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1
Ackrill, Andrew Michael. "Studies on expression of cellular genes in adenovirus-transformed cells". Thesis, University of Leeds, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328870.
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Janjua, Sadia. "Regulation of gene expression and survival in cellular stress". Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444756/.
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All organisms have developed regulated mechanisms to maintain homeostasis. At the cellular level, this normal functioning of cells is regulated by expression of regulatory genes that are required for normal cell function. Most cells in multicellular organisms are capable of altering gene expression in response to extracellular signals such as elevated temperature, ischaemia/reperfusion, inflammation, infection, cytokines, and amino acid analogues. In this thesis the effects of cellular stresses in the form of elevated temperature or simulated ischaemia have been investigated. Previous studies show that elevated temperature or simulated ischaemia can induce expression of heat shock proteins (Hsps) in order to prevent misfolding of cellular proteins. Moreover, it has been shown that the stress responsive transcription factor heat shock factor-1 (HSF-1) is phosphorylated and translocates to the nucleus to bind to heat shock elements within hsp gene promoters. In addition, HSF-1 can interact with other transcription factors such as the signal transducer and activator of transcription-1 (STAT-1), which is a latent cytoplasmic transcription factor activated in response to regulatory cytokines such as interferon gamma (IFNgamma). Preliminary data shows that elevated temperature can induce expression of Hsp90 in the STAT-1 deficient cell line (U3A) treated with IFNa (activates STAT-1 and STAT-2), but reduces the levels of Hsp90 expression in the U3A cell line treated with IFNa and IFNgammain combination. These findings suggest that there may be competition between STAT-1 homodimers and STAT-1/STAT-2 heterodimers and will require further investigation The STAT-1 transcription factor has previously been demonstrated to play a role in stress-induced apoptosis. In this study, STAT-1 is shown to be required for stress-induced apoptosis using the STAT-1 deficient U3A cell line. Cells lacking STAT-1 show reduced cell death/apoptosis in response to elevated temperature or simulated ischaemia. However, expression of STAT-1 in these cells restores sensitivity to stress-induced death. The C-terminal domain alone of STAT-1 is also able to enhance stress-induced cell death, and may be acting via a novel co-activator-type mechanism. Many protective agents have been identified that are able to reduce cell death due to ischaemic injury. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown to protect rat neonatal cardiomyocytes subjected to simulated ischaemia via the p42/p44 MAPkinase and PI-3 Kinase pathways. In addition, the unrelated peptide urocortin (Ucn) also protects cardiomyocytes via the same pathway as CT-1 in response to simulated ischaemia and both CT-1 and Ucn induce Hsp expression. In this study, Ucn has been shown to be able to induce enhanced expression of CT-1 at mRNA and protein levels in response to simulated ischaemia. Moreover, the effect is mediated by activation of the CT-1 promoter and requires the transcription factor C/EBPp /NFIL-6. This finding indicates that a common pathway exists for these two protective agents with Ucn inducing CT-1 synthesis. Overall, the work performed indicates that multiple interacting pathways modulate the cellular stress response with either protective or damaging effects.
3
Broderick, Peter. "The effect of EBV on host cellular gene expression". Thesis, University of Sussex, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444349.
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Li, Zheng. "Integrating gene expression and metabolic profiles to optimize cellular functions". Diss., Connect to online resource - MSU authorized users, 2006.
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Thesis (Ph. D.)--Michigan State University. Dept. of Chemical Engineering and Materials Science, 2006.Title from PDF t.p. (viewed on June 19, 2009) Includes bibliographical references (p. 166-180). Also issued in print.
5
Romero, Claudia. "CELLULAR IMMUNE RESPONSE AND GENE EXPRESSION PROFILING IN CROHN'S DISE". Doctoral diss., University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2704.
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Despite the chronic debate in the etiology of crohn's disease (cd), a debilitating inflammatory bowel disease (ibd) closely related to ulcerative colitis (uc), an emerging interest in a possible mycobacterial role has been marked. Granuloma and pathologic manifestations in cd resemble aspects found in tuberculosis, leprosy and paratuberculosis. The latter, a chronic enteritis in cattle, goat, sheep and primates, which is similar to human enteritis, also known as cd, is caused by a fastidious, slow growing mycobacterium avium subspecies paratuberculosis (map). Due to the similarities between cd and paratuberculosis, a mycobacterial cause in cd has been proposed. Recent discovery of a possible association between nod2/card15 mutations and risk of cd added support to microorganism-host interactions. In this study, a possible mycobacterial role in cd etiology has been evaluated by investigating the presence of map dna, the state of the cellular immune response and microarray gene expression profiling in peripheral blood and surgical tissue from cd, uc and healthy control subjects. Nested pcr detected map dna in tissue from 10/12(83%) cd patients compared to 1/6(17%) non-ibd subjects. Fluorescence in situ hybridization (fish) with the aid of confocal scanning laser microscopy (cslm) detected map dna in 8/12(67%) cd subjects compared to 0/6(0%) in non-ibd subjects. The detection of map dna by either technique in tissue from cd subjects is significant compared to non-ibd subjects (p < 0.05). Map dna was also detected in both inflamed and non-inflamed tissue from patients with cd suggesting map infiltration in human tissue. Correlation of possible map presence and the function of polymorphonuclear leukocytes (pmn) and peripheral blood mononuclear cells (pbmc) in 19 cd patients and 12 controls have been evaluated. Pmn phagocytosis of viable fitc-map was suppressed in 13/19(68%) cd patients compared to 0/12(0%) in healthy controls (p<0.05). Pbmc phagocytosis of viable fitc-map was suppressed in 5/19(26%) of cd patients compared to 0/12(0%) of healthy controls (p<0.05). The proliferative response of pbmc with t-cell majority from cd and controls subjects was evaluated against pha, candida albicans, pwm and map ppd. Dysfunctional proliferative response against pha was found in 8/19(42%) cd patients compared to 1/12(8.3%) in controls suggesting possible t-cell anergy. Pbmc from 11 cd subjects reacted normally to pha, 7/11(64%) reacted strongly to map ppd suggesting previous exposure to mycobacteria, and 3/11(27%) did not react with map ppd suggesting lack of pre-exposure to mycobacteria. From the seven mycobacterial pre-exposed samples, 6/7(86%) showed a normal ability to recall antigens by activated macrophages when exposed to c. Albicans, and all 7 samples had a normal pwm response. Finally, microarray-chip technology was employed to identify the expression profile of genes that have a role in the immune response of cd patients. Rna was isolated from fresh buffy coats from 8 healthy controls, 2 cd, and 1 uc patients. Chips with an estimated of 30,000 human genes were hybridized to cdna from these samples. We found that 17% of the total number of genes was differentially expressed. Over 200 genes were involved in the immune response, 7 genes where common to both forms of ibd (uc and cd), and 8 genes were found to be either downregulated in cd and upregulated in uc or viceversa. The ifngr1 gene, which encodes the ligand-binding chain of the ifn-gamma receptor, was found to be downregulated in 2/2(100%) of cd patients, but not in uc patients. It is known that defects in ifngr1 are a cause of atypical mycobacterial infection and bcg infection. Patients suffering from this deficiency have an immunologic defect predisposing them to infection with mycobacteria. This correlates with the proposed theory as map being the causative agent of cd. Furthermore, the results indicate a host susceptibility requirement for the establishment of mycobacterial infection in cd patients. Further characterization of ifngr1 using real-time pcr is underway. Collectively, detection of map dna in the majority of cd tissue and the alteration in pmn and pbmc to respond efficiently to map may be related to the fact that mycobacterial pathogens infect phagocytic cells of susceptible hosts and consequently the immune response is dysregulated. Furthermore, the fact that a gene linked to mycobacterial susceptibility was found to be downregulated in cd patients only, strengthens the mycobacterial etiology of cd. In general, the data suggest a possible role for a bacterial pathogen in cd pathogenesis.Ph.D.
