A5101951064- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Advanced biosensing and bioanalysis techniques
- Pancreatic function and diabetes
- Chemical Synthesis and Analysis
- Diabetes Treatment and Management
- ATP Synthase and ATPases Research
- Mass Spectrometry Techniques and Applications
- Regulation of Appetite and Obesity
- Advanced Proteomics Techniques and Applications
- Enzyme function and inhibition
- Metabolism and Genetic Disorders
- DNA and Nucleic Acid Chemistry
- Biochemical and Structural Characterization
- Alzheimer's disease research and treatments
- Biochemical and Molecular Research
- Metabolomics and Mass Spectrometry Studies
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Click Chemistry and Applications
- Biochemical Analysis and Sensing Techniques
- Diet, Metabolism, and Disease
- Alkaline Phosphatase Research Studies
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
Engineering Associates (United States)
2019-2024
Doon University
2019
Amplyx Pharmaceuticals (United States)
2013
Carnegie Mellon University
2006
Buck Institute for Research on Aging
2002-2004
University of Oregon
2002-2003
Indian Institute of Science Bangalore
2002
University of Virginia
1997
Sequenom (United States)
1995
Baxter (United States)
1992-1994
Shortcomings of previously reported preclinical models nonalcoholic steatohepatitis (NASH) include inadequate methods used to induce disease and assess liver pathology. We have developed a dietary model NASH displaying features observed clinically for objectively assessing progression. Mice fed diet containing 40% fat (of which ∼18% was trans fat), 22% fructose, 2% cholesterol three stages fatty (steatosis, with fibrosis, cirrhosis) as assessed by histological biochemical methods. Using...
Mounting evidence suggests that defects in energy metabolism contribute to the pathogenesis of Alzheimer disease (AD). Cytochrome c oxidase (CO) is kinetically abnormal, and its activity decreased brain peripheral tissue late-onset AD. CO encoded by both mitochondrial nuclear genomes. Its catalytic centers, however, are exclusively two genes, CO1 CO2 (encoding subunits I II, respectively). We searched these as well other for mutations might alter cosegregate with In present study, specific...
There is growing evidence that oxidative phosphorylation (OXPHOS) generates reactive oxygen and nitrogen species within mitochondria as unwanted byproducts can damage OXPHOS enzymes with subsequent enhancement of free radical production. The accumulation this to in brain thought lead neuronal cell death resulting neurodegeneration. predominant are nitric oxide peroxynitrite. Here we show peroxynitrite reacts mitochondrial membranes from bovine heart significantly inhibit the activities...
Two general methods which exploit the reactivity of sulfhydryl groups toward maleimides are described for synthesis oligonucleotide-enzyme conjugates use as nonradioisotopic hybridization probes. In first approach, 6-maleimidohexanoic acid succinimido ester was used to couple 5'-thiolated oligonucleotide calf intestine alkaline phosphatase provide a 1:1 conjugate in 80-85% yield. The second strategy employed N,N'-1,2-phenylenedimaleimide cross-link thiolated horseradish peroxidase or...
We examined the distribution of N-formylkynurenine, a product dioxidation tryptophan residues in proteins, throughout human heart mitochondrial proteome. This oxidized amino acid is associated with distinct subset including an over-representation complex I subunits as well V and enzymes involved redox metabolism. No relationship was observed between modification methionine oxidation, known artifact sample handling. As mitochondria were isolated from normal tissue not subject to any...
Coupling efficiencies for the covalent attachment of oligonucleotides (17-29 bases in length) to solid supports derivatized with alkyl-amino and -carboxylic functionalities have been determined. Attachment 60-80% were obtained coated long-chain alkylamino controlled pore glass (CPG) supports. Similar immobilization observed carboxyl-bearing supports, which additionally exhibited lower levels non-covalent binding. The extent terminally linked oligonucleotide was determined be 50-55% overall...
An apolipoprotein C-II peptide mimetic for the treatment of hypertriglyceridemia activates lipoprotein lipase and blocks C-III.
