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Tomc, Lyn Kathryn. "Role of MEF2 proteins in the activation of the c-jun and MCK genes in skeletal muscle /." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0018/MQ56210.pdf.
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Viveiros, Ryan. "An investigation into the genes mediating myoblast migration in the nematode : Caenorhabditis elegans." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/631.
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During C. elegans embryogenesis, myoblasts initially form two rows along the left and right lateral midlines and at ~290 min of development migrate dorsally and ventrally to form the four muscle quadrants present upon hatching (Sulston et al, 1983). As the myoblasts migrate they are still dividing, as are many other cells in their immediate environment. This means the cell-cell contact of cells during migration is dynamic and can vary from animal to animal (Schnabel et al, 1997). This situation creates an environment where the extracellular matrix (ECM) and cell surface contacts are in constant flux, which begs the questions as to how these cells navigate unerringly to their final destination.
In an attempt to identify genes mediating these migrations, I performed an RNAi based screen targeting 776 genes predicted to be members of the extracellular matrix (ECM), or one of its receptors. Using both feeding and injection based RNAi, I was able to identify three genes of interest. Knockdowns of F56B3.2 resulted in paralyzed animals with detached muscle, making it a good candidate for a new component of the muscle attachment complex. F33G12.4 knockdowns resulted in an embryonic arrest phenotype with an abnormal muscle lineage, possibly stemming from polarity defects. The only knockdown that resulted in muscle migration defects was that for lam-2, which encodes for the laminin gamma subunit. Analysis of the lam-2 knockdown, as well as knockdowns for the other laminin subunits, revealed dorsal/ventral migration defects as well as a posterior displacement of the anterior-most ventral muscle cells. Investigation of this posterior displacement has led to the identification of a previously un-described anterior muscle migration event and its dependency upon the extension of muscle processes from the leading cells.
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Einheber, Steven. "Isolation and characterization of acDNA clone encoding avian skeletal muscle C-protein : an intracellular member of the immunoglobulin superfamily /." Access full-text from WCMC, 1989. http://proquest.umi.com/pqdweb?did=744115441&sid=1&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Kocamis, Hakan. "Functional profiles of growth related genes during embryogenesis and postnatal development of chicken and mouse skeletal muscle." Morgantown, W. Va. : [West Virginia University Libraries], 2001. http://etd.wvu.edu/templates/showETD.cfm?recnum=2026.
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Thesis (Ph. D.)--West Virginia University, 2001.Title from document title page. Document formatted into pages; contains ix, 109 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 88-104).
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Amaral, Ian P. G. "Transcriptional regulation in skeletal muscle of zebrafish in response to nutritional status, photoperiod and experimental selection for body size." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/2616.
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In the present study, the ease of rearing, short generation time and molecular research tools available for the zebrafish model (Danio rerio, Hamilton) were exploited to investigate transcriptional regulation in relation to feeding, photoperiod and experimental selection. Chapter 2 describes transcriptional regulation in fast skeletal muscle following fasting and a single satiating meal of bloodworms. Changes in transcript abundance were investigated in relation to the food content in the gut. Using qPCR, the transcription patterns of 16 genes comprising the insulin-like growth factor (IGF) system were characterized, and differential regulation between some of the paralogues was recorded. For example, feeding was associated with upregulation of igf1a and igf2b at 3 and 6h after the single-meal was offered, respectively, whereas igf1b was not detected in skeletal muscle. On the other hand, fasting triggered the upregulation of the igf1 receptors and igfbp1a/b, the only binding proteins whose transcription was responsive to a single-satiating meal. In addition to the investigation of the IGF-axis, an agnostic approach was used to discover other genes involved in transcriptional response to nutritional status, by employing a whole-genome microarray containing 44K probes. This resulted in the discovery of 147 genes in skeletal muscle that were differentially expressed between fasting and satiation. Ubiquitin-ligases involved in proteasome-mediated protein degradation, and antiproliferative and pro-apoptotic genes were among the genes upregulated during fasting, whereas satiation resulted in an upregulation of genes involved in protein synthesis and folding, and a gene highly correlated with growth in mice and fish, the enzyme ornithine decarboxylase 1. Zebrafish exhibit circadian rhythms of breeding, locomotor activity and feeding that are controlled by molecular clock mechanisms in central and peripheral organs. In chapter 3 the transcription of 17 known clock genes was investigated in skeletal muscle in relation to the photoperiod and food content in the gut. The hypothesis that myogenic regulatory factors and components of the IGF-pathway were clock-controlled was also tested. Positive (clock1 and bmal1 paralogues) and negative oscillators (cry1a and per genes) showed a strong circadian pattern in skeletal muscle in anti-phase with each other. MyoD was not clock-controlled in zebrafish in contrast to findings in mice, whereas myf6 showed a circadian pattern of expression in phase with clock and bmal. Similarly, the expression of two IGF binding proteins (igfbp3 and 5b) was circadian and in phase with the positive oscillators clock and bmal. It was also found that some paralogues responded differently to photoperiod. For example, clock1a was 3-fold more responsive than clock1b. Cry1b did not show a circadian pattern of expression. These patterns of expression provide evidence that the molecular clock mechanisms in skeletal muscle are synchronized with the molecular clock in central pacemaker organs such as eyes and the pineal gland. Using the short generation time of zebrafish the effects of selective breeding for body size at age were investigated and are described in chapter 4. Three rounds of artificial selection for small (S-lineage) and large body size (L-lineage) resulted in zebrafish populations whose average standard length were, respectively, 2% lower and 10% higher than an unselected control lineage (U-lineage). Fish from the L-lineage showed an increased egg production and bigger egg size with more yolk, possibly contributing to the larger body size observed in the early larval stage (6dpf) of fish from this lineage. Fish from S- and L-lineage exposed to fasting and refeeding showed very similar feed intake, providing evidence that experimental selection did not cause significant changes in appetite control. Investigation of the expression of the IGF-axis and nutritionally-response in skeletal muscle after fasting and refeeding revealed that the pattern of expression was not different between the selected lineages, but that a differential responsiveness was observed in a limited number of genes, providing evidence that experimental selection might have changed the way fish allocate the energy acquired through feeding. For example, a constitutive higher expression of igf1a was recorded in skeletal muscle of fish from the L-lineage whereas igfbp1a/b transcripts were higher in muscle of fish from the S-lineage. These findings demonstrate the rapid changes in growth and transcriptional response in skeletal muscle of zebrafish after only three rounds of selection. Furthermore, it provides evidences that differences in growth during embryonic and larval stages might be related to higher levels of energy deposited during oogenesis, whereas differences in adult fish were better explained by changes in energy allocation instead of energy acquisition. In chapter 5 the main findings made during this study and their impact on the literature are discussed.
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GUYON, THIERRY. "Regulation de l'expression des genes codant pour les differents sous-unites du recepteur de l'acetylcholine dans les muscles de patients myastheniques." Paris 6, 1997. http://www.theses.fr/1997PA066373.
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Dans la grande majorite des serums de patients myastheniques, des auto-anticorps pathogenes specifiques des recepteurs nicotiniques de l'acetylcholine (rach) induisent un desordre de la transmission neuro-musculaire. Cependant, aucune correlation stricte n'a ete etablie entre leur titre et la quantite de rach exprimee a la surface des replis post-synaptiques. Nous avons etudie l'implication de la cellule musculaire dans la modulation de la severite de la maladie. A partir de biopsies musculaires de patients avec ou sans anticorps detectables, nous avons observe une augmentation des transcrits codant pour les differentes sous-unite du rach adulte en reponse a l'attaque auto-immune. Ce mecanisme de compensation est un nouveau parametre biologique correle a la severite de la maladie et presentant une grande variabilite d'un patient a un autre. Parallelement, les anticorps monoclonaux et les serums de patients seropositifs induisent, dans la lignee musculaire te671, une augmentation similaire des transcrits codant la sous-unite du rach, et une diminution du nombre de recepteurs exprimes. Ce mecanisme de compensation semble etre induit par l'internalisation du rach independamment de l'influence des facteurs neurotrophiques et de l'activite electrique de la cellule musculaire. En revanche, les serums de patients seronegatifs induisent une augmentation des messagers de la sous-unite du rach sans diminution du nombre de recepteurs exprimes suggerant l'existence d'un facteur serique implique dans l'alteration de la fonction du rach, via l'interaction avec une autre cible presente a la surface des cellules musculaires. L'ensemble de ces travaux suggerent un role actif de la cible musculaire dans l'evolution et dans la modulation de la severite de la myasthenie, et souleve de nouvelles hypotheses concernant la physiopathologie de la myasthenie seronegative et les mecanismes de regulation du rach.