Other
Burnett College of Biomedical Sciences
Biomolecular Sciences: Ph.D.
6
Svensson, Valentine. "Probabilistic modelling of cellular development from single-cell gene expression". Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267937.
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The recent technology of single-cell RNA sequencing can be used to investigate molecular, transcriptional, changes in cells as they develop. I reviewed the literature on the technology, and made a large scale quantitative comparison of the different implementations of single cell RNA sequencing to identify their technical limitations. I investigate how to model transcriptional changes during cellular development. The general forms of expression changes with respect to development leads to nonparametric regression models, in the forms of Gaussian Processes. I used Gaussian process models to investigate expression patterns in early embryonic development, and compared the development of mice and humans. When using in vivo systems, ground truth time for each cell cannot be known. Only a snapshot of cells, all being in different stages of development can be obtained. In an experiment measuring the transcriptome of zebrafish blood precursor cells undergoing the development from hematopoietic stem cells to thrombocytes, I used a Gaussian Process Latent Variable model to align the cells according to the developmental trajectory. This way I could investigate which genes were driving the development, and characterise the different patterns of expression. With the latent variable strategy in mind, I designed an experiment to study a rare event of murine embryonic stem cells entering a state similar to very early embryos. The GPLVM can take advantage of the nonlinear expression patterns involved with this process. The results showed multiple activation events of genes as cells progress towards the rare state. An essential feature of cellular biology is that precursor cells can give rise to multiple types of progenitor cells through differentiation. In the immune system, naive T-helper cells differentiate to different sub-types depending on the infection. For an experiment where mice were infected by malaria, the T-helper cells develop into two cell types, Th1 and Tfh. I model this branching development using an Overlapping Mixture of Gaussian Processes, which let me identify both which cells belong to which branch, and learn which genes are involved with the different branches. Researchers have now started performing high-throughput experiments where spatial context of gene expression is recorded. Similar to how I identify temporal expression patterns, spatial expression patterns can be identified nonparametrically. To enable researchers to make use of this technique, I developed a very fast method to perform a statistical test for spatial dependence, and illustrate the result on multiple data sets.
7
Simon, Kathryn D. "Effect of cellular zinc concentration on glucocorticoid induced gene expression". Diss., This resource online, 1996. http://scholar.lib.vt.edu/theses/available/etd-06062008-155344/.
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Zink, Amy Darlene. "Genetic analysis of the cellular control of [PSI] prion". Thesis, Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/25295.
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Chemutai, Patricia. "Gene Expression in Long Term Myoblast /Myocete Cultures: m RNA expression (Acetylcholine Receptor and Galectin-3 gene)". Youngstown State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1620382476783648.
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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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Samanta, Priyankar. "Gene Regulation in Biofilms". Thesis, North Dakota State University, 2011. https://hdl.handle.net/10365/29330.
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Sessile bacterial communities which form on the solid surface or solid-liquid interface
are known as biofilms. Both single species and multispecies biofilms are characterized
by an extracellular matrix of polymeric substances which gives them several hundred
times more antibiotic resistances than a planktonic bacterial culture. Though bacteria
are the most common causative agent of various diseases, because of the high
antibiotic resistance, biofilms cause complications of various diseases like cystic
fibrosis, prosthetic valve endocarditis, chronic pulmonary diseases, catheter-associated
urinary tract infections and several other diseases. From past studies,
quorum sensing has been established as a novel target mechanism against biofilms; in
this study, the two-component signal transduction systems (2CSTSs) have been
focused. Once better understood, 2CSTSs can serve as a novel drug target and
prevention mechanism for biofilm associated diseases.
According to prior high-throughput experiments and phenotype microarray
experiments by our lab, several 2CSTSs like OmpR-EnvZ, RcsCDB along with the
global regulator FlhD/FlhC were hypothesized to have an important effect on various
developmental stages of biofilm formation. From that past study, we postulated that
acetate metabolism may be an important aspect for biofilm formation. In this study,
we tested and confirmed this hypothesis. We observed biofilms formed by several
mutants in 2CSTS, as well as mutants in acetate metabolism, using Scanning Electron
Microscopy (SEM). We found quantitative and qualitative differences in the biofilm of
the acetate mutants when compared to their isogenic parental Escherichia coli strain.
An additional mutation in rcsB with acetate mutant strains forms less clumpy biofilms
whereas an additional mutation in dcuR results in the formation of less biofilms. So
the structural and the quantitative differences of acetate mutant biofilms depend on
additional mutations in rcsB and dcuR. Though a number of studies have been done on the temporal gene expression within biofilms, spatial gene expression of the mature biofilm is a big gap of knowledge. The
future aim of this study is to study the temporal as well as the spatial gene expression
of different 2CSTSs in the biofilm. In my MS thesis, I have constructed selected
promoter fused GFP /RFP plasmids and some other fusion plasmids were purchased
from the promoter collections from Open Biosystems, lastly E. coli AJW678 bacterial
strains were transformed with these GFP /RFP fused plasmids. A 96 well microtiter
plate assay was performed to study the temporal expression from the promoters by
quantifying the fluorescence intensity in the planktonic culture. According to this
experiment, the highest expression of flhD was after 20 hours whereas, the expression
of ompR increases up to 7 days, which indicates that the flhD expresses earlier than
ompR. The decreasing phase of flhD expression was paralleled by the sharpest
increase in ompR expression as phosphorylated OmpR is an inhibitor of flhD
expression.National Institutes of Health (NIH grant 1R15AI089403)
United States. Animal and Plant Health Inspection Service
12
Mixon, James Patrick. "Analyses of the regulation of cellular gene expression by human cytomegalovirus". Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620678.
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Skene, Barbara I. "Regulation of cellular gene expression by DNA tumour virus transforming proteins". Thesis, Imperial College London, 1986. http://hdl.handle.net/10044/1/38160.
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Gardner, David Paul. "Epidermal growth factor receptor: Regulation of cellular proliferation and gene expression". Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186438.
