A5021046825- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- CAR-T cell therapy research
- Cellular transport and secretion
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Hormonal Regulation and Hypertension
- Apelin-related biomedical research
- Ubiquitin and proteasome pathways
- Epilepsy research and treatment
- Neuroendocrine regulation and behavior
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Drug Transport and Resistance Mechanisms
- Adipose Tissue and Metabolism
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Botulinum Toxin and Related Neurological Disorders
- Diet and metabolism studies
- Urinary Bladder and Prostate Research
- Inflammatory mediators and NSAID effects
- Antiplatelet Therapy and Cardiovascular Diseases
- Neuroscience of respiration and sleep
Creative Commons
2015
Hospital for Sick Children
2009-2014
University of Toronto
2009-2014
SickKids Foundation
2012-2014
Evolva (Switzerland)
2009-2012
Yale University
2007-2010
Swedish Orphan Biovitrum (Sweden)
2002-2008
Inserm
2000-2007
Institut Jacques Monod
2005-2007
Sorbonne Université
2005-2007
The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination protein substrates. used massively diverse combinatorial libraries variants develop inhibitors four deubiquitinases (DUBs) and analyzed DUB-inhibitor complexes with crystallography. extended selection strategy conjugating (E2) ligase (E3) found can also enhance enzyme activity. Last, we showed bind selectively ubiquitin-binding domains....
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a new target for 2 diabetes drugs. The aim of the present study was to assess effects inhibition 11β-HSD1 on blood glucose levels, tolerance, and insulin sensitivity in mouse models diabetes. BVT.2733 is an isoform-selective inhibitor 11β-HSD1. Hyperglycemic hyperinsulinemic ob/ob, db/db, KKAy, normal C57BL/6J mice were orally administered (200 mg/kg·d, twice daily). In hyperglycemic, but not mice, lowered circulating...
How vesicular transport participates in neurite outgrowth is still poorly understood. Neurite not sensitive to tetanus neurotoxin thus does involve synaptobrevin-mediated the plasma membrane of neurons. Tetanus neurotoxin-insensitive vesicle-associated protein (TI-VAMP) a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusion [NSF] attachment [SNAP] receptor), involved apical epithelial cells, neurotoxin-resistant pathway. Here we show that TI-VAMP essential for transport-mediating...
Novel antidiabetic arylsulfonamidothiazoles are presented that exert action through selective inhibition of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme, thereby attenuating hepatic gluconeogenesis. The diethylamide derivative 2a was shown to potently inhibit human 11beta-HSD1 (IC(50) = 52 nM), whereas N-methylpiperazinamide analogue 2b only inhibited murine 96 nM). Both compounds showed >200-fold selectivity over and 11beta-HSD2. subsequently reduce glucose levels in...
Article1 December 2009Open Access Comparison of substrate specificity the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays Avinash Persaud Programs in Cell Biology Molecular Structure Function, The Hospital for Sick Children, Toronto, Ontario, Canada Departments Biochemistry Genetics, University Search more papers by this author Philipp Alberts Eva M Amsen Xuejian Xiong James Wasmuth Zachary Saadon Chris Fladd John Parkinson Daniela Rotin Corresponding Author Information Persaud1,2,...
An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (Rigvir) is approved and registered virotherapy, an active specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of Rigvir substage IB, IIA, IIB IIC patients on time progression overall survival. White (N=79) who had undergone surgical excision primary tumour were included this study. All free from disease after surgery...
Outgrowth of the dendrites and axon is basis establishment neuronal shape, it requires addition new membrane to both growing processes. It not yet clear whether one or two exocytotic pathways are responsible for respective outgrowth axons dendrites. We have previously shown that tetanus neurotoxin-insensitive vesicle-associated protein (TI-VAMP) defines a novel network tubulovesicular structures present at leading edge elongating immature hippocampal neurons developing in primary culture...
