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Full-Text Articles in Life Sciences

Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala Jan 2010

Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala

Wayne State University Dissertations

N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …


Molecular Mechanisms Of Pressure-Stimulated Cancer Cell Signaling, Christina Downey Jan 2010

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 Jan 2010

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 …


Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu Jan 2010

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …


Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka Jan 2010

Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka

Wayne State University Dissertations

SYNERGISTIC EFFECTS OF GARCINOL AND GEMCITABINE IN ENHANCING THERAPEUTIC EFFICACY IN PANCREATIC ADENOCARCINOMA CELLS AND ITS EFFECT ON MICRORNA PROFILE

By

MANSI PARASRAMKA

ADVISOR: DR. SMITI V. GUPTA

MAJOR: NUTRITION AND FOOD SCIENCE

DEGREE: DOCTOR OF PHILOSPHY

Human Pancreatic Cancer (PaCa) is one of the most hostile and fourth leading cause of cancer deaths in the United States. Current standard chemotherapeutic agent for advanced PaCa is gemcitabine, a cytotoxic nucleoside analogue which results in modest response due to high degree of inherent and acquired chemo resistance. Forthcoming evidence strongly supports that non-nutritive food components have therapeutic benefits attributable to pleiotropic …


The Cellular And Genetic Mechanisms Underlying Morphological Diversity Of Insects, Nataliya Turchyn Jan 2010

The Cellular And Genetic Mechanisms Underlying Morphological Diversity Of Insects, Nataliya Turchyn

Wayne State University Dissertations

The vast diversity of insect appendages provides an excellent model for examining the cellular and molecular basis of phenotypic changes in nature. One of the hallmarks of evolution of insect appendages is the differential enlargement of hind (T3) legs compared to their fore (T1) and mid (T2) counterparts. While basic information regarding the genetic mechanisms that regulate the size of the T3 legs became available in the past several years, virtually nothing is known about cellular mechanisms involved. To address this issue, we measured the relative mitotic activity (RMA) in Acheta domesticus (house cricket) and Oncopeltus fasciatus (milkweed bug), two …


A Role For Lipid Rafts In Egfr Tki Resistance In Breast Cancer, Mary Elizabeth Irwin Jan 2010

A Role For Lipid Rafts In Egfr Tki Resistance In Breast Cancer, Mary Elizabeth Irwin

Wayne State University Dissertations

Breast cancer can be divided into genetic sub-types including luminal, HER2+, and basal-type. With the introduction of targeted therapies against estrogen receptor and HER2 receptor mortality rates of American women with breast cancer have declined. Unfortunately, basal-type breast cancers, which have the worst clinical outcome, do not express estrogen receptor or HER2, and as such, have no targeted therapeutic option. The epidermal growth factor receptor is an attractive target for therapeutics in basal-type breast cancer, as it is over-expressed in 60% of these cases. Also, over-expression of EGFR correlates with poor patient prognosis. Unfortunately, inhibitors of EGFR have shown little …


Detecting Phenotype-Specific Interactions Between Biological Processes From Microarray Data And Annotations, Nadeem Ahmed Ansari Jan 2010

Detecting Phenotype-Specific Interactions Between Biological Processes From Microarray Data And Annotations, Nadeem Ahmed Ansari

Wayne State University Dissertations

The development of high throughput technologies such as DNA microarrays has enabled researchers to measure expression levels on a genomic scale. Correct and efficient biological interpretation of the voluminous data generated by these technologies, however, remains a challenging problem. A commonly used approach in interpreting the results of such high throughput experiments is to map the list of differentially expressed (DE) genes to gene ontology (GO) terms, which provides a list of biological processes, biochemical functions, and cellular locations associated with the DE genes. A previously unexplored aspect is the identifications of unusual associations between biological processes. Such associations may …


Metabolic Targeting Of Malignant Glioma: Modulation Of Glycolytic Flux By Erythropoietic Factors, Todd Brendon Francis Jan 2010

Metabolic Targeting Of Malignant Glioma: Modulation Of Glycolytic Flux By Erythropoietic Factors, Todd Brendon Francis

Wayne State University Dissertations

Introduction: Malignant glioma display a highly glycolytic phenotype where the tumors flux glucose to lactic acid independent of oxygen concentration ("aerobic glycolysis"). This altered phenotype is facilitated by expression of primarily fetal enzyme isoforms in these malignant tumors. The end-product lactic acid is rapidly expelled from the cytosol by selective monocarboxylate transporters expressed on the plasma membrane. GATA response element islands are present on the promoter of glioma lactate transporter genes, and GATA-1 has been shown to be over-expressed in glioblastoma. Our long-term goal is to inhibit glioma proliferation by indirectly down-regulating GATA-1 to inhibit glycolysis. (Colen et al., 2006; …


