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Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease.
Annu Rev Pharmacol Toxicol
January 2025
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA; email:
Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding , a human coronary artery disease risk locus.
View Article and Find Full Text PDFSingle-particle tracking reveals heterogeneous PIEZO1 diffusion.
Biophys J
January 2025
Department of Physiology & Biophysics, UC Irvine, Irvine, California; Department of Biomedical Engineering, UC Irvine, Irvine, California; Center for Complex Biological Systems, UC Irvine, Irvine, California; Sue and Bill Gross Stem Cell Research Center, UC Irvine, Irvine, California. Electronic address:
The mechanically-activated ion channel PIEZO1 is critical to numerous physiological processes, and is activated by diverse mechanical cues. The channel is gated by membrane tension and has been found to be mobile in the plasma membrane. We employed single particle tracking (SPT) of endogenous, tdTomato-tagged PIEZO1 using Total Internal Reflection Fluorescence Microscopy in live cells.
View Article and Find Full Text PDFRespiratory and hematological physiology of day 15 chicken embryos (Gallus gallus domesticus) during water submergence and air recovery: Implications for bird embryos experiencing nest inundation.
Comp Biochem Physiol A Mol Integr Physiol
January 2025
Developmental Integrative Biology, Department of Biological Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX 76203, United States of America.
Bird nests of coastal or inland breeding birds can temporarily flood during high tides or storms. However, respiratory physiological disruption of such water submersion and implications for post-submergence survival are poorly understood. We hypothesized that respiratory physiological disturbances caused by submersion would be rapidly corrected following return to normal gas exchange across the eggshell, thus explaining survival of nest inundation in the field.
View Article and Find Full Text PDFDark continuous noise from visual pigment as a major mechanism underlying rod-cone difference in light sensitivity.
Proc Natl Acad Sci U S A
December 2024
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Retinal rods and cones underlie scotopic and photopic vision, respectively. Their pigments exhibit spontaneous isomerizations (quantal noise) in darkness due to intrinsic thermal energy. This quantal noise, albeit exceedingly low in rods, dictates the light threshold for scotopic vision.
View Article and Find Full Text PDFRoles for TRPV4 in disease: A discussion of possible mechanisms.
Cell Calcium
December 2024
Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico. Electronic address:
The transient receptor potential vanilloid 4 (TRPV4) ion channel is a ubiquitously expressed Ca-permeable ion channel that controls intracellular calcium ([Ca]) homeostasis in various types of cells. The physiological roles for TRPV4 are tissue specific and the mechanisms behind this specificity remain mostly unclarified. It is noteworthy that mutations in the TRPV4 channel have been associated to a broad spectrum of congenital diseases, with most of these mutations mainly resulting in gain-of-function.
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