1. Mechanisms controlling the secretion of [ 3 H]noradrenaline from noradrenergic nerves guinea‐pig isolated vas deferens, prelabelled by incubation with H]noradrenaline, were studied using ( a ) different modes (extramural or transmural) electrical nerve stimulation (a total 300 shocks varying strength, and duration 2 msec) at 1‐30 Hz, b depolarizing concentrations K + (60‐110 m ). 2. The fractional rise in efflux H‐labelled material (Δ t was used to measure H]noradrenaline. 3. dependence...
Ligand binding to the receptor tyrosine kinase fibroblast growth factor (FGF) 1 (FGFR1) causes dimerization and activation by transphosphorylation of residues in domain. FGFR1 is ubiquitylated E3 ligase NEDD4 (also known as NEDD4-1), which promotes internalization degradation. Although phosphorylation required for NEDD4-dependent endocytosis, directly binds a nonphosphorylated region FGFR1. We found that led c-Src kinase-dependent NEDD4, enhancing ubiquitin activity NEDD4. Using mass...
Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP)-mediated fusion of intracellular vesicles with the plasma is crucial for neurite outgrowth, a pathway not requiring synaptobrevin-dependent exocytosis. Yet, it known how TI-VAMP trafficking regulated or coordinated cytoskeletal dynamics within growth cone that guide outgrowth. Here, we demonstrate TI-VAMP, but synaptobrevin 2, concentrates in peripheral, F-actin-rich region cones hippocampal neurons primary culture....
1. The myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum was incubated with [ 3 H]choline (1·125‐1·5 μM), and then superfused Tyrode solution containing hemicholinium‐3 (10 μM). Secretion H]acetylcholine ([ H]ACh) evoked either ( a ) by electrical field stimulation (0·5‐15 Hz, 150 shocks per period, 0·5 msec), used to ‘indirectly’ depolarize varicosities nerve terminals, or b high potassium (40 mM 1 μM‐tetrodotoxin, for 6 min, 80 without tetrodotoxin, min), ‘directly’...
Oncolytic virotherapy is a recent addition to cancer treatment. Here, we describe positive treatment outcomes in three patients using Rigvir virotherapy. One of the diagnosed with melanoma stage IV M1c, one small cell lung IIIA, and histiocytic sarcoma IV. The diagnoses all are verified by histology or cytology. All started within few months after being currently continuing degree regression disease has been determined computed tomography. Safety assessment adverse events graded according...
The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression necessary for neurite outgrowth PC12 cells and hippocampal culture. interacts with plasma endosomal target soluble N-ethylmaleimide-sensitive factor attachment receptors, suggesting mediates a recycling pathway. L1, cell-cell adhesion molecule involved axonal outgrowth, colocalized the developing brain,...
We investigated the interplay between surface trafficking and binding dynamics of immunoglobulin cell adhesion molecule L1 at neuronal growth cones. Primary neurons were transfected with constructs bearing thrombin-cleavable green fluorescent protein (GFP), allowing visualization newly exocytosed or labeling membrane molecules by Quantum dots. Intracellular L1-GFP vesicles showed preferential centrifugal motion, whereas diffused randomly, revealing two pathways to address adhesive sites....
A protein capable of binding atropine and (3H)propylbenzilylcholine mustard was solubilized purified (200-fold) from rat brain. Pronase trypsin, but not phospholipases, diminished the capacity receptor. The molecular weight salt-solubilized receptor as determined by gel filtration in absence detergents is 30,000. showed specificity toward muscarinic ligands. high low affinity dissociation constants receptor.atropine complex are 0.3 nM 0.15 muM. Binding pH-dependent with an optimum at 7.1....
The experiments were done to investigate the presence and subtype of functionally presynaptic muscarinic receptors in cholinergic nerves guinea pig urinary bladder. Bladder strips incubated with 3H-choline superfused Tyrode's solution containing eserine. Secreted 3H-acetylcholine was separated from 3H-choline. electrically evoked secretion increased stimulation frequency. 3H-Acetylcholine enhanced by antagonists, depressed carbachol alpha adrenoceptor agonists but not influenced drugs acting...