Unraveling The Molecular Mechanisms Of Insect Diversity, Steven Michael Hrycaj Jan 2010

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 …


Development Of Lower Extremity Injury Criteria And Biomechanical Surrogate To Evaluate Military Vehicle Occupant Injury During An Explosive Blast Event, Brian J. Mckay Jan 2010

Development Of Lower Extremity Injury Criteria And Biomechanical Surrogate To Evaluate Military Vehicle Occupant Injury During An Explosive Blast Event, Brian J. Mckay

Wayne State University Dissertations

Anti-vehicular (AV) landmines and improvised explosive devices (IED) have accounted for more than half of the United States military hostile casualties and wounded in Operation Iraqi Freedom (OIF). The lower extremity is the predominantly injured body region following an AV mine or IED blast accounting for 26 percent of all combat injuries in OIF (Owens et al., 2007). Detonations occurring under the vehicle transmit high amplitude and short duration axial loads onto the foot-ankle-tibia region of the occupant causing injuries to the lower leg. The current effort was initiated to develop lower extremity injury criteria and biofidelic biomechanical surrogate to …


Neural And Humoral Control Of Regional Vascular Beds Via A1 Adenosine Receptors Located In The Nucleus Of The Solitary Tract, Joseph Martin Mcclure Jan 2010

Neural And Humoral Control Of Regional Vascular Beds Via A1 Adenosine Receptors Located In The Nucleus Of The Solitary Tract, Joseph Martin Mcclure

Wayne State University Dissertations

Previous studies from our laboratory showed that activation of NTS A1 adenosine

receptors yields variable hemodynamic responses with prevailing pressor and iliac

vasoconstrictor responses. These responses are accompanied with differential

activation of regional sympathetic activity (adrenal>>renal≥lumbar) and inhibition of

baroreflex mechanisms at the level of the NTS. The variability of the hemodynamic

responses was a result of simultaneous Β-adrenergic vasodilation counteracted with

sympathetic and unknown humoral vasoconstriction. Among many potential

vasoconstrictors vasopressin, angiotensin II and circulating norepinephrine were

considered. Therefore, blood pressure and iliac vascular responses evoked by

selective stimulation of NTS A1 adenosine receptors (CPA 330 …


Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor Jan 2010

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 …


Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente Jan 2010

Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente

Wayne State University Dissertations

The data presented in this research is central to establishing the role that the base excision repair pathway (BER) plays in the development and progression of colon cancer when dietary folate is deficient. Both cellular folate restriction and BER deficiencies have been shown to result in the accumulation of endogenous damage and lesions that could eventually develop into carcinogenesis. In this study, a dietary folate deficiency (FD) resulted in a significant increase in aberrant crypt foci (ACF) formation and triggered liver tumorogenesis in wildtype (WT) animals, as did a BER deficiency in DNA polymerase Β haploinsufficient (Β-pol+/-) mice exposed to …


Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita Jan 2010

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 …


Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan Jan 2010

Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan

Wayne State University Dissertations

Sin3A has been previously shown to be an essential gene for Drosophila viability and is implicated in the regulation of cell cycle. In this study, we show that SIN3 is not only required for embryonic viability but also for post-embryonic development. Genetic analysis suggests that the different isoforms of SIN3 may regulate unique sets of genes during development. The developmental lethality occurring due to ubiquitous knock down of SIN3 is hypothesized to be to the result of defects in cell proliferation. Conditional knock down of SIN3 in the wing discs results in a curly wing phenotype in the adult fly. …


The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier Jan 2010

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 Jan 2010

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 Jan 2010

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 Jan 2010

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 …


Matriptase/Pdgf D/Beta-Pdgfr Signaling Axis In Human Prostate Cancer: The Role Of Pten In The Regulation Of Pdgf D Expression, M. Katie Conley-Lacomb Jan 2010

Matriptase/Pdgf D/Beta-Pdgfr Signaling Axis In Human Prostate Cancer: The Role Of Pten In The Regulation Of Pdgf D Expression, M. Katie Conley-Lacomb

