A5024088165- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Classical Antiquity Studies
- Classical Philosophy and Thought
- Neuroscience and Neural Engineering
- American Constitutional Law and Politics
- Nicotinic Acetylcholine Receptors Study
- Substance Abuse Treatment and Outcomes
- Behavioral Health and Interventions
- Community Health and Development
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- School Choice and Performance
- Mental Health Research Topics
- Homelessness and Social Issues
- Organic Chemistry Synthesis Methods
- Health Policy Implementation Science
- Pluripotent Stem Cells Research
- Historical Education Studies Worldwide
- Travel Writing and Literature
- Education Systems and Policy
- Cholinesterase and Neurodegenerative Diseases
- Botulinum Toxin and Related Neurological Disorders
LabCorp (United States)
2024
Granta Design (United Kingdom)
2018-2024
Pfizer (United Kingdom)
2009-2021
DePaul University
2009-2019
University of New Orleans
2014-2017
Pfizer (United States)
2011-2015
Medway School of Pharmacy
2014
University of Kent
2014
University of Oxford
2014
University of Warwick
2006-2008
A selective Nav1.7 sodium channel blocker reduced hyperexcitability of iPSC-derived sensory neurons and alleviated pain in a subpopulation patients with an inherited disorder.
Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation. However, defining Nav1.7 contribution to nociceptive signalling has been hampered by lack selective inhibitors. Here we report two potent and arylsulfonamide inhibitors; PF-05198007 PF-05089771, which have used directly interrogate Nav1.7’s role in nociceptor physiology. We predominant functional TTX-sensitive Nav mouse human nociceptors contributes initiation...
The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. ion-conducting α-subunit of the is regulated by two known auxiliary subunits, β1 and β2. We have identified rat human forms an additional subunit, β3. It most closely related to product separate gene localized chromosome 11q23.3. When expressed in Xenopus oocytes, β3 inactivates opening more slowly than does. Structural modeling has amino...
The generation of human sensory neurons by directed differentiation pluripotent stem cells opens new opportunities for investigating the biology pain. inability to generate this cell type has meant that up until now their study been reliant on use rodent models. Here, we a combination population and single-cell techniques perform detailed molecular, electrophysiological, pharmacological phenotyping derived from embryonic cells. We describe evolution populations over 6 weeks differentiation;...
mysterious disappearance of Williams' original document granting McQueen power attorney. And, finally, having authored the Report on Barbarous Indians Province Texas, Padilla possessed knowledge local which might have allowed him to arrange McQueen's murder. Why was this account included? McLean's objective prove that Sterling C. Robertson, also standing gain from death, not murderer. Too, according Robertson family tradition, while traveling Monclova present his case, survived a murder...
NaV 1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers treatment chronic pain. Here, we describe effects PF-01247324, a new generation, selective, orally bioavailable Nav channel blocker novel chemotype.The inhibition by PF-01247324 was studied using in vitro patch-clamp electrophysiology and oral bioavailability antinociceptive demonstrated vivo rodent models inflammatory neuropathic pain.PF-01247324 inhibited native...
1. Cardiac sodium channels are composed of a pore-forming alpha-subunit, SCN5a, and one or more auxiliary beta-subunits. The aim this study was to investigate the role recently discovered member beta-subunit family, SCN3b, in heart. 2. Northern blot Western studies show that SCN3b is highly expressed ventricles Purkinje fibres but not atrial tissue. This contrast uniform expression SCN1b throughout 3. Co-expression with cardiac-specific alpha-subunit SCN5a Xenopus oocytes resulted threefold...
Acute treatment aftercare in the form of sober living environments-i.e., recovery houses-provide an inexpensive and effective medium-term alternative for many with substance use disorders. Limited evidence suggests that house-situated social relationships associated support are critical determinants how successful these residential experiences their members, but little is known about mechanisms underlying relationships. This study explored feasibility using dynamic network modeling to...
TWIK-related K(+) 1 (TREK1) potassium channels are members of the two-pore domain channel family and contribute to background conductances in many cell types, where their activity can be regulated by a variety physiologic pharmacologic mediators. Fenamates such as FFA (flufenamic acid; 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid), MFA [mefenamic 2-(2,3-dimethylphenyl)aminobenzoic acid], NFA [niflumic 2-{[3-(trifluoromethyl)phenyl]amino}nicotinic diclofenac...
Background and Purpose TREK two‐pore‐domain potassium (K 2P ) channels play a critical role in regulating the excitability of somatosensory nociceptive neurons are important mediators pain perception. An understanding roles perception and, indeed, other pathophysiological conditions, has been severely hampered by lack potent and/or selective activators inhibitors. In this study, we describe new, opener channels, GI‐530159. Experimental Approach The effect GI‐530159 on was demonstrated using...
Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage-gated sodium channel alpha-subunits. However, the auxiliary subunits, beta1 is expressed preferentially in only large- and medium-diameter neurons DRG while beta2 absent all cells. In view this, we compared distribution rat spinal cord with novel, recently cloned beta1-like subunit, beta3. situ hybridization studies demonstrated high levels beta3 mRNA small-diameter c-fibres, was virtually these cell types but...
1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with auxiliary Nabeta1.1 and Nabeta2.1 novel, recently cloned subunit, beta3. 2. In situ hybridisation studies demonstrated high levels Nav1.2, Nav1.3, Nav1.6 beta3 at embryonic stages whilst was absent throughout this period. 3. expression occurred after postnatal day 3 (P3), increasing steadily in most brain regions until adulthood. differentially decreased P3 certain areas...
Previous research found that self-regulation and self-efficacy were linked to substance use abstinence. This study examined the relationships between changes in as predictors of A total 150 adult individuals abuse recovery participated a randomized, longitudinal comparing communal housing model versus usual aftercare. The change (p = .014) .032) significantly predictive likelihood Additionally, largely independent. These findings suggest future for examining research.
The putative cache (Ca 2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the α2δ voltage-gated Ca auxiliary subunit family. CACHD1 mRNA were highly expressed in male mammalian CNS, particular thalamus, hippocampus, cerebellum, with a broadly similar tissue distribution V 3 subunits, 3.1. In expression studies, increased cell-surface localization 3.1, these proteins close proximity at cell surface, consistent formation...
Journal Article The Rise of Literacy and the Common School in United States: A Socioeconomic Analysis to 1870. By Lee Soltow Edward Stevens. (Chicago: University Chicago Press, 1981. xii + 247 pp. Maps, illustrations, charts, tables, notes, bibliography, index. Paper, $20.00.) Get access Harvey J. Graff Texas, Dallas Search for other works by this author on: Oxford Academic Google Scholar American History, Volume 69, Issue 2, September 1982, Pages 442–443, https://doi.org/10.2307/1893854...
Studies of self-regulation suggested that self-control requires finite resources which, in turn, may present a significant challenge for those trying to recover from or control addictive behaviors. The study examined the relationships between and abstinence maintenance among adults recovery (n = 606: 407 men, 199 women; M age 38.5 years) residing self-governed, communal living, abstinent homes across United States. Self-regulation scores (controlling sex age) were positively related length...
Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described optimization Nav1.8 modulator series to deliver subtype selective, state, use-dependent chemical matter that is efficacious preclinical models