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Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

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.

Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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

Efficacy of transdermal testosterone gel in treatment for female infertility remained unknown. Authors conducted randomized clinical trial to show transdermal testosterone did not improve clinical pregnancy rates.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

In this work, researchers build a scalable photonic Chern insulator by twisting a fibre during fabrication, breaking an effective time-reversal symmetry and inducing a pseudo-magnetic field. The team reveals a ‘Goldilocks’ regime that guarantees topological protection against fabrication-induced disorder of any symmetry class in the fibre cross-section.

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.

Becker et. al developed a proteomic proximity labeling platform named POCA, which makes use of a photosensitizer for singlet oxygen production and protein capture in the presence of amine, enabling profiling of interactomes of proteins and lipids in living cells.

A single intravenous dose of the psychedelic dimethyltryptamine, combined with psychological support, produces rapid and lasting reductions in depressive symptoms in adults with major depressive disorder.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

The study shows how ship traffic in the Baltic Sea modifies seafloor morphology and disrupts water layers, thereby increasing the mixing of oxygen, nutrients and greenhouse gases, suggesting broad impacts on Baltic marine ecosystems.

This study presents a clinical-grade autonomous pipeline combining high-resolution whole-slide tomography, edge computing and artificial intelligence, achieving high accuracy in cervical cytology and enabling scalable and objective diagnostics.

This study introduces the Lipid Nanoparticle Database (LNPDB) and web tool that consolidates lipid nanoparticle structure-function data. LNPDB facilitates molecular dynamics and deep learning approaches to advance data-driven design for nucleic acid delivery.

Immunotherapies that employ engineered T cells rely on the selective and high expression of the targeted antigen in cancer cells and thus tumor heterogeneity compromises therapeutic success. Here authors generate an engineered T cell coreceptor that targets a secondary antigen and selectively enhances antigen receptor sensitivity in T cells.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

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

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.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

How microglia regulate adult hippocampal neurogenesis and cognitive and affective behavior remains poorly understood. Here, the authors show that TGF-β-deficient microglia increase adult neurogenesis in the subgranular zone and alter anxiety-like behavior in mice.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

A genome assembly method called hifiasm (ONT) allows the assembly of chromosomes from telomere to telomere without the need for ultra-long reads, and outperforms conventional methods on most evaluation metrics.

In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

The authors conduct a national inventory on individual tree carbon stocks in Rwanda using aerial imagery and deep learning. Most mapped trees are located in farmlands; new methods allow partitioning to any landscape categories, effective planning and optimization of carbon sequestration and the economic benefits of trees.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

This study utilized a longitudinal cohort of adolescents to identify distinct brain signatures linked to ADHD symptom trajectories, revealing that specific cortical and subcortical changes correlate with symptom persistence, remission and emergence, enhancing predictive capabilities for ADHD outcomes.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

This study advances methods for benchmarking macromolecular complex predictions by introducing a scalable open-source framework used in recent community assessments to compare structures, interfaces and ligand interactions against experimental data.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Discovery proteomics offers deep insights but is currently not applied clinically in diagnostics. Here, the authors present ADAPT-MS, a flexible machine learning framework that enables fast, personalized diagnostic and prognostic decisions directly from proteome-wide data.

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

The authors estimate genomic vulnerability for closely related species of rainbowfish. They find that narrow endemic species that have hybridized with a warm-adapted generalist show reduced vulnerability to climate change and that hybridization may facilitate evolutionary rescue for such species.

The effects of current protected areas on freshwater biodiversity are poorly understood. Here, the authors show that European protected areas have overall limited influence on changes in river biodiversity, underscoring the urgent need for improved effectiveness.

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.

Human impacts on marine ecosystems are increasing the likelihood of pathogenic outbreaks, harmful algal blooms and coral stress. Here the authors develop a CRISPR biomonitoring tool that can help detect key marine species that are important to public health, the aquaculture sector and marine ecosystems.

Population-based studies from Sweden with replication in Norway identify associations between host genetic variants and gut microbial composition and implicate short-chain fatty acid chemosensors as modulators of gut microbial richness.

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.

Here, the authors find that time-varying brain network analysis better captures cognitive processing than static methods and reveals network measurement linked to task performance and psychopathology that offer precise neural markers for mental health risks.

The protospacer-adjacent motif specificity of several Cas enzymes is customized using protein language models.