ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.

Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.

Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.

Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance.

Expansion and revision of the genus and proposal of gen. nov.

The nitrogen-fixing, chemolithoautotrophic genus is found across numerous diverse environments worldwide and is an important member of many ecosystems. These species serve as model systems for their metabolic properties and have industrial applications in bioremediation and sustainable protein, food and fertilizer production. Despite their abundance and utility, the majority of strains are without a genome sequence, and only eight validly published species are known to date.

The Burden of Motor Neuron Diseases in the United States, 1990-2021: A Systematic Analysis of the Global Burden of Disease Study 2021.

Introduction/aims: There is a lack of up-to-date information on the burden of motor neuron diseases (MNDs) in the United States (US). This study aimed to estimate trends in the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) for MNDs in the US from 1990 to 2021.

Methods: We performed a secondary analysis of MNDs in the US using estimates of prevalence, incidence, and mortality obtained from analyses of the Global Burden of Disease 2021 dataset.

Ensuring Biosecurity and Research Agility for Outbreak Response: A Researcher's Perspective on the Federal Nucleic Acid Screening Framework.

The Framework for Nucleic Acid Synthesis Screening (FNASS), introduced by the U.S. White House Office of Science and Technology Policy, establishes new biosecurity measures to address emerging concerns about the potential misuse of synthetic nucleic acid sequences.

Learning ecosystem-scale dynamics from microbiome data with MDSINE2.

Although dynamical systems models are a powerful tool for analysing microbial ecosystems, challenges in learning these models from complex microbiome datasets and interpreting their outputs limit use. We introduce the Microbial Dynamical Systems Inference Engine 2 (MDSINE2), a Bayesian method that learns compact and interpretable ecosystems-scale dynamical systems models from microbiome timeseries data. Microbial dynamics are modelled as stochastic processes driven by interaction modules, or groups of microbes with similar interaction structure and responses to perturbations, and additionally, noise characteristics of data are modelled.

Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.

Antibody-drug conjugates (ADCs) are effective targeted therapeutics but are limited in their ability to incorporate less-potent payloads, varied drug mechanisms of action, different drug release mechanisms and tunable drug-to-antibody ratios. Here we introduce a technology to overcome these limitations called 'antibody-bottlebrush prodrug conjugates' (ABCs). An ABC consists of an IgG1 monoclonal antibody covalently conjugated to the terminus of a compact bivalent bottlebrush prodrug that has payloads bound through cleavable linkers and polyethylene glycol branches.

Adverse Outcome Pathways Applied to Space Radiation Research.

Long-duration spaceflight exposes astronauts to various stressors that can alter human physiology, potentially causing immediate and long-term health effects. These stressors can damage biomolecules, cells, tissues, and organs, leading to adverse outcomes. Developing adverse outcome pathways (AOPs) relevant to radiation exposure can guide research priorities and inform risk assessments of future space exploration activities.

A Multimodal Imaging Framework to Advance Phenotyping of Living Label-free Breast Cancer Cells.

We present multimodal confocal Raman micro-spectroscopy (RS) and tomographic phase microscopy (TPM) for quick morpho-chemical phenotyping of human breast cancer cells (MDA-MB-231). Leveraging the non-perturbative nature of these advanced microscopy techniques, we captured detailed morpho-molecular data from living, label-free cells in their native physiological environment. Human bias-free data processing pipelines were developed to analyze hyperspectral Raman images (spanning Raman modes from 600 cm to 1800 cm, which uniquely characterize a wide range of molecular bonds and subcellular structures), as well as morphological data from three-dimensional refractive index tomograms (providing measurements of cell volume, surface area, footprint, and sphericity at nanometer resolution, alongside dry mass and density).

Corrigendum to "The Dietary Biomarkers Development Consortium: An Initiative for Discovery and Validation of Dietary Biomarkers for Precision Nutrition. [Current Developments in Nutrition, Volume 9, Issue 5, May 2025, 107435]".

[This corrects the article DOI: 10.1016/j.cdnut.

Genetic and Cellular Architecture of Breast Cancer Risk in Multi-Ancestry Studies of 159,297 Cases and 212,102 Controls.

Breast cancer genome-wide association studies (GWAS) have identified over 200 independent genome-wide significant susceptibility markers. However, most studies have focused on one or two ancestral groups. We examined breast cancer genetic architecture using GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR) and Hispanic/Latina (H/L) samples, totaling 159,297 cases and 212,102 controls, comprising the largest multi-ancestry study of breast cancer to date.

Genetic Adaptation to Brackish Water and Spawning Season in European Cisco.

How species adapt to diverse environmental conditions is essential for understanding evolution and the maintenance of biodiversity. The European cisco (Coregonus albula) is a salmonid that occurs in both fresh and brackish water, and this together with the presence of sympatric spring- and autumn-spawning lacustrine populations provides an opportunity for studying the genetics of adaptation in relation to salinity and timing of reproduction. Here, we present a high-quality reference genome of the European cisco based on PacBio HiFi long read sequencing and HiC-directed scaffolding.