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Binding of epidermal growth factor (EGF) to the EGF receptor stimulates the tyrosine kinase activity of the receptor and initiates a signal transduction cascade culminating in a mitogenic response. In many tumor derived cell lines which overexpress EGF receptor, exposure to EGF results in growth inhibition. The mechanism for this is unclear. This work involves analysis of growth inhibition by EGF, mechanisms of EGF receptor overexpression and regulation of the EGF receptor gene. The first two studies utilize a cell line (PC-10) that overexpresses EGF receptor without gene amplification. PC-10 cells appear to adopt a novel mechanism to overexpress EGF receptor; one that involves stabilization of the receptor message rather than the more common gene amplification. PC-10 cells were found to be killed by EGF in a cell density dependent manner. However, chronic exposure to EGF subsequently allowed proliferation under conditions which previously resulted in cell death. These "adapted" cells had similar levels of EGF receptor on the cell surface and similar EGF binding parameters. The tyrosine kinase activity of the receptor in response to EGF in the adapted cells was significantly reduced both in vitro and in vivo. Evidence was also found that the signal transduction cascade initiated by EGF was altered by adaptation. These data provide evidence for a unique mechanism for EGF receptor-overexpressing cells to survive EGF toxicity, one that involves a reduction in the tyrosine kinase activity of the EGF receptor in the absence of a decrease in the number of EGF receptor. Finally, additional studies were carried out on the response of the EGF receptor gene to activation of protein kinase C (PKC) in A549 cells. Activation of PKC resulted in increased levels of EGF receptor mRNA. No induction of a transfected reporter gene containing EGF receptor regulatory DNA could be seen. Repression of the reporter gene, however, was consistently seen. The cis-element for repression was mapped to 233 base pairs in the EGF receptor regulatory region. Additional data support the hypothesis that a previously characterized repressor protein called GCF may be responsible for this repression.
15
Hutchin, Timothy Paul. "Effects of adenovirus E1A gene expression on intermediate filaments in rat fibroblasts". Thesis, University of Essex, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280433.
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Marcinowski, Lisa. "Regulation of viral and cellular gene expression upon lytic murine cytomegalovirus infection". Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-152095.
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Murphy, D. "Viral DNA integration and cellular gene expression in SV40-transformed mouse cells". Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37794.
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Lok, Chun-nam, i 陸振南. "Regulation of transferrin receptor expression in human leukemic HL-60 cells: gene expression and cellular signaling". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31235141.
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Lok, Chun-nam. "Regulation of transferrin receptor expression in human leukemic HL-60 cells : gene expression and cellular signaling /". Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17310659.
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Somberg, Monika. "Cellular and Viral Factors that Control Human Papillomavirus Type 16 Late Gene Expression". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-150706.
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Human papillomavirus type 16 (HPV-16) is the major cause of cervical cancer. We speculate that inhibition of HPV-16 late gene expression is a prerequisite for establishment of persistence and progression to cervical cancer. This is based on the findings that the late proteins are found only in the nuclei of terminally differentiated epithelium, and are never detected in human papillomavirus infected cervical cancer cells. It is therefore of great importance to understand how HPV-16 controls the onset of the immunogenic proteins L1 and L2 in an infected cancer cell. HPV-16 late gene expression is tightly regulated by differentiation-dependent transcription as well as by post-transcriptional mechanisms. The long-term goal of these studies was to understand how HPV late gene expression is regulated. The specific aim of this thesis was to identify cellular and viral factors that force the virus to switch on the late genes, and to determine the mechanism of action of these factors. This will help us to understand under which circumstances HPV establish persistent infections that could progress to cancer. We found three cellular factors; PTB, ASF/SF2 and SRp30c, and one viral factor; AdE4orf4, that in four distinctive ways were involved in the regulation of HPV-16 late gene expression. Interestingly, over-expression of PTB, AdE4orf4 or SRp30c produced different types of spliced late mRNAs. PTB induced the unspliced L2/L1 mRNA, while AdE4orf4 and SRp30c induced the spliced L1 and L1i mRNA, respectively. The three proteins had different mechanisms of action and different target sites within the HPV-16 genome, which revealed the many and complex pathways in HPV-16 gene regulation. These findings have contributed to a broader understanding of how the expression of HPV-16 late genes is controlled.
21
Leavenworth, Jonathan Dean. "Investigation of cellular stress-responsive proteins and PGF gene expression in human trophoblast /". Available to subscribers only, 2009. http://proquest.umi.com/pqdweb?did=1791777421&sid=3&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (Ph. D.)--Southern Illinois University Carbondale, 2009."Department of Medical Microbiology Immunology and Cell Biology." Keywords: Placenta, Trophoblasts, Cellular stress. Includes bibliographical references (p. 67-81). Also available online.
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Leavenworth, Jonathan Dean. "Investigations of cellular stress-responsive proteins and PGF gene expression in human trophoblast". OpenSIUC, 2009. https://opensiuc.lib.siu.edu/dissertations/296.
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Placenta growth factor (PGF) expression is downregulated in preeclampsia (PE), a leading cause of maternal morbidity and mortality. The pathophysiology of PE is thought to be manifested by a poorly perfused placenta hampered by hypoxic stress. Two stress-mediate angiogenic responses include post-transcriptional regulation of mRNA stability, and regulation of PML sequestering protein. We investigate whether these mechanisms occur in hypoxic stressed trophoblast and preeclamptic placenta. Methods: To determine transcript stability, PGF mRNA was measured in normal vs. stressed conditions, and the PGF 3'UTR was analyzed for consensus 3'AREs. To characterize stability regulation, the PGF 3'UTR was cloned into a reporter construct. To investigate the association between PGF mRNA and RNA binding proteins, an RNA-Immunoprecipitation assay was performed on trophoblast. PML study: Normal (n=6) and preeclamptic (n=6) placentae were assessed for PML expression. Immunoblot, qRT-PCR and immunohistochemistry techniques were used to determine PML gene expression and localization in placental tissue and primary cells. Results: Two consensus ARE motifs were detected within the human PGF 3'UTR at the 42nd nucleotide and the 91st nucleotide downstream from the PGF coding region. Identical and spatially conserved ARE motifs were found in bovine, rat and mouse PGF 3'UTR. Actinomycin D transcription inhibitor ii studies that were used to measure RNA decay rates in hypoxic and normal conditions, demonstrated a transcriptional response of PGF mRNA to hypoxic stress. Additionally, the PGF 3'UTR did not alter gene expression significantly relative to a site-directed mutant after 24 hours hypoxia. However, PGF 3'UTR decreased reporter activity relative to parental control, suggesting that it could function to regulate stability, but not in hypoxic stress. Western blots and immunohistochemical analyses showed the presence of three potential ARE binding proteins in trophoblast. RNA-Immunoprecipitation assays suggest that PGF mRNA may interact weakly with HuR protein. Upregulation of RNABP expression by insulin was investigated for its effects to upregulate RNABP, and was found to transcriptionally downregulate PGF mRNA. Tumor necrosis factor alpha (TNFa) treatment initiated a short-term upregulation of PGF mRNA. PML Study Results: PML protein was immunolocalized within nuclei of villus mesenchyme, but largely absent in trophoblast nuclei. A trend for increased PML reactivity in placenta of preeclamptic patients was observed. Immunoblot analyses of nuclear extracts confirmed relative increases (~3 fold) of PML expression in preeclamptic placentae (p< 0.05). Conversely, less PML mRNA (~2 fold) was detected in preeclamptic versus normal placental samples. In vitro, PML expression could be increased by hypoxia in cultured endothelial cells but not trophoblast. Conclusion: These results suggest that a post-transcriptional mechanism directed through the 3'UTR does not regulate PGF mRNA expression in stressed trophoblast. PML Study conclusion: Increased PML protein expression in preeclamptic villi suggests it could contribute to decreased vascularity and placental growth and/or function.
