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A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.
Proc Natl Acad Sci U S A
January 2025
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.
View Article and Find Full Text PDFUbiquitination of OsCSN5 by OsPUB45 activates immunity by modulating the OsCUL3a-OsNPR1 module.
Sci Adv
January 2025
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
The COP9 signalosome (CSN) is a highly conserved protein complex in eukaryotes, with CSN5 serving as its critical catalytic subunit. However, the role of CSN5 in plant immunity is largely unexplored. Here, we found that suppression of in rice enhances resistance against the fungal pathogen and the bacterial pathogen pv.
View Article and Find Full Text PDFCo-evolution of atypical BRAF and KRAS mutations in colorectal tumorigenesis.
Mol Cancer Res
January 2024
University of Oxford, Oxford, United Kingdom.
BRAF mutations in colorectal cancer (CRC) comprise three functional classes: Class 1 (V600E) with strong constitutive activation, Class 2 with pathogenic kinase activity lower than Class 1, and Class 3 which paradoxically lacks kinase activity. Non-Class 1 mutations associate with better prognosis, microsatellite stability, distal tumour location and better anti-EGFR response. Analysis of 13 CRC cohorts (n=6,605 tumours) compared Class 1 (n=709, 10.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Alabama at Birmingham, Birmingham, AL, USA.
Progranulin is a secreted pro-protein that is necessary for maintaining lysosomal function and exerts anti-inflammatory and neurotrophic effects in the brain. Loss-of-function GRN mutations, most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Other GRN variants are associated with risk for FTD, Alzheimer's disease (AD) and Parkinson's disease.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Background: Patients with Alzheimer's Disease and related dementias associated with the accumulation of pathological tau (tauopathies) in neurons have an increased incidence of epileptic episodes and sub-clinical epileptiform activity. This neuronal hyperexcitability represents some of the earliest changes in patient brains, is associated with more severe symptoms, and presents an opportunity for early therapeutic intervention. Despite these provocative observations, the molecular details of how tau and neuronal excitability are connected in tauopathies remain unknown.
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