A5031946422- Hearing, Cochlea, Tinnitus, Genetics
- Ion channel regulation and function
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Biochemical Analysis and Sensing Techniques
- Viral Infections and Immunology Research
- Neuroscience and Neuropharmacology Research
- Obesity, Physical Activity, Diet
- Vestibular and auditory disorders
- Integrated Circuits and Semiconductor Failure Analysis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Birth, Development, and Health
- Advanced Fluorescence Microscopy Techniques
- Single-cell and spatial transcriptomics
- Sports Performance and Training
- Retinal Development and Disorders
- Advanced Electron Microscopy Techniques and Applications
- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Hair Growth and Disorders
- Cardiovascular Function and Risk Factors
Michigan State University
2022
Menlo School
2014
Aratome (United States)
2014
Cytokinetics (United States)
2011
University of Virginia
2001-2003
University of Oregon
1994-2002
University of California, Davis
1991-1993
Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, small-molecule, direct activator myosin. Here, show that it binds to the myosin catalytic domain and operates an allosteric mechanism transition rate into strongly actin-bound force-generating state. Paradoxically,...
We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small such as FM1-43 rapidly specifically label hair in inner ear entering open mechanotransduction This labeling can be blocked pharmacological or mechanical closing phenomenon is not limited cell transduction channels, because human embryonic kidney 293T expressing vanilloid receptor (TRPV1)...
We used electron tomography to map the three-dimensional architecture of ribbon-class afferent synapses in frog saccular hair cells. The synaptic body (SB) at each synapse was nearly spherical (468 ± 65 nm diameter; mean SD) and covered by a monolayer vesicles (34.3 8.8% coefficient variation), many them tethered it ∼20-nm-long filaments, an average density 55% close-packed (376 133 per SB). These could support ∼900 msec exocytosis reported maximal rate, which cells can sustain for least 2...
Abstract Cells from the embryonic quail retina were immortalized with v‐mil oncogene and cloned by limiting dilution. Their phenotype was examined using whole‐cell patch clamp method. Three membrane currents, I k(IR) , Na K found at different frequencies within a sample of 170 cells drawn large clone. Nearly all combinations these three markers frequency showed that assorted independently. Examination clones less than 10 heterogeneity originates high probability clones, arguing chromosomal...
Abstract To determine how voltage‐gated ion channels segregate between sibling cells at cytokinesis, we used a whole‐cell patch clamp to measure the electrophysiological phenotypes of siblings within 45 min division. Recently born in an immortalized line embryonic retinal were identified as pairs spherical adhering one another. All electrically coupled when simultaneously voltage clamped, whereas nonsiblings not coupled. Twelve paris isolated by mechanical separation so that their could be...
Smooth muscle myosin is a mechanochemical enzyme that hydrolyzes ATP to generate mechanical force; ultimately all signaling pathways modulate smooth tone converge on the regulation of this motor protein. We previously showed novel inhibitor, CK‐2019165, inhibited methacholine‐induced bronchoconstriction in rat models with short duration action (~ 2 hours). Here we describe discovery and characterization long acting inhibitor for bronchodilation. Using high throughput screening, identified...
The proportion of Americans with overweight/obesity continues to rise such that 40% children and teens are impacted 14% toddlers considered obese. Many long-term health consequences associated childhood obesity demonstrating the importance diet quality early in life. objective this study was use data from a longitudinal cohort determine juice sugar-sweetened beverage (SSB) consumption compare national data. Data were collected through surveys filled out by mothers when child 12 (n = 44), 24...
Abstract Hair cells, the mechanotransducers of inner ears and lateral lines vertebrates offer an excellent preparation for study presynaptic mechanisms at fast chemical synapses. They compact, almost cylindrical shape epithelial cell without entangling dendrites axons, make afferent synapses directly from body. The biology hair cells demands unusually high performance output synapse, requiring continuous, very quickly modulated transmitter exocytosis. Release follows small receptor potential...