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Matsakas, Antonios [Verfasser]. "Effect of exercise on the mRNA expression of growth factors, metabolic genes and myosin heavy chain isoforms in skeletal muscles of the rat / Antonios Matsakas." Hamburg : Diplom.de, 2004. http://d-nb.info/118563598X/34.
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Lacour, Floriane. "Contrôle des voies de signalisation Wnt par R-spondin1 au cours de la régénération du muscle squelettique adulte." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB035/document.
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Le muscle squelettique adulte a une importante capacité à se régénérer après une lésion. La régénération musculaire dépend de divers signaux moléculaires tels que l’activation de la signalisation Wnt dans les cellules souches musculaires, appelées cellules satellites. Les protéines R-spondins (Rspo) composent une famille de quatre protéines qui ont un rôle d’activateurs/potentialisateurs sur les voies Wnt dans les cellules souches de différents tissus. Bien qu’il soit connu que ces protéines sont importantes pour la régénération de ces tissus, leur rôle dans la myogenèse régénérative n’a pas été étudié à ce jour. L’expression génique de R-spondin1 étant sur-régulée par Pax7, le marqueur des cellules satellites, nous avons émis l’hypothèse que R-spondin1 participe à la régénération musculaire. Nous avons, tout d’abord, isolé les cellules souches musculaires des modèles murins d’invalidation constitutive pour Rspo1 et avons observé qu’une déficience de R-spondin1 n’altère pas le cycle cellulaire de ces cellules. Cependant, une altération de l’expression de Rspo1 induit un défaut global de la cinétique de différenciation myogénique. Nous montrons que R-spondin1 inhibe la fusion des cellules musculaires puisque les myotubes déficients pour R-spondin1 possèdent un plus grand nombre de noyaux. Nous avons ensuite induit la régénération du muscle squelettique Tibalis Antérieur par une injection de Cardiotoxine et nous avons analysé les muscles à différents temps de régénération. Nos données prouvent qu’en l’absence de R-spondin1, les cellules souches présentent un retard de différenciation alors qu’elles possèdent une plus grande capacité de fusion, ayant pour conséquence une hypertrophie des myofibres dans le muscle. Concordant au rôle de R-spondin dans les cellules souches intestinales ou dans le follicule pileux, la protéine R-spondin1 stimule l’expression des gènes cibles de la voie Wnt canonique dans les cellules souches musculaires. Nous avons mis en évidence que R-spondin1 potentialise la voie Wnt canonique et régule négativement l’activation de la voie non-canonique dans les cellules. Nos résultats démontrent que la protéine R-spondin1 contribue à la régénération du muscle squelettique adulte par la régulation de l’activation des voies WntAdult mammalian skeletal muscles have the remarkable ability to repair after injury. Muscle regeneration depends on various cellular and molecular responses, such as activation of Wnt signaling pathways in muscle stem cells called satellite cells. R-spondin (Rspo) proteins are able to potentiate Wnt signaling pathways in vivo in many stem cells and play important role for regeneration of several tissues. The role of R-spondin in injury-induced myogenesis has not been studied. Given that R-spondin1 gene expression is up-regulated by Pax7, the satellite cell-specific transcription factor, we explored the hypothesis that R-spondin1 plays a role during skeletal muscle regeneration. We firstly isolated primary myoblasts from Rspo1 constitutive knock-out mice and observed that a depletion of Rspo1 did not alter cell cycle of these cells. However, a lack of R-spondin1 on cells resulted in global alteration of differentiation kinetics. We found that R-spondin1 inhibits muscle cell fusion, as Rspo1 knock-out myotubes contain an higher number of myonuclei. Then, we injured the Tibialis Anterior (TA) muscle of Rspo1-null mice and littermates controls by Cardiotoxin injection and analyzed muscle regeneration at different time points following injury. Our data show that R-spondin1 removal results in a delay of stem cell differenciation. In contrast, a R-spondin1 deficiency leads to better cell capacity to fuse to dommaged myofibers, giving rise to myofiber hypertrophy. As with other tissue-specific stem cells, such as hair follicle or intestinal crypt stem cells, R-spondin1 potentiates canonical Wnt signaling target genes expression in muscle stem cells. We proved that R-spondin1 potentiates canonical Wnt signaling target genes expression and negatively regulates non-canonical signaling in muscle stem cells. Our results demonstrate that R-spondin1 is crucial for adult muscle regeneration through a tighly cross-talk regulation between Wnt signalings
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Sallum, Adriana Maluf Elias. "Correlações da expressão de MHC-I e II, C5b-9 e fenotipagem de células inflamatórias em tecido muscular na dermatomiosite juvenil (DMJ)." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-02102014-094536/.
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A presença de uma inflamação crônica no músculo, a associação com outras doenças e a presença de auto-anticorpos, sugere o envolvimento de um mecanismo autoimune na patogênese da DMJ. Trinta e sete fragmentos musculares de pacientes com o diagnóstico de DMJ foram estudados com o objetivo de avaliar a expressão de MHC classes I e II, C5b-9 e fenotipagem das células inflamatórias CD4, CD8, CD20 e CD68 em tecido muscular e correlacionar com os principais parâmetros clínicos, laboratoriais, histológicos e terapêuticos desta doença. Os achados foram comparados à expressão em oito fragmentos musculares de pacientes com polimiosite (PM), cinco de dermatomiosite (DM) e quatro de distrofia. As expressões de MHC-I, MHC-II e C5b-9 foram identificadas por imunohistoquímica, através da técnica de imunoperoxidase StreptABComplex/HRP; as células CD20 e CD68, pelo sistema LSAB+ e CD4 e CD8, pela técnica EnVision-AP. A expressão de MHC-I apresentou positividade em 97,2% dos casos, enquanto que a expressão de MHC-II foi observada em apenas 21,6% dos casos. C5b-9 (83,8% de positividade), correlacionou-se com a presença de calcinose e envolvimento cardíaco. A presença de linfócitos CD4 (81,1% de positividade), CD8 (86,5% de positividade) e CD20 (62,2 % de positividade), e CD68 (97,2% de positividade) correlacionaram-se com o grau de inflamação observada na histologia muscular. A presença de CD4 e CD68, e marcação de C5b-9 também se correlacionaram com a intensidade de fraqueza muscular, e laboratorialmente, CD4 correlacionou-se com níveis elevados de CK e CD20 com DHL. Na DMJ observou-se maior expressão de C5b-9, CD4 e CD8 e menor expressão de MHC-I e II em comparação à DM e PM. A expressão destes marcadores foi sempre menor na distrofia. A expressão de MHC-I, adjuvante ao envolvimento dos linfócitos CD4 e CD8, sugere um mecanismo inicial celular citotóxico relacionado a maior gravidade do envolvimento muscular. A concomitância da maior expressão de C5b-9 foi um fator preditivo de comprometimento sistêmico e demanda de terapêutica imunossupresssora. Os resultados deste estudo apontam para o papel do MHC-I e II, C5b-9, CD4, CD8, CD20 e CD68 na patogênese da DMJThe presence of chronic muscle inflammation, in association with other diseases and seric autoantibodies in JDM patients, suggest the involvement of an autoimmune mechanism in the pathogenesis of this inflammatory myopathy. Thirty seven muscle biopsy specimens from patients with JDM were analyzed in order to assess the expression of MHC-I and II, C5b-9, CD4, CD8, CD20 and CD68 and to correlate with the clinical, laboratorial, histological and therapeutical parameters. These findings were compared to the expression in five dermatomyositis (DM), eight polymyositis (PM) and four dystrophy cases. Immunohistochemical reactions for MHC-I and II and C5b-9 (StreptABCcomplex/HRP), CD4, CD8 (EnVision-AP) and CD20, CD68 (LSAB+) were evaluated. MHC-I expression was positive in 97.2% of the cases, whilst MHC-II was positive in only 21.6% of the cases. C5b-9 expression (positivity of 83.8%) correlated with calcinosis and cardiac involvement. The presence of lymphocytes CD4 (positivity of 81.1%), CD8 (positivity of 86.5%), CD20 (positivity of 62.2%), and CD68 (positivity of 97.2%) correlated with inflammation in muscular histology. The presence of CD4 and CD8 and expression of C5b-9 also correlated with the severity of muscle weakness, and CD4 expression correlated with serum levels of CK and CD20 with LDH. In JDM, the expressions of C5b-9, CD4 and CD8 were statistically more significant when compared to PM and DM, while expressions of MHC-I and II were lower in JDM. All expressions were lower in dystrophy. MHC-I expression, adjuvant to the presence of CD4 and CD8 lymphocytes, corroborates the involvement of the cytotoxic cellular mechanism of muscular lesion in JDM, which correlates to severity. Concomitantly, C5b-9 expression was a predictive factor of systemic involvement and of the need for imunossupressive treatment. The results of this study indicate for the function of MHC-I and II, C5b-9, CD4, CD8, CD20 e CD68 at JDM pathogenesis
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Singh, Anish D. "Regulation and function of the non-muscle [beta]-actin and [gamma]-actin genes." Phd thesis, Department of Paediatrics and Child Health, Faculty of Medicine, 2004. http://hdl.handle.net/2123/11556.
