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Articles 1 - 18 of 18
Full-Text Articles in Life Sciences
Adenovirus-5 Infection Affects Lipid Metabolism In Hepatic And Adipose Tissues, Marianna Sukholutsky
Adenovirus-5 Infection Affects Lipid Metabolism In Hepatic And Adipose Tissues, Marianna Sukholutsky
Theses and Dissertations
Our recent studies have shown a link between Adenovirus-5 (Ad-5) and elevated lipids, which prompted the hypothesis that Ad-5 infection might augment hepatic and/or adipose tissue lipid metabolism. To test our hypothesis, mice were infected with Ad-5 and screened for changes in lipogenesis and plasma markers associated with the metabolic syndrome. We observed increased expression of sterol regulatory element binding protein 1 (SREBP-1) in infected liver tissues, but not in adipose tissues and this correlated with elevated plasma and hepatic triglyceride levels. Elevated expression of adiponectin was seen in Ad-5 infected adipose tissues and this correlated with phosphorylated AMPK in …
The Regulation Of The Alternative Splicing Of Caspase 9, Rachel Goehe
The Regulation Of The Alternative Splicing Of Caspase 9, Rachel Goehe
Theses and Dissertations
The pro-apoptotic, caspase 9a, and the anti-apoptotic, caspase 9b, are derived from the caspase 9 gene by alternative splicing. This study demonstrates that the alternative splicing of caspase 9 is dysregulated in a large percentage of non-small cell lung cancer (NSCLC) tumors of the adenocarcinoma type. Furthermore, modulation of the levels of splice variants of caspase 9 had dramatic effects on the anchorage-independent growth and tumorigenic capacity of NSCLC cells. Due to these findings, the molecular mechanisms regulating the post-transcriptional processing of caspase 9 were therefore examined and an exonic splicing silencer (ESS) regulating the pre-mRNA processing of caspase 9 …
Specificity Determinants Of Arma, A Ribosomal Rna Methyltransferase That Confers Antibiotic Resistance, Tamara Zarubica
Specificity Determinants Of Arma, A Ribosomal Rna Methyltransferase That Confers Antibiotic Resistance, Tamara Zarubica
Theses and Dissertations
Bacterial resistance to 4,6-type aminoglycoside antibiotics, which target the 30S ribosomal subunit, has been traced to the arm/rmt family of rRNA methyltransferases. These plasmid-encoded enzymes transfer a methyl group from S-adenosylmethionine to N7 of the buried G1405 in the aminoglycoside binding site of 16S rRNA in the 30S ribosomal subunit. Neither 16S rRNA alone nor intact 70S ribosome is an efficient substrate for armA methyltransferase. To more fully characterize this family of enzymes, xiii we have investigated the substrate requirements of ArmA. We determined the Mg2+ dependence of ArmA activity and found that the enzyme could recognize both translationally active …
Contribution Of Nuceliec Acids On The Structure Of Recombinant Hepadnavirus Core Antigens, Maimuna Bruce
Contribution Of Nuceliec Acids On The Structure Of Recombinant Hepadnavirus Core Antigens, Maimuna Bruce
Theses and Dissertations
The Hepatitis B core antigen (HBcAg) has been proposed to be an ideal candidate for use as an adjuvant due to its immunogenicity, and tolerance to manipulations such as insertions of epitopes or covalent attachment of ligands. HBcAg is a complex macromolecule containing protein and nucleic acid. We investigated the effect of the removal and reconstitution of nucleic acids upon its structure. It’s been shown that the RNA content of hepadnavirus core antigens can be reduced significantly, but not be completely removed. Following removal of some of the RNA, antigens retain the ability to bind added nucleic acids, in particular, …
Function And Regulation Of Matrix Metalloproteinase-1 In Glioblastoma Multiforme, Monika Anand
Function And Regulation Of Matrix Metalloproteinase-1 In Glioblastoma Multiforme, Monika Anand
Theses and Dissertations
