Background: Eukaryotic genome is compartmentalized into structural and functional domains. One of the concepts of higher order organization of chromatin posits that the DNA is organized in constrained loops that behave as independent functional domains. Nuclear Matrix (NuMat), a ribo-proteinaceous nucleoskeleton, provides the structural basis for this organization. DNA sequences located at base of the loops are known as the Matrix Attachment Regions (MARs). NuMat relates to multiple nuclear processes and is partly cell type specific in composition. It is a biochemically defined structure and several protocols have been used to isolate the NuMat where some of the steps have been critically evaluated. These sequences play an important role in genomic organization it is imperative to know their dynamics during development and differentiation.
Results: Here we look into the dynamics of MARs when the preparation process is varied and during embryonic development of D. melanogaster. A subset of MARs termed as "Core-MARs" present abundantly in pericentromeric heterochromatin, are constant unalterable anchor points as they associate with NuMat through embryonic development and are independent of the isolation procedure. Euchromatic MARs are dynamic and reflect the transcriptomic profile of the cell. New MARs are generated by nuclear stabilization, and during development, mostly at paused RNA polymerase II promoters. Paused Pol II MARs depend on RNA transcripts for NuMat association.
Conclusions: Our data reveals the role of MARs in functionally dynamic nucleus and contributes to the current understanding of nuclear architecture in genomic context.
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http://dx.doi.org/10.1186/s12864-022-08944-4 | DOI Listing |
Menopause
January 2025
National Institute of Health, Cheongju, Republic of Korea.
Objectives: We examined the health-related quality of life (HRQoL) during menopause transition (MT) among middle-aged Korean women.
Methods: This cross-sectional study comprised 2,290 middle-aged women who completed web-based questionnaires between 2020 and 2022. Based on self-reported menstrual cycle patterns, menopause status was classified as premenopausal, early or late transition, or postmenopausal.
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
The Ca/calmodulin-dependent protein kinase II α (CaMKIIα) plays a crucial role in regulating neuronal signaling and higher brain functions, being involved in various brain diseases. Utilization of small molecules targeting the CaMKIIα hub domain has proved to be a promising strategy for specific CaMKIIα modulation and future therapy. Through an structure-based virtual screening campaign, we herein identified 2-arylthiazole-4-carboxylic acids as a new class of high-affinity CaMKIIα hub ligands.
View Article and Find Full Text PDFSci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Psychiatry, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.
Background: Despite transcranial direct current stimulation (tDCS) has demonstrated encouraging potential for modulating the circadian rhythm, little is known about how well and sustainably tDCS might improve the subjective sleep quality in older adults. This study sought to determine how tDCS affected sleep quality and cognition, as well as how well pre-treatment sleep quality predicted tDCS effects on domain-specific cognitive functions in patients with mild neurocognitive disorder due to Alzheimer's disease (NCD-AD).
Methods: This clinical trial aimed to compare the effectiveness of tDCS and cognitive training in mild NCD-AD patients (n = 201).
PLoS One
January 2025
Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
The ongoing increase in the prevalence and mutation rate of the influenza virus remains a critical global health issue. A promising strategy for antiviral drug development involves targeting the RNA-dependent RNA polymerase, specifically the PB2-cap binding domain of Influenza A H5N1. This study employs an in-silico approach to inhibit this domain, crucial for viral replication, using potential inhibitors derived from marine bacterial compounds.
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