A5020921049- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cardiovascular Effects of Exercise
- Cellular Mechanics and Interactions
- Genetics, Aging, and Longevity in Model Organisms
- Air Quality and Health Impacts
- Force Microscopy Techniques and Applications
- Viral Infections and Immunology Research
- Genomics and Chromatin Dynamics
- Trace Elements in Health
- Energy and Environment Impacts
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Advanced Fluorescence Microscopy Techniques
- Inhalation and Respiratory Drug Delivery
- Academic Writing and Publishing
- Cardiovascular and exercise physiology
- Cognitive Abilities and Testing
- FOXO transcription factor regulation
- Cardiac Health and Mental Health
- Smart Materials for Construction
- Nanoparticles: synthesis and applications
- Heme Oxygenase-1 and Carbon Monoxide
- Neonatal Respiratory Health Research
Institute of Molecular Biology
2024
Papworth Hospital NHS Foundation Trust
2022
Abcam (United Kingdom)
2019
Norwich Research Park
2016
University of East Anglia
2016
Massachusetts Institute of Technology
2012-2013
Howard Hughes Medical Institute
2012-2013
Boston University
2000-2009
Johns Hopkins University
2009
Boston Biomedical Research Institute
2009
In cardiac and skeletal muscles tropomyosin binds to the actin outer domain in absence of Ca(2+), this position inhibits muscle contraction by interfering sterically with myosin-actin binding. The globular troponin is believed produce B-state thin filament (Lehman, W., Hatch, V., Korman, V. L., Rosol, M., Thomas, L. T., Maytum, R., Geeves, M. A., Van Eyk, J. E., Tobacman, S., Craig, R. (2000) Mol. Biol. 302, 593-606) via I-actin interactions that constrain tropomyosin. present study shows...
Ca(2+) control of troponin-tropomyosin position on actin regulates cardiac muscle contraction. The inhibitory subunit troponin, troponin (cTn)I is primarily responsible for maintaining a tropomyosin conformation that prevents crossbridge cycling. Despite extensive characterization cTnI, the precise role its C-terminal domain (residues 193 to 210) unclear. Mutations within this region are associated with restrictive cardiomyopathy, and deletion in some species, has been myocardial stunning.We...
Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions the elimination of cells during development, maintenance tissue homeostasis, responses to cellular damage. Although a growing body research suggests programmed cell death occur absence caspases, mammalian studies caspase-independent confounded by existence at least seven caspase homologs function redundantly promote death. Caspase-independent is also thought invertebrate nematode Caenorhabditis...
Smooth muscle caldesmon binds actin and inhibits actomyosin ATPase activity. Phosphorylation of by extracellular signal-regulated kinase (ERK) reverses this inhibitory effect weakens binding. To better understand function, we have examined the phosphorylation-dependent contact sites on low dose electron microscopy three-dimensional reconstruction filaments decorated with a C-terminal fragment, hH32K, human containing principal actin-binding domains. Helical negatively stained demonstrated...
Abstract As knowledge about size dependency of particle toxicity continues to grow, attention has been focused on ultrafine particles (i.e., < 0.1 μm in diameter). In recent studies with rats, investigators learned that likely have greater pulmonary than larger particles, and it is possible exposure to, accumulation of, these the human lung may be associated adverse respiratory health effects. part an ongoing study, authors performed bronchoalveolar lavage 14 healthy current nonsmokers...
Knowledge of the local and regional doses inhaled particulates is crucial for inhalation therapy understanding progression pulmonary disease. We studied deposition pattern radioactively tagged particles in rats with chronic bronchitis. Rats were exposed to sulfur dioxide (SO2; 236 +/- 14 ppm) 5 h/d, d/wk 7 wk produce bronchitis (CB). Control room air. The control animals gained 85% more weight over 7-wk period than did CB rats. Five five then 30 min an insoluble 99mTc-labeled aerosol. killed...
Ca2+–calmodulin-dependent phosphorylation of myosin regulatory light chains by the catalytic COOH-terminal half chain kinase (MLCK) activates II in smooth and nonmuscle cells. In addition, MLCK binds to thin filaments situ F-actin vitro via a specific repeat motif its NH2 terminus at stoichiometry one per three actin monomers. We have investigated structural basis MLCK–actin interactions negative staining helical reconstruction. was decorated with peptide containing NH2-terminal 147 residues...
Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosaminetreated hamsters, which we hypothesized might modulate epithelial phenotype by expressing gene(s) homologous to human chromosome 3p deleted small carcinoma of the (SCLC). We differentially screened a 3 library using nitrosamine-treated versus normal hamster cDNAs identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) injured lung. HGFL/MSP mRNA is low...
Striated muscle thin filaments contain hundreds of actin monomers and scores troponins tropomyosins. To study the cooperative mechanism filaments, “mini-thin filaments” were generated by isolating particles nearly matching minimal structural repeat filaments: a double helix subunits with each strand approximately seven actins long spanned troponin–tropomyosin complex. One end was capped gelsolin (segment 1–3)–TnT fusion protein (substituting for normal TnT), other tropomodulin. EM showed...
Tropomyosin (Tm) is an alpha-helical coiled-coil actin-binding protein present in all eukaryotes from yeast to man. Its functional role has been best described muscle regulation; however its much wider cytoskeletal actin regulation still be clarified. Isoforms vary size 284 or 248 amino acids vertebrates, 199 and 161 yeast, spanning 7 4 binding sites respectively. In Saccharomyces cerevisiae, the larger yTm1 produced by internal 38-amino acid duplication, corresponding a single site. We have...
Striated muscle thin filaments adopt different quaternary structures, depending upon calcium binding to troponin and myosin actin. Modification of actin subdomain 2 alters troponin-tropomyosin-mediated regulation, suggesting that this region may contain important protein-protein interaction sites. We used yeast mutant D56A/E57A examine issue. The mutation increased the affinity tropomyosin for 3-fold. addition Ca<sup>2+</sup> containing troponin-tropomyosin produced little increase in...
Wearable activity monitors, together with smartphone-based health and fitness applications (apps), are becoming more accessible their widespread use provides an additional opportunity for the recording of cardiovascular metrics in patients disease. The selected by cardiac rehabilitation (CR) programmes allows facilitation individualized tailored positive lifestyle changes to places patient at centre recovery programme. To investigate role such devices on outcomes a CR programme,...
Summary Fifteen male friendship pairs and 15 female at three grade levels (5th, 7th, 9th) were administered the Self-Rating Scale of Intelligence (SRSI) Lorge-Thorndike intelligence test. The SRSI allowed each S to express an perception self, friend, ideal expected rating self by friend. Results indicated a tendency for perceptions become more stable in females with increasing age, while reverse characterized males' perceptions. Friend-ideal friend congruency increased age females, but...