23
Dixon, Katherine. "Characterization of the Global and Locus-Specific Regulation of Gene Expression During Early Myogenic Differentiation". Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35079.
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During cellular differentiation, gene expression is globally regulated through changes in the epigenome. How a single genome can give rise to a diversity of cell and tissue types remains a complex area of investigation, and here we sought to explore the molecular regulation of gene expression during the differentiation of skeletal muscle cells from committed myogenic progenitors. Using a systematic and integrated analysis of global transcriptional and epigenetic data, we characterized the regulation of gene expression in differentiating myoblasts and found that muscle-specific gene expression is regulated through differential activation of tissue-specific regulatory DNA elements by the myogenic transcription factor MyoD. In addition, the genome-wide localization of MyoD, and the mechanisms underlying its function in transcriptional regulation, varies between myogenic progenitors and differentiating myoblasts. Our study explores the recruitment and function of MyoD at regulatory elements of target genes and additionally describes a novel role for ligand-inducible signaling in the regulation of MyoD function and ultimately in myogenic differentiation.
24
Petrova, Sofia. "Cellular microenvironment in Burkitt's lymphoma : gene expression profiling of tumour-associated macrophages in situ". Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/9561.
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Tumour-associated macrophages (TAM) are a major component of the inflammatory infiltrate that typifies most malignancies. Among them, Burkitt’s lymphoma (BL), a high-grade non Hodgkin lymphoma (NHL) of B-cell origin, represents a characteristic example. Studies from our group have shown that TAM in BL exert pivotal roles that are mainly supportive of tumourigenesis such as maintaining an immunosuppressive microenvironment. In order to unravel the molecular mechanisms underlying TAM functions in BL, solid tumours from a mouse xenograft model of BL have been used to obtain TAM and assess their activation status in vivo. Laser-capture microdissection has been successfully used to procure intact macrophage sections from the tumour site, allowing the production of a pure, in situ gene expression signature of TAM in BL. Tingible-body Mφ from lymph node germinal-centres and resident tissue Mφ from resting lymph nodes of non-tumour bearing mice were chosen for direct comparison with TAM. Whole-genome microarray technology has revealed a distinct TAM gene expression profile, with 454 genes being significantly up-regulated (fc ≥ 2, p<0.05) and 1293 genes being significantly down-regulated (fc ≤ -2, p<0.05) between TAM and either of the two normal Mφ populations. Further bioinformatics analysis of gene functions has highlighted matrix remodeling, phagocytosis, and immune response among the processes most highly enriched in TAM. Importantly, mRNA and tissue expression of selected differentially expressed genes relevant to these processes was validated by real-time qPCR and immunofluorescence labeling respectively. Following the generation of the TAM profile in situ, in vitro experimental approaches were undertaken in order to investigate how specific elements of the BL microenvironment drive the observed TAM signatures. Specifically, the direct role of apoptotic tumour cells, a key component of the BL microenvironment, versus that of viable tumour cells in driving TAM matrix remodelling gene expression was assessed in short-term mouse and human Mφ-NHL cell co-cultures. From the aforementioned cluster, emphasis was given to MMP12 and MMP2 transcripts: mRNA and protein expression of these MMPs was found to be up-regulated in Mφ following viable tumour cell co-cultures and this effect was further enhanced following apoptotic tumour cell co-cultures, implying that apoptotic NHL cells could directly shape TAM matrix remodeling phenotype in BL in vivo. Whereas the mRNA of both MMPs was solely Mφ-derived in this system, MMP12 and MMP2 protein was surprisingly found also to be increased in NHL cells in the apparent absence of increased mRNA. Detailed examination of MMP12 production by NHL cells revealed that it is most likely an apoptosis-dependent process, since apoptotic NHL cells generated through different apoptosis stimuli, as well as apoptotic cell-derived microparticles, showed markedly increased MMP12 protein levels. In conclusion, the data presented in this thesis, provide the first insight into the in vivo activation status of TAM in high-grade NHL, through generation of the TAM gene signature in situ. Upon further in vitro studies, apoptotic NHL cells were shown to directly modulate the matrix remodelling component of the TAM signature as well as to actively produce matrix remodelling mediators themselves, suggesting distinct roles for tumour cell apoptosis within the NHL microenvironment that can profoundly influence the disease outcome.
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Michael, Bindhu. "Human T lymphotropic virus type 1 (HTLV-1) accessory protein p30(II) modulates cellular and viral gene expression". Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1088784889.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xvii, 250 p.; also includes graphics (some col.) Includes bibliographical references (p. 207-250). Available online via OhioLINK's ETD Center
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Stolze, Ineke Petra. "Cellular oxygen sensing and the regulation of hypoxia-inducible gene expression in mammalian cells". Thesis, Oxford Brookes University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444283.
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Burkhardt, Jana, Mechthild Blume, Elisabeth Petit-Teixeira, Vitor Hugo Teixeira, Anke Steiner, Elfi Quente, Grit Wolfram i in. "Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression". Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-151575.
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In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional
consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p,1026) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also
found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.
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Andrews, Janice M. "The modulation of htlv-1 gene expression following induction of the cellular stress response /". The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487935573771058.
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Schroeder, Mark Wesley. "Regulation of Angiogenic Gene Expression in Human Trophoblast by Cellular Stressors: Implications in Preeclampsia". OpenSIUC, 2017. https://opensiuc.lib.siu.edu/theses/2203.