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Kim, Soo Hyun. "Gene therapy demonstrates that muscle is not a primary target for non-cell autonomous toxicity in familial ALS." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164829314.
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Coll-Lladó, Clara. "Evolution of muscle regulatory genes in chordates." Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/16136.
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Render, Timothy John. "A study of muscle pattern formation in Drosophila melanogaster." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240123.
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Bestard, Jennifer. "Dystrophin gene regulation in muscle." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0016/MQ54086.pdf.
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Piper, Tony Andrew. "A study of the transfer of recombinant dystrophin genes into skeletal muscle cells." Thesis, Royal Holloway, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286683.
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White, Peter. "Nutritional regulation of muscle gene expression." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624160.
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Raue, Ulrika. "Skeletal muscle gene expression with age." Virtual Press, 2007. http://liblink.bsu.edu/uhtbin/catkey/1370882.
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The aim of this research was to investigate myogenic (i.e. growth) and proteolytic (i.e. breakdown) gene expression (GE) in skeletal muscle of young and old women. Myogenic (MyoD, MRF4, Myf5, myogenin, myostatin) and proteolytic (Atrogin-1, MuRF-1, FOXO3A) genes were examined in the basal state and after resistance exercise (RE). Six old women (OW: 85 ± 1 y) and eight young women (YW: 23 ± 1) performed 3 x 10 knee extensions at 70% of 1-repetition-maximum. Muscle biopsies were obtained from the vastus lateralis (i.e. thigh) before and 4 hours after RE.In the basal state, OW expressed higher levels (p<0.05) of MyoD, MRF4, myf5, myogenin, myostatin, FOXO3A and MuRF-1 compared to YW. Fiber type specific GE analysis in the OW showed that slow-twitch muscle fibers (MHC I) expressed higher levels (p<0.05) of myogenin and Atrogin-1, compared to fast-twitch (MHC Ila) fibers. In response to RE both YW and OW increased (p<0.05) mRNA levels of MyoD and MRF4, while a decrease (p<0.05) was observed for myostatin. MuRF-1 mRNA increased (p<0.05) in both age groups, while there was an age-specific induction (p<0.05) of Atrogin-1 after RE. Fiber type specific GE after RE in the old women showed that MHC Ila fibers did not induce myogenic GE. Robust increases (p<0.05) in MyoD, MRF4, and myogenin were only observed in the MHC I fibers. Both fiber types decreased (p<0.05) myostatin, and increased Atrogin-1 with RE. MuRF-1 mRNA levels increased specifically in MHC Ila fibers. In summary, skeletal muscle of OW expresses higher levels of mRNA for most selected genes at rest. With RE, aging skeletal muscle retains the ability to induce myogenic GE, although exclusive to MHC I fibers. After RE, proteolytic GE induction is greater in OW and most pronounced in MHC Ila fibers. Collectively, these data suggest that an imbalance exists in the regulation of the myogenic and proteolytic program in aging skeletal muscle. This research also provides the first evidence of intrinsic molecular differences between MHC I and MHC Ila fibers in OW, and may, in part, explain the MHC Ila atrophy apparent in sarcopenic muscle.School of Physical Education, Sport, and Exercise Science
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Rose, Patricia Camela. "Gene Expression in Vascular Smooth Muscle:." ScholarWorks @ UVM, 2007. http://scholarworks.uvm.edu/graddis/199.
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Vascular diseases such as hypertension are marked by changes in calcium (Ca2+) and extracellular signal regulated kinase (ERK) signaling in the arterial wall. The overall goal of this project was to better understand pathways leading to altered gene regulation in cerebral arteries. Two models were tested to determine if, 1) Ca2+/cAMP response element binding protein (CREB) is regulated in intact cerebral arteries by multiple sources of Ca2+, and 2) hypertensive disease causes changes in genes regulated by ERK and CREB. Ca2+-mediated phosphorylation of CREB (P-CREB) was measured by immunofluorescence in both cultured vascular smooth muscle cells (VSMCs) and in intact cerebral arteries. The level of P-CREB was increased by both Ca2+ influx through voltage-dependent calcium channels (VDCCs) and store-operated Ca2+ entry (SOCE) in VSMCs. A similar increase in P-CREB was observed following stimulation of VDCCs and SOCE in intact cerebral arteries. However, unlike the results obtained from VSMCs phosphorylation of CREB following Ca2+ store depletion using thapsigargin, was partially dependent on Ca2+ entry through VDCCs, suggesting that communication between Ca2+ entry pathways in intact arteries may be lost during cell culture. The second model was tested using immunocytochemistry and RNA analysis to measure differences in cerebral artery signal transduction and gene expression caused by chronic hypertension in the Dahl salt sensitive genetic hypertensive rat model. Arteries from hypertensive animals exhibited increased phosphorylation of ERK and expression of Ki-67, a marker of proliferation, when compared to controls. In addition, microarray analysis of arterial RNA revealed overexpression of the matricellular ERK-regulated genes osteopontin (OPN), and plasminogen activator inhibitor 1 (PAI-1), and the activator protein transcription factor (AP-1) member junB in cerebral arteries, with validation using RT qPCR. To elucidate a role for CREB, ERK and JunB in the transcriptional regulation of OPN and PAI-1, VSMCs were treated with angiotensin II (Ang II), a vasoconstrictor linked to hypertension, and confirmed activator of OPN and PAI-1 transcription. Ang II induced an ERK-dependent transient increase in junB mRNA and protein prior to OPN, and PAI-1 induction. Gene silencing experiments indicated that OPN and PAI-1 are reciprocally regulated by junB and CREB, respectively, and that CREB is a negative regulator of OPN. Data from cell culture confirms that the Ang II response in VSMCs is transient, in contrast to the hypertensive in vivo model, suggesting that the CREB and ERK response induces long term changes. Together, these data have revealed mechanisms for regulation of gene expression that are linked to proliferation and remodeling in the arterial wall. Future experiments will explore an in vivo role for Ang II and SOCE in the mediation of ERK- and CREBregulated gene expression. This research has the potential to help in defining therapeutic strategies to prevent arterial remodeling caused by arterial pathologies such as hypertension.
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Davignon, Laurianne. "Identification and characterisation of new genes associated to multiminicore disease." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066696/document.
