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Pathogenic BRCA2 truncating variants in heterozygosis drive distinct cancer-linked mechanisms. Here the authors show that one causes PARPi sensitivity and HR loss via haploinsufficiency, while another expresses a truncated protein that rewires transcription by hijacking PCAF, reducing H4 acetylation and NF-κB activity.

The mechanisms generating the head direction cell signal in rats are not fully understood. Here, two distinct types of head direction cells in the lateral mammillary and dorsal tegmental nuclei were identified: one type is angular head velocity independent, while the second type depends on the animal’s angular head velocity.

The spontaneous emergence of autocatalytic RNAs is central to origin of life. Here, the authors use machine learning, high-throughput screening and statistical physics to explore large neutral space of catalytic RNAs.

Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

Errors in oocyte division can cause infertility and birth defects. Here, authors combine a genetic strategy with a novel optochemical tool to show that spindle pole-localized F-actin is essential for proper meiotic spindle assembly and chromosome segregation.

While our brain is primarily composed of lipids, their functions have largely remained unexplored. Here, authors show that specific lipids can be linked to the structural organization and functional hierarchy of the human and macaque brain.

The Macaque Biobank initiated by Zhang et al. provides a comprehensive genetic and phenotypic characterization of Chinese rhesus macaques (CRMs). This resource enhances our understanding of the genetic diversity of CRMs and holds potential for biomedical research.

Vinyl acetate is an important polymer building block, but the mechanisms governing its catalytic production are not well understood. This study shows that dynamic palladium-acetate clusters determine catalyst efficiency and selectivity in vinyl acetate synthesis.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

HIV-1 integrase is critical for viral DNA integration and RNA packaging at distinct stages of the replication cycle. Here, authors report structures of integrase assemblies, revealing how structural plasticity imparts the protein with dual functionality.

The authors show that a bacterial histone, HLp from Leptospira perolatii, forms tetramers that wrap and compact DNA, revealing an unexpected mechanism by which bacteria organize their genetic material.

Infection may induce multi-organ thrombosis, but the underlying inflammatory mechanism remains elusive. Here, using Salmonella Typhimurium infectious mouse model, the authors reveal organ specific and broad inflammatory events like TNF for thrombosis in liver and spleen.

Authors demonstrate that four distinct heterodimeric complexes catalyze chondroitin sulfate chain polymerization in humans. The synthase proteins possess catalytic activity, while the polymerization factors are essential for complex formation.

The detection of the auroral footprint of Jupiter’s moon Callisto is challenging, but a shift in Jupiter’s bright main auroral oval could provide an opportunity for potential detections. Here, the authors show observation of the ultraviolet footprint of Callisto using Juno spacecraft data, benefiting from such opportunity.

Here, the authors investigate gene dosage compensation in mouse pluripotent stem cells to better understand the process of X-chromosome upregulation. They report that mammalian cells can sense when segments of one of the two X chromosomes are genetically deleted in cis and compensate gene expression by upregulation in trans.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Here, the authors present archaeology of the Namorotukunan site in Kenya’s Turkana Basin that demonstrates adaptive shifts in hominin tool-making behaviour spanning 300,000 years and increasing environmental variability. They contextualize these findings with paleoenvironmental proxies, dating, and geological descriptions.

In this work, researchers address a key question for maternal group B Streptococcus (GBS) vaccine assessment: What newborn antibody concentrations protect against invasive infant GBS disease? They present serologic thresholds by age at onset and serotype based on a large U.S. case-control study.

The alveolar bone supports the tooth’s lifelong functionality. Here, the authors identify a tooth-specific mechanism of bone formation in which the Hedgehog–Foxf pathway regulates the alveolar bone osteoblast fates of DF progenitor cells.

This Analysis illustrates how nature-positive targets aimed at protecting biodiversity can be achieved at the scale of organizations. A canteen at one UK university college is used as a case study for the application of a four-step participatory approach comprising an estimation of food-related biodiversity impacts; definition of biodiversity targets; assessment of possible interventions; and exploration of different strategies.

This study reveals how infections that increase long-term dementia risk can contribute to longitudinal brain volume loss and regulate immunological proteins in plasma, and which of these proteins may drive infection-specific neurodegeneration.

Electronic health records are a rich source of clinical data but identifying associations with outcomes is complex. Here, the authors propose a modelling framework ‘InfEHR’ that identifies patient trajectories in electronic health records and generates a likelihood for clinical phenotypes.

Understanding asteroid materials is critical for determining deflection methods for planetary defense. Here the authors show, via experiments performed in High-Radiation to Materials facility at CERN, that iron-rich asteroid materials can absorb more energy without structural failure than standard material parameters would suggest.

