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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 PDFEstablishment of a human ovarian endometrioid carcinoma cell line by constitutive expression of cyclin-dependent kinase 4, cyclin D1 and telomerase reverse transcriptase.
Hum Cell
January 2025
Department of Tumor Pathology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan.
Only a few human ovarian endometrioid carcinoma cell lines are currently available, partly due to the difficulty of establishing cell lines from low-grade cancers. Here, using a cell immortalization strategy consisting of i) inactivation of the p16-pRb pathway by constitutive expression of mutant cyclin-dependent kinase 4 (R24C) (CDK4) and cyclin D1, and ii) acquisition of telomerase reverse transcriptase (TERT) activity, we established a human ovarian endometrioid carcinoma cell line from a 46-year-old Japanese woman. That line, designated JFE-21, has proliferated continuously for over 6 months with a doubling time of ~ 55 h.
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