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Les myopathies congénitales sont des pathologies génétiques rares caractérisées par une hypotonie néonatale, un retard moteur et une faiblesse musculaire. Notre laboratoire s'intéresse à la myopathie à multiminicore (MmD) qui se caractérise par une réduction de l'activité mitochondriale en de multiples points focaux et une désorganisation des sarcomères au sein de la fibre musculaire. Notre groupe est à l'origine de l'identification de la plupart des gènes mutés dans cette pathologie. Néanmoins, 30% des cas restent à ce jour sans diagnostic moléculaire. L'étude d'une famille consanguine a permis d'identifier une mutation homozygote tronquante dans la région codante d'un coactivateur transcriptionnel (appelé TCA) dont la fonction n'a jamais été associée au muscle. L'analyse des cellules de patients a révélé l'absence d'ARN messager ainsi que l'absence de protéine. Par des analyses transcriptomiques sur un modèle d'extinction transitoire de TCA, j'ai pu mettre en évidence une diminution de l'expression des protéines musculaires contractiles (en différenciation) et une augmentation des protéines du cycle cellulaire (en prolifération) suggérant que TCA joue un rôle dans la balance prolifération/différenciation au sein du tissu musculaire. Nous présentons ici une nouvelle forme de myopathie congénitale avec un profil histologique original qui met en évidence l'existence de nombreux points communs entre les différentes formes de myopathies mais également avec les dystrophies musculaires. Nous avons identifié un nouveau gène impliqué dans les maladies génétiques humaines qui se trouve être un acteur de la balance prolifération/différenciation au sein du muscleCongenital myopathies are rare genetic disorders characterized by neonatal hypotonia, delayed motor development and muscle weakness. Our laboratory is particularly interested in the study of multi-minicore disease (MmD), which is characterised by multiple foci of mitochondria depletion and short sarcomere disorganisation areas (cores) within muscle fibers. Our group identified most of the genes associated to this genetically and phenotypically heterogeneous condition. However, at least 30% of multiminicore disease cases are not associated with the known genes and remain genetically uncharacterized. The study of a large consanguineous family by homozygosity mapping allowed the identification of a homozygous nonsense mutation in the coding sequence of a transcriptional coactivator (named thereafter TCA), which had never been associated with a muscle condition. qPCR and western blotting showed absence of messenger and protein on patient samples. A microarray performed on a transient TCA silencing model, which disclosed a tendency to downregulation of muscle and contractile proteins (in differentiation conditions), and an upregulation of cell cycle proteins (in proliferative conditions), suggesting a role of TCA in regulating the proliferation/differentiation balance in muscle. Thus, we report a novel congenital muscle condition with a unique histological pattern, stressing the histological overlap of different forms of congenital myopathies and muscular dystrophies. We characterize a new gene in human genetic conditions and a novel regulator of the proliferation/differentiation balance in muscle
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Nowacka, Lidia. "Muscle gene transfer studies of a 27-BP segment of the troponin I fast gene IRE enhancer." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111563.
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The fast-skeletal-muscle-fiber-specific expression of the troponin I(fast) (TnIfast) gene is driven by an Intronic Regulatory Element (IRE) located within the first intron of the gene. The IRE is a 148 bp transcriptional enhancer that contains several known and suspected cis-regulatory elements. These include the E-box, the closely-spaced MEF2 site and CACT box, the CACC site, and the CAGG element. Previous loss-of-function studies performed using the quail TnIfast IRE suggest that its activity depended on the MEF2 and CACT elements. The goal of my thesis research was to determine whether the MEF2 and CACT sites were not only necessary, but also sufficient, to support IRE activity. I prepared head-to-tail multimers of a 27-bp IRE segment that consisted largely of the near-adjacent MEF2 and CACT elements and did not contain any other known/suspected elements. These multimers were cloned upstream of a reporter gene consisting of the minimal promoter of the quail TnIfast gene linked to sequences encoding human placental alkaline phosphatase. The transcriptional capabilities of the constructs were assessed by gene transfer into the mouse soleus muscle in vivo by intramuscular injection/electroporation, and histochemical analysis of reporter enzyme plap expression including quantitative microdensitometry. I found that expression of these constructs was readily detectable and that it was markedly reduced by prior mutation of the CACT and, especially, of the MEF2 sites. These data indicate that the short DNA segment containing MEF2 and CACT elements is sufficient to drive expression in skeletal muscle and confirms the functional importance of these specific elements.Although constructs containing the wild-type IRE 27-bp region were expressed, there was little preferential expression in fast fibers, in contrast to expression driven by the complete 148-bp IRE. Thus my results indicate that the MEF2 and CACT elements are not sufficient to drive fast fiber-type-specific expression, and suggest that additional elements outside of the 27-bp region tested are also necessary for fiber-type-specificity.
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Lau, Justine Yeeman, and jlau@med usyd edu au. "Novel genes associated with airway smooth muscle proliferation in asthma." University of Sydney, 2008. http://hdl.handle.net/2123/5134.
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Doctor of Philosophy (PhD)It is well recognised that both genetic and environmental factors determine an individual’s predisposition to asthma. In recent years, the airway smooth muscle (ASM) cell has come to the attention of researchers to, not merely be a contractile cell of the airway, but one that orchestrates events affecting airway remodelling and proliferation. Experiments described in this thesis have, for the first time, examined genes that are associated with various aspects of the pathogenesis of asthma by using the candidate gene approach and a genome wide search. Genes have not only been identified to be differentially expressed in ASM cells derived from asthmatic and non-asthmatic participants, but have also been linked with a functional consequence of asthma. The three genes found to be differentially regulated between ASM cells derived from asthmatic and non-asthmatic participants were Peroxisome Proliferator-Activated Receptor- gamma (PPARγ), mimecan and fibulin-1. Expression of the anti-proliferative transcriptional factor PPARγ, found by the candidate gene approach, was elevated in ASM cells derived from asthmatic participants. Whilst elevated, the anti-proliferative effect of PPARγ was absent in ASM cells derived from asthmatic participants. By microarray analysis, mimecan, an anti-proliferative agent was identified. Mimecan levels, although not different basally in ASM cells, were upregulated by transforming growth factor β (TGFβ) only in asthmatic derived ASM cells. Silencing mimecan, by the use of specific oligonucleotides, increased proliferation of ASM cells. This suggested that by increasing mimecan expression, the proliferation of ASM cells may be halted. Fibulin-1, also found by microarray analysis and the final gene examined in this thesis, was found in elevated levels in BAL fluid, serum and ASM cells obtained from asthmatic participants. In addition, ASM cells derived from asthmatic participants, for the first time were shown to have faster wound healing rates compared with nonasthmatics. The elevated fibulin-1 levels in ASM cells derived from asthmatic participants, in the presence of TGFβ, were demonstrated to contribute to this increased wound healing. Specifically, fibulin-1 was found to affect wound healing by increasing proliferation rather than migration. The current available treatments for asthma, target the contractility and inflammatory conditions in the airway. Through this thesis, novel genes discovered to be associated with proliferation may be potential therapeutic targets to treat asthma. In particular, the fibulin-1 gene is outstandingly promising, as it was shown that silencing fibulin-1 resulted in slower wound healing rates through decreased cell proliferation, to possibly inhibit the airway remodelling observed in asthma, and furthermore, corticosteroid therapy was demonstrated not to affect to this gene.
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Cooper, Brian. "Regulation of two muscle-specific genes during Xenopus heart development." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327029.
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Verardo, Lucas Lima. "Differentially expressed genes and miRNA identification in pig skeletal muscle." Universidade Federal de Viçosa, 2011. http://locus.ufv.br/handle/123456789/4757.
