Myogenin Modulates Exercise Endurance By Altering Skeletal Muscle Metabolism,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Myogenin Modulates Exercise Endurance By Altering Skeletal Muscle Metabolism, James Eric Meadows
Dissertations and Theses (Open Access)
The function of myogenic regulatory factors (MRFs) during adult life is not well understood. The requirement of one of these MRFs, myogenin (Myog), during embryonic muscle development suggests an equally important role in adult muscle. In this study, we have determined the function of myogenin during adult life using a conditional allele of Myog. In contrast to embryonic development, myogenin is not required for adult viability, and Myog-deleted mice exhibited no remarkable phenotypic changes during sedentary life. Remarkably, sedentary Myog-deleted mice demonstrated enhanced exercise endurance during involuntary treadmill running. Altered blood glucose and lactate levels in sedentary Myog-deleted mice after …
Smooth Muscle Hyperplasia Due To Acta2/Myh11 Mutations: Identification Of Novel Pathology And Pathways Leading To Aneurysms And Diverse Vascular Occlusive Diseases,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Smooth Muscle Hyperplasia Due To Acta2/Myh11 Mutations: Identification Of Novel Pathology And Pathways Leading To Aneurysms And Diverse Vascular Occlusive Diseases, Christina L. Papke
Dissertations and Theses (Open Access)
Missense mutations in smooth muscle cell (SMC) specific ACTA2 (á-actin) and MYH11 (â-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs …
The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
The Consequences Of Disrupting The Mdm2-P53 Balance In Hematopoiesis, Hussein A. Abbas
Dissertations and Theses (Open Access)
The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses …
New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver, Svitlana M. Kurinna
Dissertations and Theses (Open Access)
The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target …
Survival Prediction For Brain Tumor Patients Using Gene Expression Data,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato
Dissertations and Theses (Open Access)
Brain tumor is one of the most aggressive types of cancer in humans, with an estimated median survival time of 12 months and only 4% of the patients surviving more than 5 years after disease diagnosis. Until recently, brain tumor prognosis has been based only on clinical information such as tumor grade and patient age, but there are reports indicating that molecular profiling of gliomas can reveal subgroups of patients with distinct survival rates. We hypothesize that coupling molecular profiling of brain tumors with clinical information might improve predictions of patient survival time and, consequently, better guide future treatment decisions. …
Mechanism-Based Strategies To Enhance The Actions Of A,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Mechanism-Based Strategies To Enhance The Actions Of A, Fabiola C. Gomez
Dissertations and Theses (Open Access)
Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due …
Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot
Dissertations and Theses (Open Access)
Cellular invasion represents a critical early step in the metastatic cascade, and many proteins have been identified as part of an “invasive signature.” The non-receptor tyrosine kinase Src is commonly upregulated in breast cancers, often in conjunction with overexpression of EGFR. Signaling from this pathway stimulates cell proliferation, migration, and invasion and frequently involves proteins that regulate the cytoskeleton. My data demonstrates that inhibition of Src, using the small-molecule inhibitor dasatinib, impairs cellular migration and invasion. Furthermore, Src inhibition sensitizes the cells to the effects of the chemotherapeutic doxorubicin resulting in dramatic, synergistic inhibition of proliferation with combination treatments. The …
Inhibition Of Deubiquitinase Activity And Ubiquitination Of Jak2 Blocks Cytokine Signaling And Induces Tumor Cell Apoptosis,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
Inhibition Of Deubiquitinase Activity And Ubiquitination Of Jak2 Blocks Cytokine Signaling And Induces Tumor Cell Apoptosis, Vaibhav Kapuria
Dissertations and Theses (Open Access)
