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A Statistically-Robust Model of the Axomyelin Unit under Normal Physiologic Conditions with Application to Disease States.
ASN Neuro
January 2025
Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois, USA.
Despite tremendous progress in characterizing the myriad cellular structures in the nervous system, a full appreciation of the interdependent and intricate interactions between these structures is as yet unfulfilled. Indeed, few more so than the interaction between the myelin internode and its ensheathed axon. More than a half-century after the ultrastructural characterization of this axomyelin unit, we lack a reliable understanding of the physiological properties, the significance and consequence of pathobiological processes, and the means to gauge success or failure of interventions designed to mitigate disease.
View Article and Find Full Text PDFCryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting.
Nucleic Acids Res
January 2025
Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States.
The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states.
View Article and Find Full Text PDFVolume electron microscopy reveals unique laminar synaptic characteristics in the human entorhinal cortex.
Elife
January 2025
Instituto Cajal (CSIC), Madrid, Spain.
The entorhinal cortex (EC) plays a pivotal role in memory function and spatial navigation, connecting the hippocampus with the neocortex. The EC integrates a wide range of cortical and subcortical inputs, but its synaptic organization in the human brain is largely unknown. We used volume electron microscopy to perform a 3D analysis of the microanatomical features of synapses in all layers of the medial EC (MEC) from the human brain.
View Article and Find Full Text PDFThe impact of signaling pathways on the desmosome ultrastructure in pemphigus.
Front Immunol
January 2025
Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilan-Universität (LMU) Munich, München, Germany.
Introduction: The autoantibody-driven disease pemphigus vulgaris (PV) impairs desmosome adhesion in the epidermis. In desmosomes, the pemphigus autoantigens desmoglein 1 (Dsg1) and Dsg3 link adjacent cells. Dsgs are clustered by plaque proteins and linked to the keratin cytoskeleton by desmoplakin (Dp).
View Article and Find Full Text PDFSubcellular mitochondrial heterogeneity enables opposing metabolic demands.
Trends Endocrinol Metab
January 2025
Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Michigan Medicine at the University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Mitochondria perform essential metabolic processes that sustain cellular bioenergetics and biosynthesis. In a recent article, Ryu et al. explored how mitochondria coordinate biochemical reactions with opposing redox demands within the same cell.
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