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O suíno (Sus scrofa) é considerado um animal de grande importância para produção de carne, sendo seu potencial de crescimento muscular objeto de grande interesse e geralmente associado com características determinadas na fase pré-natal durante a miogênese. Para o estudo de genes responsáveis por estas características, as etiquetas de sequências expressas (Expressed Sequence Tags - EST) fornecem informações diretas sobre o transcriptoma e indiretas sobre a relação entre o genoma e diferentes fenótipos, proporcionando o conhecimento sobre genes diferencialmente expressos (GDE) bem como sequências genômicas transcritas para o controle da expressão gênica como, por exemplo, alguns RNAs não codificantes. Características de tecidos musculares em suínos podem ser influenciadas diretamente por genes, e estes sendo regulados como, por exemplo, através de miRNAs, em diferentes fases de desenvolvimento. O presente trabalho teve como objetivo a identificação e a anotação in sílico de GDE e sequências não codificantes, com enfoque aos miRNAs, de bibliotecas de cDNA construídas a partir do músculo esquelético semi-membranoso de três diferentes raças de suínos (Duroc, Large White e naturalizada brasileira Piau) bem como a análise dos níveis de expressão dos genes identificados e miRNAs em sete fases de desenvolvimento do Longissimus Dorsi (21, 40, 70 e 90 dias pré-natal e 107, 121 e 171 dias pós-natal) de animais de linha comercial. Foram identificados 34 GDE sendo 21 pertencentes a uma rede gênica musculo-específica. Destes, 13 genes tiveram seus perfis de expressão analisados com o uso do qRT-PCR durante os sete períodos citados, formando quatro grupos de expressão semelhantes, um com maior expressão na fase pós-natal e três na fase pré-natal. Nas análises das sequências não codificantes um resultado importante foi a identificação de dois novos miRNAs em suínos, os quais tiveram suas sequências maduras similares aos miRNAs hsa-miR-1207-5p e hsa-miR-665 foram classificadas como verdadeiras pelo programa MiPred e formaram estruturas secundárias. Destes, encontrou-se 289 e 214 genes regulados por eles respectivamente, dos quais quatro são músculo-específicos. Os novos miRNAs tiveram seus perfis de expressão analisados com o uso do PCR em tempo real durante os sete períodos citados juntamente com outros três já identificados em suínos. Seus níveis de expressão mostraram diferenças entre os estágios pré- e pós-natal. Estes estudos podem fornecer valiosas informações possibilitando um maior entendimento dos mecanismos moleculares envolvidos no desenvolvimento muscular. As análises de GDE em fases pré e pós-natal sugerem a presença de genes atuando especificamente em determinados estágios de desenvolvimento do músculo, contribuindo para melhor explicar suas funções. A identificação de dois novos miRNAs, somados a outros já identificados e postados nos bancos de dados em suínos, podem contribuir para um maior entendimento dos modos de regulação gênica, sendo de importância para os estudos de genética e melhoramento animal, permitindo o entendimento da fisiologia da deposição de músculo para produção de carne em suínos.
The pig (Sus scrofa) is considered an important animal for meat production. This interest revolves around the potential for muscle growth, which usually is associated with certain characteristics during prenatal myogenesis. To study the genes responsible for these characteristics, expressed sequence tags (EST) provide direct information about the transcriptome and indirectly on the relationship between the genome and different phenotypes, supplying knowledge about differentially expressed genes (DEG) as well as other transcribed genomic sequences for the control of gene expression, e.g., some non-coding RNAs. Characteristics of muscle tissue in pigs may have been directly influenced by genes, and those being regulated, for example, by miRNAs, in different stages of development. This study aimed to identify by in silico annotation, DEG and non-coding sequences, focusing on miRNAs, using cDNA libraries constructed from semi-membranous skeletal muscle of three different pig breeds (Duroc, Large White and naturalized Brazilian Piau ) as well as analysis of gene expression profiles of identified genes and miRNAs during seven stages of development (21, 40, 70 and 90 days prenatal and 107, 121 and 171 days postnatal) from commercial line animals Longissimus Dorsi muscle. Twenty-one identified genes out of 34 DEGs belongs to the muscle-specific path. From these, 13 genes had their expression profiles analyzed by qRT-PCR during the seven periods, forming four clusters of similar expression, with one having greater expression in the postnatal period and three in the prenatal. In the analysis of non-coding sequences, an important result was the identification of two new miRNAs in pigs, which had their sequences similar to mature miRNAs hsa-miR-1207- 5p and hsa-miR-665 which had their precursor sequences forming secondary structures and classified as real precursor sequence by MiPred program. From these, we found 289 genes and 214 respectively regulated by them, of which four are muscle-specific. The new miRNAs and other three which have been identified in previous studies in pigs had their expression levels analyzed by quantitative real time PCR during the mentioned seven periods. Their levels of expression differed between pre-and postnatal stages. These studies may provide valuable information allowing a better understanding of the molecular mechanisms involved in muscle development. Analyses of DEG in the pre-and postnatal periods suggest the presence of genes acting specifically on certain stages of muscle development, contributing to better explain their functions. The identification of two new miRNAs, together with other previously identified and posted on the databases in pigs, may contribute to a better understanding of gene regulation and is important for studies of genetics and animal breeding, allowing the understanding of the muscle deposition physiology to meat production in pigs.
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Lau, Justine Y. "Novel genes associated with airway smooth muscle proliferation in asthma." Connect to full text, 2008. http://hdl.handle.net/2123/5134.
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Thesis (Ph. D.)--University of Sydney, 2009.Title from title screen (viewed Aug. 11, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Pharmacology, Faculty of Medicine. Degree awarded 2009; thesis submitted 2008. Includes bibliographical references. Also available in print form.
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Sundaram, Priyanka. "The deubiquitinating enzyme USP19 negatively regulates the expression of muscle-specific genes in L6 muscle cells /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111547.
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Muscle wasting is a significant complication of many diseases including diabetes mellitus, renal and liver failure, HIV/AIDS, and cancer. Sustained loss of skeletal muscle can severely impair a patient's quality of life and often results in poor tolerance and responsiveness to disease treatments. The increased protein breakdown observed during muscle atrophy has been attributed to accelerated activity of the ubiquitin-proteasome pathway, but the precise mechanisms by which this activation stimulates muscle protein loss are poorly understood. Previous work showed that the deubiquitinating enzyme USP19 is upregulated in rat skeletal muscle in various forms of muscle wasting, including streptozotocin induced diabetes, cancer, and dexamethasone treatment. 1 To further explore the role of USP19 in muscle wasting, siRNA-mediated depletion of the enzyme was carried out in L6 myotubes. Knockdown of USP19 resulted in more rapid differentiation of myoblasts into myotubes, with a greater extent of myoblast fusion. It also produced tubes that were visibly larger than those formed by myoblasts transfected with a control siRNA. At the molecular level, silencing of USP19 increased the amount of myosin heavy chain (MHC) and tropomyosin proteins. It also increased levels of MHC transcript, suggesting that USP19 acts at the level of gene transcription or mRNA stability rather than protein degradation. USP19 may mediate its effects on muscle-specific gene expression through the myogenic transcription factor myogenin, since depletion of USP19 increased protein and mRNA levels myogenin but did not affect protein levels of the related transcription factor Myf5. Moreover, the increased tropomyosin and MHC observed upon USP19 knockdown could be abolished when myogenin was simultaneously depleted using siRNA. Collectively, these results suggest that USP19 functions to inhibit the synthesis of key muscle proteins and may therefore be a promising target for the treatment of muscle atrophy.
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Boyd, Jacqueline. "Analysis of dauer pathway genes in the parasitic nematode Trichinella spiralis." Thesis, University of Aberdeen, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288288.
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Trichinella spiralis is a parasitic nematode of mammalian skeletal muscle. Its life cycle includes two stages where developmental progression appears to be inhibited until a specific host niche is encountered. The newborn larva, released within the host intestine depends upon entry to skeletal muscle for continued development. The muscle larva encapsulates within skeletal muscle and further reproductive development is dependent upon ingestion by a new host. Developmental arrest has been extensively characterised in Caenorhabditis elegans, where an alternative L3 larva, the dauer larva, is formed in response to environmental conditions refractive to continued reproductive development. Using the wealth of genetic information regarding C. elegans dauer formation, putative periods of arrest were examined in T. spiralis. TGF-b-like and insulin-like signalling pathways are critical mediators of C. elegans dauer formation. A T. spiralis TGF-b-ligand was identified and designated ts-tll-1. Sequencing and analysis revealed ts-tll-1 to be similar to vertebrate bone morphogenetic proteins and C. elegans DBL-1, is involved in body size regulation. EST mining identified putative type I and II TGF-b receptors and a subtilsin-like proprotein convertase, suggesting conservation of TGF-b-like signalling in T. spiralis. A partial Trichinella gene encoding an orthologue of the C. elegans insulin-like, tyrosine kinase receptor, DAF-2, was identified by degenerate PCR and designated ts-tkr. ts-tkr is most similar to C. elegans daf-2 within the highly conserved tyrosine kinase domain. Two alternative transcripts of ts-tkr were identified by 3’ RACE, which differed in their 3’ UTRs. Semi-quantitative RT-PCR analysis suggested ts-tkr expression was greatest in adult worms, implying a role in promoting reproductive development. Semi-quantitative RT-PCR was also to assess the expression of selected housekeeping and ES protein encoding genes during the T. spiralis life cycle. While transcription in the C. elegans dauer is depressed, there was no obvious transcriptional repression in Trichinella newborn or muscle larva.