Glioblastoma Multiforme (GBM) is an aggressive and fatal cancer of the brain. It is characterized with augmented morbidity and elusion to therapies due in part to the incessant infiltration and spread of tumor cells in normal brain. We investigated the function of Matrix metalloproteinase-1, an important enzyme noted to be responsible for invasion in other cancers, in GBM and its regulation by epidermal growth factor receptor (EGFR) signaling. Previous studies from our laboratory demonstrated elevated levels of MMP-1 in GBM. Further studies indicated the involvement of MMP-1 in GBM invasion. The GBM cell lines T98G, U251MG and U87MG were used …
Role Of Xrcc3 In Acquisition And Maintenance Of Invasiveness Through Extracellular Matrix In Breast Cancer Progression, Siddharth Saini
Role Of Xrcc3 In Acquisition And Maintenance Of Invasiveness Through Extracellular Matrix In Breast Cancer Progression, Siddharth Saini
Theses and Dissertations
Acquisition of invasiveness through extracellular matrix is a crucial characteristic of transition to malignancy in the breast. It was previously shown that Polo-like kinase 1 (PLK-1), a mitotic kinase and genome stability regulator, is involved in acquisition of invasiveness in a breast cell model (HMT-3522 cell line) of pre-invasive to invasive transition. This and other data led to the suggestion that a new class of genes called GISEM for Genome Instability and Extracellular Matrix Invasiveness may exist. Previous lab data show that XRCC3 is found downregulated in progression from preinvasive to invasive phenotype. This led to the hypothesis that XRCC3 …
Double-Strand Break Repair Mechanisms In Human Embryonic Stem Cells, Bret Adams
Double-Strand Break Repair Mechanisms In Human Embryonic Stem Cells, Bret Adams
Theses and Dissertations
Central to the progression of all organisms is the maintenance of a stable genome despite continuous insults arising from genotoxic and environmental stresses. Embryonic stem cells show promise for treatment of a variety of diseases as well as for providing normal human tissue to conduct scientific research. A major obstacle for their application is that genomic instability arises in stem cells after prolonged cell culture. The most detrimental form of DNA damage is the DNA double-strand break (DSB), which is managed by cells through complex mechanisms, designated the DNA damage response. There are two major types of DSB repair; homologous …
Strategies To Employ Androstenediol To Reverse Steroid Inhibited Healing In A Rat Model Of Trauma, Francis Diskin
Strategies To Employ Androstenediol To Reverse Steroid Inhibited Healing In A Rat Model Of Trauma, Francis Diskin
Theses and Dissertations
Much of our current understanding regarding trauma, mechanisms of healing, and treatment strategies have evolved as a result of injuries suffered during armed conflict. While our understanding of these processes has advanced during and since these conflicts, treatment methods of traumatic wound healing have failed to progress significantly in the last forty years. The overall objective of this research was to test the hypothesis that the immune regulating hormone Androstenediol (AED) modulates the host’s immune system to promote wound healing under conditions where it has been inhibited by stress and infection. In an effort to characterize the effects of Androstenediol …
Pathogenic Role Of Phosphodiesterase Type 5 Upregulation In Cardiac Ischemia/Reperfusion Injury, Daniel Hobbs
Pathogenic Role Of Phosphodiesterase Type 5 Upregulation In Cardiac Ischemia/Reperfusion Injury, Daniel Hobbs
Theses and Dissertations
Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results …
Novel Mechanism In Astrocyte Gene Regulation And Function, Sandeep Singh
Novel Mechanism In Astrocyte Gene Regulation And Function, Sandeep Singh
Theses and Dissertations
