Life Sciences Commons^™

Hla Class Ii Alleles In The Otomi Population Of The Mezquital Valley. A Genetic Approach To The History Of Interethnic Migrations In The Mexican Central Plateau, Ana Itzel Juárez-Martín, Blanca Zoila González-Sobrino, Ángel Eduardo Camarena Olvera, Ramcés Falfán-Valencia

Human Biology Open Access Pre-Prints

From a historic and genetic point of view, the Otomi of the Mezquital Valley are a frontier people that have played an important role in the making of the population dynamics of the Mexican Central Plateau. Due to their antiquity in the area, the Otomi may be bearers of ancient genetic variability, shared mainly today with other groups belonging to the Otomanguean linguistic family and with the Nahua.

This study analyzes the HLA class II allele frequencies reported in Mexican indigenous populations, in order to provide an intra-regional level historical perspective of the genetic relationships between the Otomi of the …

Influence Of Introgression And Geological Processes On Phylogenetic Relationships Of Western North American Mountain Suckers (Pantosteus, Catostomidae), Peter J. Unmack, Thomas E. Dowling, Nina J. Laitinen, Carol L. Secor, Richard L. Mayden, Dennis K. Shiozawa, Gerald R. Smith

Biological Sciences Faculty Research Publications

Intense geological activity caused major topographic changes in Western North America over the past 15 million years. Major rivers here are composites of different ancient rivers, resulting in isolation and mixing episodes between river basins over time. This history influenced the diversification of most of the aquatic fauna. The genus Pantosteus is one of several clades centered in this tectonically active region. The eight recognized Pantosteus species are widespread and common across southwestern Canada, western USA and into northern Mexico. They are typically found in medium gradient, middle-elevation reaches of rivers over rocky substrates. This study (1) compares molecular data …

The Mechanism Of Regulation Of Autosomal Heterochromatic Genes In Drosophila Melanogaster Males By Rox Rna And Msl Proteins, Satya Kiran Koya

Wayne State University Dissertations

In humans and flies, males and females have different set of sex chromosomes contributing to different levels of X-linked gene expression. To equalize X-linked gene dosage between sexes, both humans and flies developed independent strategies which are called dosage compensation. Human females randomly inactivate one of their X chromosome into barr body and Drosophila males up regulate their single X chromosome two fold. Both strategies equalize of X linked gene dose between sexes.

In Drosophila, dosage compensation is brought about by the ribonucleoprotein Male Specific Lethal (MSL) complex that binds hundreds of sites along the X chromosome and modifies …

Matriptase Mediated C-Met Signaling In Breast Cancer, Gina Lynn Zoratti

Wayne State University Dissertations

MATRIPTASE MEDIATED c-MET SIGNALING IN CRITICAL FOR BREAST CANCER PROGRESSION

by

GINA ZORATTI

Historically proteases have been associated with tumor progression and metastasis through degradation of the basement membrane. However, in recent years these enzymes have also been shown to play key roles in the activation of growth factors and cytokines, thereby activating pro-oncogenic signaling pathways. Matriptase (MT-SP1, ST14) is an epithelia-specific pericellular protease which has received considerable attention in recent years spurred by the consistent dysregulation of the protease in human epithelial tumors including breast cancer. We have performed both functional and mechanistic studies of matriptase in breast cancer …

Approaches To Improving Detection Of Invasive Fish Species In Western Lake Erie Through Analysis Of Monitoring Efficiencies And Metrics Of Community Distribution, Joshua Alan Southern

Wayne State University Theses

Efficient monitoring programs are essential for the early detection of invasive species. The Ohio Department of Natural Resources (ODNR) monitoring program encompassing 21 years of fish survey data from western Lake Erie was evaluated using Chao biodiversity analysis to determine the efficiency and precision of collection strategies of trawl and gillnet sampling, at detecting rare or non-native species. Overall, ODNR sampling annually accounted for ~80% of extant fish species, leaving gaps in coverage where rare and invasive species may be overlooked and proliferate.Obtaining 90% efficiency would require an estimated doubling of previous sampling effort. Computer simulations calculating different proportions of …

General Transcription Factors Play Dual Roles In Initiation And Termination, Scott Alan Medler

Wayne State University Dissertations

Gene looping, defined as the interaction of the promoter and the terminator regions of a gene during transcription, is emerging as an important gene regulatory mechanism in eukaryotes. The role of promoter bound general transcription factors during initiation is well established. However, recent studies have revealed that some initiation factors also interact with the 3' end of a gene. The biological role of initiation factors at the 3' end of a gene is unknown. The general transcription factors TFIIB and TFIIH have been found to interact genetically with Ssu72, a component of CPF 3' end processing complex. Accordingly, we found …

Cytogenetic Evaluation Of Low Dose Hyper-Radiosensitivity In Human Lymphoblastoid Cell Lines Exposed To Cobalt-60 Gamma Radiation., Gnanada Sameer Joshi

Wayne State University Dissertations

The dose-effect relationships of cells exposed to ionizing radiation are frequently described by linear quadratic (LQ) models over an extended dose range. However, many mammalian cell lines, when acutely irradiated in G2 at doses below 30 cGy, show hyper-radiosensitivity (HRS) as measured by reduced clonogenic cell survival, thereby indicating greater cell lethality than is predicted by extrapolation from high-dose responses. We therefore hypothesized that the cytogenetic response in G2 cells to low doses would also be steeper than predicted by LQ extrapolation from high doses. We tested our hypothesis by exposing four normal human lymphoblastoid cell lines to 0 - …

The Effects Of Phragmites Australis Litter On Seed Emergence In The Erie-Huron Corridor, Michigan, Travis White