The Jak-stat pathway is critical for cellular proliferation and is commonly found to be deregulated in many solid tumors as well as hematological malignancies. Such findings have spurred the development of novel therapeutic agents that specifically inhibit Jak2 kinase, thereby suppressing tumor cell growth. Tyrphostin AG490, the first described Jak2 inhibitor, displays poor pharmacology and requires high concentrations for anti-tumor activities. Our research group screened a small library of AG490 structural analogues and identified WP1130 as a potent inhibitor of Jak2 signaling. However, unlike AG490, WP1130 did not directly inhibit Jak2 kinase activity. Our results show that WP1130 induces rapid …
The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation,
2010
University of Texas Graduate School of Biomedical Sciences at Houston
The Ubiquitin Ligase Ube4b Is Required For Efficient Epidermal Growth Factor Receptor Degradation, Natalie Sirisaengtaksin
Dissertations and Theses (Open Access)
The length of time that integral membrane proteins reside on the plasma membrane is regulated by endocytosis, a process that can inactivate these proteins by removing them from the membrane and may ultimately result in their degradation. Proteins are internalized and pass through multiple distinct intracellular compartments where targeting decisions determine their fate. Membrane proteins initially enter early endosomes, and subsequently late endosomes/multivesicular bodies (MVBs), before being degraded in the lysosome. The MVB is a subset of late endosomes characterized by the appearance of small vesicles in its luminal compartment. These vesicles contain cargo proteins sorted from the limiting membrane …
Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex,
2010
The Texas Medical Center Library
Cellular And Developmental Functions Of The Xenopus Arvcf-Catenin:Kazrin Complex, Kyucheol Cho
Dissertations and Theses (Open Access)
Xenopus ARVCF (xARVCF), a member of p120-catenin subfamily, binds cadherin cytoplasmic domains to enhance cadherin metabolic stability, or when dissociated, modulates Rho-family GTPases. We previously found that xARVCF binds directly to Xenopus KazrinA (xKazrinA), a widely expressed, conserved protein that bears little homology to established protein families. xKazrinA is also known to influence keratinocyte proliferation-differentiation and cytoskeletal activity. In my study, I first evaluated the expression pattern of endogenous Kazrin RNA and protein in Xenopus embryogenesis as well as in adult tissues. We then collaboratively predicted the helical structure of Kazrin’s coiled-coil domain, and I obtained evidence of Kazrin’s dimerization/oligomerization. …
Genetic And Biochemical Studies Of Plasmid Pir52-1 In Lactobacillus Helveticus,
2010
Utah State University
Genetic And Biochemical Studies Of Plasmid Pir52-1 In Lactobacillus Helveticus, Cody Alexander Tramp
Undergraduate Honors Capstone Projects
Lactobacillus helveticus is a species of lactic acid bacteria. These bacteria, which produce lactic acid as a major product of carbohydrate metabolism, are used industrially to produce cheese and other fermented dairy products (Ebringer et al., 2008). Many species of lactic acid bacteria also possess probiotic characteristics and when ingested potentially confer increased immune function, regulate gut microbiota, and improve digestion in the host (Reid, 2008). Genetic studies of these probiotic effects and other characteristics of L. helveticus and related species have been hindered by the lack of stably replicating plasmid vectors. Plasmid vectors for several Lactobacillus species have been …
A Guide To The Continuing Investigation Of The Relationship Between The Cytoskeleton And Cell Wall In Developing Buds Of Physcomitrella Patens,
2010
University of Rhode Island
A Guide To The Continuing Investigation Of The Relationship Between The Cytoskeleton And Cell Wall In Developing Buds Of Physcomitrella Patens, Derek Brockman
Senior Honors Projects
Persistent questions in biology address the nature of tissue organization and how information encoded in the genome can be manifested as a physical form. While the ‘final’ product of gene expression is a protein, science has yet to elucidate how those proteins are able to interact with other cellular components and external forces to generate a specific cell shape. This complex process is critical in determining not only the shape of an individual cell but also that of an entire organ. In plants, cell shape is controlled by cellulose microfibrils of the cell wall, which are typically oriented perpendicular to …
The Rho Family Gtpase: Determining Gef Specificity Through Recombinant Expression,
2010
Bemidji State University
The Rho Family Gtpase: Determining Gef Specificity Through Recombinant Expression, Farrah Steinke
Honors Capstones
Capstone submitted as a graduation requirement for the BSU Honors Program.