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Preeclampsia (PE) affects 5-8% of pregnancies worldwide and is one of the leading contributors of maternal and fetal morbidity and mortality during pregnancy. Its high prevalence coupled with its significant contribution to health crises during pregnancy emphasizes the importance of research and development of a cure to its clinical pathology. It is believed that insufficient remodeling of the maternal spiral arteries of the uterus lead to decreased perfusion of the placenta and a relatively hypoxic, inflammatory, and endoplasmic reticulum stressed placenta. This hypoxic stress has been shown to decrease the secretion of the proangiogenic molecule placental growth factor (PlGF), as well as increase the production of its antiangiogenic decoy receptor, soluble fms-like tyrosine kinase (sFlt1) by trophoblast. This results in what is commonly referred to as the “angiogenic imbalance of PE.” Hypertension and proteinuria are the clinical manifestations of PE and represent the effect of decreased systemic vasodilation and compromised glomerular endothelial integrity in the mother caused by the angiogenic imbalance. Recently, is has been shown that endoplasmic reticulum stress in the syncytiotrophoblast of the placenta correlates with a down regulation of PlGF protein expression by these cells. The molecular mechanisms which cause the decrease in PlGF production by trophoblast during PE are not known. The aims of this thesis were to elucidate whether hypoxia, inflammation, and ER stress lead to decreases in the expression and function of one of the main transcription factors of PlGF in trophoblast, glial cell missing-1(GCM1). Furthermore, we wanted to know if these insults worked in conjunction or independently of one another to decrease GCM1 and PlGF expression. Treatment of JEG3 choriocarcinoma cells with inflammatory cytokine TNFα and overexpression of pro-inflammatory transcription factor, NFκBp65, did not significantly alter the expression of GCM1 or PlGF mRNA. Treatment of JEG3 cells with ER stress inducer tunicamycin significantly decreased GCM1 and PlGF mRNA expression. ER stress induction in JEG3 cells transduced with a 1.5kb 5`UTR of PlGF linked to a GFP reporter significantly decreased GFP expression. These results suggest that ER stress decreases transcription in the 1.5kb 5`UTR of PlGF. This region of the 5`UTR of PlGF was recently shown to be under transcriptional regulation by GCM1. Finally, 1%O2 treatment of JEG3 choriocarcinoma cells significantly decreased GCM1 and PlGF gene expression while significantly increasing the expression of an ER stress marker, CHOP. These data indicate that hypoxia can lead to ER stress in trophoblast which can decrease GCM1 expression. As GCM1 is a principle transcription factor of PlGF in trophoblast, this results in decreased transcription and expression of PlGF. Thus, inhibiting the occurrence of ER stress in trophoblast of preeclamptic pregnancies, possibly though drug delivery to the preeclamptic mother, may provide a novel therapeutic approach. By reducing ER stress of trophoblast we hypothesize that expression of PlGF will be increased in maternal serum. This may function to correct the “angiogenic imbalance of PE” and may alleviate preeclamptic symptoms, allowing for prolongation of pregnancy and therefore decreased risk of maternal and fetal morbidity and mortality.
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Rashid, Susan Basel. "Protein Profile and Directed Gene Expression of Developing C2C12 cells". Youngstown State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1442433668.
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Robinson, Lucas. "Deciphering Gene-regulatory Processes in Cellular Senescence : the role of PARP1 in the regulation of senescence - associated gene expression". Thesis, Université de Paris (2019-....), 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=4767&f=29840.
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La sénescence cellulaire est une réaction de stress complexe qui arrête la prolifération cellulaire et s'accompagne de bouleversements généralisés du métabolisme, de la structure de la chromatine et de l'expression des gènes, y compris la surexpression et la sécrétion de facteurs inflammatoires. La sénescence cellulaire a des effets bénéfiques en tant que mécanisme suppresseur de tumeurs et facilite le développement embryonnaire ainsi que la régénération tissulaire. Cependant, ce processus est également considéré comme un acteur important du vieillissement et des maladies liées à l'âge, principalement par son phénotype inflammatoire, appelé SASP (Senescence-associated secretory phenotype). Les recherches actuelles pointent vers un rôle de PARP1 (poly(ADP-ribose) polymérase 1) dans la régulation transcriptionnelle des processus inflammatoires et la modulation de la structure de la chromatine. Néanmoins, les mécanismes exacts par lesquels PARP1 exerce ses fonctions de régulation et ses rôles dans le contexte de la régulation transcriptionnelle de la sénescence demeurent peu connus. Dans ma thèse, j'ai entrepris de définir le rôle fonctionnel des activités catalytique et de liaison à la chromatine de PARP1 dans la régulation transcriptionnelle et la structure de la chromatine dans les cellules en sénescence. J'ai réalisé des analyses transcriptomiques à résolution temporelle, des études d'accessibilité de la chromatine et du paysage chromatinien de PARP1 par ChIP-Seq, ainsi que de la chromatine ADP-ribosylée en développant une nouvelle technique le CRAP-seq (Chromatin-Ribosylation-Affinity-Pulldown). Ces analyses ont permis d’identifier une dichotomie de la fonction de PARP1 - l'une liée à son activité enzymatique d’ADP-ribosylation et l'autre à son activité de liaison à la chromatine non enzymatique - avec des impacts distincts sur le programme transcriptionnel de la sénescence. Sur la base de ces résultats, j’ai pu définir un nouveau rôle global pour PARP1 dans la modulation de la structure de la chromatine, d’une part par la stabilisation du positionnement des nucléosomes au niveau des promoteurs géniques et d’autre part par l’ADP-ribosylation des éléments régulateurs en cis pour finement réguler la transcription des gènes peu exprimés. Ainsi, ces recherches permettent d’envisager le rôle des inhibiteurs de PARP dans les thérapies ciblant la sénescence (thérapies sénolytiques) pour le traitement des pathologies liées au vieillissementCellular senescence is a complex stress response that arrests cell proliferation and is accompanied by widespread changes in metabolism, chromatin structure, and gene-expression, including the overexpression and secretion of inflammatory factors. Cellular senescence is health-promoting as a tumor-suppressive mechanism, facilitating embryonic development and tissue regeneration. However, it is also considered a major contributor to aging and age-related diseases, mostly through its inflammatory phenotype, the so-called SASP (senescence-associated secretory phenotype). Current research supports the role of PARP1 (Poly (ADP-ribose) polymerase 1) in the transcriptional regulation of inflammatory processes and modulation chromatin structure. However, the exact mechanisms by which PARP1 exerts its regulatory functions, and its roles in the context of regulating senescence gene-expression are underexplored. In my thesis, I set out to define the functional role of PARP1 catalytic and chromatin binding activities in gene regulation and chromatin structure in cells undergoing senescence. I performed time-resolved transcriptomics, chromatin-accessibility studies, and mapping of the genome-wide locations of PARP1 using ChIP-seq and ADP-ribosylated chromatin using a novel technique CRAP-seq (Chromatin-Ribosylation-Affinity-Pulldown). Together, I identified a dichotomy of PARP1 function – one related to its enzymatic ADP-ribosylation activity and the other related to its non-enzymatic chromatin binding activity – with distinct impacts on the senescence transcriptional program. Based on these findings, I can define a novel and global role for PARP1 in and chromatin structure modulation by stabilizing nucleosomes positioning at gene promoters and ADP-ribosylation of cis-regulatory modules to fine-tune transcription of lowly expressed genes. Indeed, based on my investigations, the role of PARP-inhibitors in senescence targeting therapies (senolytic therapies) for the treatment of age-related pathologies can be envisioned
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Lin, Chengyuan. "Neuroendocrine regulation and signal transduction for prolactin gene expression in grass carp". Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42664433.
