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Although river protection is core to social and environmental well-being, the extent to which river conservation policies are effective is difficult to assess. This study reveals that, under all relevant protection mechanisms in the contiguous USA, only 12% of rivers are adequately protected.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

A cortical premotor network in HVC, once initiated, can sustain and regulate the sequential production of zebra finch song syllables without major extrinsic inputs.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

An alternative mating system, termed parasex, produces progeny with high levels of genotypic diversity and is able to fulfil the roles of meiosis when it is absent in the fungal pathobiont Candida albicans.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

He et al. elucidated that TREM2 is essential for sulfatide loss-induced microgliosis, but not astrogliosis, myelin lipid disruption, or behavioral deficits in Alzheimer’s disease (AD), suggesting that lipidome and astrocyte homeostasis may be key in slowing AD progression.

The links between meat production and immunity in cattle can affect agricultural production. Here, Li et al. identify genetic and environmental factors that shape immune responses in cattle, which can guide breeding for improved health.

CELSR1 is a core component of the tissue/planar cell polarity pathway. Here, the authors report a CELSR1-related disorder featuring brain malformations, neurodevelopmental delay and epilepsy, and use mice to explore the pathophysiological mechanisms.

The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

Melting from the Greenland Ice Sheet triggers land uplift beneath the ice sheet and changes to Earth’s gravitational field and rotation axis, a process called Glacial Isostatic Adjustment. Lewright et al. find that this process will lead to a local sea level fall along Greenland’s coast over this century.

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

The somitic mesoderm is seen as the main source of brown adipose tissue, although some depots are of partially unknown origin. Here, the authors show that Osr1 labels multipotent dorsal aorta progenitors at E9.5 that contribute to cartilage, muscle, and adipose tissues, revealing a non-somitic contribution to several brown adipose depots.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

Ramaglia and colleagues show that aberrant formation of B cell-rich lymphoid structures in the brain meninges is associated with high CXCL13:BAFF ratios. Inhibiting the kinase BTK reduces the lymphotoxin signaling needed to sustain such structures, lowers CXCL13:BAFF ratios and reduces cortical tissue injury.

This study shows that high-molecular weight tau has enhanced seeding capacity, and seeding differences can define molecular subtypes of progressive supranuclear palsy, underpinning the disease’s heterogeneity.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

In vitro models using tissue-specific progenitors recapitulate the lumen with gland-like structures and functional characteristics of the human stomach epithelium in a patient-specific disease model.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

The authors developed an LXR inverse agonist, TLC-2716, and show it is effective in reducing triglycerides and cholesterol in dysmetabolic preclinical models. Additionally, a phase 1 trial in healthy participants shows that TLC-2716 is well tolerated and reduces plasma triglycerides and postprandial remnant cholesterol, highlighting its potential for managing cardiovascular risk.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

With its attribution to Paranthropus, a 2.6-million-year-old partial mandible expands the range of the genus into the Afar region of Ethiopia and adds to our understanding of hominin evolution in eastern Africa.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Nagahata, Kato and Yamada et al. provide cryo-electron microscopy structures of four phylogenetically diverse RNA-guided nucleases—HfmIscB, TbaIscB, YnpsCas9 and NbaCas9—each in complex with its guide RNA and target DNA, providing insights into CRISPR–Cas9 evolution.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

Generative large language models (for example, ChatGPT and Claude) were used to score Big-Five traits from open-ended thoughts and video diaries. Large language model scores aligned with self-reports and predicted behaviour, showing personality’s expression in everyday language.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

Changes in ocean fronts could impact biological productivity and carbon exchange. By analysing satellite and reanalysis data, the authors identify areas with active frontal activity and rapid change in properties, as well as highlighting the correspondence with surface productivity and CO₂ uptake.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

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.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

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.

ADGRL4 is a cancer-implicated adhesion GPCR whose ability to couple to G proteins had been unclear. Here, authors show that ADGRL4 weakly engages Gq and determine its 3.1 Å active-state structure, revealing its mechanism of activation.

This study introduces two new measures of brain function at the gray–white matter boundary, revealing distinct patterns of signal transmission and metabolic activity that deepen our understanding of brain organization and development.

Multi-trait genome-wide analyses identify variants associated with comorbid lung diseases. Polygenic scores leveraging shared components of heritable risk improve prediction of asthma, chronic obstructive pulmonary disease and lung cancer in a multi-ancestry cohort.

AvrPm4 is a chimeric powdery mildew effector that is recognized by the wheat kinase fusion resistance protein Pm4. The pathogen can evade Pm4 recognition by expressing the suppressor SvrPm4, an RNase-like effector with multiple roles.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

Greenland’s icebergs transport 450 megatonnes of sediment to its fjords each year, representing one-third of the ice sheet’s total sediment export. This ice-rafted debris builds shoals at tidewater glacier margins and provides key nutrients for marine ecosystems.

In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations.