin vector after reduced-intensity conditioning achieves long-term engraftment, albeit not transfusion independence, with benign clonal expansions, warranting cautious monitoring of patients.

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

Baculoviruses are used as insecticides, gene therapy tools, and protein production vectors. Here, the authors report the structure of the Autographa californica MNPV nucleocapsid and its fold conservation across all baculoviruses.

Parkinson’s disease is lacking easily accessible biomarkers. Here the authors show, that targeted blood proteomics is feasible to identify the patients and to predict the phenoconvertion in prodromal subjects up to 7 years before symptom onset.

Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.

The TREK K_2P channel activity is dynamically regulated by protein kinase-dependent signaling pathways involved in the development of various human diseases. Here, the authors report how phosphorylation at the proximal C-terminus induces allosteric deactivation of the selectivity filter gate.

Mass spectrometry and structural studies demonstrate the specific changes in protein composition that accompany the transition of ribosomes in zebrafish and Xenopus eggs from a dormant to an active state during early embryogenesis.

The response of marine species to the Pleistocene climate change is largely unknown. Foote et al. find that the bowhead whale tracked shifting habitat at the end of the Pleistocene and increased in effective population size as suitable habitat and population connectivity increased.

SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1’s role in muscle homeostasis, offering insights for new therapeutic strategies.

An ensemble of climate model simulations, as well as hydrological modelling and flood risk mapping, are used to show the role of anthropogenic warming on the extreme rainfall that caused the 2013/14 floods in southern England.

The European X-ray FreeElectron Laser Facility generates ultrashort hard X-ray pulses with megahertz repetition rate. Here, the authors probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy at the European XFEL.

Infection or chronic inflammation is a risk factor for childhood B-cell precursor acute lymphoblastic leukemia. Here, the authors show that the DNA editing enzyme AID is expressed in infected B cells but using genetic mouse models show that it does not contribute to leukemia pathogenesis.

Legal cases to force governments to reduce emissions or to pursue compensation for climate change-related losses are increasing. The scientific evidence used in such cases is found to be lagging behind state-of-the-art climate science; using up-to-date methodologies could improve causation claims.

The authors use interacting internal wave theory and global observational databases to calculate the turbulent energy rate available for ocean mixing, which is a critical metric for climate prediction that is still lacking rigorous understanding.

Click editing uses DNA polymerases, HUH endonucleases and oligonucleotide templates for genome modification.