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Β-Catenin Regulation Of Adult Skeletal Muscle Plasticity, Yuan Wen 2018 University of Kentucky

Β-Catenin Regulation Of Adult Skeletal Muscle Plasticity, Yuan Wen

Theses and Dissertations--Physiology

Adult skeletal muscle is highly plastic and responds readily to environmental stimuli. One of the most commonly utilized methods to study skeletal muscle adaptations is immunofluorescence microscopy. By analyzing images of adult muscle cells, also known as myofibers, one can quantify changes in skeletal muscle structure and function (e.g. hypertrophy and fiber type). Skeletal muscle samples are typically cut in transverse or cross sections, and antibodies against sarcolemmal or basal lamina proteins are used to label the myofiber boundaries.

The quantification of hundreds to thousands of myofibers per sample is accomplished either manually or semi-automatically using generalized pathology software ...


Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan 2018 Wilfrid Laurier University

Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan

Theses and Dissertations (Comprehensive)

This study investigated ovarian development in Fundulus heteroclitus (mummichog), through molecular characterization of key mediators in the ovarian steroidogenic pathway; these included ovarian StAR (steroidogenic acute regulatory protein), cytochrome P450 enzymes, estrogen receptors (ERα, ERβ1 and ERβ2), and gonadotropin receptors (FSHr and LHr); additionally, hepatic vitellogenin (VTG1) and ERs, and brain P450 aromatase (P450arom; CYP19b) were studied. Fish were staged into cortical alveolus, vitellogenic, early mature, late mature, and ovulating stages of maturation; blood (plasma), ovary (tissue and isolated ovarian follicles per stage), liver, and brains were collected. Testosterone (T), 17β-estradiol (E2) and maturation inducing steroid (MIS), measured from ...


Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted ...


Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1751, Mrub_1752 and Mrub_1753 (KEGG map number 02010). We predict these genes encode components of a D-xylose ATP Binding Cassette (ABC) transporter: 1) Mrub_1752 (DNA coordinates 1809004-1810224 on the forward strand) encodes the permease component (aka transmembrane domain), predicted to be an ortholog and 2) Mrub_1753 (DNA coordinates 1810227-1811000 on the forward strand) encodes the ATP-binding domain (aka nucleotide binding domain); and 3) Mrub_1751 (DNA coordinates 1807855-1808892 on the forward strand) encodes the solute binding protein. The ABC-transporter for M. ruber to transport D-xylose is homologous with the transporter ...


Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers 2017 The University of Western Ontario

Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers

Electronic Thesis and Dissertation Repository

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I aimed ...


The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, John J. Amante, Hira Lal Goel, Arthur M. Mercurio 2017 University of Massachusetts Medical School

The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, John J. Amante, Hira Lal Goel, Arthur M. Mercurio

UMass Metabolic Network Publications

Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides and is a target of ferroptosis inducers, such as erastin. The alpha6beta4 integrin protects adherent epithelial and carcinoma cells from ferroptosis induced by erastin. In addition, extracellular matrix (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by alpha6beta4. The mechanism that enables alpha6beta4 to evade ferroptosis involves its ability to protect changes in membrane lipids that are proferroptotic. Specifically, alpha6beta4-mediated activation of Src and STAT3 suppresses expression of ACSL4, an ...


Temporal Regulation Of Chromatin During Myoblast Differentiation, Yasuyuki Ohkawa, Anthony N. Imbalzano 2017 Kyushu University, Japan

Temporal Regulation Of Chromatin During Myoblast Differentiation, Yasuyuki Ohkawa, Anthony N. Imbalzano

UMass Metabolic Network Publications

The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The ...


Examining The Electrical Excitation, Calcium Signaling, And Mechanical Contraction Cycle In A Heart Cell, Kristen Deetz, Nygel Foster, Darius Leftwich, Chad Meyer, Shalin Patel, Carlos Barajas, Matthias K. Gobbert, Zana Coulibaly 2017 Eastern University

Examining The Electrical Excitation, Calcium Signaling, And Mechanical Contraction Cycle In A Heart Cell, Kristen Deetz, Nygel Foster, Darius Leftwich, Chad Meyer, Shalin Patel, Carlos Barajas, Matthias K. Gobbert, Zana Coulibaly

Spora: A Journal of Biomathematics

As the leading cause of death in the United States, heart disease has become a principal concern in modern society. Cardiac arrhythmias can be caused by a dysregulation of calcium dynamics in cardiomyocytes. Calcium dysregulation, however, is not yet fully understood and is not easily predicted; this provides motivation for the subsequent research. Excitation-contraction coupling (ECC) is the process through which cardiomyocytes undergo contraction from an action potential. Calcium induced calcium release (CICR) is the mechanism through which electrical excitation is coupled with mechanical contraction through calcium signaling. The study of the interplay between electrical excitation, calcium signaling, and mechanical ...


Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, Roger J. Davis 2017 University of Massachusetts Medical School

Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, Roger J. Davis

UMass Metabolic Network Publications

Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that ...