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Zhang, Yi. "Studies of heparanase (HPA) gene expression, cellular localization and functions in neural tissues of the rat". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39634061.
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Zhang, Yi, i 張怡. "Studies of heparanase (HPA) gene expression, cellular localization andfunctions in neural tissues of the rat". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39634061.
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Bain, Peter A., i n/a. "Gene Expression Profiling of Cylindrospermopsin Toxicity". Griffith University. School of Biomolecular and Physical Sciences, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20080404.145834.
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Cylindrospermopsin (CYN) is a toxic alkaloid produced by several freshwater cyanobacterial species, the most prevalent in Australian waters being Cylindrospermopsis raciborskii. The occurrence of CYN-producing cyanobacteria in drinking water sources worldwide poses a potential human health risk, with one well-documented case of human poisoning attributed to the toxin. While extensive characterisation of CYN-induced toxicity has been conducted in rodents both in vivo and in primary cell cultures, little is known about mechanisms of toxicity in human cell types. This thesis describes studies undertaken to further define the molecular mechanisms of CYN toxicity in human cells. Concentration-response relationships were determined in various cultured human cell types using standard toxicity assays. As expected, CYN caused dose-dependent decreases in the growth of three cell lines, HepG2, Caco-2 and HeLa, and one primary cell type, human dermal fibroblasts, according to tetrazolium reduction assays. CYN treatment did not disrupt cellular membranes according to the lactate dehydrogenase release assay in HepG2 or Caco-2 cells after 24, 48 or 72 h exposure, but did cause membrane disruption in fibroblasts after 72 h exposure to relatively high concentrations of the toxin. Apoptosis occurred more readily in HeLa cells than HepG2 cells or fibroblasts, with 72 h exposure to 1 &mug/mL required before statistically significant rates of apoptosis occurred in the latter cell types. CYN did not appear to directly affect the structure of actin filaments or microtubules under the conditions used in the present study. The major portion of the work presented in this thesis comprises a large-scale interrogation of changes in gene expression induced by the toxin in cultured cells. To assess the effects of CYN on global gene expression, relative messenger RNA (mRNA) levels in human dermal fibroblasts and HepG2 cells after 6 h and 24 h exposure to 1 &mug/mL CYN were determined using oligonucleotide microarrays representing approximately 19 000 genes. Overall, the number of transcripts significantly altered in abundance was greater in fibroblasts than in HepG2 cells. In both cell types, mRNA levels for genes related to amino acid biosynthesis, carbohydrate metabolism, and protein folding and transport were reduced after CYN treatment, while transcripts representing genes for apoptosis, RNA biosynthesis and RNA processing increased in abundance. More detailed data analyses revealed the modulation of a number of stress response pathways—genes regulated by NF-&kappaB were induced, DNA damage response pathways were up-regulated, and a large number of genes involved in endoplasmic reticulum stress were strongly down-regulated. Genes for the synthesis and processing of mRNA, tRNA and rRNA were strongly up-regulated, indicating that CYN treatment may increase the turnover of all forms of cellular RNA. A small group of genes were differentially expressed in HepG2 cells and fibroblasts, revealing cell-specific responses to the toxin. Selected changes in transcript level were validated using real-time quantitative reverse transcriptase PCR (qRT-PCR). The modulation of stress response pathways by CYN, indicated by microarray analysis, was further investigated using other methods. The role of tumour suppressor protein p53 in CYN-mediated gene expression was confirmed by measuring the expression of known p53-regulated genes following CYN treatment of HepG2 cells and human dermal fibroblasts using qRT-PCR. Western blotting of protein extracts from CYNtreated cells showed that p53 protein accumulation occurred in HepG2 cells, providing additional evidence of the activation of the p53 pathway by CYN in this cell line. The immediate-early genes JUN and FOS were found to be induced by CYN in a concentration-dependent manner, and MYC was induced to a lesser extent. The mitogen-activated protein kinase c-Jun NH2-terminal kinase, implicated in the ribotoxic stress response initiated by damage to ribosomal RNA, appeared to become phosphorylated in HeLa cells after CYN exposure, suggesting that ribotoxic stress may occur in response to CYN in at least some cell types. The expression of a reporter gene under the control of a response element specific for NF-&kappaB was induced at the mRNA level but inhibited at the protein level. This shows that while transcription factors such as p53 and NF-&kappaB are apparently activated in response to the toxin, transactivation of target genes may not necessarily manifest a corresponding increase at the protein level. The current work contributes significantly to the current understanding of cylindrospermopsin toxicity in human-derived cell types, and provides further insight into putative modes of action.
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Bain, Peter A. "Gene Expression Profiling of Cylindrospermopsin Toxicity". Thesis, Griffith University, 2007. http://hdl.handle.net/10072/367068.
Pełny tekst źródłaStreszczenie:
Cylindrospermopsin (CYN) is a toxic alkaloid produced by several freshwater cyanobacterial species, the most prevalent in Australian waters being Cylindrospermopsis raciborskii. The occurrence of CYN-producing cyanobacteria in drinking water sources worldwide poses a potential human health risk, with one well-documented case of human poisoning attributed to the toxin. While extensive characterisation of CYN-induced toxicity has been conducted in rodents both in vivo and in primary cell cultures, little is known about mechanisms of toxicity in human cell types. This thesis describes studies undertaken to further define the molecular mechanisms of CYN toxicity in human cells. Concentration-response relationships were determined in various cultured human cell types using standard toxicity assays. As expected, CYN caused dose-dependent decreases in the growth of three cell lines, HepG2, Caco-2 and HeLa, and one primary cell type, human dermal fibroblasts, according to tetrazolium reduction assays. CYN treatment did not disrupt cellular membranes according to the lactate dehydrogenase release assay in HepG2 or Caco-2 cells after 24, 48 or 72 h exposure, but did cause membrane disruption in fibroblasts after 72 h exposure to relatively high concentrations of the toxin. Apoptosis occurred more readily in HeLa cells than HepG2 cells or fibroblasts, with 72 h exposure to 1 µg/mL required before statistically significant rates of apoptosis occurred in the latter cell types. CYN did not appear to directly affect the structure of actin filaments or microtubules under the conditions used in the present study. The major portion of the work presented in this thesis comprises a large-scale interrogation of changes in gene expression induced by the toxin in cultured cells. To assess the effects of CYN on global gene expression, relative messenger RNA (mRNA) levels in human dermal fibroblasts and HepG2 cells after 6 h and 24 h exposure to 1 µg/mL CYN were determined using oligonucleotide microarrays representing approximately 19 000 genes. Overall, the number of transcripts significantly altered in abundance was greater in fibroblasts than in HepG2 cells. In both cell types, mRNA levels for genes related to amino acid biosynthesis, carbohydrate metabolism, and protein folding and transport were reduced after CYN treatment, while transcripts representing genes for apoptosis, RNA biosynthesis and RNA processing increased in abundance. More detailed data analyses revealed the modulation of a number of stress response pathways—genes regulated by NF-?B were induced, DNA damage response pathways were up-regulated, and a large number of genes involved in endoplasmic reticulum stress were strongly down-regulated. Genes for the synthesis and processing of mRNA, tRNA and rRNA were strongly up-regulated, indicating that CYN treatment may increase the turnover of all forms of cellular RNA. A small group of genes were differentially expressed in HepG2 cells and fibroblasts, revealing cell-specific responses to the toxin. Selected changes in transcript level were validated using real-time quantitative reverse transcriptase PCR (qRT-PCR). The modulation of stress response pathways by CYN, indicated by microarray analysis, was further investigated using other methods. The role of tumour suppressor protein p53 in CYN-mediated gene expression was confirmed by measuring the expression of known p53-regulated genes following CYN treatment of HepG2 cells and human dermal fibroblasts using qRT-PCR. Western blotting of protein extracts from CYNtreated cells showed that p53 protein accumulation occurred in HepG2 cells, providing additional evidence of the activation of the p53 pathway by CYN in this cell line. The immediate-early genes JUN and FOS were found to be induced by CYN in a concentration-dependent manner, and MYC was induced to a lesser extent. The mitogen-activated protein kinase c-Jun NH2-terminal kinase, implicated in the ribotoxic stress response initiated by damage to ribosomal RNA, appeared to become phosphorylated in HeLa cells after CYN exposure, suggesting that ribotoxic stress may occur in response to CYN in at least some cell types. The expression of a reporter gene under the control of a response element specific for NF-?B was induced at the mRNA level but inhibited at the protein level. This shows that while transcription factors such as p53 and NF-?B are apparently activated in response to the toxin, transactivation of target genes may not necessarily manifest a corresponding increase at the protein level. The current work contributes significantly to the current understanding of cylindrospermopsin toxicity in human-derived cell types, and provides further insight into putative modes of action.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Faculty of Science, Environment, Engineering and Technology
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McLean, Adam George. "Patterns of graft infiltration and cytokine gene expression during the first ten days of kidney transplantation". Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390513.