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Martin, Agnès. "Role of the glucocorticoid pathway in skeletal muscle wasting and hepatic metabolism rewiring during cancer cachexia in ApcMin/+ mice – Functional implication of myostatin gene invalidation." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSES034.
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La cachexie affecte environ la moitié des patients atteints d’un cancer et est caractérisée par une perte progressive de la masse corporelle résultant principalement d’une perte de masse musculaire squelettique. Cette perte de masse musculaire squelettique associée à une perte de force musculaire contribue fortement à réduire la qualité de vie des patients, l’efficacité des traitements et à terme, la survie des patients. Plusieurs facteurs sont connus pour être impliqués dans la régulation de la masse musculaire. Parmi eux, les glucocorticoïdes sont des hormones stéroïdiennes sécrétées sous le contrôle de l’axe hypothalamo-hypophysaire qui sont connues pour induire l’atrophie musculaire mais aussi pour avoir une action systémique via l’activation ou l’expression de gènes dans plusieurs tissus. Nous faisons l’hypothèse que la voie des glucocorticoïdes pourrait être activée pendant la cachexie associée au cancer dans les souris ApcMin/+, un model murin de cancer intestinal. Nous rapportons ici que l’activation du catabolisme musculaire était associée à une reprogrammation complète du métabolisme du foie. En outre, nous montrons une activation de l’axe hypothalamo-hypophysaire associée à une augmentation du niveau en corticostérone (le glucocorticoïde principal chez les rongeurs) dans le sérum, le muscle quadriceps et le foie des souris à un stade avancé de la cachexie associée au cancer. La signature transcriptionnelle dans le muscle quadriceps et le foie des souris à un stade avancé de la cachexie associée au cancer reflète celle observée dans des souris traitées avec de la dexaméthasone, un analogue des glucocorticoïdes. Il est important de souligner que l’inhibition de la cachexie associée au cancer par l’inactivation du gène de la myostatine dans les souris ApcMin/+ a restauré les niveaux en corticostérone et abolit la reprogrammation génique dans le muscle squelettique et le foie. Ensemble, ces données indiquent que les glucocorticoïdes induisent un programme transcriptionnel pour réguler de façon coordonnée la perte de masse musculaire et le remaniement du métabolisme hépatique. L’inhibition de cette réponse par l’invalidation du gène de la myostatine souligne l’existence d’un dialogue moléculaire entre le muscle squelettique et le foieCachexia affects about half of cancer patients and is characterized by a progressive body mass loss mainly resulting from skeletal muscle depletion. This loss of skeletal muscle mass together with a decrease in muscle force strongly contribute to reduce cancer patient quality of life, treatment efficiency and ultimately patient survival. Many factors are known to be involved in the regulation of skeletal muscle homeostasis. Among them, glucocorticoids are steroid hormones secreted under the control of the hypothalamic-pituitary axis that have been well described to promote skeletal muscle atrophy but also to exert systemic actions through activation or repression of gene expression in many tissues. We hypothesized that the glucocorticoid pathway could be activated during cancer cachexia in ApcMin/+ mice, a mouse model of intestinal cancer. Here, we reported that activation of skeletal muscle catabolism was associated with a complete reprogramming of liver metabolism. Moreover, we showed an activation of the hypothalamus-pituitary axis that was associated with an increase in the level of corticosterone (the main glucocorticoid in rodent) in serum, quadriceps muscle and liver of advanced cancer cachectic mice. The transcriptional signature in quadriceps muscle and liver of advanced cancer cachectic mice significantly mirrored that observed in mice treated with dexamethasone, an analog glucocorticoid. Importantly, the inhibition of cancer cachexia by myostatin gene invalidation in ApcMin/+ mice restored corticosterone levels and abolished skeletal muscle and liver gene reprogramming. Together, these data indicate that glucocorticoids drive a transcriptional program to coordinately regulate skeletal muscle mass loss and hepatic metabolism rewiring. The inhibition of this response by myostatin gene invalidation highlights the existence of a molecular dialog between skeletal muscle and liver
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Waardenberg, Ashley Jacob. "VMus3D - A New Gene Expression Visualisation Approach and Application to Striated Muscle." Thesis, Griffith University, 2012. http://hdl.handle.net/10072/367325.
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Systems Biology and Bioinformatics have emerged as scientific fields as a consequence
of our increasing capacity to use systems-wide technologies to understand biology.
However, the internal scales of Systems Biology and Bioinformatics are currently
unbalanced: informatically obese and biologically anorexic. The scale of information
collected in a single experiment is now vast, but very often the use is limited. Producing
meaning from this data has not been elevated to the same level as data collection and so
by comparison our understanding of biology remains relatively anorexic.
How best to deal with large amounts of gene expression data has been a research topic of
nearly two decades. This research has provided improvements to technologies, processing
algorithms and the understanding of the translation of genome to transcriptome.
However, it remains that the current and interwoven challenges for understanding biology
are; (i) to invent technologies that can determine how the genome is used; (ii) to identify
and validate biological mechanisms, and; (iii) to provide meaning to data collected in a
high-throughput biologically driven experiment. The focus of this thesis is to provide
context to data collected from high-throughput gene expression experiments related
specifically to striated muscle.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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Holder, Emma L. (Emma Lesley). "Gene expression in muscle tissue and cells." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=69755.
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Cellular differentiation is accompanied by the modulation of gene expression. I have compared the expression of various genes, using the slot-blot technique, in two different systems. First, the level of expression of a wide variety of genes was analyzed in the hypertrophied heart of transgenic mice expressing the polyomavirus large T-antigen gene, and compared to normal control heart. I have shown that most changes in gene expression occurred mainly during early stages of heart hypertrophy. These genes code for proteins known to play a role in signal transduction, and transcriptional and growth control. The latter stages of cardiac hypertrophy are accompanied by changes in the expression of genes that are mostly involved in stress responses. Second, we analyzed the expression of various genes in three mouse myogenic cell lines undergoing differentiation in several culture conditions. The adult (C2C12) and fetal-derived (G7 and G8) myoblast cell lines were exposed to either retinoic acid, dimethyl sulfoxide, or transforming growth factor $ beta$. These three molecules are known to have profound effects on cellular growth and differentiation. I have shown that these treatments result in significant changes in expression of a wide variety of genes. Interestingly, all three cell lines differed considerably in their pattern of gene expression. Results from the analysis of these two systems demonstrate that differentially induced morphological changes of muscle cells, result in cell type specific changes in expression of a variety of genes.
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Richard-Fiardo, Peggy Pitard Bruno. "Les copolymères à blocs pour le transfert de gènes dans le muscle squelettique." [S.l.] : [s.n.], 2006. http://castore.univ-nantes.fr/castore/GetOAIRef?idDoc=27846.
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Warner, Adam Dennis. "Identification of novel genes affecting body wall muscle in Caenorhabditis elegans." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31429.
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Muscular diseases affect many people worldwide. While we have learned much
about the sarcomere, the basic building block of muscle cells, there are still numerous
questions that remain to be answered. In fact, all of the proteins involved in the formation
and maintenance of the sarcomere have yet to be catalogued and studied. We must learn
more about proteins expressed in muscle and how they interact so that better treatments for
myopathies can be produced. In this thesis, several novel sarcomeric proteins have been
identified using Caenorhabditis elegans as a model organism.
A list of genes expressed in muscle cells was compiled using available Serial
Analysis of Gene Expression (SAGE) and microarray data. By eliminating or severely
reducing the expression of each gene using RNA interference (RNAi), we were able to
determine which genes were required for proper myofilament organization. Of 23 genes
known to affect muscle, 16 were identified using this methodology. In total 119 genes were
found to be necessary for proper myofilament organization, 103 of which are genes without a
previously characterized role in muscle.
