National Institutes of Health

Aberrant one-carbon metabolism and ancestral genetics underlie edematous severe acute malnutrition

Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic...

Genotype-specific molecular and functional trajectories in NGLY1 deficiency: a comparative multi-omics study of patient-derived iPSC neurons

Background NGLY1 deficiency is an ultra-rare congenital disorder of deglycosylation with prominent neurodevelopmental impairment and marked allelic heterogeneity. Prior human neuronal models have characterized NGLY1 loss largely within single genetic backgrounds, leaving open whe...

Primer: Functions and evolution of viral proteins

ABSTRACT Viruses encode an enormous variety of proteins that jointly comprise the largest pool of protein diversity on Earth. At coarse grain, the viral pan-proteome can be partitioned into four classes of proteins that differ in their evolutionary conservation, spread across the...

Exploration of the genetic architecture of ANCA-associated vasculitis

Background Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a complex autoimmune disease with distinct clinical and serological subtypes. Previous genome-wide association studies (GWAS) have identified several susceptibility loci, particularly within the major h...

Loss of Hippo Signaling Causes Coloboma via Steric Obstruction of Optic Fissure Fusion

Purpose: Pathogenic variants in the Hippo pathway effector YAP1 causes uveal coloboma in humans, a potentially blinding congenital eye malformation resulting from failure of optic fissure (OF) closure. Here, we characterize the pathogenesis of coloboma in zebrafish lacking the Hi...

Immunohistochemistry vs Molecular Breast Cancer Subtyping Among African Populations

Importance Breast cancer subtyping based on immunohistochemistry (IHC) guides systemic therapy where gene expression profiling assays are unavailable, yet its validity against molecular reference standards remains poorly characterized in African populations, where laboratory infr...

Understanding histotripsy ablation safety: a systematic review of pre-clinical and clinical adverse events

Abstract Histotripsy is the first cavitation-based ablation modality. Given limited clinical experience, synthesis of pre-clinical and early clinical data is essential to guide safe adoption. A PubMed and SCOPUS search was performed focused on pre-clinical and clinical adverse ev...

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis

Abstract Background Differential expression analysis is a central tool for studying the biological processes altered in human diseases via transcriptomic signatures. However, transcriptomic datasets are systematically confounded by latent variables from two distinct sources: unme...

A phosphoinositide and RAB switch controls early macropinocytosis

Macropinocytosis is a non-selective endocytic process by which cells take up large amounts of extracellular fluid into giant vesicles known as macropinosomes. This mechanism is used by immune cells to sample the surroundings for antigens and can be exploited by cancer cells for n...

Clathrin recruitment and assembly of phosphorylated B cell receptor is impaired in human diffuse large B cell lymphoma

The B cell receptor (BCR) drives the differentiation of naive B cells into activated plasma cells that produce antibodies. The BCR consists of a plasma membrane-bound surface immunoglobulin (sIg) that binds antigens, and two coreceptor subunits CD79A and CD79B. The intracellular...

Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis

Background: Available literature shows a marginal or no effect of disease-modifying therapies on paramagnetic rim lesions (PRLs), a promising magnetic resonance imaging marker of chronic inflammation in multiple sclerosis. Objective: To investigate longitudinal changes in PRL cou...

Dual inhibition of JAK and MEK suppresses T-cell acute lymphoblastic leukemia induced by mutant IL7R and RASGRP1 overexpression

Gain-of-function mutant IL-7Rα (mutIL7R) occurs in approximately 10% of patients with Tcell acute lymphoblastic leukemia (T-ALL), an aggressive pediatric cancer. Nearly half of patients with T-ALLs also overexpress RAS guanyl nucleotide exchange factor (RASGRP1), an activator of...

Biomarker discrepancies following chimeric antigen receptor T cells: implications in B-cell acute lymphoblastic leukemia

Not available.

Residential proximity to intensive animal agriculture associates with increased prevalence of antimicrobial resistance in homes

BACKGROUND: Antimicrobial resistance (AMR), a global public health threat, affects rural communities disproportionately due to their unique regional exposures, including proximity to animal feeding operations (AFOs), a source of AMR genes. OBJECTIVE: We evaluated residential prox...

Corticosteroids drive oral candidiasis by impairing type-17 immunity without inducing interferon-gammopathy

ABSTRACT Oral candidiasis arises from either genetic immune defects or iatrogenic immune suppression, most commonly due to corticosteroid therapy. Although the cortisone acetate mouse model is widely used to study corticosteroid-associated oral candidiasis, the underlying mechani...

MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation

MATRIN3 (MATR3) is a broadly expressed nuclear RNA-binding protein. However, the mechanisms by which MATR3 maintains human cellular health remain poorly understood. In this study, we employed gene editing to model MATR3 deficiency in human induced pluripotent stem cells (iPSCs) a...

Δ133p53α, a senescence-inhibitory p53 isoform, attenuates accelerated aging in progeria mice

Abstract Research on progeria not only contributes to the development of treatments for the disease but also enhances our understanding of physiological aging. In a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), transgenic expression of Δ133p53α, a senescence-inhibit...

Metrology, Standards, and Mission: Synopsis of the 2026 Annual Meeting of the Council on Ionizing Radiation Measurements and Standards (CIRMS)

The Council on Ionizing Radiation Measurements and Standards (CIRMS) is an independent, non-profit council composed of experts from academia, government, and industry across all areas of ionizing radiation science and technology, providing leadership, focus, and coordinated actio...

Using multi-trait polygenic scores to predict lithium responsiveness in patients with bipolar disorder

Background The predictive power of polygenic scores (PGSs) for lithium treatment response in bipolar disorder remains limited. Aims To enhance the prediction of lithium responsiveness by developing a multi-trait PGS (mt-PGS) combining genetic information from multiple phenotypes...

The Ethics of Relying on Research Participants’ Altruism

Abstract We examine the ethics of enrolling individuals in research that poses net health risks by appealing to their altruism. We argue that it is permissible to enroll individuals who are motivated by altruism when (i) they autonomously consent; and (ii) the net health risks ar...