A5103130908- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Neuropeptides and Animal Physiology
- Pregnancy and preeclampsia studies
- Receptor Mechanisms and Signaling
- Peptidase Inhibition and Analysis
- Cardiac electrophysiology and arrhythmias
- Birth, Development, and Health
- Adenosine and Purinergic Signaling
- Cancer Mechanisms and Therapy
- Nicotinic Acetylcholine Receptors Study
- Venous Thromboembolism Diagnosis and Management
- Cell Adhesion Molecules Research
- Synthesis of β-Lactam Compounds
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neurobiology and Insect Physiology Research
- Nitric Oxide and Endothelin Effects
- Maternal and fetal healthcare
- Blood Coagulation and Thrombosis Mechanisms
- Gestational Diabetes Research and Management
- Metabolism and Genetic Disorders
- Phytochemical compounds biological activities
- Neonatal Respiratory Health Research
Manchester Metropolitan University
2016-2025
Louisiana State University Health Sciences Center Shreveport
2024
University of Leicester
1987-2021
University of Manchester
2013-2015
St Mary's Hospital
2015
Manchester Academic Health Science Centre
2015
St Mary's Hospital
2014
Royal United Hospital
2014
University of Reading
2007-2012
University of Arizona
2012
Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these may enhance inflammation which accelerates the disease progression. We aim to investigate prevalence of and their association with prognosis patients ST-segment elevation myocardial infarction (STEMI).Targeted deep sequencing inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed 485 STEMI. Major adverse...
The thromboxane A2 receptor (TPαR) plays an important role in the amplification of platelet responses during thrombosis. Receptor activity is regulated by internalization and desensitization. mechanism which constitutive surface expression TPαR unknown. Recently, it has been demonstrated that proviral insertion murine lymphoma (Pim) kinase inhibitors reduce functional a TPαR-dependent manner. To investigate whether Pim kinases regulate expression. was measured platelets, human embryonic...
The calcium current of bullfrog sympathetic neurons activates and deactivates rapidly (tau less than 3 ms). For brief depolarizations, the can be fit reasonably well by a Hodgkin-Huxley-type model with single gating particle charge +3. With 2 mM Ca2+ as carrier, half-maximal activation occurs at approximately -5 mV, near voltage where deactivation are slowest. When extracellular divalent ion concentrations reduced, monovalent ions (e.g., Na+ methylammonium) produce kinetically similar inward...
Calcium currents in bullfrog sympathetic neurons inactivate slowly and partially during depolarizations lasting 0.5-1 s. There is also a slower (minutes) inactivation process with broad voltage dependence. An irreversible loss of current (rundown) prominent low concentrations intracellular Ca2+ buffers, either or Ba2+ as the charge carrier. The extent rate more rapid are maximal near at which peak inward generated, suggesting that might be dependent. However, occurs carrier, not prevented by...
The large B cells of bull‐frog sympathetic ganglia are well known to be depolarized by slow synaptic transmission, muscarinic agonists, analogues luteinizing hormone‐releasing hormone (LHRH), and substance P. Voltage‐clamp analysis shows that these actions result from two underlying mechanisms: inhibition the M‐current, a voltage‐dependent potassium current; in some cells, an inward current associated with increase conductance. additional appears as voltage‐insensitive change instantaneous...
Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate permeability in individual cells or couple between adjacent to form gap junctions and thereby provide pathway for regulated intercellular communication. We have examined the role connexins platelets, blood circulate isolation but on tissue injury adhere each other vessel wall prevent loss facilitate wound repair.We report presence notably connexin37,...
1. Sodium currents were recorded from the cell bodies of single dissociated sympathetic neurones bull‐frogs, using patch electrodes in whole‐cell configuration, Cs+‐loaded cells, external Mn2+ to block calcium currents. 2. A discontinuous single‐electrode voltage‐clamp method was used. Switching frequencies 40‐50 kHz possible with 0.5‐2 M omega electrodes, giving clamp settling times approximately 0.2 ms and adequate up 30 nA. 3. The sodium required unusually positive voltages for both...
