A5079616335- Genetics, Aging, and Longevity in Model Organisms
- Hearing, Cochlea, Tinnitus, Genetics
- Ion channel regulation and function
- Neural dynamics and brain function
- Tryptophan and brain disorders
- Hearing Loss and Rehabilitation
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Receptor Mechanisms and Effects
- Gastrointestinal motility and disorders
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Neuroendocrine regulation and behavior
- Animal Vocal Communication and Behavior
- Circadian rhythm and melatonin
- Neuroscience and Neural Engineering
- Marine animal studies overview
- Infant Health and Development
- Pelvic floor disorders treatments
- Genetics and Neurodevelopmental Disorders
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Congenital gastrointestinal and neural anomalies
Mirna Therapeutics (United States)
2025
Dermatology Specialists
2020-2022
The University of Texas at Austin
2005-2020
Institute of Molecular and Cell Biology
2016-2018
University of Rochester
2007
In mammals, principal neurons of the medial superior olive (MSO) exhibit biophysical specializations that enable them to detect sound localization cues with microsecond precision. present study, we used whole-cell patch recordings examine development intrinsic electrical properties these in brainstem slices from postnatal day 14 (P14) P38 gerbils. week after hearing onset (P14-P21), observed dramatic reductions somatic EPSP duration, input resistance, and membrane time constant....
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report identification of a novel class Sig2R ligands and their cellular in vivo activity experimental models Alzheimer's disease (AD). We SAS-0132 DKR-1051, selective Sig2R, modulate intracellular Ca2+ levels human SK-N-SH neuroblastoma cells. The JVW-1009 are neuroprotective C. elegans model amyloid precursor protein-mediated...
Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation their rate action potential firing. Previous intracellular studies in vitro have shown that potentials appear highly attenuated at soma MSO neurons, potentially reflecting specialized initiation and/or a physically distant site generation. To examine this more directly, we made dual patch-clamp recordings from principal gerbil brainstem slices. Using somatic and dendritic...
Principal neurons of the medial superior olive (MSO) compute azimuthal sound location by integrating phase-locked inputs from each ear. While previous experimental and modeling studies have proposed that voltage-gated sodium channels (VGSCs) play an important role in synaptic integration MSO, these appear at odds with unusually weak active backpropagation action potentials into soma dendrites. To understand spatial localization biophysical properties VGSCs, we isolated currents MSO principal...
Alcohol directly modulates the BK potassium channel to alter behaviors in species ranging from invertebrates humans. In nematode Caenorhabditis elegans, mutations that eliminate channel, SLO-1, convey dramatic resistance intoxication by ethanol. We hypothesized certain conserved amino acids are critical for ethanol modulation, but not basal function. To identify such residues, we screened C. elegans strains with different missense SLO-1 channel. A strain mutation T381I RCK1 domain was highly...
The nematode Caenorhabditis elegans, with tractable genetics and a well-defined nervous system, provides unique whole-animal model system to identify novel drug targets therapies for neurodegenerative diseases. Large-scale or target screens in models that recapitulate the subtle age- cell-specific aspects of diseases are limited by technological requirement high-throughput analysis neuronal morphology. Recently, we developed single-copy amyloid precursor protein (SC_APP) induced...
Abstract Background Mahana™ IBS is a Food and Drug Administration‐cleared prescription mobile application designed to deliver 3 months of gut‐directed cognitive behavioral therapy (CBT) adults ≥22 years old with irritable bowel syndrome (IBS). We assessed whether CBT delivered digitally improved outcomes in management. Methods studied users who had dispensed physician for between August 2021 2023. The primary outcome was change symptom severity (IBS‐SSS) score. Key Results For the 843...
Abstract Symptoms of withdrawal from chronic alcohol use are a driving force for relapse in dependence. Thus, uncovering molecular targets to lessen their severity is key breaking the cycle Using nematode Caenorhabditis elegans, we tested whether one highly conserved ethanol target, large-conductance, calcium-activated potassium channel (known as BK or Slo1), modulates withdrawal. Consistent with previous report, found that C. elegans displays withdrawal-related behavioral impairments after...