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Lin, Chengyuan, i 林成源. "Neuroendocrine regulation and signal transduction for prolactin gene expression in grass carp". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42664433.
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Lerner, A. "Development of the sea urchin apical organ : cellular mapping of gene expression and FGF signalling". Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1406547/.
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The sea urchin apical organ constitutes a fundamental part of the larval nervous system and forms a neuro-sensory structure capable of sensing environmental cues and coordinating swimming behaviour. However, the gene regulatory network (GRN) that underlies the specification of this structure is poorly understood. The first step in building an apical organ GRN, is the high-resolution characterisation of regulatory genes in both time and space. This information then allows the regulatory states of the apical domain to be determined and identifies the existence of different spatial domains. In this study, spatial and temporal expression data of regulatory genes were overlaid onto cellular maps of the apical domain at different developmental stages. These cellular maps were then used to establish the different regulatory states that occur in the apical domain and their dynamics during development. This analysis illustrated that the spatial organisation of the apical domain is far more complex and dynamic than previously thought. The rest of the thesis focuses on functional analysis, and addresses the role of FGF signalling in the development of the apical organ. Embryos injected with a fgfr1 morpholino or incubated with SU5402, a common chemical inhibitor of FGFR1, show an upregulation in a limited group of apical organ genes. Surprisingly, the two methods of disrupting FGFR1 did not affect similar genes, and suggests that an unspecific perturbation is occurring. Functional analysis was also carried out on zic2, an apical organ transcription factor upregulated by SU5402 treatment. The results show that zic2 represses itself and is required for a normal complement of serotonergic neurons.
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Chotani, Maqsood Ahmed. "Cellular and molecular analysis of regulatory mechanisms of human fibroblast growth factor-1 gene expression /". The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487946103565201.
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Pandit, Ashish V. "REGULATION OF MITOCHONDRIAL GENE EXPRESSION IN MULTIPLE SCLEROSIS CORTEX". Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1334214461.
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Kim, Yeonhee. "The Design and Assembly of 3D Liver Mimetic Cellular Architectures". Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/39454.
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We report the assembly of three-dimensional (3D) liver sinusoidal mimics comprised of primary rat hepatocytes, human or rat liver sinusoidal endothelial cells denoted as hLSECs and rLSECs respectively, and an intermediate chitosan-hyaluronic acid (HA) polyelectrolyte multilayer (PEM). The height of the PEMs ranged from 30-55nm and exhibited a shear modulus of ~ 100kPa. Primary rat hepatocytes coated with 5 and 15 PE layers exhibited stable urea and albumin production over a seven day period and these values were either comparable or superior to that in a collagen sandwich (CS). Hepatocyte-PEM-hLSEC liver mimics exhibited stable urea production and increasing albumin secretion over the culture period in comparison to hepatocyte-LSEC samples. In the 3D liver mimics, hLSEC phenotype was maintained and verified by the uptake of acetylated low-density lipoprotein (AcLDL). A sixteen-fold increase in CYP1A1/2 activity was observed for hepatocyte-PEM-10,000 hLSEC samples, thereby, suggesting that interactions between hepatocytes and hLSECs play a key role in enhancing hepatic phenotypes in in vitro cultures. As the first step towards elucidating key signaling pathways involved in cell-cell communications, global genome-wide transcriptional profiles of primary hepatocytes cultured in CS and hepatocyte monolayers (HMs) were performed over an eight-day period using DNA microarray measurements and Gene Set Enrichment Analysis (GSEA) in order to derive biologically meaningful information at the level of gene sets. The gene expression in CS cultures steadily diverged from that in HMs. Gene sets up-regulated in CS are those linked to liver metabolic and synthetic functions, such as lipid, fatty acid, alcohol and carbohydrate metabolism, urea production, and synthesis of bile acids. Monooxygenases such as CYP enzymes were significantly up-regulated starting on day 3 in CS cultures. These results serve as a baseline for further investigation into the systems biology of engineered liver tissues. 3D hepatic constructs were also assembled with primary rat hepatocytes and rLSECs, and a chitosan-HA PEM. In these hepatic models, the phenotype of hepatocytes and rLSECs were maintained. rLSEC phenotype was verified over a twelve-day period through immunostaining with the sinusoidal endothelial-1 (SE-1) antibody. In contrast, rLSECs cultured as monolayers lost their phenotype within 3 days. A two-fold increase in albumin production was observed only in the 3D liver models. rLSEC-PEM-hepatocyte cultures exhibited three- to six-fold increased CYP1A1/2 and CYP3A enzymatic activity. Well-defined bile canaliculi were observed in only 3D hepatic constructs. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte constructs can be used as liver models for future studies.Ph. D.
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Cheng, Wai-sheung. "PTEN-PKB in endometriosis and related malignant transformation /". View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31540764.
