A5081900582- Erythrocyte Function and Pathophysiology
- Neurobiology and Insect Physiology Research
- Cellular Mechanics and Interactions
- Ion Channels and Receptors
- Blood properties and coagulation
- Nuclear Receptors and Signaling
- Traumatic Brain Injury Research
- Pain Mechanisms and Treatments
- GDF15 and Related Biomarkers
- Neuropeptides and Animal Physiology
- RNA regulation and disease
- Pharmacological Effects of Natural Compounds
- Hemoglobin structure and function
- Skin and Cellular Biology Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Wind and Air Flow Studies
- Cardiac Arrest and Resuscitation
- Cardiac electrophysiology and arrhythmias
- 3D Printing in Biomedical Research
- Building Energy and Comfort Optimization
- Cell Adhesion Molecules Research
- Postharvest Quality and Shelf Life Management
AbbVie (United States)
2023-2024
Northwestern University
2019-2023
University at Buffalo, State University of New York
2012-2020
Abstract While studying the physiological response of primary rat astrocytes to fluid shear stress in a model traumatic brain injury (TBI), we found that induced Ca 2+ entry. The influx was inhibited by MK-801, specific pore blocker N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred absence agonists. Other NMDA open channel blockers ketamine memantine showed similar effect. competitive glutamate antagonists AP5 GluN2B-selective inhibitor ifenprodil reduced NMDA-activated...
Traumatic brain injury (TBI) elevates Abeta (Aβ) peptides in the and cerebral spinal fluid. Aβ are amphipathic molecules that can modulate membrane mechanics. Because mechanosensitive cation channel PIEZO1 is gated by tension curvature, it prompted us to test effects of on PIEZO1. Using precision fluid shear stress as a stimulus, we found monomers inhibit at femtomolar picomolar concentrations. The oligomers proved much less potent. effect Aβs Piezo gating did not involve peptide-protein...
Microglia are important mediators of neuroinflammation, which underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity not well-understood. Here, we investigated role Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion in microglia attenuates Ca 2+ signaling production inflammatory cytokines by proalgesic agonists. Conditional attenuated proliferation dorsal horn, spinal cytokine levels, potentiation...
Abstract Aim Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the integrated stress response (ISR) within central nervous system (CNS). Methods We determined GDF15 levels utilizing in vitro and vivo neuronal systems wherein ISR was activated. Primarily, we used murine model vanishing white matter disease (VWMD), neurological driven by persistent CNS, to establish link between cerebrospinal fluid (CSF) gene expression signature CNS. also CSF VWM patients....
Traumatic brain injury (TBI) refers to damage resulting from external mechanical force, such as a blast or crash. Our current understanding of TBI is derived mainly in vivo studies that show measurable biological effects on neurons sampled after TBI. Little known about the early responses cells during stimuli and which features stimulus are most critical cell injury. We generated defined shear stress microfluidic chamber using fast pressure servo examined intracellular Ca(2+) levels cultured...
Store-operated Orai1 calcium channels function as highly Ca2+-selective ion and are broadly expressed in many tissues including the central nervous system, but their contributions to cognitive processing largely unknown. Here, we report that measures of synaptic, cellular, behavioral models learning markedly attenuated mice lacking forebrain excitatory neurons. Results with focal glutamate uncaging hippocampal neurons support an essential role amplifying NMDA-receptor-induced dendritic Ca2+...
Store-operated Orai1 channels regulate a wide range of cellular functions from gene expression to cell proliferation. Previous studies have shown that gating is regulated by the outer pore residues V102 and F99, which together function as hydrophobic gate block ion conduction in resting channels. Opening this occurs through conformational change moves F99 away permeation pathway, leading hydration conduction. In addition gate, several postulated presence an inner formed basic R91, K87, R83...
Stromal interaction molecule 1 (STIM1) is a widely expressed protein that functions as the endoplasmic reticulum (ER) Ca2+ sensor and activator of Orai1 channels. In resting cells with replete stores, an inhibitory clamp formed by coiled-coil (CC1) domain interacting CRAC-activation (CAD) STIM1 helps keep in quiescent state. Following depletion ER brake released, allowing CAD to extend away from membrane enabling it activate However, molecular determinants CC1–CAD interactions enforce are...
Mechanical perturbations increase intracellular Ca2+ in cells, but the coupling of mechanical forces to influx is not well understood. We used a microfluidic chamber driven with high-speed pressure servo generate defined fluid shear stress cultured astrocytes, and simultaneously measured cytoskeletal using force sensitive actinin optical sensor Ca2+. Fluid generated non-uniform that critically depended on stimulus rise time emphasizing presence viscoelasticity activating sequence. A short...
The large energy demand from the HVAC industry for residential buildings, along with ever growing need utilization of renewable sources energy, has brought considerable attention to area induced ventilation. Windcatchers are green architectural structures historically used passive ventilation indoor spaces minimal non-renewable consumption. In this paper, a computational fluid dynamics (CFD) model is assess windcatcher’s performance different characteristics windcatcher design. For single...
(Cell Reports 33, 108464-1–108464-14.e1–e6; December 1, 2020) In the originally published version of this article, Figure S1G showed an image Orai1 expression from Allen Brain Atlas website. Because error in unsupervised search output site that tagged unrelated protein for Orai1, we inadvertently protein. The panel has been updated with correct mRNA (verified by re-blasting template probe), and corrected S1 now appears here revised supplemental information online. This change does not affect...
ABSTRACT Microglia are important mediators of neuroinflammation that underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity not well-understood. We investigated role Orai1 channels for microglia-mediated following nerve injury and find deletion in microglia attenuates Ca 2+ signaling production inflammatory cytokines by proalgesic agonists. Conditional attenuated proliferation dorsal horn, spinal levels, potentiation excitatory neurotransmission...
ABSTRACT Aim Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the Integrated Stress Response (ISR) within Central Nervous System (CNS). Methods We determined GDF15 levels utilizing in vitro and vivo neuronal systems wherein ISR was activated. Primarily, we used murine model Vanishing White Matter disease (VWMD), neurological driven by persistent CNS, to establish link between cerebrospinal fluid (CSF) gene expression signature CNS. also CSF VWM patients....
External mechanical forces can reach the cell nucleus causing changes in nuclear morphology, size and motility. A common explanation is that these are transmitted by surrounding cytoskeleton network through its linkage to envelope; shear stress causes reorganization of cytoskeleton, thus, shape. In this study, we measured shape intracellular Ca2+ under fluid MDCK cells using a parallel plate microfluidic chip. We show (1.1 dyn/cm2, 3 hrs) significant cells, from flat disk having larger area...