In addition, a bioinformatics based screen that utilized tissue specific SAGE data in
C. elegans yielded a number of potential candidate muscle affecting genes, and one,
C28H8.6 was further studied. C28H8.6 consists of both an ' a ' and a ' b ' isoform, one of
which, C28H8.6a has 4 LIM domains and bears striking sequence similarity to the focal
adhesion protein paxillin. In animals homozygous for a mutation that knocks out both
isoforms of C28H8.6, movement is uncoordinated and development is arrested at the first
larval stage. We have demonstrated using isoform specific RNAi that knocking down
expression of C28H8.6b has no observable effect on development, while C28H8.6a is
required for proper larval growth and movement. Further study on this isoform verified that
C28H8.6a co-localizes to dense bodies with a- actinin and is required for proper organization
of myofilaments within the sarcomere.Medicine, Faculty of
Medical Genetics, Department of
Graduate
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Cha, Jeeyeon. "The role of muscle segment homeobox genes in early pregnancy events." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1377871689.
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Baptista, Igor Luchini. "Papel de E3 ligases na plasticidade muscular esquelética." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-17042013-113528/.
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Neste estudo analisamos o envolvimento de E3 ligases sob três aspectos da plasticidade muscular esquelética: a perda de massa decorrente do desuso, a manutenção de fibras tipo I e II e a regeneração do tecido muscular. O primeiro objetivo foi determinar se leucina atenuaria a perda de massa provocada pela atrofia. Nossos dados mostraram que este aminoácido evitou a perda de massa, sobretudo através da inibição da expressão de E3 ligases. A seguir, analisamos se a ausência de duas E3 ligases, MuRF1 e MuRF2, poderia alterar a proporção de miofibras tipo I e tipo II. Detectamos que na ausência destas E3 ligases, a identidade de fibras tipo II era perdida, além destas fibras estarem protegidas da atrofia sem MuRF1. Por fim, analisamos o papel de MuRF1 e MuRF2 durante a regeneração. Os resultados mostraram que estas E3 ligases em conjunto são cruciais para a fisiologia das células-satélites e portanto para a regeneração do tecido. Esta tese mostrou que determinadas E3 ligases exercem um papel crucial para a plasticidade muscular.In the present thesis we analyzed the involvement of E3 ligases under three aspects of skeletal muscle plasticity: mass loss resulting from disuse, maintenance of fiber type I and II and regeneration of muscle tissue. Our first aim was to determine whether leucine, was able to attenuate the mass loss caused by wasting. Our results showed that this amino acid prevented the mass loss, mainly by inhibiting the expression of E3 ligases. The second aim was to determine whether the absence of two E3 ligases, MuRF1 and MuRF2, could alter the proportion of type I and type II fibers. We found that in the absence of these E3 ligases, the identity of type II fibers was lost, and these fibers were protected against atrophy in the absence of MuRF1. Lastly, we analyze the role of MuRF1 and MuRF2 in muscle tissue regeneration. The results showed that these E3 ligases together are crucial to satellite-cells physiology and consequently an adequate tissue regeneration. This thesis show that certain E3 ligases can play a crucial role in muscle plasticity.
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Sjöberg, Gunnar. "Nestin : filament formation and expression in myogenesis and muscle disorders /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2687-5.
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Larochelle, Nancy. "Gene transfer to skeletal muscle using adenoviral recombinants." Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-2567.
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Willemsen, Kristin R. "Improving adenoviral vectors for muscle-directed gene therapy." Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/28115.
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Gene therapy is a promising approach for the treatment of Duchenne Muscular Dystrophy (DMD). Adenoviral vectors (Ad) are the most commonly used vectors in gene therapy studies however, the overall large size of the Ad particles (162nm), due in part to the fiber proteins that extrude from the surface of the virion, prevent their efficient distribution in muscle. The objective of this project was to evaluate the transduction performance of Ad5 based vectors genetically modified to encode shorter fiber proteins derived from Ad serotypes 35 and 9. Optimal transduction was dependent on fiber length in some cell lines and in mdx muscle. However, fiber-modified viruses have an improved viral dispersion and improved transduction up to 10-fold in normal muscle. In addition, an optimized non-immunogenic reporter gene ideal for monitoring vector function in murine disease models was presented. The results of these experiments will contribute to the understanding of Ad transduction in muscle and aid in the design of efficient vectors for DMD therapy.
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Tan, Yu Yin Nicole Medical Sciences Faculty of Medicine UNSW. "Gene expression during activation of smooth muscle cells." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43615.
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Cardiovascular disease, which involves the cardiac, cerebrovascular and peripheral vascular system, is the major cause of morbidity and mortality in the western world. Changes in the vascular microenvironment trigger cascades of molecular events involving altered signaling, transcription and translation of a gene. The aim of this thesis was to increase our understanding on the molecular regulation of activated vascular smooth muscle cells. The first study looking at PDGF-D expression provides new insights into the regulatory mechanisms controlling the phosphorylation of Sp1. Studies performed identified three amino acids in Sp1 (Thr668, Ser670 and Thr681) that is phosphorylated by PKC-zeta activated by AngII. In the second study, the translational regulatory role of a novel gene YrdC induced by injury was investigated. Current knowledge of translational regulators controlling altered gene expression is little and studies in this thesis shows a splice variant of YrdC playing an important role in controlling mRNA translation and thus protein synthesis in the context of injury. The final study investigated in this study was the increased expression of the apoptotic FasL by the activation of GATA6. Although FasL has been extensively studied over the years, this is the first study linking a GATA factor with FasL in any cell type and provides key insights into the transcriptional events underpinning FasL-dependent SMC apoptosis following exposure to AngII.
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Dodds, Emma. "Cationic lipid mediated gene delivery to skeletal muscle." Thesis, Royal Holloway, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314358.
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Shaw, James Alistair MacGregor. "Towards muscle-targeted gene therapy for diabetes mellitus." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325232.
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Gray, Sarah Lauren. "Down Regulation of Muscle Strength Genes in Orthognathic Surgery Patients with Asymmetry." Master's thesis, Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/316137.
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Oral BiologyM.S.
