A5047987570- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
- Oral microbiology and periodontitis research
- Signaling Pathways in Disease
- Urinary Bladder and Prostate Research
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- Cancer Mechanisms and Therapy
- Microtubule and mitosis dynamics
- Dental Health and Care Utilization
- Receptor Mechanisms and Signaling
- Cancer Research and Treatment
- Memory and Neural Mechanisms
- Gut microbiota and health
- Cardiac pacing and defibrillation studies
- Cardiac Arrhythmias and Treatments
- TGF-β signaling in diseases
- Ion Channels and Receptors
- Protein Structure and Dynamics
- Cardiac, Anesthesia and Surgical Outcomes
- Peptidase Inhibition and Analysis
Pfizer (United States)
2021-2024
At Bristol
2019-2024
Southmead Hospital
2014-2022
Laboratoire d’immunologie intégrative du cancer
2021
University of Bristol
2008-2020
Array BioPharma (United States)
2004-2013
Dorothy Pattison Hospital
2013
MRC Unit the Gambia
1988-2009
University Hospital Southampton NHS Foundation Trust
2008
Southampton General Hospital
2007
KRASG12D, the most common oncogenic KRAS mutation, is a promising target for treatment of solid tumors. However, when compared to KRASG12C, selective inhibition KRASG12D presents significant challenge due requirement inhibitors bind with high enough affinity obviate need covalent interactions mutant protein. Here, we report discovery and characterization first noncovalent, potent, inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improvement shown be...
Abstract: Markers of serotonin synapses in entire temporal lobe and frontal neocortex were examined for changes Alzheimer's disease by use both neurosurgical autopsy samples. Uptake [ 3 H]sero‐tonin, binding H]imipramine, content indola‐mines all significantly reduced, indicating that nerve terminals are affected. Binding H]serotonin was also whereas H]qui‐nuclidinyl benzilate, H]muscimol, H]dihydroal‐prenolol unaltered. When the samples subdivided according to age, reduction a feature only...
Abstract: Indices of presynaptic cholinergic nerve endings were assayed in neocortical biopsy samples from patients with presenile dementia. For those whom Alzheimer's disease was histologically confirmed, [ 14 C]acetylcholine synthesis, choline acetyltransferase activity and uptake all found to be markedly reduced (at least 40%) below mean control values. The changes occurred both the frontal temporal lobes for synthesis decrease similar under conditions high low neuronal (as assessed by...
The neurological deterioration associated with Alzheimer’s disease, involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is evident neuroinflammation. This now seen to be a significant contributor pathology. Recently the tenet privileged status brain, regarding microbial compromise, has been questioned, particularly in terms neurodegenerative diseases. It being considered that microbiological incursion into central nervous system could either an initiator or these....
Besides being essential for correct development of the vertebrate nervous system neurotrophins also play a vital role in adult neuron survival, maintenance and regeneration. In addition they are implicated pathogenesis certain neurodegenerative diseases, may even provide therapeutic solution some. particular there have been number studies on involvement nerve growth factor (NGF) brain derived neurotrophic (BDNF) Alzheimers disease. This disease is growing concern as longevity increases...
Abstract: Atrophy with ageing of human whole brain, entire temporal lobe, and caudate nucleus was assessed in autopsy specimens, by biochemical techniques. Only the showed changes. Markers for several neurotransmitter systems were also examined changes age. In neocortex lobe small decreases detected markers cholinergic nerve terminals, whereas a large decrease (79%) occurred nucleus. Findings similar striatum from 3–33‐month‐old rats. No change binding [ 3 H]quinuclidinyl benzilate samples....
The origin of pain in osteoarthritis is poorly understood, but it generally thought to arise from inflammation within the innervated structures joint, such as synovium, capsule and bone. We investigated role nerve growth factor (NGF) development murine OA, analgesic efficacy soluble NGF receptor, TrkAD5. OA was induced mice by destabilisation medial meniscus assessed measuring hind-limb weight distribution. RNA extracted joints, TNF expressions were quantified. effect tumour necrosis (TNF)...
The use of Next Generation Sequencing (NGS) techniques has generated a wide variety blood microbiome data. Due to the large variation in bacterial DNA profiles between studies and likely high concentrations cell-free blood, it is still not clear how such data relates viable microbiota. For these reasons much remains be understood about true nature any possible healthy microbiota bacteraemic events associated with disease. gut, reproductive tracts, skin, oral cavity are all sources...
Abnormalities in vascular constriction and dilatation are associated with early diabetes contribute to diabetic complications. However, mechanisms underlying such dysfunction remain be fully elucidated. The current study tests the role of cyclooxygenase-2 (COX-2) smooth muscle dysfunction.Small mesenteric artery aorta isolated from type 2 db/db control mice. Isometric contractions response serotonin, angiotensin II, phenylephrine high potassium determined small spiral arterial or aortic...
The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons basal forebrain rodents. Chronic intracerebroventricular infusion nerve growth factor induces 3- to 4-fold increase gene expression these neurons. Here we report loss third medial septum and vertical limb diagonal band adult mice carrying targeted loss-of-function mutation gene. These deficits are associated 2-fold number apoptotic cells at postnatal...
Low density lipoprotein (LDL) interactions with the endothelium are thought to play a major role in development of atherosclerosis. The mechanism(s) involved not fully understood, although several lines evidence support idea that oxidation LDL increases its atherogenicity. In this study we report for first time native (n-LDL) binding receptor (100-700 mug/ml) triggers rise intracellular calcium which acts as second messenger induce vascular cell adhesion molecule-1 (VCAM-1) expression human...