Bivalent Epigenetic Control Of Oncofetal Gene Expression In Cancer, Seth E. Frietze, Jonathan A. Gordon, Jessica L. Heath, Terri Messier, Deli Hong, Joseph R. Boyd, Mingu Kang, Anthony N. Imbalzano, Jane B. Lian, Janet L. Stein, Gary S. Stein 2017 University of Vermont

Bivalent Epigenetic Control Of Oncofetal Gene Expression In Cancer, Seth E. Frietze, Jonathan A. Gordon, Jessica L. Heath, Terri Messier, Deli Hong, Joseph R. Boyd, Mingu Kang, Anthony N. Imbalzano, Jane B. Lian, Janet L. Stein, Gary S. Stein

UMass Metabolic Network Publications

Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, noncoding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., genome regions that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G1 phase of the pluripotent stem cell cycle contributes to cell fate decisions. Recently, some cancer types have been shown to exhibit partial recapitulation of bivalent chromatin modifications that are lost along with pluripotency ...


Casein Kinase 2-Mediated Phosphorylation Of Brahma-Related Gene 1 Controls Myoblast Proliferation And Contributes To Swi/Snf Complex Composition, Brian T. Nasipak, Amanda L. Paskavitz, Dominic T. Haokip, Jake M. Schnabl, Jeffrey A. Nickerson, Anthony N. Imbalzano 2017 University of Massachusetts Medical School

Casein Kinase 2-Mediated Phosphorylation Of Brahma-Related Gene 1 Controls Myoblast Proliferation And Contributes To Swi/Snf Complex Composition, Brian T. Nasipak, Amanda L. Paskavitz, Dominic T. Haokip, Jake M. Schnabl, Jeffrey A. Nickerson, Anthony N. Imbalzano

UMass Metabolic Network Publications

Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCbeta1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases. Here, we report that Brg1 is also a target of casein kinase 2 (CK2), a serine/threonine kinase, in proliferating myoblasts. We found that CK2 interacts with Brg1, and mutation ...


Mitochondrial Stress Restores The Heat Shock Response And Prevents Proteostasis Collapse During Aging, Renee M. Brielmann, Mario F. Neto, Yi-Fan Lin, Cole M. Haynes, Richard I. Morimoto 2017 Northwestern University

Mitochondrial Stress Restores The Heat Shock Response And Prevents Proteostasis Collapse During Aging, Renee M. Brielmann, Mario F. Neto, Yi-Fan Lin, Cole M. Haynes, Richard I. Morimoto

UMass Metabolic Network Publications

In Caenorhabditis elegans, the programmed repression of the heat shock response (HSR) accompanies the transition to reproductive maturity, leaving cells vulnerable to environmental stress and protein aggregation with age. To identify the factors driving this event, we performed an unbiased genetic screen for suppressors of stress resistance and identified the mitochondrial electron transport chain (ETC) as a central regulator of the age-related decline of the HSR and cytosolic proteostasis. Mild downregulation of ETC activity, either by genetic modulation or exposure to mitochondria-targeted xenobiotics, maintained the HSR in adulthood by increasing HSF-1 binding and RNA polymerase II recruitment at HSF-1 target ...


Decreasing Cb1 Receptor Signaling In Kupffer Cells Improves Insulin Sensitivity In Obese Mice, Sarah M. Nicoloro, Zhou Zhou, Yuefei Shen, Jie Liu, Nathan J. Coffey, Resat Cinar, Grzegorz Godlewski, Bin Gao, Myriam Aouadi, Michael P. Czech, George Kunos 2017 National Institutes of Health

Decreasing Cb1 Receptor Signaling In Kupffer Cells Improves Insulin Sensitivity In Obese Mice, Sarah M. Nicoloro, Zhou Zhou, Yuefei Shen, Jie Liu, Nathan J. Coffey, Resat Cinar, Grzegorz Godlewski, Bin Gao, Myriam Aouadi, Michael P. Czech, George Kunos

UMass Metabolic Network Publications

OBJECTIVE: Obesity-induced accumulation of ectopic fat in the liver is thought to contribute to the development of insulin resistance, and increased activity of hepatic CB1R has been shown to promote both processes. However, lipid accumulation in liver can be experimentally dissociated from insulin resistance under certain conditions, suggesting the involvement of additional mechanisms. Obesity is also associated with pro-inflammatory changes which, in turn, can promote insulin resistance. Kupffer cells (KCs), the liver's resident macrophages, are the major source of pro-inflammatory cytokines in the liver, such as TNF-alpha, which has been shown to inhibit insulin signaling in multiple cell types ...


Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe 2017 University of Louisville

Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe

Posters-at-the-Capitol

Traumatic brain injury (TBI) was associated with impaired short-term memory with causes of vehicle accidents and falls. Protein plaques containing fibrinogen (Fg), are associated with memory loss. After TBI, Fg in blood was higher than normal (>~2 mg/ml), which resulted in increased Fg in extravascular space. Therefore, Fg bonded to its endothelial receptor intercellular adhesion molecule-1 (ICAM-1). Fg then interacted with cellular prion protein (PrPC), which had a strong effect on the loss of memory and cognition. Mechanisms of Fg and PrPC complex formation and its functional implication are not known. This present study tested the level of Fg-PrPC ...