Defects of the NADH dehydrogenase complex are predominantly manifested in mitochondrial diseases and significantly associated with development many late onset neurological disorders such as Parkinson's disease. Here we describe an immunocapture procedure for isolating this multisubunit membrane-bound from human tissue. Using small amounts immunoisolated protein, one-dimensional two-dimensional gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) peptide...
Recent evidence suggests that mitochondria are closely linked with the aging process and degenerative disorders such as Alzheimer's disease Parkinson's disease. Thus, there has been increasing interest in cataloging mitochondrial proteomes to identify potential diagnostic therapeutic targets. We have previously reported results of a one-dimensional electrophoresis/liquid chromatography MS/MS study characterize proteome normal human heart (Taylor et al. Nat. Biotechnol. 2003, 21, 281−286)....
Abstract Objective Because articular chondrocytes reside in a hypoxic milieu, anaerobic glycolysis is central generating ATP to support chondrocyte matrix synthesis and viability, with mitochondrial oxidative phosphorylation possibly providing physiologic reserve generation. Nitric oxide (NO) potently suppresses phosphorylation. enhanced cartilage NO generation occurs osteoarthritis (OA), we systematically tested for dysfunction the pathogenesis of OA. Methods We assessed depletion situ...
•Duodenal mucosal resurfacing elicits a metabolic benefit in patients with T2DM.•At 6 months post-duodenal resurfacing, HbA1c decreases by 1.0-1.5%.•In high ALT baseline levels, duodenal an reduction of ~40–50%.•FIB-4 scores decrease significantly after resurfacing.•Duodenal insulin-sensitizing, lipid-lowering, anti-inflammatory, and antioxidant effects Insulin resistance is core pathophysiological defect underscoring type 2 diabetes mellitus (T2DM) non-alcoholic fatty liver disease (NAFLD)....
An alternative strategy for mitochondrial proteomics is described that complementary to previous investigations using 2D PAGE techniques. The involves (a) obtaining highly purified preparations of human heart mitochondria metrizamide gradients remove cytosolic and other subcellular contaminant proteins; (b) separation protein complexes sucrose density after solubilization with n-dodecyl-beta-D-maltoside; (c) 1D electrophoresis the gradient fractions; (d) high-throughput robotic gel band...
The kinetics of PaeR7 endonuclease-catalysed cleavage reactions fluorophor-labeled oligonucleotide substrates have been examined using fluorescence resonance energy transfer (FRET). A series duplex were synthesized with an internal CTCGAG PaeKl recognition site and donor (fluorescein) acceptor (rhodamine) dyes conjugated to the opposing 5′ termini. time-dependent increase in resulting from restriction these was continuously monitored initial rate data fitted Michaelis - Menten equation....
The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment metabolic diseases are described. These molecules display enhanced pharmacokinetic profile potent glucoregulatory weight lowering actions compared to native exenatide. [Leu14]exenatide-ABD is an 88 residue peptide amide incorporating Albumin Binding Domain (ABD) scaffold. [Leu14]exenatide-ABP a 53 short Peptide (ABP). exhibited nanomolar functional GLP-1 receptor potency were metabolically stable...
The catalytically essential amino acid in the active site of bacterial alkaline phosphatase (Ser-102) has been replaced with a cysteine by site-directed mutagenesis. resulting thiol enzyme catalyzes hydrolysis variety phosphate monoesters. rate-determining step hydrolysis, however, is no longer same for catalysis when protein nucleophile changed from hydroxyl serine to cysteine. Unlike steady-state kinetics native phosphatase, those mutant show sensitivity leaving group ester.
Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared monotherapy. Here, we extend this hypothesis by linking known anti-diabetic with an anti-obesity into novel hybrid, which termed...
Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed treat type diabetes, their efficacy limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate for use as monotherapy, the development of tolerance agents. Consequently, combination therapies frequently employed effectively regulate blood glucose levels....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect Measurement of Thermodynamic and Kinetic Parameters DNA Triple Helix Formation by Fluorescence SpectroscopyMengsu Yang, Soumitra S. Ghosh, David P. MillarCite this: Biochemistry 1994, 33, 51, 15329–15337Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/bi00255a014https://doi.org/10.1021/bi00255a014research-articleACS PublicationsRequest...