Wayne State University Theses

The invasive reed, Phragmites australis, is widespread within the Great Lakes region, and is often blamed for habitat degradation. Once established, it creates dense litter mats that may persist following remediation efforts of living stock removal. We investigated the effects of P. australis and Typha angustifolia, narrow-leaf cattail, litter on seedling emergence from the native seed bank by harvesting soils from five Great Lakes coastal marshes densely populated by either Phragmites or Typha and exposing them to Phramities or Typha litter in treatments of varying litter depths. Seedling emergences were quantified for six weeks. Soils from Phragmites dominated sites had …

The Phenotypic Analysis Of The Knockdown Of The Sin3a Complex Components And Their Role In Recruitment And Cell Proliferation, Kelly Ann Laity

Wayne State University Theses

The SIN3A-RPD3 complex components have previously been identified in Drosophila melanogaster. The role of these components in SIN3A function and recruitment was not known. Polytene chromosome analysis following RNAi knockdown was performed to determine if any of the complex members affect the ability of SIN3A to bind to chromatin. The complex components effect on cell proliferation was also examined through clonal analysis of imaginal wing discs. The results of this work implicate a role of several members of the SIN3A complex for proper recruitment and localization to chromatin. All of the SIN3A complex members had some varying effect on cell …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …

Bystander Effects Due To Neutrons, And Low-Dose Hyper-Radiosensitivity To Gamma Rays In Human Cells Using Cytogenetics, Isheeta Seth

Wayne State University Dissertations

Chapter 2:

Micronuclei have been used extensively in studies as an easily-evaluated indicator of DNA damage but little is known about their association with other types of damage such as nucleoplasmic bridges and nuclear buds. Radiation-induced clastogenic events were evaluated via the cytokinesis-block micronucleus assay in two normal human lymphoblastoid cell lines exposed to neutrons or gamma radiation. Micronuclei, nucleoplasmic bridges and nuclear buds were enumerated by recording the coincident presence of these endpoints within individual cells, and the associations among these three endpoints were evaluated for all treatment conditions. The common odds ratios for micronuclei and nucleoplasmic bridges were …

Characterization And Identification Of Novel Regulators Of The Synthesis Of Phospholipids, Cunqi Ye

Wayne State University Dissertations

Phospholipids are the most abundant lipids in cell membranes. The synthesis of phospholipids is crucial for cellular membrane biogenesis and nearly all aspects of cellular processes. Understanding the regulation of synthesis of phospholipids is beneficial to our fundamental knowledge of cell biology as well as human health.

Regulation of the synthesis of phospholipids is intensively studied in the yeast S. cerevisiae. Most notably, the synthesis of phospholipids is coordinated with the synthesis of inositol, a precursor of inositol-containing lipids, by controlling expression of the genes encoding phospholipid biosynthetic enzymes. In addition to this well-characterized regulatory circuit controlled by the …

Role Of The Pkna And Pknb Kinases In Mycobacterium Tuberculosis, Tripti Anandan

Wayne State University Dissertations

To respond to environmental changes, M. tuberculosis possesses eleven "eukaryotic-type" Ser/Thr protein kinases. The aim of the study described in this dissertation was to identify role of two of these kinases; PknA and PknB that are essential in M. tuberculosis. Two approaches are described to screen for potential in vivo substrates of PknA/PknB. First approach is based on proteomic search by over-expressing PknA/PknB in M. tuberculosis. Proteomic search led to identification of proteasome to be a substrate of PknA and PknB in M. tuberculosis. Furthermore, I demonstrate that the phosphorylation of PrcA and PrcB by PknA regulates processing of Pre-PrcB. …

Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh

Wayne State University Dissertations

Inositol is a six-carbon cyclitol that is ubiquitous in biological systems. It is a precursor for the synthesis of numerous biologically important compounds, including inositol phosphates and phosphoinositides that are essential for cell function and viability. Inositol compounds play a role in membrane formation, gene regulation, signaling, regulation of ion channels, and membrane trafficking. Furthermore, inositol regulates hundreds of genes, including those involved in the biosynthesis of inositol and phospholipids. While transcriptional regulation of inositol biosynthesis has been extensively studied and well characterized, regulation of inositol biosynthesis at the enzymatic level has not been addressed. The current study shows that …

Sex And Heterochromatin: An Investigation Of Sexual Dimorphism In Drosophila Melanogaster, Manasi S. Apte

Wayne State University Dissertations

Over 30% of Drosophila genome is assembled into heterochromatin. Heterochromatin is relatively gene poor, transcriptionally less active and remains condensed during interphase. Previous studies established that roX RNA and some of the Male Specific Lethal (MSL) proteins, all components of the dosage compensation complex, are required for full expression of autosomal heterochromatic genes in male flies but not in females. This was surprising since heterochromatin is generally not thought to be sexually dimorphic. The genetic basis for the regulation of sex-specific heterochromatin was completely unknown.

To determine if roX RNAs localize directly at the heterochromatic regions that they regulate, I …

The Tumor-Suppressive Role Of Secreted Maspin Via The Exosomes, Ivory Dean

Wayne State University Dissertations

This dissertation highlights several novel findings. Maspin has been consistently detected in the conditioned media of maspin-expressing cells of normal and tumor breast, prostate and lung origin. Furthermore, extracellular maspin has been demonstrated to have anti-tumor effects. Interestingly, maspin has been reported as cargo of the exosomes, which highlights one of the secretion mechanisms of maspin. Maspin secretion as an exosomal molecule was verified by electron microscopy, atomic force microscopy, light scattering dynamic analysis and immunoblot analysis.

The data showed that exosomes derived from the non-malignant cell lines have two distinct populations that do no overlap in their size distributions. …