The application of cochlear implants can be studied with computational models. The electrical potential distribution induced by an implanted device is evaluated with a volume conductor model, which is used as input for neuron models to simulate the reaction of cochlear neurons to micro-stimulation. In order to reliably predict the complex excitation profiles it is vital to consider an accurate representation of the human cochlea geometry including detailed three-dimensional pathways of auditory neurons reaching from the organ of Corti through the cochlea-volume. In this study, high-resolution micro-CT imaging (Δx = Δy = Δz = 3 μm) was used to reconstruct the pathways of 30 tonotopically organized nerve fiber bundles, distributed over eight octaves (11500-40 Hz). Results of the computational framework predict: (i) the peripheral process is most sensitive to cathodic stimulation (CAT), (ii) in many cases CAT elicits spikes in the peripheral terminal at threshold but with larger stimuli there is a second spike initiation site within the peripheral process, (iii) anodic stimuli (ANO) can excite the central process even at threshold, (iv) the recruitment of fibers by electrodes located in the narrowing middle- and apical turn is complex and impedes focal excitation of low frequency fibers, (v) degenerated cells which lost the peripheral process are more sensitive to CAT when their somata are totally covered with 2 membranes of a glial cell but they become ANO sensitive when the myelin covering is reduced.
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http://dx.doi.org/10.1016/j.heares.2020.108001 | DOI Listing |
Curr Top Med Chem
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
Background: Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina.
View Article and Find Full Text PDFNat Hum Behav
January 2025
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems.
View Article and Find Full Text PDFNat Rev Mol Cell Biol
January 2025
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Membrane Biology, Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear.
View Article and Find Full Text PDFCell Death Dis
January 2025
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.
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