Hdac3 Regulates Lymphovenous And Lymphatic Valve Formation, Zachary J. Milstone, Masahiro Shin, Nathan D. Lawson, John F. Keaney Jr., Chinmay M. Trivedi 2017 University of Massachusetts Medical School

Hdac3 Regulates Lymphovenous And Lymphatic Valve Formation, Zachary J. Milstone, Masahiro Shin, Nathan D. Lawson, John F. Keaney Jr., Chinmay M. Trivedi

UMass Metabolic Network Publications

Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve development; yet the epigenetic modifiers underlying lymphatic valve morphogenesis remain elusive. Here, we showed that during mouse development, the histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of both lymphovenous valves, which maintain the separation of the blood and lymphatic vascular systems, and the lymphatic valves. Endothelium-specific ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective lymphovenous valve morphogenesis, improper lymphatic drainage, defective lymphatic valve maturation, and complete lethality. Hdac3-deficient lymphovenous valves and lymphatic vessels exhibited reduced expression of the transcription factor Gata2 and its target ...


Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar 2017 Harvard Medical School

Role Of Granulocyte-Macrophage Colony-Stimulating Factor Production By T Cells During Mycobacterium Tuberculosis Infection, Britni L. Stowell, Girija Goyal, Claudio Nunes-Alves, Qianting Yang, Kadamba Papavinasasundaram, Christopher M. Sassetti, Glenn Dranoff, Xinchun Chen, Jinhee Lee, Samuel M. Behar

UMass Metabolic Network Publications

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF(-/-)) are highly susceptible to infection with Mycobacterium tuberculosis, and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T ...


Age-Associated Microrna Expression In Human Peripheral Blood Is Associated With All-Cause Mortality And Age-Related Traits, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H. Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E. Freedman, Martin G. Larson, Joanne M. Murabito, Daniel Levy 2017 The Framingham Heart Study

Age-Associated Microrna Expression In Human Peripheral Blood Is Associated With All-Cause Mortality And Age-Related Traits, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H. Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E. Freedman, Martin G. Larson, Joanne M. Murabito, Daniel Levy

UMass Metabolic Network Publications

Recent studies provide evidence of correlations of DNA methylation and expression of protein-coding genes with human aging. The relations of microRNA expression with age and age-related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole-blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 x 10(-4) (Bonferroni-corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age-associated mRNA expression possibly driven by age-associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict 'microRNA age' that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Deltaage) and found that Deltaage was associated with all-cause mortality (hazards ratio 1.1 per year difference, P = 4.2 x 10(-5) adjusted for sex and chronological age). Additionally, Deltaage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole-blood microRNA expression profiling. Age-associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age-related diseases. Wiley and Sons Ltd.


Heads And Tails, Julie Simons 2017 The California Maritime Academy

Heads And Tails, Julie Simons

Annual Symposium on Biomathematics and Ecology: Education and Research

No abstract provided.


Role Of Nitric Oxide In Embryonic Heart Development And Adult Aortic Valve Disease, Yin Liu 2017 The University of Western Ontario

Role Of Nitric Oxide In Embryonic Heart Development And Adult Aortic Valve Disease, Yin Liu

Yin Liu

Congenital heart disease (CHD) is the most common birth defect in infants. Identifying factors that are critical to embryonic heart development or CHDs in general could further our understanding of the disease and may lead to new strategies of its prevention and treatment. Endothelial nitric oxide synthase (NOS3/eNOS) is known for many important biological functions including vasodilation, vascular homeostasis and angiogenesis. Previous studies have shown that deficiency in NOS3 results in congenital septal defects, cardiac hypertrophy and postnatal heart failure. In addition, NOS3 is pivotal to morphogenesis of aortic valve and myocardial capillary development. The aim of my thesis ...


Role Of Nitric Oxide In Embryonic Heart Development And Adult Aortic Valve Disease, Yin Liu 2017 The University of Western Ontario

Role Of Nitric Oxide In Embryonic Heart Development And Adult Aortic Valve Disease, Yin Liu

Yin Liu

Congenital heart disease (CHD) is the most common birth defect in infants. Identifying factors that are critical to embryonic heart development or CHDs in general could further our understanding of the disease and may lead to new strategies of its prevention and treatment. Endothelial nitric oxide synthase (NOS3/eNOS) is known for many important biological functions including vasodilation, vascular homeostasis and angiogenesis. Previous studies have shown that deficiency in NOS3 results in congenital septal defects, cardiac hypertrophy and postnatal heart failure. In addition, NOS3 is pivotal to morphogenesis of aortic valve and myocardial capillary development. The aim of my thesis ...


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