ABSTRACT Bullfrog ganglia contain two classes of neurone, B and C cells, which receive different inputs exhibit slow synaptic potentials. to most effort has been directed, possess late EPSPs. The sEPSP reflects a muscarinic action acetylcholine released from boutons on whereas the is caused by peptide (similar teleost LHRH) cells. During either there selective reduction in potassium conductances, designated ‘M’ ‘AHP’. M conductance voltage dependent AHP calcium dependent. Normally they act...
Extracellular nucleotides are ubiquitous signalling molecules, acting via the P2 class of surface receptors. Platelets express three receptor subtypes, ADP-dependent P2Y1 and P2Y12 G-protein-coupled receptors ATP-gated P2X1 non-selective cation channel. Platelet can generate significant increases in intracellular Ca2+, leading to shape change, movement secretory granules low levels αIIbβ3 integrin activation. also synergise with several other amplify functional events platelet. In...
Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, regulating sites mechanisms remain unclear. We hypothesised that placental vessels dictate FGR exhibit endothelial dysfunction flow-mediated vasodilatation (FMVD). Resistance was measured normal pregnancies (n = 10) both vivo by umbilical artery Doppler velocimetry ex dual perfusion. Ex FMVD is reduction fetal-side inflow hydrostatic...
Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques versican hyaluronan more prominent eroded plaques. Following disruption, the exposure extracellular matrix (ECM) proteins triggers platelet adhesion thrombus formation. In this study, impact differential composition on function formation was investigated. Platelet adhesion, activation under shear stress conditions were assessed response to...
We have investigated the gating kinetics of calcium channels in A7r5 cell line at level single and whole currents, absence presence dihydropyridine (DHP) channel agonists. Although latencies to first opening macroscopic currents are strongly voltage dependent, analysis amplitude histograms indicates that primary open-closed transition is independent. This suggests molecular mechanisms for sensing distinct, but coupled. propose a modified Monod-Wyman-Changeux (MWC) model activation, where...
Currents carried by Ba2+ through calcium channels were recorded in the whole-cell configuration isolated frog sympathetic neurons. The effect of surface charge on apparent saturation channel with was examined varying [Ba2+]o and ionic strength. current increased [Ba2+]o, I-V relation activation curve shifted to more positive voltages. shift could be described Gouy-Chapman theory, a density 1 e-/140 A2, calculated from Grahame equation. Changes strength (replacing N-methyl-D-glucamine...
Escherichia coli K12 grows on 2-phenylethylamine as sole carbon and energy source by converting it, via phenylacetaldehyde, to phenylacetic acid. Phenylacetaldehyde was formed the action of an inducible amine oxidase catalase activity increased sixfold, presumably ensure removal H202 that expected be a product oxidation. The phenylacetaldehyde oxidized acid NAD+-dependent dehydrogenase. Mutants defective in dehydrogenase cannot grow but can still use it nitrogen source.
Integrin-linked kinase (ILK) has been implicated in the regulation of a range fundamental biological processes such as cell survival, growth, differentiation, and adhesion. In platelets ILK associates with beta1- beta3-containing integrins, which are paramount importance for function platelets. Upon stimulation this association integrins is increased activity up-regulated, suggesting that may be important coordination platelet responses. study conditional knockout mouse model was developed...
A delayed rectifier voltage‐gated K + channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at molecular level. Quantitative RT‐PCR all known Kv α ancillary subunits showed that only Kv1.3 ( KCNA3 ) substantially expressed in human platelets. Furthermore, megakaryocytes from −/− mice or wild‐type exposed to blocker margatoxin completely lacked currents displayed depolarised resting membrane potentials. In platelets, reduced P2X 1 ‐...
Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and source of endogenous NO in vivo remain undefined. In addition, endothelial synthase (NOS-3) critically regulates vessel tone but its modulating function is unclear. this paper we have investigated roles NOS-3 regulating determined functional contribution made by platelet-derived NO.We used a mouse model for directly assessing responses situ presence an intact vascular endothelium with supporting vitro...