Role Of Protein Kinase C In Tbt-Induced Inhibition Of Lytic Function And Mapk Activation In Human Natural Killer Cells,
2010
Tennessee State University
Role Of Protein Kinase C In Tbt-Induced Inhibition Of Lytic Function And Mapk Activation In Human Natural Killer Cells, Abraham B. Abraha, Krupa Rana, Margaret M. Whalen
Chemistry Faculty Research
Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposure of NK cells to tributyltin (TBT) greatly diminishes their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C (PKC) as well as MAPK activity. TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to …
Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis,
2010
Cornell University
Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio
Dartmouth Scholarship
For over a century, muscle formation in the ascidian embryo has been representative of 'mosaic' development. The molecular basis of muscle-fate predetermination has been partly elucidated with the discovery of Macho1, a maternal zinc-finger transcription factor necessary and sufficient for primary muscle development, and of its transcriptional intermediaries Tbx6b and Tbx6c. However, the molecular mechanisms by which the maternal information is decoded by cis-regulatory modules (CRMs) associated with muscle transcription factor and structural genes, and the ways by which a seamless transition from maternal to zygotic transcription is ensured, are still mostly unclear. By combining misexpression assays with CRM analyses, …
Effects Of Butyltin Exposures On Map Kinase-Dependent Transcription Regulators In Human Natural Killer Cells,
2010
Tennessee State University
Effects Of Butyltin Exposures On Map Kinase-Dependent Transcription Regulators In Human Natural Killer Cells, Rachel J. Person, Margaret M. Whalen
Chemistry Faculty Research
Natural killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT), have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of …
Pcdp1 Is A Central Apparatus Protein That Binds Ca2+-Calmodulin And Regulates Ciliary Motility,
2010
Dartmouth College
Pcdp1 Is A Central Apparatus Protein That Binds Ca2+-Calmodulin And Regulates Ciliary Motility, Christen G. Dipetrillo, Elizabeth F. Smith
Dartmouth Scholarship
For all motile eukaryotic cilia and flagella, beating is regulated by changes in intraciliary calcium concentration. Although the mechanism for calcium regulation is not understood, numerous studies have shown that calmodulin (CaM) is a key axonemal calcium sensor. Using anti-CaM antibodies and Chlamydomonas reinhardtii axonemal extracts, we precipitated a complex that includes four polypeptides and that specifically interacts with CaM in high [Ca2+]. One of the complex members, FAP221, is an orthologue of mammalian Pcdp1 (primary ciliary dyskinesia protein 1). Both FAP221 and mammalian Pcdp1 specifically bind CaM in high [Ca2+]. Reduced expression of Pcdp1 complex …
An Entrepreneurial Approach To Librarianship,
2010
Utah State University
An Entrepreneurial Approach To Librarianship, Flora Shrode, Jennifer Duncan, Wendy Holliday
Library Faculty & Staff Publications
Librarians from Utah State University explain recent efforts to encourage subject librarians to take a more holistic view of their roles. We are shifting from a traditional emphasis primarily on collection development and refocusing on natural connections between collections, instruction, liaison, and reference service. The poster provides background about Utah State University’s situation and explains our approach to analyzing local needs and culture to inform development of a new organizational structure. We describe our vision of subject librarianship, the process by which we assessed librarians’ ideas and goals for performing as subject librarians, and the actions we are taking to …
The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives,
2010
Western Kentucky University
The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao
Masters Theses & Specialist Projects
Water soluble platinum complexes are a recent area of emphasis of cisplatin chemistry. The water soluble complexes could have a reduced toxicity compared with cisplatin. Oxaliplatin, which has an oxalate leaving group, has previously been shown to have less nephro-toxicity and higher water solubility than cisplatin. [Pt(en)(oxalate)] (en = ethylenediamine) has been prepared from Pt(en)Cl2 and silver oxalate. This complex has been reacted with methionine and N-acetylmethionine at different molar ratios. At high Pt: methionine ratios, chelates with the sulfur and nitrogen atoms of the methionine are dominant; at lower Pt: methionine ratios, a bis-methionine product is formed. The en …
Dysautonomia Due To Reduced Cholinergic Neurotransmission Causes Cardiac Remodeling And Heart Failure,
2010
Universidade Federal de Minas Gerais
Dysautonomia Due To Reduced Cholinergic Neurotransmission Causes Cardiac Remodeling And Heart Failure, Aline Lara, Denis D. Damasceno, Rita Pires, Robert Gros, Eneas R. Gomes, Mariana Gavioli, Ricardo F. Lima, Diogo Guimaraes, Patricia Lima, Carlos Roberto Bueno Jr., Anilton Vasconcelos, Danilo Roman-Campos, Cristiane A. S. Menezes, Raquel A. Sirvente, Vera M. Salemi, Charles Mady, Marc G. Caron, Anderson J. Ferreira, Patricia C. Brum, Rodrigo R. Resende, Jader S. Cruz, Marcus Vinicius Gomez, Vania F. Prado, Alvair P. De Almeida, Marco A. M. Prado, Silvia Guatimosim
Anatomy and Cell Biology Publications
Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase …
