A5073624652- Receptor Mechanisms and Signaling
- Pharmacological Effects and Assays
- Cardiac Fibrosis and Remodeling
- Cardiomyopathy and Myosin Studies
- Geographies of human-animal interactions
- Adipose Tissue and Metabolism
- Cardiac Ischemia and Reperfusion
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuropeptides and Animal Physiology
- Cardiovascular Function and Risk Factors
- Signaling Pathways in Disease
- Posthumanist Ethics and Activism
- Cardiovascular Effects of Exercise
- Social Policy and Reform Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Spatial and Cultural Studies
- Heart Failure Treatment and Management
- Pulmonary Hypertension Research and Treatments
- Mass Spectrometry Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Eicosanoids and Hypertension Pharmacology
- Anesthesia and Neurotoxicity Research
San Francisco VA Medical Center
2015-2025
University of California, San Francisco
2015-2025
University of Plymouth
2011-2024
Norwich University
2022
Lucerne University of Applied Sciences and Arts
2020
Northern California Institute for Research and Education
2018
Buck Institute for Research on Aging
2017
Royal Holloway University of London
2015
Queen's University Belfast
1992-2015
University of California, Berkeley
2014
Catecholamines may be one of the molecular signals linking increased circulatory demand to myocardial hypertrophy, and I have found previously that norepinephrine stimulates hypertrophy cultured neonatal rat heart muscle cells through an alpha 1-adrenergic receptor. Since catecholamine stimulation contractility is believed under beta-adrenergic control, asked whether these had dual pathways regulating growth alpha- receptors, respectively. examined effect adrenergic agents on beating...
Proliferating nonmyocardial cells (NMCs) complicate primary heart cultures and may influence myocardial cell (MC) differentiation.In from the day-old rat ventricle, we validated a method to arrest this proliferation; quantitated cross-striated chronotropic response isoproterenol assess MC differentiation.MCs were cultured at single density using an improved method.By 4 days, all could be identified as MCs or NMCs.In treated for 3 days with bromodeoxyuridine (BrdU), 0.1 miw, serial counts...
The role of hormones and other humoral factors in the regulation myocardial hypertrophy has been difficult to evaluate. We asked whether cell could be demonstrated cultures from day-old rat ventricle evaluated effect serum concentration catecholamines on growth process. Two single-cell preparations were used: serum-supplemented, bromodeoxyuridine-treated serum-free with transferrin insulin. Both characterized by predominance (about 75--80% total cells) constant numbers. Myocardial size was...
Cardiac myocytes are activated by hormonal and mechanical signals respond in a variety of ways, from altering contractile function to inducing cardio-protection growth responses. The use genetic mouse models allows one examine the role cardiac-specific other genes cardiac function, hypertrophy, cardio-protection, diseases such as ischemia heart failure. However, studies at cellular level have been hampered lack suitable techniques for isolating culturing calcium-tolerant, adult myocytes. We...
This paper examines geography’s engagements with phenomenology. Tracing phenomenology’s influence, from early humanist reflections on the lifeworld to non-representational theories of practice, identifies emergence a distinct post-phenomenological way thinking. However, there is currently no clear articulation what differentiates post-phenomenology phenomenology as set or ideas, nor trajectories along which such difference can be pursued further. In response this, outlines three key elements...
Abstract Cortical state, defined by population-level neuronal activity patterns, determines sensory perception. While arousal-associated neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes remains unknown. Furthermore, general mechanisms regulating synchrony in wake state are poorly understood. Using vivo imaging and electrophysiology mouse visual cortex, we describe a critical role for astrocytes circuit resynchronization. We characterize...
In addition to activation of muscle contraction by Ca 2+ , recent studies suggest that also affects passive mechanical properties. The goal this study was determine if regulates the stiffness cardiac muscle, independent active contraction. response stretch for mouse demembranated trabeculae probed at different levels after eliminating using a combination two myosin ATPase inhibitors: para -nitroblebbistatin (PNB, 50 μM), plus mavacampten (Mava, μM). Myocardial force level assessed during...
The mechanism of hormonally induced cell hypertrophy is unknown. Stimulation cardiac myocytes by alpha 1-adrenergic agents, phorbol esters, and serum induces an increase in the size nondividing primary culture. Expression c-myc gene, known to be increased growth factor-induced division, was studied this model hypertrophy. alpha-adrenergic agonist norepinephrine (0.002-20 microM) levels c-myc-encoded mRNA 10-fold over control levels. This detectable at 30 min, peaked 2 hr, returned baseline 6...
