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Full-Text Articles in Life Sciences

Group Via Calcium-Independent Phospholipase A2 Regulates Bcl-Xl Protein Levels In Mice Lung, Sang-Jin Nam Jan 2014

Group Via Calcium-Independent Phospholipase A2 Regulates Bcl-Xl Protein Levels In Mice Lung, Sang-Jin Nam

Theses and Dissertations

With previous indication of the Group VIA phospholipase A2 (iPLA2β) enzyme regulating ER-stress induced apoptosis in β-cells by regulating the anti-apoptotic protein Bcl-xL via alternative splicing, our lab postulated iPLA2β to be utilizing a similar mechanism to regulate apoptosis in mice lung. Our previous lab work has shown implications of lung function compromise in iPLA2β-/- mice, and we speculated the cause to be due altered lung architecture stemming from the attenuation of apoptosis. The western blot analysis in this study suggested that iPLA2β is involved in the regulation of Bcl-xL, but the mRNA ratios of the splice variants suggested that …


Evolution And Divergence Of The Structural And Physical Properties Of Dna Binding By Methyl-Cytosine Binding Domain Family Members 2 And 3, Jason Cramer Jan 2014

Evolution And Divergence Of The Structural And Physical Properties Of Dna Binding By Methyl-Cytosine Binding Domain Family Members 2 And 3, Jason Cramer

Theses and Dissertations

The studies presented in this dissertation, Evolution And Divergence Of The Structural And Physical Properties Of DNA Binding By Methyl-Cytosine Binding Domain Family Members 2 And 3, pertain primarily to two key epigenetic regulators involved with the biological interpretation of methylated DNA marks. We provide insights into the emergence and evolution of the MBD2 and MBD3 and how those molecular entities influence heritable changes in gene activity. We further provide details regarding the mystery surrounding MBD3 function and the MBD2-mediated capacity of primitive animals to carry out methylation-specific epigenetic mechanisms. In chapter two, we describe the DNA binding properties of …


Atm, Brca1, And Aurora A: Mechanisms Of G2/M Checkpoint Control In Human Embryonic Stem Cells, Jason Beckta Jan 2014

Atm, Brca1, And Aurora A: Mechanisms Of G2/M Checkpoint Control In Human Embryonic Stem Cells, Jason Beckta

Theses and Dissertations

When cultured in vitro, human embryonic stem cells (hESCs) acquire genetic abnormalities that have slowed their therapeutic use. As hESCs have a “leaky” G1/S boundary, the pressure of ensuring genetic integrity falls on the G2/M checkpoint, which can be activated by failed chromosomal decatenation (among other stimuli). It is hypothesized that hESCs have a deficient decatenation checkpoint, but little data supports this. Evidence suggests that the ataxia telangiectasia mutated (ATM) kinase controls the G2/M decatenation and DNA damage checkpoints, though previous reports are conflicting on this point. My work demonstrates that inhibition of decatenation activates ATM and arrests hESCs in …


The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin Jan 2014

The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin

Theses and Dissertations

Breast cancer is the second leading cause of death amongst women ages 20 to 59. Despite advancements in cancer therapies, more research is necessary to improve the diagnoses and treatment of several types of breast cancer. Paclitaxel (Taxol) is a commonly utilized anti-cancer drug for various types of solid tumors. However, the molecular mechanism utilized by paclitaxel to induce cell death is still elusive. Previous studies in our laboratory have shown that the pro-apoptotic BCL-2 family protein, BAK (BCL-2 homologous antagonist/killer) plays an important role in paclitaxel-induced cell death. In untreated breast cancer cells, BAK is associated with the anti-apoptotic …


Folate Conjugated Dendrimers For Targeted Anticancer Therapy, Shannon Andrews Jan 2014

Folate Conjugated Dendrimers For Targeted Anticancer Therapy, Shannon Andrews

Theses and Dissertations

Anticancer therapeutics are often limited to suboptimal doses due to their lack of selectivity for tumor cells and resultant damage to healthy tissue. These limitations motivated researchers to develop tumor-specific delivery systems for improved therapeutic efficacy and reduced unintended cytotoxicity. Polyamidoamine dendrimers offer an ideal platform for designing targeted therapeutics with tunable characteristics that optimize pharmacokinetic behavior and targeting specificity. Ligand conjugation to dendrimer provides the biochemical interaction necessary to activate tumor-specific receptors for receptor-mediated endocytosis and effective internalization of polyplexes. Tumor-specific receptors overexpressed in carcinomas, like folate receptor-alpha (FOLRα), are targeted by ligand-conjugated dendrimer to allow enhanced internalization of …