Reproducible single-cell annotation of programs underlying T cell subsets, activation states and functions.

T cells recognize antigens and induce specialized gene expression programs (GEPs), enabling functions like proliferation, cytotoxicity and cytokine production. Traditionally, different T cell classes are thought to exhibit mutually exclusive responses, including T1, T2 and T17 programs. However, single-cell RNA sequencing has revealed a continuum of T cell states without clearly distinct subsets, necessitating new analytical frameworks.

A human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.

Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies.

Navigating the life stage after stroke: From Life 2.0 to stroke prevention models of care - A qualitative exploration of younger and middle-aged adult stroke patients' experiences and recommendations.

Background: Global stroke incidence has been rising among adults 65 years of age or younger. A dearth of research exists exploring and understanding younger and middle-aged adults' lifestyle-related knowledge and habits along with associated facilitators and/or barriers with the adoption, maintenance, and support needs for development of new brain health interventions, which this study sought to address.

Methods: A qualitative study was conducted, followed by virtual, semi-structured focus groups.

Noble Metal Coating on Perovskite Microcrystals for Robust and Plasmonic Lasing Applications.

Lead halide perovskites (LHP) are solution-processible semiconductor materials with high optical gain and broad wavelength tunability, making them well-suited for laser applications. Here, we present a solution-based method for the three-dimensional conformal coating of LHP microcrystals with noble metals. A nanoscale metal coating layer was found to significantly enhance both laser performance and environmental stability.

The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development.

The RNA-binding protein TRIM71 is essential for brain development, and recent genetic studies in humans have identified as a risk gene for congenital hydrocephal-us (CH). Here, we show that monoallelic missense mutations in are associated with hearing loss (HL) and inner ear aplasia in humans. Utilizing conditional knockout mice carrying a CH and HL-associated mutation, we demonstrate that loss of TRIM71 function during early otic development (embryonic day 9 to 10) causes severe HL.

Mitigating antimicrobial resistance by innovative solutions in AI (MARISA): a modified James Lind Alliance analysis.

Antimicrobial resistance (AMR) is a critical global health threat and artificial intelligence (AI) presents new opportunities for our response. However, research priorities at the AI-AMR intersection remain undefined. This study aimed to identify and prioritise key areas for future investigation.

Mature and migratory dendritic cells promote immune infiltration and response to anti-PD-1 checkpoint blockade in metastatic melanoma.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells.

Gesture encoding in human left precentral gyrus neuronal ensembles.

Understanding the cortical activity patterns driving dexterous upper limb motion has the potential to benefit a broad clinical population living with limited mobility through the development of novel brain-computer interface (BCI) technology. The present study examines the activity of ensembles of motor cortical neurons recorded using microelectrode arrays in the dominant hemisphere of two BrainGate clinical trial participants with cervical spinal cord injury as they attempted to perform a set of 48 different hand gestures. Although each participant displayed a unique organization of their respective neural latent spaces, it was possible to achieve classification accuracies of ~70% for all 48 gestures (and ~90% for sets of 10).

Tamoxifen induces PI3K activation in uterine cancer.

Mutagenic processes and clonal selection contribute to the development of therapy-associated secondary neoplasms, a known complication of cancer treatment. The association between tamoxifen therapy and secondary uterine cancers is uncommon but well established; however, the genetic mechanisms underlying tamoxifen-driven tumorigenesis remain unclear. We find that oncogenic PIK3CA mutations, common in spontaneously arising estrogen-associated de novo uterine cancer, are significantly less frequent in tamoxifen-associated tumors.

Objectively and Subjectively Measured Physical Activity and Their Associations With Cardiometabolic Risk in the UK Biobank: Retrospective Cohort Study.

Background: The association between physical activity (PA) behavior and cardiometabolic risk factors has depended largely on questionnaire-based reporting. More studies are turning to mobile health (mHealth) device solutions to measure PA. While there are differences between self-reported activity levels and objectively measured accelerometer-based activity, how these differences manifest in disease risk is unknown.

TIGER: A tdTomato in vivo genome-editing reporter mouse for investigating precision-editor delivery approaches.

In vivo genome editing has the potential to address many inherited and environmental disorders. However, a major hurdle for the clinical translation of genome editing is safe, efficient delivery to disease-relevant tissues. A modality-agnostic reporter animal model that facilitates rapid, precise, and quantifiable assessment of functional delivery and editing could greatly enhance the evaluation and translation of delivery technologies.

Rapid Generation of Hypervariable Chemical Libraries.

Combinatorial peptidomimetic libraries facilitate the economical identification and refinement of lead compounds directed at diverse therapeutic targets. Further development of selection-based approaches to drug discovery utilizing such libraries is impeded, however, both by the slow pace of library generation and by the physical limitations to library diversity inherent to current methods. To overcome these barriers, we describe here the adaptation of peptide flow synthesis technology to the generation of combinatorial libraries.