Life Sciences Commons^™

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly …

Development Of A Dreissena Bioassay To Assess The Toxicity Of Contaminants Across Two Life-History Stages, Caroline Joyce Addis

Wayne State University Theses

Dreissenid mussels (Dreissena polymorpha and D. bugensis) have rapidly become widespread and ubiquitous in North America since their introduction into the Great Lakes in the 1980s. The resulting environmental and economic impacts of their invasion have been extensive, negatively affecting biodiversity and costing millions of dollars in control efforts and damage to power generation and water treatment facilities. Although dreissenids are often associated with negative impacts, they may present a practical tool for toxicology studies. The typically sessile behavior of the benthic adults coupled with the planktonic nature of the veligers allow for a more complete evaluation of water quality …

Functional Characterization Of The Novel Prdm Gene Apox In Tribolium Castaneum, Xin Wang

Wayne State University Theses

Previous work revealed that embryonic and post-embryonic knockdown (KD) of Tribolium Prdm gene Apoptix (Apox) leads to phenotypes, such as melanotic spots in external tissue of larval and pupal body. One part of my research is screening for Apox-specific phenotypes by RNA interference with a second Apox dsRNA. My results revealed that Apox is essential for the embryonic and post-embryonic survival and plays an important role in the regulation of embryonic and post-embryonic development in Tribolium, such as bristle formation. In addition, previous work showed that phenotypes of Apox KD Tribolium were significantly rescued by combinatorial knockdown of Apox and …

Ecology Of Coyotes (Canis Latrans) In The Greater Detroit Area Of Southeastern Michigan, William B. Dodge

Wayne State University Dissertations

Coyote distribution and habitat use, diet and foraging behavior and space use patterns were investigated in the greater Detroit area of southeastern Michigan. We found evidence of coyotes on 24 of 30 (80%) suburban and 7 of 11 (64%) urban plots. Overall fifty-eight percent of coyote evidence was found within edge habitats, with den sites and tracks the only types of evidence found strictly in interior habitats. Land cover around evidence points included more wooded land cover than expected in suburban areas, suggesting the importance of tree cover for coyote occupancy, and more open space and wooded land cover than …

Analyzing Sumo-2/3 Modification In Regulation Of Breast Cancer Progression And Mitotic Chromosome Segregation, Divya Subramonian

Wayne State University Dissertations

Roles of SUMOylation in cancer metastasis and mitotic progression has been elucidated in this thesis. This vital and dynamic post-translational modification has been known to be dysregulated in several kinds of cancer. Global SUMO-2/3 conjugation is upregulated in a mouse metastatic breast cancer cell line, 66cl4, compared to a non-metastatic cell line 168FARN from the same genetic background. In order to identify the SUMO-2/3 substrates, SILAC labeled lysates from the two cell lines were immunopurified using SUMO-2/3 monoclonal antibodies. By using SUMO-2/3 epitope peptide elution (SUMO-2/3-ePIPE) and quantitative mass spectrometry, 66 SUMO-2/3 targets were identified, of which 15 targets are …

Genome Wide Analysis Identifies Sphingolipid Metabolism As A New Target Of Valproic Acid, Shyamalagauri Jadhav Jadhav

Wayne State University Dissertations

Bipolar disorder (BD), which is characterized by depression and mania, affects about 1% of the total world population. Current treatments are effective in only 40-60% of cases and cause severe side effects. Valproic acid (VPA), a branched short-chain fatty acid, is one of the most widely used drugs for the treatment of BD. Although many hypotheses have been postulated to explain the molecular mechanism of action of this drug in BD, the therapeutic mechanism is not understood. This knowledge gap has hampered the development of new drugs to treat this disorder. To identify candidate pathways affected by VPA, I performed …

Unraveling The Molecular Mechanisms Of Aposematic Pigmentation In Oncopeltus Fasciatus, Jin Liu

Wayne State University Dissertations

Insects display the extraordinary amount of morphological variation, particularly in regard to their colorations. This diversity in coloration exists both in terms of the array of colors as well as the patterning of pigments. Previous studies have revealed that melanin, ommochrome, and pteridine are the most common pigments constituting insect color patterns. Among these three, the melanin pathway has been best studied so far and presents the foundation of the current understanding of insect coloration. At the same time, though, most of this insight relied on work performed in model systems such as Drosophila and Tribolium, which have significant limitations …

Imaging Anti-Proliferative Compounds With Flt-Pet, Christopher Mchugh

Wayne State University Dissertations

Imaging is critical in the detection and management of malignancies, and positron emission tomography (PET) is an imaging approach that provides information regarding cancer physiology through the tracking of molecular pathways and receptors. 3’-fluoro-3’-deoxythymidine (FLT) is a PET tracer designed to image cellular proliferation, which is a hallmark of cancer. FLT has been used to study the response of cancer to a variety of treatments such as chemotherapy, targeted agents, and radiation.