Wayne State University Dissertations

Platelet Derived Growth Factor (PDGF) is a family of mesenchymal growth factors that regulate cell proliferation, migration, and differentiation. Unlike the classic PDGF ligands A and B, which are secreted as active dimers, PDGF D must undergo extracellular proteolytic processing to remove its N-terminal CUB domain from the C-terminal PDGF growth domain before the ligand is able to stimulate its receptor, PDGF receptor beta (?-PDGFR). Importantly, recent clinical studies have shown that ?-PDGFR is upregulated in primary prostate cancer and bone metastases. However, PDGF B, formerly thought to be the sole ligand for ?-PDGFR, is not expressed in clinical prostate …


Comparison Of Affective Analgesia And Conditioned Place Preference Following Cholinergic Activation Of, Elena Schifirnet Jan 2010

Comparison Of Affective Analgesia And Conditioned Place Preference Following Cholinergic Activation Of, Elena Schifirnet

Wayne State University Dissertations

Activation of the dopaminergic mesolimbic reward circuitry that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress affective reactions to noxious stimuli (affective analgesia, AA). VTA dopamine neurons are activated via cholinergic inputs, and we have observed that microinjections of the acetylcholine agonist carbachol suppressed vocalizations of rats that occur following administration of brief (1 sec) tail-shocks (vocalization afterdischarges = VAD). VADs are a validated rodent model of pain affect. In addition, the capacity of carbachol to support reinforcement appears to be regionally dependent within VTA. Ikemoto and Wise (2002) reported that carbachol was self-administered in the …


Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development, John Hunt Lillvis Jan 2010

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 …


Single Molecule Studies Of Spliceosomal Snrnas U2-U6, Zhuojun Guo Jan 2010

Single Molecule Studies Of Spliceosomal Snrnas U2-U6, Zhuojun Guo

Wayne State University Dissertations

Spliceosomes catalyze the maturation of precursor mRNAs in organisms ranging

from yeast to humans. Their catalytic core comprises three small nuclear RNAs (U2, U5

and U6) involved in substrate positioning and catalysis. It has been postulated, but never

shown experimentally, that the U2-U6 complex adopts at least two conformations that

reflect different activation states. We have used single-molecule fluorescence to probe the

structural dynamics of a protein-free RNA complex modeling U2-U6 from yeast and

mutants of highly conserved regions of U2-U6. Our data show the presence of at least

three distinct conformations in equilibrium. The minimal folding pathway consists of …


Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane Jan 2010

Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane

Wayne State University Dissertations

Prenylation pathways have been targeted via several different compounds that inhibit farnesyl transferase (FTase) and/or geranylgeranyl transferase (GGTase) enzymes in many cellular and animal models of cancer. Some of these have also been evaluated in clinical trials with limited success. Multiple mechanisms of action have been elucidated for such compounds, including cell cycle arrest, proteasome inhibition, apoptosis and most recently, autophagy. However, there is still an urgent need of effective agents of this class of anti-tumor therapeutics. In this dissertation, I sought to delve into this issue by characterizing our novel prenylation inhibitors and their potential as anti-tumor agents. Novel …


Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson Jan 2010

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 …


Determination Of The Essential Functions Of A Conserved Cyclin, Cyclin Y, In Drosophila, Dongmei Liu Jan 2010

Determination Of The Essential Functions Of A Conserved Cyclin, Cyclin Y, In Drosophila, Dongmei Liu

Wayne State University Dissertations

The Drosophila gene CG14939 encodes a member of a highly conserved family of cyclins, the Y type cyclins, which have not been functionally characterized in any organism. Here I report the generation and phenotypic characterization of a null mutant of CG14939, which we rename Cyclin Y (CycY). I show that the null mutant, CycYE8, is homozygous lethal with most mutant animals arresting during pupal development. The mutant exhibits delayed larval growth and major developmental defects during metamorphosis. Heat shock-induced expression of CycY at different times during development resulted in variable levels of rescue, the timing …


The Impact Of Mitochondria On Preimplantation Development In The Rhesus Macaque, Tiffini Charieace Gibson Jan 2010

The Impact Of Mitochondria On Preimplantation Development In The Rhesus Macaque, Tiffini Charieace Gibson

Wayne State University Dissertations

Assisted Reproduction Technologies (ART) have been used to treat infertility since 1790. In the centuries following, dramatic advances have been made in the field of infertility research through the employment of a variety of species. Despite these advances, determination of oocyte and embryo quality remains largely subjective. Ascertainment of methods to measure oocyte and embryo quality to improve selection in ART clinics and increase pregnancy success rates is imperative. These methods are only possible with a more comprehensive understanding of the cellular and molecular properties of oocytes and preimplantation embryos. A key component of all cells, including oocytes and embryos, …


Investigating The Metal Binding Sites In Znta, A Zinc Transporting Atpase, Sandhya Muralidharan Jan 2010

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 …