Abstract Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest pharmaceutical applications for modulating BK channel function. Here we report a novel channel-targeted peptide with functional activity vitro vivo . This 9-amino acid peptide, LS3, has unique action, suppressing gating rather than blocking the pore heterologously human channels. With IC 50 high picomolar range,...
Abstract In some songbirds perturbing auditory feedback can promote changes in song structure well beyond the end of learning. One factor that may drive vocal change such deafened birds is ongoing addition new vocal‐motor neurons into system. Without to guide their incorporation, these could disrupt established pattern. To assess this hypothesis, authors determined if neuronal recruitment motor nucleus HVC affected by neural signals influence adult birds. Such appear be conveyed via LMAN, a...
Genetic and epidemiological studies have found that variations in the amyloid precursor protein (
Tinnitus is the phantom perception of sound that has no external source. A neurological signature tinnitus, and frequently associated hyperacusis, an imbalance between excitatory inhibitory activity in central auditory system (CAS), leading to dysregulated network excitability. The large conductance, calcium-activated potassium (BK) channel a key player pre- post-synaptic excitability through its mediation K+ currents. Changes BK are with aberrant sensory regions CNS, raising possibility...
Alcohol is a widely used and abused substance. A major unresolved issue in the alcohol research field determining which of many target proteins identified to date responsible for shaping each specific alcohol-related behavior. The large-conductance, calcium- voltage-activated potassium channel (BK channel) conserved ethanol. Genetic manipulation highly BK<i>α</i> influences behaviors across phylogenetically diverse species that include worm, fly, mouse, man. pharmacological tool prevents...
Alcohol modulates the highly conserved, voltage- and calcium-activated potassium (BK) channel, which contributes to alcohol-mediated behaviors in species from worms humans. Previous studies have shown that calcium-sensitive domains, RCK1 Ca(2+) bowl, are required for ethanol activation of mammalian BK channel vitro. In nematode Caenorhabditis elegans, activates vivo, deletion worm SLO-1, confers strong resistance intoxication. To determine if conserved calcium bowl domains were also critical...
Abstract Congenital sensorineural hearing loss (SNHL) affects thousands of infants each year and results in significant delays speech language development. Previous studies have shown that early exposure to a simple augmented acoustic environment (AAE) can limit the effects progressive SNHL on sensitivity. However, is also accompanied by not assessed standard audiological examinations, such as reduced temporal processing acuity. To assess whether sound therapy may improve these deficits,...
Abstract Congenital sensorineural hearing loss (SNHL) affects thousands of infants each year and results in significant delays speech language development. Previous studies have shown that early exposure to a simple augmented acoustic environment (AAE) can limit the effects progressive SNHL on sensitivity. However, is also accompanied by “hidden loss” not assessed standard audiological exams, such as reduced temporal processing acuity. To assess whether sound therapy may improve these hidden...
Abstract The severity of withdrawal from chronic ethanol is a driving force for relapse in alcohol dependence. Thus, uncovering molecular changes that can be targeted to lessen symptoms key breaking the cycle Using model nematode Caenorhabditis elegans , we tested whether one highly conserved target, BK potassium channel, may play major role withdrawal. Consistent with previous report, found C. displays behavioral impairment during reduced by low-dose ethanol. We discovered degree...
Abstract Genetic and epidemiological studies have found that variations in the amyloid precursor protein ( APP ) apoliopoprotein E APOE genes represent major modifiers of progressive neurodegeneration Alzheimer’s disease (AD). An extra copy or gain-of-function mutations lower age AD onset. Compared to other isoforms APOE3 APOE2 ), ε4 allele APOE4 hastens exacerbates early late onset forms AD. Convenient vivo models study how interact at cellular molecular level influence are lacking. Here,...