Here we explored FLT retention as a biomarker to monitor the anti-proliferative effect of the synthetic glucocorticoid (GC) dexamethasone (Dex) on non-small cell lung cancer (NSCLC). The basis …

Role Of Secretory Granule Heterogeneity In Calcium-Triggered Exocytosis, Tejeshwar Rao

Wayne State University Dissertations

The sympathetic nervous system is activated by a variety of threats to organismal homeostasis. The adrenomedullary chromaffin cell is the core effector of sympathetic activity in the peripheral nervous system. By design, the chromaffin cell secretory response is mutable so that release can be rapidly tuned to drive context-dependent changes in physiological function. However, the mechanisms by which this tuning is achieved with such high temporal fidelity and context specificity remain unclear. This represents a major gap in our understanding of the sympatho-adrenal system since it is known to modify the function of nearly every organ system in the body. …

Cardiolipin Is Required For Optimal Acetyl-Coa Metabolism, Vaishnavi Raja

Wayne State University Dissertations

The phospholipid cardiolipin (CL) is crucial for many cellular functions and signaling pathways, both inside and outside of mitochondria. My thesis focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites needed for these processes, and the stabilization of electron transport chain supercomplexes, require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine-acetylcarnitine translocase, which transports acetyl-CoA into the mitochondria, is CL dependent. The presence of substantial amounts of CL in the peroxisomal …

Short Germ Insects Utilize Both The Ancestral And Derived Mode Of Polycomb Group-Mediated Epigenetic Silencing Of Hox Genes, Yuji Matsuoka, Tetsuya Bando, Takahito Watanabe, Yoshiyasu Ishimaru, Sumihare Noji, Aleksander Popadic, Taro Mito

Biological Sciences Faculty Research Publications

In insect species that undergo long germ segmentation, such as Drosophila, all segments are specified simultaneously at the early blastoderm stage. As embryogenesis progresses, the expression boundaries of Hox genes are established by repression of gap genes, which is subsequently replaced by Polycomb group (PcG) silencing. At present, however, it is not known whether patterning occurs this way in a more ancestral (short germ) mode of embryogenesis, where segments are added gradually during posterior elongation. In this study, two members of the PcG family, Enhancer of zeste (E(z)) and Suppressor of zeste 12 (Su(z)12), were analyzed in the …

Low Mitochondrial Dna Diversity In An Ancient Population From China: Insight, Yu Dong, Chunxiang Li, Fengshi Luan, Zhenguang Li, Hongjie Li, Yinqiu Cui, Hui Zhou, Ripan S. Malhi

Human Biology Open Access Pre-Prints

To gain insight into the social organization of a population associated with the Dawenkou period, ancient DNA analysis of 18 individuals from human remains from Fujia site, Shandong Province, China was completed. Directly radiocarbon dated to 4800–4500 cal BP, the Fujia site is assumed to be associated with a transitional phase from matrilineal clans to patrilineal monogamous families. Our results reveal a low mitochondrial DNA diversity from the site and population. Combined with Y-chromosome data, the pattern observed at the Fujia site is most consistent with a matrilineal community. The patterns also suggest that the bond of marriage were de-emphasized …

Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan

Wayne State University Dissertations

SIN3, the scaffold protein of a histone modifying complex is conserved from yeast to mammals. Drosophila SIN3 associates with both a histone deactylase RPD3 and a histone demethylase dKDM5/LID. Immunopurification of dKDM5/LID verifies a previously observed interaction with SIN3 and RPD3. Furthermore, deficiency of dKDM5/LID phenocopies deficiency of SIN3 in many cellular and developmental processes. Knockdown of both Sin3A and lid hinder cell proliferation in Drosophila cultured cells and developing flies. Knockdown of these genes also results in a curved wing phenotype implicating a role in wing development. Analysis of underlying gene expression changes upon decreased expression of SIN3, dKDM5/LID …

Acoustic Cues Of Physical Formidability In Cage Fighters, Stefan Mattias-Maria Goetz

