123,302 results match your criteria: "National Institutes of Health[Affiliation]"
Lancet Oncol
December 2024
Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:
Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.
View Article and Find Full Text PDFAm J Hum Genet
December 2024
Division of Evolution, Infection and Genomics, School of Biological Sciences, the University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, the University of Manchester NHS Foundation Trust, Manchester M13 9WL, UK. Electronic address:
The mitochondrial ribosome (mitoribosome) synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA, and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders and frequently show combined oxidative phosphorylation deficiency.
View Article and Find Full Text PDFCell Syst
December 2024
National Library of Medicine (NLM), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address:
Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data.
View Article and Find Full Text PDFAm J Respir Crit Care Med
December 2024
NIH, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States.
G3 (Bethesda)
December 2024
Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
The Sperm Neck provides a stable connection between the sperm head and tail, which is critical for fertility in species with flagellated sperm. Within the Sperm Neck, the Head-Tail Coupling Apparatus serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the Drosophila melanogaster genome that contain genetic elements that influence Head-Tail Coupling Apparatus formation, we undertook a 2 part screen using the Drosophila Deficiency kit.
View Article and Find Full Text PDFScience
December 2024
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown.
View Article and Find Full Text PDFScience
December 2024
Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Cellular RNAs directly regulate the activity of an antiviral immune signaling complex.
View Article and Find Full Text PDFPLoS One
December 2024
Center for Interventional Oncology, Clinical Center, National Institutes of Health, Bethesda, MD, United States of America.
Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Introduction: Metastatic cancer affects millions of people worldwide annually and is the leading cause of cancer-related deaths. Most patients with metastatic disease are not eligible for surgical resection, and current therapeutic regimens have varying success rates, some with 5-year survival rates below 5%. Here, we test the hypothesis that metastatic cancer can be genetically targeted by exploiting single base substitution mutations unique to individual cells that occur as part of normal aging prior to transformation.
View Article and Find Full Text PDFJ Gen Physiol
January 2025
Unit of Cardiac Physiology, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Cardiac ischemia followed by reperfusion results in cardiac cell death, which has been attributed to an increase of mitochondrial Ca2+ concentration, resulting in activation of the mitochondrial permeability transition pore (PTP). Evaluating this hypothesis requires understanding of the mechanisms responsible for control of mitochondrial Ca2+ in physiological conditions and how they are altered during both ischemia and reperfusion. Ca2+ influx is thought to occur through the mitochondrial Ca2+ uniporter (MCU).
View Article and Find Full Text PDFJ Natl Cancer Inst
December 2024
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States.
Elife
December 2024
Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, United States.
Cells react to stress by triggering response pathways, leading to extensive alterations in the transcriptome to restore cellular homeostasis. The role of RNA metabolism in shaping the cellular response to stress is vital, yet the global changes in RNA stability under these conditions remain unclear. In this work, we employ direct RNA sequencing with nanopores, enhanced by 5' end adapter ligation, to comprehensively interrogate the human transcriptome at single-molecule and -nucleotide resolution.
View Article and Find Full Text PDFCurr Opin Pediatr
February 2025
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Ann Neurol
December 2024
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.
View Article and Find Full Text PDFAnal Chem
December 2024
SCIEX, Concord, Ontario L4K 4V8, Canada.
We report the first implementation of ion mobility mass spectrometry combined with an ultrahigh throughput sample introduction technology for high-throughput screening (HTS). The system integrates differential mobility spectrometry (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the substrates and products of isomerase-mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens, offering an opportunity as a drug target for a variety of microbial and parasite borne diseases.
View Article and Find Full Text PDFKidney Int Rep
December 2024
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
Introduction: Kidney Disease Improving Global Outcomes guidelines indicate that glucocorticoids and immunosuppressants comprise the first therapeutic regimens after 4 to 6 months of treatment for high-risk primary membranous nephropathy (PMN). However, some patients cannot achieve complete or partial remission at 6 months. This study aimed to evaluate the efficacy of traditional immunotherapy combined with hydroxychloroquine (HCQ), a well-known immune regulator, in patients with PMN.
View Article and Find Full Text PDFBrain Commun
November 2024
Magnetic Resonance Physics of Aging and Dementia Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Myelin's role in processing speed is pivotal, as it facilitates efficient neural conduction. Its decline could significantly affect cognitive efficiency during ageing. In this work, myelin content was quantified using our advanced MRI method of myelin water fraction mapping.
View Article and Find Full Text PDFAlcohol Res
December 2024
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
Prev Med Rep
January 2025
Vanderbilt University Medical Center, 2525 West End Avenue, Nashville, TN 37203, USA.
Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.
Methods: Data were drawn from a surveillance study of households with children ( = 1913) recruited from 12 U.
J Cereb Blood Flow Metab
December 2024
Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY, USA.
Alzheimer's disease (AD), a neurodegenerative disorder with progressive cognitive decline, remains clinically challenging with limited understanding of etiology and interventions. Clinical studies have reported vascular defects prior to other pathological manifestations of AD, leading to the "Vascular Hypothesis" for the disorder. However, assessments of cerebral vasculature in AD rodent models have been constrained by limited spatiotemporal resolution or field of view of conventional imaging.
View Article and Find Full Text PDFBMC Biol
December 2024
Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
CRISPR are adaptive immunity systems that protect bacteria and archaea from viruses and other mobile genetic elements (MGE) via an RNA-guided interference mechanism. However, in the course of the host-parasite co-evolution, CRISPR systems have been recruited by MGE themselves for counter-defense or other functions. Some bacteriophages encode fully functional CRISPR systems that target host defense systems, and many others recruited individual components of CRISPR systems, such as single repeat units that inhibit host CRISPR systems and CRISPR mini-arrays that target related viruses contributing to inter-virus competition.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Genomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Background: Systemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients.
View Article and Find Full Text PDFPediatr Res
December 2024
Department of Pediatrics, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
Background: PECOS is an ongoing study aimed to characterize long-term outcomes following pediatric SARS-CoV-2 infection.
Methods: This is a cross-sectional analysis of infected and uninfected cohorts at baseline. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected.
Nature
December 2024
Protein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Much of the human genome is transcribed into RNAs, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded-are conformationally heterogeneous and flexible, which is a prerequisite for function, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold for protein structure prediction do not apply to RNA.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
The cannabinoid receptor 1 (CBR) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CBR antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted their further therapeutic development. The peripherally restricted CBR inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CBR inhibitors while sparing the negative psychiatric effects.
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