This dissertation sheds light on several novel mechanistic findings in astrocyte specific gene regulation and function by the NFI-X transcription factor which can be further extrapolated to astrocyte differentiation and glial tumor invasion. First, we cloned and analyzed human NFI-X3, a novel splice variant of the nfix gene, which contains a unique transcriptional activation (TA) domain completely conserved in primates. In contrast to previously cloned NFI-X1, overexpression of NFI-X3 potently activates NFI reporters, including GFAP reporter, in astrocytes and glioma cells. The expression of NFI-X3 is dramatically upregulated during the differentiation of neural progenitors to astrocytes and precedes the expression …
A Computational Biology Approach To The Analysis Of Complex Physiology: Coagulation, Fibrinolysis, And Wound Healing, Nathan Menke
A Computational Biology Approach To The Analysis Of Complex Physiology: Coagulation, Fibrinolysis, And Wound Healing, Nathan Menke
Theses and Dissertations
The birth of complexity research derives from the logical progression of advancement in the scientific field afforded by reductionist theory. We present in silico models of two complex physiological processes, wound healing and coagulation/fibrinolysis based on two common tools in the study of complex physiology: ordinary differential equations (ODE) and Agent Based Modeling (ABM). The strengths of these two approaches are well-suited in the analysis of clinical paradigms such as wound healing and coagulation. The complex interactions that characterize acute wound healing have stymied the development of effective therapeutic modalities. The use of computational models holds the promise to improve …
A Novel Role Of Sirt1 In Sildenafil Induced Cardioprotection In Mice, Mona Shalwala
A Novel Role Of Sirt1 In Sildenafil Induced Cardioprotection In Mice, Mona Shalwala
Theses and Dissertations
Phosphodiesterase-5 inhibitor, sildenafil (SIL) protects against myocardial ischemia/reperfusion (I-R) injury. We hypothesized that SIL-induced protection may be mediated through activation of SIRT1, an enzyme which deacetylates proteins involved in cellular stress response. Adult male ICR mice were treated with SIL (0.7mg/kg ip), Resveratrol (RSV) (5mg/kg ip) (positive control), or saline (0.2 ml ip). The hearts were harvested 24 h later and homogenized for SIRT1 activity analysis. Both SIL and RSV increased cardiac SIRT1 activity (P<0.001) as compared to Saline. Adult mouse ventricular cardiomyocytes pre-treated with either SIL or RSV (1µM) in vitro also upregulated SIRT1 activity (P<0.05). SIL also reduced infarct size following 30 min. ischemia and 24 h reperfusion in vivo. Sirtinol (5mg/kg in 10% DMSO, ip), a SIRT1 inhibitor abolished the infarct-limiting effect of SIL and RSV (P<0.001). In conclusion, activation of SIRT1 by SIL plays an essential role in cardioprotection against I-R injury.
Tied Together: A Molecular Role For Tie1 In Angiopoietin Tie2 Signaling, Tom Cm Seegar
Tied Together: A Molecular Role For Tie1 In Angiopoietin Tie2 Signaling, Tom Cm Seegar
Theses and Dissertations
The primary function of the vascular system is the maintenance of oxygen homeostasis for all metazoan tissue. Angiogenesis, the remodeling and maintenance of new blood vessels from an existing vessel, is primarily controlled through the endothelial specific receptor tyrosine kinase Tie2, and the orphan receptor tyrosine kinase, Tie1. Although these receptors share highly conserved, genetic and biochemical analysis has shown these receptors have distinct and essential roles in angiogenesis. Tie2 activation typically results in vessel stability and quiescences and has further been shown to interact with all four sub-types of the angiopoietin signaling factors, Ang1-4. Conversely, Tie1 is involved in …
Role Of Jak/Stat Pathway In The Pathogenesis Of Breast Cancer, Qifang Zhang
Role Of Jak/Stat Pathway In The Pathogenesis Of Breast Cancer, Qifang Zhang
Theses and Dissertations