Wayne State University Theses

Across the animal kingdom, the sex that experiences the most reproductive variance tends to evolve sexually dimorphic traits—both behavioral and morphological—which aid in reproduction. Human evolution has been marked by greater male intrasexual selection and as a result, men display a variety of secondary sexual characteristics, putatively serving to enhance biological fitness. Among these, fundamental frequency, closely related to perception of pitch, among men is half that of women. Likewise, monotonicity, that is, variance in pitch across an utterance, is higher in men (i.e., women show greater variance in pitch) while formant dispersion, which gives the voice its timbre, is …

Drosophila Cyclin J And The Somatic Pirna Pathway Cooperate To Regulate Germline Stem Cells, Paul Michael Albosta

Wayne State University Dissertations

Cyclin J (CycJ) is a highly conserved cyclin that is uniquely expressed specifically in ovaries in Drosophila. Deletion of the genomic region containing CycJ and adjacent genes resulted in a genetic interaction with neighboring piRNA pathway gene, armitage (armi). Here I assessed oogenesis in CycJ null in the presence or absence of mutations in armi or other piRNA pathway genes. Although CycJ null flies had decreased egg laying and hatching rates, ovaries appeared normal indicating that CycJ is dispensable for oogenesis under normal conditions. Further double mutant analysis of CycJ and neighbor armi, as well as two other piRNA pathway …

The Loss Of Genomic Uracil Homeostasis And Aid-Dependent Accumulation Of Dna Damage In B Cell Lymphomas, Sophia Shalhout

Wayne State University Dissertations

Activation-induced deaminase (AID) is a sequence-selective DNA cytosine deaminase that introduces uracils in immunoglobulin genes. This DNA mutator is required for somatic hypermutation and class switch recombination- processes involved in the affinity maturation and diversification of antibodies. AID, however, can also lead to deleterious mutations and translocations promoting lymphomagenesis. The introduction of uracils throughout the genome of activated B cells and the ability of UNG2 glycosylase to excise these uracils is examined here. This interplay was also studied in cancerous B cells, with different results emerging in transformed cells versus healthy cells. Genomic uracil levels are found to remain at …

A Protective Role Of Autophagy In A Drosophila Model Of Friedreich's Ataxia (Frda), Luan Wang

Wayne State University Dissertations

Friedreich’s ataxia (FRDA) is an inherited autosomal recessive neurodegenerative disease. It affects 1 in every 50,000 people in central Europe and North America. FRDA is caused by deficiency of Frataxin, an essential mitochondrial iron chaperone protein, and the associated oxidative stress damages. Autophagy, a housekeeping process responsible for the bulk degradation and turnover of long half-life proteins and organelles, is featured by the formation of double-membrane vacuoles and lysosomal degradation. Previous researches indicate that Danon’s disease, the inherited neural disorder disease that shares similar symptoms with FRDA, is due to the malfunction of autophagy. Based on this, we raise the …

Novel Biochemical And Phenotypical Findings On The Nodal Signaling Components Lefty And Cripto, Amapola Balancio

Wayne State University Theses

ABSTRACT

NOVEL BIOCHEMICAL AND PHENOTYPICAL FINDINGS ON THE NODAL SIGNALING COMPONENTS LEFTY AND CRIPTO

by

Amapola Balancio

December 2014

Advisor: Dr. William Branford, Jr.

Major: Biological Sciences (Molecular and Developmental Biology)

Degree: Master of Science

Nodal, a Transforming Growth Factor-β (TGF-B), is a key regulator of proper development along with its atypical TGF-B inhibitor Lefty and its EGF-CFC co-receptor Cripto. Studies have shown that Nodal is unable to signal in the absence of a functional Cripto, indicating that it is a Nodal obligate co-receptor. In fact, one of the ways that Lefty prevents Nodal is by binding to Cripto and …

The Contribution Of The Melanin Pathway To Overall Body Pigmentation Changes During Ontogenesis Of Periplaneta Americana, Thomas Roger Lemonds

Wayne State University Theses

Pigmentation is one of the most diverse and distinguishable features of insect morphology. The most prominent colors observed in insects are black or brown, whose production is attributed to the melanin pathway. At present, though, the contribution of this pathway to overall body pigmentation throughout ontogenesis is still lacking. To address this question we examined the roles of four key melanin genes (TH, DDC, ebony, and aaNAT), in embryonic and post-embryonic development of Periplaneta americana. Our results show show that while the melanin pathway plays no role during the earliest nymphal stages, it is required during the later stages of …

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 …