Objective: Genetic loci for ATP2A2 kinase, NUAK1, and phosphatase PPP1CC are associated with skeletal muscle strength phenotypes. ATP2A2 is a calcium ion transport ATPase in sarcoplasmic reticulum that is predominantly expressed in cardiac and slow-twitch fibers. NUAK1, an AMP-activated protein kinase, and PPP1CC, a subunit of protein phosphatase 1, are involved in glycogen metabolism during skeletal muscle contraction. The aim of this study is to investigate whether these genes are associated with masseter muscle composition and function in the development of skeletal malocclusion. Methods: A total of 56 orthognathic surgery patients were classified as having skeletal Class I, Class II, or III sagittal malocclusions with normal, open, or deep bites vertically, with or without facial asymmetry. Masseter muscle samples were collected during the mandibular osteotomies, frozen, and sent to the Kornberg School of Dentistry. Tissue from eleven patients was used for gene expression analysis on Affymetrix HT2.0 microarray chips and a principle components analysis. Then, these plus an additional 45 masseter samples were used for quantitative RT-PCR. Expression data for the three genes of interest were evaluated in the microarray and corroborated and expanded upon with RT-PCR data. ANOVA and unpaired t-tests were performed to determine correlations between ATP2A2, NUAK1, and PPP1CC expression levels and vertical and sagittal malocclusion classifications. Additional ANOVA and unpaired t-tests were performed to determine correlations between ATP2A2 expression level and signs and symptoms of temporomandibular disorder (TMD) with and without pain and facial asymmetry, and relative to the expression levels of a second gene associated with muscle strength phenotypes (ACTN3). Finally, Kendall Tau analyses were performed to compare ATP2A2 expression levels in subjects grouped by malocclusion classification to masseter muscle composition, including mean fiber area (MFA) and mean percent occupancy (MPO) of each fiber type. Results: Principle component analysis revealed two patients with genetic expression levels that deviated from the group. These were the only patients diagnosed with facial asymmetry. Microarray data showed that in these patients ATP2A2 and PPP1CC were significantly decreased. NUAK1 was decreased to a lesser extent. Also, among other genes in the same functional categories, ATP2A1 expression was -30.45 fold (P<6.11X10-6) and PPP3CC expression was -2.96 fold (P<2.03X10-5) in the patients with facial asymmetry. RT-PCR results showed NUAK1 and PPP1CC were differentially expressed at lower, but not statistically significant levels in subjects with craniofacial asymmetry. However, RT-PCR did verify that ATP2A2 expression is down regulated in subjects with mild to severe forms of asymmetry as compared to subjects with facial symmetry (p=0.022). ANOVA and unpaired t-test analyses illustrated that there was no significant differences in ATP2A2 expression in patients with different vertical, saggital, or combined vertical/sagittal malocclusion diagnoses. There was a significant association between the lateral differences in ATP2A2 expression, between right- and left-sided masseter biopsies within the same individual, in subjects with Class III malocclusions with different vertical diagnoses. Here, lateral differences were greatest in open bite, intermediate in deep bite, and lowest in normal Class III subjects. Kendall tau analyses were performed to compare ATP2A2 expression levels and masseter composition (MFA/MPO of type I, hybrid, and type II fibers) in all subjects, subjects with Class II malocclusions, and subjects with Class III malocclusions. Regardless of sagittal malocclusion, all subjects showed a negative correlation with type IIA MPO that was highly significant (r=-0.46; p=0.004). Also, ATP2A2 associations in Class II subjects were positive with type I MFA (r=0.36; p=0.04) and negative with type IIA MPO (r=-0.59; p=0.001). Correlations for Class III subjects were typically negative and not significant. Also, Kendall tau correlations were performed to compare ATP2A2 expression with the composition of each fiber type in patients grouped by both sagittal and vertical malocclusion classification. These found decreased type IIA fiber MPO correlated significantly (p = 0.024) with increased relative ATP2A2 expression in subjects with Class II, normal bite malocclusions (n = 6, R2 = 0.8127). Finally, ATP2A2 expression was not associated with most phenotypic traits exhibited by the surgery subjects such as presence of signs/symptoms of TMD with and without pain and facial asymmetry. However there was an association between decreased lateral differences in ATP2A2 expression in subjects with asymmetry with the TC ACTN3 genotype as compared to subjects with the TC ACTN3 genotype and facial symmetry. Conclusions: ATP2A2 promotes calcium transport in slow twitch and cardiac muscle contraction-relaxation cycling. Decreased expression of this gene in patients with asymmetries suggests that down regulation of the calcium handling capacities of muscle fibers may influence the development of abnormal craniofacial phenotypes. Both NUAK1 and PPP1CC are thought to play metabolic regulatory or responsive roles to muscle contraction. Decreased expression of these genes may accompany alterations of fiber-type form and metabolic properties to adversely affect jaw development. Additionally, ATP2A2 correlations indicate that this calcium channel protein may be important for type I fiber function, but not type IIA in masseter muscle from Class II subjects, suggesting a functional influence on malocclusions. ATP2A2 does not appear to function differentially in fiber types that influence development of Class III malocclusion. Further studies with more subjects are needed to increase experimental power.
Temple University--Theses
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Zahoor, Imran. "Genetics of muscle and meat quality in chicken." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8085.
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Skeletal muscles in broilers are generally characterised by pathological muscle damage, indicated by greater plasma creatine kinase (CK) activity, higher incidence of haemorrhages, lighter and less coloured breast muscles, compared with layers and traditional breeds of chicken. Muscle damage is further exacerbated by exposure to stressful conditions such as high ambient temperatures which results in a further decrease in the quality of broiler meat and leads to the production of pale, soft and exudative (PSE) meat. This growing incidence of poor quality poultry meat is causing substantial losses to the meat industry. However, in contrast to pork the genetics of poor muscle and meat quality in chicken is unknown. The present project was conducted to identify the underlying genetics of this low quality meat by using heat-stress as a tool to amplify muscle damage and expression of the relevant genes. Whole-genome expression studies in broiler and layer breast muscles were conducted before and after heat-stress and some phenotypic data were also recorded. From the gene expression studies, 2213 differentially expressed genes (P<0.05) were found. About 700 of these genes had no gene ontology (GO) terms associated with them for biological process or function. The significant gene set was analysed in BioLayout Express and interesting clusters of the genes, based on their positive correlation with each other, were selected for further investigation. Genes were grouped together in 6 different categories or clusters, on the basis of their expression pattern. The genes in the selected clusters were analysed in Ingenuity Pathway Analysis (IPA) software, for each category separately, and relevant biological pathways and networks for those genes were studied. Similarly, the genes filtered out by BioLayout Express at a Pearson threshold of 0.80 were also analysed in IPA separately and interesting pathways and networks were selected. From the pathways and networks analyses of these genes, it was discovered that genes involved in inflammatory, cell death, oxidative stress and tissue damage related functions were up-regulated in control broilers compared with control and similar to heat-stressed layers. After exposure to heat-stress the expression levels of these genes were further increased in broilers. These results led us to develop the hypothesis that breast muscles in broilers are under stress-related damage even under the normal rearing conditions. This hypothesis was tested by rearing the broilers birds at normal/conventional and comparatively low ambient temperature and its effects on breast muscle quality and meat quality were studied. Significant improvement of breast muscle redness was observed. Additionally substantial numerical improvements for other meat and muscle quality traits like breast muscle lightness and histopathology were observed. From the key positions of interesting significant pathways and networks, candidate genes were selected for further investigation. In total, 25 candidate genes were selected for SNP genotyping: 19 genes were selected from the interesting pathways and networks and 6 genes were selected on the basis of their GO terms. For each gene 4-5 SNPs were selected, where possible, that were present in exons and promoter regions of the candidate genes. The selected SNPs were genotyped for muscle and meat quality traits in 34 breeds of chicken and significant causative SNPs for each trait including plasma CK activity, pHi and pHu for breast muscles, colour (L*, a*, and b*) traits for breast and thigh muscles were found. These SNPs were responsible for explaining a moderate to high (15-55%) percentage of phenotypic variance for these traits. To our knowledge this is the first study in which gene-expression in chicken breast muscle was conducted in response to heat-stress and additionally, for the first time, a set of novel SNPs for all of these traits were identified. Some of the significant causative SNPs were lying in the protein coding sequences and some were present in the promoter regions of the candidate genes.
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Vyas, Dharmesh R. "In vivo regulation of [beta]-myosin heavy chain gene expression in skeletal muscle /." free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9998522.
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Salva, Maja Zavaljevski. "Transcriptional regulation : applications toward rAAV-based gene therapies in striated muscle /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8030.
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Harrison, Adrian Paul. "Regulation of porcine skeletal muscle growth and differentiation." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360936.
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Chen, Shen Liang. "Function of transcription cofactors in terminal muscle differentiation /." St. Lucia, Qld, 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16099.pdf.
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Moss, Stephen James. "Cloning and expression of the genes encoding the chick muscle nicotinic acetylcholine receptor." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47576.
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Pari, Giovanna. "Muscle-specific gene expression in differentiated embryonal carcinoma cells." Thesis, University of Ottawa (Canada), 1990. http://hdl.handle.net/10393/6014.
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A chimeric gene consisting of the human cardiac actin promoter linked to the lac Z reporter gene encoding $\beta$-galactosidase ($\beta$-gal), was permanently transfected into P19 cells. Differentiation of these cultures into cardiac muscle resulted in high levels of $\beta$-gal activity, while differentiation along the neuroectodermal lineage did not lead to any increase in the expression of the actin-lacZ chimeric gene. The transcription of various muscle-specific genes can be activated in different nonmuscle cell lines by the expression of MyoD, a regulatory factor of skeletal myo-genesis. MyoD activates muscle-specific genes in cooperation with other factors which interact directly or indirectly at the various cis-acting regulatory sequences of the target gene. The role of MyoD in muscle differentiation was investigated in permanent transfections of P19 cells with the MyoD expression vector. MyoD transcripts were absent during the de novo differentiation of P19 cells into cardiac muscle. The myogenic differentiation program seems to be controlled by complex interactions among multiple upstream regulatory elements and myogenic factors that are functional only in the appropriate cellular context. (Abstract shortened by UMI.)
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Horvath, Andras. "Viral gene therapy for non-muscle invasive bladder cancer." Thesis, University of Surrey, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540942.
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Ho, Liza Kwok-Fung. "Proliferation and gene expression of vascular smooth muscle cells." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319970.
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Pitstick, Amy L. "Nuclear Reorganization and Gene Expression During Muscle Cell Differentiation." Wright State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1309997417.
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