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A large brain imaging study of over 2000 people worldwide shows that fear conditioning engages brain regions linked to emotion and attention, with differences in individuals with anxiety or depression and strong influences from task design.

How nicotine impacts the adolescent development of neural circuitry is not fully understood. Here authors show that early adolescent nicotine exposure in male mice blocked the maturation of nicotine-evoked dopamine signaling, causing an immature, vulnerable behavioral response in adult mice. Restoring their adult-like nicotine-evoked signaling unmasks a mature behavioral response in male mice.

Simultaneous recordings were made of hundreds of neurons in the rat frontal cortex and striatum, showing that decision commitment involves a rapid, coordinated transition in dynamical regime and neural mode.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

An analysis of T cell responses in people with amyotrophic lateral sclerosis shows that the C9orf72 antigen is a key target of autoimmune responses in the disease, and identifies C9orf72 epitopes that are recognized.

Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in Scn2a haploinsufficient mice and human neurons.

SARS-CoV-2 immune responses after vaccination in individuals with multiple sclerosis (MS) remain poorly understood. Here, using mass cytometry, the authors demonstrate that, following three doses of mRNA vaccine, patients with MS have distinct metabolic profiles in antigen-specific B and T cells.

Mutation of positively charged binding sites on the eastern equine encephalitis virus (EEEV) E2 glycoprotein affects both heparan sulfate and protein receptor binding, identifying an unexpected linkage between engagement of these two receptor types.

In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.

Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role in determining the distribution of tau pathology.

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly

Aging is a risk factor for Parkinson’s disease; however, how DNA damage accumulation, a hallmark of aging, contributes to its pathophysiology remains incompletely understood. Here, the authors identify a blood-based DNA damage signature that is associated with disease progression in patients with Parkinson’s disease.

Dendritic cells experience cell shape changes while migrating within the complex physical environment of tissues. Sensing of these shape changes modifies their migratory properties and imprints these cells with immunoregulatory properties.

Targeting histone deacetylases (HDACs) alone has shown limited success in solid tumours. Here, authors report that the HDAC1/2 inhibitor romidepsin confers responsiveness to receptor tyrosine kinase inhibitors, with enhanced therapeutic effects in models of hepatocellular carcinoma, leading to tumour regression and an immune-stimulatory profile.

Using a mouse model harboring a WHIM Syndrome-linked gain-of-function CXCR4 mutation and bone marrow samples from WHIM patients, the authors show that proper CXCR4 signaling termination is essential for bone tissue homeostasis.

Autism is characterized by diverse symptoms, including impaired social skills, motor and perceptual atypicalities. Here, using computational modelling, the authors show that impaired synchronization ability in autism stems from reduced error correction, supporting a slow-updating account of autism.

Chronic stress is a risk factor for depression, yet the mechanisms are unclear. Here, the authors show in mice that stress drives interferon-mediated neutrophil recruitment from the skull to the brain’s outer membranes, contributing to depressive behaviors.

Alzheimer’s disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, the authors show an AI-guided model enhances patient stratification, improving outcomes and increasing efficiency in the AMARANTH trial.

Here, in a cohort of mother-child dyads, the authors show that maternal prenatal social disadvantage and psychosocial stressors associate with distinct gut microbiome taxonomic and functional diversity in both the mothers and their four-month children.

The vertebrate brain forms during embryonic development through mechanical processes that are precisely coordinated in space and time. Here, the authors uncover how extrinsic forces regulate tissue flows and cellular rearrangements to shape the early neural plate during zebrafish gastrulation.

Cocaine chemogenetics in rats is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

Relapsed and/or refractory acute myeloid leukemia (AML) postallogeneic hematopoietic cell transplantation has limited treatment options. Here the authors report the clinical results and immune correlates of a phase I/II trial of adoptively transferred virus-specific donor CD8 + T cells engineered to express a WT1-specific T cell receptor in patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Understanding the brain’s diversity requires spatially resolved maps of transcripts and proteins. Here, the authors construct an integrated molecular atlas of the mouse hippocampus revealing local enrichment profiles and compartmental organization.

Calendula, a plant used in traditional medicine for centuries, helps reduce inflammation. Here the authors identify natural compounds that are key to its anti-inflammatory activity, revealing how they work and how plants evolved the ability to make them

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Frank et al. find that a subregion in the zebrafish homolog of olfactory cortex maps odor space onto a representation of valence. Learning shapes this odor-to-valence map through plasticity processes that modify inhibition.

Cell migration in confined environments is initiated by a cytoplasmic pool of anillin and Ect2 that promotes RhoA/myosin II-mediated activation at the poles of migrating cells, in a process dependent on the extracellular environment stiffness.

A horizon scan of international respondents identifies and discusses ten developing challenges in Antarctic conservation, revealing an increased emphasis on challenges related to governance, geopolitics and economics compared to a similar scan from 2012.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.

Loss of epigenetic information is a hallmark of cellular aging. Here, authors examine changes in the epigenetic landscape at three stages of Huntington neurodegenerative disease (HD) in two mouse models and demonstrate accelerated de-repression of developmental genes in HD striatal neurons.

This study shows that epigenetic gene body DNA methylation regulates transcription and accounts for much of its variance in the Arabidopsis population, efficiently identifies genes regulating diverse traits and may facilitate local adaptation.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

Ataxia-telangiectasia mutated protein (ATM) phosphorylates CD98HC to promote neutral amino acid antiporter trafficking. Here the authors show that ATM loss impairs glutamate, cystine, and arginine transport, driving metabolic stress and ataxia telangiectasia–like phenotypes.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

In this work, authors show that exclusive breastfeeding reduces antimicrobial resistance gene burden in infants by promoting Bifidobacterium, counteracting C-section and antibiotic effects, and supporting healthy gut microbiome development during early life.

Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.

DNA double strand break repair pathways ensure genome stability and prevent disease. Here the authors show that the actin nucleating factor DIAPH1 and γ-actin promote homologous recombination (HR)-dependent repair. Inherited mutations in DIAPH1 or ACTG1 give rise to clinical deficits similar to those associated with defective HR.

Flies have evolved two distinct strategies for managing mechanical stresses during embryogenesis: out-of-plane cell division in midges and transient out-of-plane tissue folding in fruit flies.

Hereditary deafness lacks effective biological treatments. Here, the authors develop a base editing therapy that corrects a common MPZL2 deafness gene mutation in a humanized mouse model and restores hearing, highlighting base editing as a potential treatment for hereditary deafness.

Dengue virus transmission by Ae. aegypti mosquitoes poses a significant public health threat, necessitating innovative control strategies. Here, the authors demonstrate that, while successive blood feeding increases earlier dengue virus dissemination, the inhibitory effects of Wolbachia remain strong, highlighting Wolbachia’s potential to disrupt dengue transmission under natural feeding conditions.

The authors develop and validate mFISHseq, a spatially informed assay that tackles several unmet needs in breast cancer, including discordance in molecular subtyping and prognostic risk and identification of biomarkers predicting response to immunotherapies and antibody-drug conjugates.

The paralogs cytidine diphosphate diacylglycerol synthase 1 and 2 form a potentially targetable synthetic lethal relationship in mesenchymal-like cancers that involves disruption of lipid metabolism.

Cichon et al. show that ketamine induces a switch in the active population of excitatory neurons across cortical layers and regions that contributes to impairments in sensory processing characteristic of a dissociative-like state.