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Articles 1 - 12 of 12
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Investigating The Metal Binding Sites In Znta, A Zinc Transporting Atpase, Sandhya Muralidharan
Investigating The Metal Binding Sites In Znta, A Zinc Transporting Atpase, Sandhya Muralidharan
Wayne State University Dissertations
ZntA from Escherichia coli is a member of the PIBtype ATPase family of transporters. The PIB-type ATPase pumps maintain cellular homeostasis of heavy metals such as Zn2+, Co2+, Cu2+, Cu+, and mediate resistance to toxic metals such as Pb2+, Cd2+ and Ag+. ZntA confers resistance to Pb2+, Cd2+, and Zn2+ by pumping these ions out of the cytoplasm. ZntA has two metal binding sites, one in the hydrophilic N-terminal domain and the other in the transmembrane region. The …
Molecular Mechanisms Of Pressure-Stimulated Cancer Cell Signaling, Christina Downey
Molecular Mechanisms Of Pressure-Stimulated Cancer Cell Signaling, Christina Downey
Wayne State University Dissertations
ABSTRACT
MOLECULAR MECHANISMS OF PRESSURE-STIMULATED CANCER CELL SIGNALING
by
CHRISTINA DOWNEY
June 2010
Advisor: Dr. Marc Basson, MD, PhD
Major: Cancer Biology
Degree: Doctor of Philosophy
Increased extracellular pressure stimulates cancer cell adhesion by a mechanism that is dependent upon beta-1-integrin activation, an intact cytoskeleton, and FAK and Src activation. By a different mechanism, increased extracellular pressure modulates cancer cell proliferation in a manner that is regulated by protein kinase C, but not Src or an intact cytoskeleton. Previous studies from our laboratory have shown that paxillin is a necessary mediator in the pathway by which pressure stimulates adhesion; however, …
Creg1 And Its Enhancement Of P16ink4a-Induced Senescence, Benchamart Moolmuang
Creg1 And Its Enhancement Of P16ink4a-Induced Senescence, Benchamart Moolmuang
Wayne State University Dissertations
Bypassing cellular senescence, an irreversible growth arrest of cells that is activated in normal cells to become immortal is one of the prerequisites for carcinogenesis. Cellular senescence can be triggered by shortening of telomeres and certain cellular stresses. Using spontaneously immortalized Li-Fraumeni Syndrome (LFS) fibroblasts, we found that CREG1 (Cellular Repressor of E1A-stimulated Genes1) is one of genes whose expression fit the criteria of senescence-associated genes, decreased expression during immortalization and increased in senescence. Moreover, we found that epigenetic mechanisms regulate CREG1 expression in LFS fibroblasts. CREG1 is a secreted glycoprotein that was shown to bind Rb-family pocket proteins and …
Unraveling The Molecular Mechanisms Of Insect Diversity, Steven Michael Hrycaj
Unraveling The Molecular Mechanisms Of Insect Diversity, Steven Michael Hrycaj
Wayne State University Dissertations
ABSTRACT
UNRAVELING THE MOLECULAR MECHANISMS OF INSECT DIVERSITY
by
STEVEN MICHAEL HRYCAJ
April 2010
Advisor: Dr. Aleksandar Popadic´
Major: Biological Sciences
Degree: Doctor of Philosophy
While it has long been recognized that the arthropods represent the most diverse animal phylum, the molecular bases defining these large-scale differences in body plans and appendages are only now becoming clear. Specifically, the recent merger between the fields of evolutionary and developmental biology ("evo-devo") have provided several examples illustrating that this extraordinary diversification may be due to evolved variation(s) in the developmental networks that control the formation of these structures. In addition, the delineation …
Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor
Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor
Wayne State University Dissertations
Progression through meiosis occurs through a strict sequence of events, so that one round of DNA replication precedes programmed recombination and two nuclear divisions. Cyclin dependent kinase 1 (Cdk1) is required for meiosis, and any disruption in its activity leads to meiotic defects. The Cdk1 inhibitor, Sic1, regulates the G1-S transition in the mitotic cell cycle and the analogous transition in meiosis. We have employed a form of Sic1, Sic1deltaPHA, that is mutated at multiple phosphorylation sites and resistant to degradation. Meiosis specific expression of Sic1deltaPHA disrupts Cdk1 activity and leads to significant accumulation of over replicated …
Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita
Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita
Wayne State University Dissertations