The TRPM7 channel enables endosomal acidification, which is vital for the entry of many enveloped viruses. Here, the authors show that loss of TRPM7 protects cells from various pandemic-threat viruses, pointing to a new strategy for broad-spectrum antiviral drugs.

CO oxidation catalysts face a tradeoff between high activity and stability due to oxidation-induced deactivation. By trapping Pt clusters at stepped CeO₂ pockets, this work circumvents the stability-activity dilemma.

This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

To what extent regeneration recapitulates embryonic development is a longstanding question. Here, they show that embryonic gene modules are re-used, rewired, and interconnected to specific injury-induced down-stream targets during regeneration.

The authors study epitaxial thin films of the pyrochlore-sublattice compound LiTi2O4 by RIXS and ARPES. They observe cooperation between strong electron correlations and strong electron-phonon coupling, giving rise to a mobile polaronic ground state in which charge motion and lattice distortions are coupled.

Argonaute proteins degrade specific invader nucleic acids in eukaryotic and prokaryotic innate immunity. Here, Kanevskaya et al. describe a bacterial immune system in which RNA-guided recognition of invader DNA by Argonaute triggers formation of HNH nuclease filaments with collateral activity, protecting the bacterial population from invaders.

Researchers analyzed 5,279 plasma proteins in 40 people undergoing feminizing gender-affirming hormone therapy over 6 months, revealing significant changes in 299 proteins. Such changes could have implications for reproductive capacity, immune regulation and long-term health.

Benefits on health have been found to vary across different levels of physical activity (PA) for chronic conditions including cancer. Here the authors report that each minute of vigorous intensity PA is equivalent to various minutes of moderate and light PA in terms of all-cause, cardiometabolic disease and cancer mortality outcomes in a device-based population.

Early experiences shape cognition. Here, authors show that early environmental enrichment or deprivation alters cognition in mice, linked to gene expression and chromatin changes in hippocampal excitatory neurons, with AP-1 as a key regulator.

Epigenome editing programs gene silencing without inducing DNA breaks but challenges in delivery into human cells limit its broader use. Here, the authors present the RENDER platform, which uses virus-like particles to enable CRISPR-based epigenome editing for durable gene silencing in human cells.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Using a novel method for isolating cognitive and motor neural dynamics, the authors show that dynamics often attributed to cognitive processes were corrupted by movements and that distinct populations of neurons encode cognitive and motor variables.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Dissecting the effects of hypothermic and hypometabolic states on aging processes, the authors show that activation of neurons in the preoptic area induces a torpor-like state in mice that slows epigenetic aging and improves healthspan. These pro-longevity effects are mediated by reduced T_b, reinforcing evidence that T_b is a key mediator of aging processes.

Rossi and colleagues assemble an in vitro enzymatic pipeline using enzymes from distinct domains of life to recapitulate eukaryotic N-glycosylation. This work advances the synthesis of bespoke glycopeptides with biomedical and biotechnological applications.

Field induced tunneling is one of the fundamental processes of light-matter interaction. Here the authors reconstruct the  temporal properties of tunneling using two-color electron holography with attosecond time resolution using argon atoms.

Sargassum biomass in the north Sargasso Sea declined drastically since 2015, co-occurring with related reductions in the northwest Gulf of Mexico and an expansion of the Great Atlantic Sargassum Belt, according to in situ and satellite observations.

Bond et al. predict mechanism of action of hit compounds from a pooled screen of Mycobacterium tuberculosis mutants underproducing essential proteins by comparing the strain-specific responses of screening hits to those elicited by known antimicrobials.

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.

Jupiter’s magnetodisk mediates mass, momentum, and energy exchange between Jupiter’s atmosphere, ionosphere, magnetosphere, and moon tori. Here, the authors show that pressure anisotropy-driven instabilities regulate its nonequilibrium dynamics.

Li et al. introduced tract-geometry coupling (TGC) to quantify the coupling between white matter tracts and cortical geometry in the human brain, shedding light on how the brain’s wiring and shape evolve together and its support for behavior and growth.

A two-component system, DbfRS, regulates biofilm formation in Vibrio cholerae. Here, Nguyen et al. identify a small periplasmic protein that controls the activity of the system’s receptor, and show that DbfRS responds to membrane stress and regulates additional processes such as metabolism and cell envelope biosynthesis.

Across 13 longitudinal studies (3,737 adults), the authors show that brain atrophy parallels memory loss, with a stronger coupling in later life. APOE ε4 increases decline, yet genetic risk does not modify the brain–memory relationship.