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Roberts, Kim G. "Exploration of the ErbB/Ras/MAPK signaling pathway in cancer by gene expression profiling with isoform-specific assay development and microarray technology". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 169 p, 2007. http://proquest.umi.com/pqdweb?did=1362532051&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Jiang, Quan, i 姜权. "Neuroendocrine regulation and signal transduction of somatolactin secretion and gene expression in grass carp". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45553464.
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O'Brien, Siobhan. "Regulation of Cellular and HIV-1 Gene Expression by Positive Transcription Elongation Factor B: A Dissertation". eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/528.
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RNA polymerase II-mediated transcription of HIV-1 genes depends on positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We show that P-TEFb interacts with H1 and that H1 phosphorylation in cell culture correlates with P-TEFb activity. Importantly, P-TEFb also directs H1 phosphorylation during Tat transactivation and wild type HIV-1 infection. Our results also show that P-TEFb phosphorylates histone H1.1 at a specific C-terminal site. Expression of a mutant H1.1 that cannot be phosphorylated by P-TEFb disrupts Tat transactivation as well as transcription of the c-fos and hsp70 genes in HeLa cells. P-TEFb phosphorylation of H1 also plays a role in the expression of muscle differentiation marker genes in the skeletal myoblast cell line C2C12. Additionally, ChIP experiments demonstrate that H1 dissociates from the HIV-1 LTR in MAGI cells, stress-activated genes in HeLa cells, and muscle differentiation marker genes in C2C12 cells under active P-TEFb conditions. Our results overall suggest a new role for P-TEFb in both cellular and HIV-1 transcription through chromatin.
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Brown, Kayla A. "Changes in Gene Expression of Neurospora crassa in Response to Quinic Acid". Youngstown State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1484090465840537.
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Kennedy, Daniel Edward II. "Phenotypic Characterization and Gene Expression Analyses of a Penicillium marneffei Septin Mutant". Youngstown State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1340653587.
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Fettig, Amy E. "Identification of cellular targets influenced by ectopic expression of TAL1 and LMO1 genes". Virtual Press, 2001. http://liblink.bsu.edu/uhtbin/catkey/1222830.
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Cancer has been a disease, which has generated intense research interest for many years. Misexpression of two oncoproteins, TAL 1 and LMO 1, has been found to help induce a particular type of leukemia, called T-cell acute lymphoblastic leukemia (T-ALL). Presently, it is not completely understood how these proteins induce leukemogenesis or what other cellular proteins they interact with to drive this progression. In this study, a series of experiments were conducted to identify downstream targets of TALI and LMO1. Using retroviral gene transfer, both genes were introduced, either singly or in combination, into a murine T-cell line called AKR-DP-603. Empty vectors were introduced as controls. In order to assay the effects of TALI and LMO I expression on expression of other proteins, a series of Western blots were completed on all populations of engineered cells. It was determined that there were differences in expression of Bcl-2 and p16 as indicated by differences in band intensities on the blots. This is important because it implies an effect on protein levels by TAL 1 and LMO 1. However, there were no differences in protein expression levels for Bax or cyclin D1. This suggests that TAL1 and LMOI do not have any regulatory effects on these proteins. In addition, apoptotic assays were completed on all populations of cells. The results of both a TUNEL assay and ethidium bromide/acridine orange staining protocol showed TAL1- and LMO1expressing cells to have an increase in cell survival under starvation conditions and a lower frequency of apoptosis. Statistical analysis verified significant difference in the apoptosis assays. The data suggests an up-regulation of anti-apoptotic proteins. The finding of this research allow a clearer understanding of the process of leukemogenesis and may lead to a development of better cancer treatments.Department of Biology
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Newsome, Laura Jean. "Global Gene Expression Profiles and Proteomic Assessments in Adult Females with Obstructive Sleep Apnea Syndrome". Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/77306.
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Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by repetitive bouts of upper airway collapse during sleep, causing subsequent intermittent hypoxia, hypercapnia, and fragmented sleep and is also associated with significant morbidity including daytime sleepiness, hypertension, and elevated cardiovascular risk. OSAS affects at least 4% of men and 2% of women; unfortunately, it is estimated that 80% to 90% of adults with OSAS remain undiagnosed. Both clinical characteristics and complex genetic and environmental interactions have made it difficult to understand OSAS disease etiology and identifying patients at risk is still elusive. A pattern of gene expression in cells or tissues related to a disease state for OSAS would provide beneficial information to be most effective in screening or diagnosing this disease.
Objectives: The objectives of this study were to: 1) map out the study design and bench assay strategies by which to investigate this issue; 2) find out if there are specific differences in the global gene expression profiles of adult females with OSAS compared to those without OSAS, under conditions in which subjects were clinically similar (BMI, diabetes, cardiovascular disease, etc.); and 3) assess the protein expression differences that could potentially be linked via well-established molecular pathways associated with any differences found in global gene expression profiles in the presence and absence of OSAS.
Methods: Subjects were overweight premenopausal Caucasian women with untreated OSAS (n=6; age = 40.7 ± 3.4; BMI = 49.04 ± 6.97; apnea-hypopnea index = 27.3 ± 16.02), and control subjects (n=10) (age = 38.2 ± 7.6; BMI = 47.94 ± 6.15; apnea-hypopnea index < 5), and matched for other clinical characteristics (diabetes, cardiovascular disease status, medications, etc.) recruited from either Carilion Clinic Pulmonary/Sleep Medicine or Carilion Clinic Bariatric Surgery practices. Subjects provided a fasting blood sample in which the monocytes were isolated from whole blood. The RNA was extracted from the monocytes, assessed for purity and quantity, frozen and shipped to collaborators at Dana-Farber Cancer Institute and hybridized to Affymetrix whole human genome chips on a gene chip. The initial computational evaluation and interpretation generated the hypothesis. Two-step quantitative real time polymerase chain reaction (qPCR) was performed to verify the results from the microarray analysis. The laminin enzyme immunoassay (EIA), and cellular adhesion assays were performed to determine if genomic changes resulted in proteomic and phenotypic assessments.
Results: OSAS subjects had nine aberrantly regulated genes, of which three genes (LAMC-1, CDC42, and TACSTD2) showed a pattern in segregation between OSAS and controls subjects based on expression patterns. In addition, qPCR indicated a 2.1 fold increase in LAMC-1 and a 1.1 fold increase CDC42 expression unique to the tissue samples of patients with OSAS. Though the serum laminin EIA did not differ between groups, a statistically significant increase in peripheral blood mononuclear cells (PBMC) cellular adhesion in OSAS patients versus control subjects was found. The OSAS subjects had a well cell count of 9.27 ± 1.54 cells vs. controls 5.75 ± 0.78 cells (p Ë‚ 0.05), which is relative to the 103 cells/field that were plated.
Conclusions: Cells isolated from women with moderate-severe OSAS show an abnormality in cellular adhesion, a process driven in part by the gene LAMC-1, which was also aberrantly expressed in these subjects. This suggests that inflammation may be linked to the pathogenesis of OSAS. This pilot study has provided the framework and preliminary data needed to propose a larger study with extramural research funding.Ph. D.