Vibrio cholera, the causative agent of the severe diarreal illness cholera, uses a complex array of gene regulation to induce its virulence determinants. During the early stage of infection, and upon response to unknown signals, virulence genes are turned on. ToxT protein is the primary virulence gene transcription activator. Once ToxT is produced, it amplifies its own expression through an auto-regulatory loop and directly binds and activates expression of various virulence factors including the toxin-coregulated pilus (TCP) and cholera toxin (CT). During the late stage of infection, virulence genes are turned off and the bacteria escape the host to resume …
The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier
The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier
Wayne State University Dissertations
Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …
Evolution Of Lactate Dehydrogenase Genes In Primates, With Special Consideration Of Nucleotide Organization In Mammalian Promoters, Zack Papper
Wayne State University Dissertations
Concomitant with an increase in brain volume and mass, the allocation of energetic resources to the brain increased during stem anthropoid evolution, leading to humans. One mechanism by which this allocation may have occurred is through greater use of lactate as a neuronal fuel. Both the production of lactate, and conversion to pyruvate for use in aerobic metabolism, are catalyzed, in part, by the tetrameric enzyme lactate dehydrogenase (LDH). The two primary LDH genes, LDHA and LDHB, confer different rates of substrate turnover to the LDH enzyme, and these rates lend to the argument that LDHA supports anaerobic while LDHB …
Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang
Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang
Wayne State University Dissertations
Arsenic is a metalloid toxicant that is widely distributed throughout the earth's crust and causes a variety of health and environment problems. As an adaptation to arsenic-contaminated environments, organisms have developed resistance systems. In bacteria and archaea various ars operons encode ArsAB ATPases that pump the trivalent metalloids As(III) or Sb(III) out of cells. In these operons, an arsD gene is almost always adjacent to the arsA gene, suggesting a related function. ArsA is the catalytic subunit of the pump that hydrolyzes ATP in the presence of arsenite or antimonite. ArsB is a membrane protein which containing arsenite-conducting pathway. ArsA …
Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson
Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson
Wayne State University Dissertations
The P13K/Akt pathway is a critical mediator of growth factor signaling involving many cellular functions. The deregulation of this pathway has been shown to be involved in the development of various cancers. One of the main targets of this pathway is FoxO3a, a transcription factor whose target genes are involved in important cellular processes such as apoptosis, cell cycle control, and glucose metabolism. FoxO3a is regulated by various post translational modifications including acetylation, ubiquitination and phosphorylation. The transcription factor is directly phosphorylated by Akt on 3 residues: Threonine 32, Serine 253 and Serine 315. Phosphorylation by Akt generates binding sites …
Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development, John Hunt Lillvis
Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development, John Hunt Lillvis
Wayne State University Dissertations
Abdominal aortic aneurysm (AAA) is a common disease for which mechanisms of formation are still not well understood. Despite a strong genetic component to AAA risk, specific risk alleles are still largely unidentified. AAA is also a localized disease with a majority occurring in the infrarenal abdominal aorta and is six times more common than aneurysms of the thoracic aorta. To determine whether risk alleles are present in functional positional candidate genes. we: 1. performed a genetic association study using DNA from AAA cases and controls in ten candidate genes and 2. performed exon sequencing on three genes with evidence …
Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson
Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson
Wayne State University Dissertations
The dominant paradigm for cancer research focuses on the identification of specific genes for cancer causation and for the discovery of therapeutic targets. Alternatively, the current data emphasize the significance of karyotype heterogeneity in cancer progression over specific gene-based causes of cancer. Variability of a magnitude significant to shift cell populations from homogeneous diploid cells to a mosaic of structural and numerical chromosome alterations reflects the characteristic low-fidelity genome transfer of cancer cell populations. This transition marks the departure from micro-evolutionary gene-level change to macro-evolutionary change that facilitates the generation of many unique karyotypes within a cell population. Considering cancer …