The Jak/Stat signaling cascade mediates cell proliferation, differentiation, survival, apoptosis and immune responses. Aberrant activation of this pathway mediates neoplastic transformation and abnormal growth of many malignancies including breast cancer, the most common cancer among women, and the second leading cause of cancer deaths in women in United States. The mechanism by which the Jak/Stat pathway modulates the pathogenesis of breast cancer is unclear. This dissertation elucidates roles of Jak/Stat members that mediate the pathogenesis of breast cancer. For these studies, we used 4T1 mouse mammary tumor cells as a model which mimics human breast cancer. First, we investigated the …
Biochemical Characterization Of Suppressor Of Ikk-Ε And Nak-Associated Protein 1, Jonathan Forbes
Biochemical Characterization Of Suppressor Of Ikk-Ε And Nak-Associated Protein 1, Jonathan Forbes
Theses and Dissertations
Innate immunity provides the first line of defense against invading pathogen by recognizing and mounting a response to the pathogenic challenge. Among the cellular mechanisms of the innate immune response, Toll-like receptor 3 (TLR3) recognizes viral dsRNA and signals subsequent production of type-I interferon. The TLR3:interferon signaling cascades contains a kinase complex composed of two kinases and a scaffold protein, NAK-associated protein 1 (NAP1). The role of NAP1 in modulating kinase activation or regulation is unknown. A key inhibitory protein identified in the TLR3:interferon pathway, silencer of inhibitor of κBα kinase ε (SIKE), blocks the activity of this kinase complex …
Ipla2Β, Alternative Splicing And Apoptosis Of Pancreatic Islets, Bhargavi Emani
Ipla2Β, Alternative Splicing And Apoptosis Of Pancreatic Islets, Bhargavi Emani
Theses and Dissertations
Ceramides are bioactive lipids that can promote splicing of apoptosis-related genes, including caspase 9 and BCL-x. A recent study demonstrated that expression of neutral sphingomyelinase (NSMase), an enzyme that hydrolyzes sphingomyelins to generate ceramide, is regulated by Group VIA phospholipase A2 (iPLA2β)-dependent mechanism during β-cell apoptosis. This prompted us to hypothesize that iPLA2 is upstream of ceramide generation in the process regulating splicing of apoptotic genes. To test this, Jurkat T cells were treated with the selective inhibitor of iPLA2β, bromoenol lactone (BEL), RNA was isolated and converted to cDNA, and caspase 9 and BCL-x mRNA viii species were amplified …
Influence Of Retinal States On The Development And Maintenance Of Retinofugal Projections, Duncan Morhardt
Influence Of Retinal States On The Development And Maintenance Of Retinofugal Projections, Duncan Morhardt
Theses and Dissertations
Vision provides a critical interface with the physical world. This work examines visual development and vision loss in mice to glean the influence of the retinal state on visual connections. I first assessed the impact of retinal activity on the eye-specific segregation of retinal afferents in the lateral geniculate nucleus (LGN) of young Gβ5 -/- mice. Gβ5 is the fifth member of the β subfamily of heterotrimeric G proteins. Gβ5 binds and stabilizes the R7 family of regulators of G-protein signaling (RGS), which accelerate Gi/o GTP hydrolysis. Gβ5 -/- mice, which lack R7RGS activity, have malformed synapses in the outer …
Cell-Cell Junction Signaling Regulating Dna Double-Strand Break Repair In Breast Cells, Sinduja Ethiraj
Cell-Cell Junction Signaling Regulating Dna Double-Strand Break Repair In Breast Cells, Sinduja Ethiraj
Theses and Dissertations
Genomic instability and acquisition of invasiveness through the basement membrane extracellular matrix (ECM) are two major processes for epithelial cell malignancy in breast cancer. DNA double-strand break repair (DSBR) is one of the processes that get misregulated during breast cancer progression. In addition, radiation induced breaks such as those induced during radiation therapy to treat breast cancer patients are repaired by DSBR, rendering this pathway relevant for therapy as well. DSBR can occur either by homologous recombination (HR) or non-homologous end-joining (NHEJ). HR is accepted as the more error-free pathway. HR is regulated by the cell cycle status such that …