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Manganese exposure induces parkinsonism-like symptoms by Serpina3n-TFEB-v/p-ATPase signaling mediated lysosomal dysfunction.
Cell Biol Toxicol
January 2025
Department of Environmental Medicine, School of Medicine, Chongqing University, Chongqing, China.
Manganese (Mn) is a neurotoxin that has been etiologically linked to the development of neurodegenerative diseases in the case of overexposure. It is widely accepted that overexposure to Mn leads to manganism, which has clinical symptoms similar to Parkinson's disease (PD), and is referred to as parkinsonism. Astrocytes have been reported to scavenge and degrade extracellular α-synuclein (α-Syn) in the brain.
View Article and Find Full Text PDFMultiscale footprints reveal the organization of cis-regulatory elements.
Nature
January 2025
Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.
View Article and Find Full Text PDFDysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome.
Sci Rep
January 2025
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
Increasing shreds of evidence suggest that neurogenic-to-gliogenic shift may be critical to the abnormal neurodevelopment observed in individuals with Down syndrome (DS). REST, the Repressor Element-1 Silencing Transcription factor, regulates the differentiation and development of neural cells. Downregulation of REST may lead to defects in post-differentiation neuronal morphology in the brain of the DS fetal.
View Article and Find Full Text PDFPushing the envelope - How the genome interacts with the nuclear envelope in health and disease.
Adv Protein Chem Struct Biol
January 2025
Genome Organisation and Dynamics Cluster, Center for Genome Engineering and Maintenance, Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, London, United Kingdom. Electronic address:
The nuclear envelope has for long been considered more than just the physical border between the nucleoplasm and the cytoplasm, emerging as a crucial player in genome organisation and regulation within the 3D nucleus. Consequently, its study has become a valuable topic in the research of cancer, ageing and several other diseases where chromatin organisation is compromised. In this chapter, we will delve into its several sub-elements, such as the nuclear lamina, nuclear pore complexes and nuclear envelope proteins, and their diverse roles in nuclear function and maintenance.
View Article and Find Full Text PDFUrinary Selenium, Cranial MRI, and Cognitive Function in American Indians: The Strong Heart Study.
Environ Res
January 2025
Missouri Breaks Industries Research Inc, Eagle Butte, SD; Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND.
Introduction: Selenium (Se), a trace element found in soil and groundwater, is necessary for many biological functions, including cerebrovascular health, through selenoprotein formation. However, high concentrations may be harmful. American Indians face elevated cerebrovascular disease rates, which may be associated with other trace elements, such as Se.
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