Protein kinase C (PKC)1 isozymes comprise a family of related cytosolic kinases that translocate to the cell particulate fraction on stimulation. The activated enzyme is thought be plasma membrane. However, phosphorylation protein substrates occurs throughout and inconsistent with membrane localization. Using an isozyme-specific monoclonal antibody we found that, activation, this PKC isozyme translocates myofibrils in cardiac myocytes microfilaments fibroblasts. Translocation cytoskeletal...
Abstract— Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including α- β-myosin heavy chain (MyHC) sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), TH treatment can reverse molecular functional abnormalities hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism but serum levels are usually normal. We studied the regulation receptors (TRs) β1, α1, α2 physiological...
Myocardial hypertrophy in vivo is associated with reexpression of contractile protein isogenes characteristic fetal and neonatal development. The molecular signals for isogene switching are unknown. We studied alpha (sarcomeric)-actin messenger RNA (mRNA) expression cultured cardiac myocytes from the rat. In cells, as adult heart vivo, alpha-actin (cACT) predominated over that skeletal (sACT) mRNA, fetal/neonatal isoform. 1-Adrenergic receptor stimulation induced these increasing total...
Cardiac hypertrophy produced in vivo by pressure overload is characterized selective up-regulation of the fetal/neonatal beta-cardiac myosin heavy chain (MHC) isogene. However, a molecular signal for beta-MHC isogene induction has not been identified. We examined cardiac MHC expression cell culture model hypertrophy. alpha-MHC and iso-protein iso-mRNA levels cultured myocytes were quantified during stimulated alpha 1-adrenergic agonist, norepinephrine (NE). content was increased 3.2-fold vs....
α1-adrenergic receptors (ARs) play a major role in blood pressure regulation. The three α1-AR subtypes (A/C, B, and D) stimulate contraction of isolated arteries, but it is uncertain how different contribute to regulation the intact animal. We studied α1A/C subtype by using gene knockout. knockout (KO) mice were viable overtly normal. LacZ reporter replaced coding sequence KO, β-galactosidase staining was present resistance arteries arterioles, not thoracic aorta or its main branches. By...
Catecholamines and α1-adrenergic receptors (α1-ARs) cause cardiac hypertrophy in cultured myocytes transgenic mice, but heart size is normal single KOs of the main α1-AR subtypes, α1A/C α1B. Here we tested whether α1-ARs are required for developmental by generating α1B double KO (ABKO) which had no binding. In male ABKO growth after weaning was 40% less than WT, smaller due to myocytes. Body other organ weights were unchanged, indicating a specific effect on heart. Blood pressure mice same...
Induction of the fetal isogenes skeletal α-actin (skACT) and β-myosin heavy chain (β-MHC) is characteristic cardiac growth in many models, suggesting a conserved signaling pathway. However, divergent regulation has also been observed. β-Protein kinase C (PKC) transcriptional enhancer factor-1 (TEF-1) are involved induction β-MHC α1-adrenergic-stimulated hypertrophy cultured myocytes (Kariya, K., Farrance, I. K. G., Simpson, P. C.(1993) J. Biol. Chem. 268, 26658-26662; Kariya, Karns, L. R.,...
This paper develops means of apprehending the rhythms everyday practices and performances. Emerging from context recent calls for more explicit engagements with issues surrounding research methods methodologies in doing cultural geography, particular examination geographies practices, responds to critiques discussions urban social that highlight limitations articulation actually rhythms. As such, conversation Lefebvre’s portrait rhythmanalyst other works interested significance rhythm...
Rationale: It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), β1, β2, β3, α1A, and α1B. The β1 β2 are thought to be dominant ARs. Objective: Quantify ARs in individual myocytes. Methods Results: We studied myocytes from wild-type mice, mice with α1A α1B knockin reporters, knockout mice. Using isolated cells, we measured mRNAs, signaling (phosphorylation extracellular signal–regulated kinase phospholamban), contraction. found that were...
AbstractJogging is a relatively under-researched mobile practice with much existing literature focusing on ‘serious’ and competitive running. In this paper, we provide an account of some the movements, meanings experiences that together help produce jogging in south-western English city Plymouth. Drawing upon participant diaries interviews, uncover rich detail about how joggers ascribe not one but number to their practice. Some these are positive, negative; complement each other compete...
Abstract Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors Ca 2+ dynamics fully gate effect synapses as astrocyte-specific deletion three astrocyte-silencing approaches all render...