Cell and Developmental Biology Commons^™

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

The Effects Of Sustained, High-Velocity Exercise On Gene Expression In California Yellowtail (Seriola Lalandi), Kelli Hatter

Undergraduate Honors Theses

California Yellowtail muscle fibers have been observed to exhibit two drastically different development patterns resulting from the speeds at which they are exercised. When fish are exercised at a moderate rate their epaxial fast-twitch muscle fibers grow in diameter—hypertrophy; when they are exercised at a fast speed, more new epaxial fast-twitch muscle fibers are produced—hyperplasia. To determine the underlying reason for this difference in muscle development, my summer research project and honors thesis exercised fish at: fast, moderate, and control speeds for a sustained amount of time to determine what is happening on a cellular level to cause the observed …

Expressing And Characterizing Mechanosensitive Channels In Xenopus Oocytes, Grigory Maksaev, Elizabeth S. Haswell

Biology Faculty Research

The oocytes of the African clawed frog (Xenopus laevis) comprise one of the most widely used membrane protein expression systems. While frequently used for studies of transporters and ion channels, the application of this system to the study of mechanosensitive ion channels has been overlooked, perhaps due to a relative abundance of native expression systems. Recent advances, however, have illustrated the advantages of the oocyte system for studying plant and bacterial mechanosensitive channels. Here we describe in detail the methods used for heterologous expression and characterization of bacterial and plant mechanosensitive channels in Xenopus oocytes.

Environmental Stimuli And Intragenerational Epigenetics, Nicholas J. Napier

Student Scholarship

Epigenetics is the study of any change in gene expression that is not mediated by DNA sequence. The effects of environmental stimuli on epigenetic changes have been studied extensively in recent years. Multiple reviews have provided comprehensive summations of the effects of environmental stimuli on transgenerational epigenetic changes, but few reviews have focused upon environment-induced intragenerational epigenetic changes. This review will summarize current knowledge of the intragenerational epigenetic changes that are induced by two groups of well-studied environmental stimuli: nutritional deficiencies and carcinogens. This survey of intragenerational epigenetic changes will focus upon the mechanisms behind them, the disorders associated with …

Cytoskeletal Dynamics: A View From The Membrane, Magdalena Bezanilla, Amy S. Gladfelter, David R. Kovar, Wei-Lih Lee

Dartmouth Scholarship

Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro; yet, how the cytoskeleton integrates signals in vivo across cellular membranes is far less understood. Recent work has demonstrated that the membrane alone, or through membrane-associated proteins, can effect dynamic changes to the cytoskeleton, thereby impacting cell physiology. Having identified mechanistic links between membranes and the actin, microtubule, and septin cytoskeletons, these studies highlight the membrane’s central role in coordinating these cytoskeletal systems to carry out essential processes, such as endocytosis, spindle positioning, and cellular compartmentalization.

Hearing Sensitivity And The Effect Of Sound Exposure On The Axolotl (Ambystoma Mexicanum), Amy K. Fehrenbach

Masters Theses & Specialist Projects

The axolotl (Ambystoma mexicanum) has been used as a model organism for studying development, genetics, and regeneration. Although the sensory hair cells of the lateral line of this species have been shown to be able to regenerate, it is not known whether this also occurs in the inner ear. In fact, little is known about the hearing capabilities of the axolotl or other salamander species. I recorded auditory evoked potentials (AEPs) of six axolotls at eleven frequencies (0.1, 0.25, 0.4, 0.6, 0.8, 1, 1.5, 2, 3, 4, and 6 kHz) in order to produce baseline audiograms of underwater pressure sensitivity. …

Development Of Quantitative Tools For The Characterization And Analysis Of The Blood Brain Barrier In Normal And Mps Iiib Mice, Sara M. Rigney

Dissertations, Masters Theses, Capstones, and Culminating Projects

The Blood Brain Barrier (BBB) functions to control homeostasis within the central nervous system (CNS) via strict control over the passage of molecules into and out of the brain. The goal of this barrier is to protect the CNS from harmful external factors while allowing entry of essential nutrients and removal of metabolic byproducts. This restrictive nature of the BBB is due to the protein network at the borders of adjoining cerebral endothelial cells known as the tight junctions (TJs) and the relationship of other supporting cells and proteins such as astrocytes, pericytes, microglia, and the basement membrane and extracellular …

Characterization Of A Novel Clade Of Transporters In Phytophthora, Stephanie Padula, Paul F. Morris Dr, Howard Casey Cromwell Dr., Menaka Ariyaratne, Andrew Wagner

Honors Projects

The oomycete Phytophthora parasitica has a worldwide distribution and is an economically important pathogen of more than 100 species⁴. RNA-seq analysis showed that one gene, PPTG_16698 has the 5^th highest level of expression of all transport proteins in the zoospore stage, and is highly conserved throughout Phytophthora species. This project attempts to characterize the important biological role that PPTG_16698 plays in P. parasitica and other oomycetes. Three strategies have been implemented to accomplish this goal: growth analysis by heterologous expression in yeast, metabolite analysis in yeast, and construction of a GFP fusion protein to enable localization of …

The Reproductive Ecology Of The Timber Rattlesnake, Crotalus Horridus, In Northwestern Arkansas: Interactions Between Environment, Steroid Hormones, And Life History, Craig Michael Lind

Graduate Theses and Dissertations

In this dissertation I examined the relationship between individual energetic status, hormone production, and life history trait expression in field-active Timber Rattlesnakes, Crotalus horridus. In chapter one I reviewed what is known regarding these relationships in snakes and defined major research goals. In chapter two I described the seasonal profile of testosterone (T) and corticosterone (CORT) in relation to the breeding season and to individual energetic status in males. Results showed that the seasonal pattern of T production in C. horridus was different than other pit viper species with similar mating patterns. Testosterone was elevated in the months leading up …

Progressive Decline Of Testicular Function In Leptinreceptor Deficient Obese Mice, Jennifer Long

Masters Theses

The incidence of obesity and metabolic syndrome among the human population is increasing, but the effects on male fertility are unresolved. Leptin insensitivity appears to show a consistent relationship between obesity and fertility problems in men. Genetically modified mice lacking the leptin hormone (ob/ob) or leptin receptor (db/db) are reported to be subfertile and/or infertile but there is only minimal information about testicular function (sperm and hormone production) and the progression of infertility. Therefore, this study was designed to investigate testicular function using a leptin-receptor-deficient obese mouse model (the POUND mouse; Charles River). Testicular sperm production is reduced in POUND …

The Hippo Pathway Effector Yki Downregulates Wg Signaling To Promote Retinal Differentiation In The Drosophila Eye, Erika Lynn Wittkorn, Ankita Sarkar, Kristine Garcia, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of theDrosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. …

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua

Dissertations and Theses (Open Access)

Gliomas are clinically challenging brain tumors with dismal survival rates due to its infiltrative nature and ineffective standard therapy. Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the contributions of intracellular IGFBP2 to tumor development and progression are poorly understood. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via …

Atp-Citrate Lyase Links Cyclin E To Cellular Metabolism In Breast Cancer, Kim Lucenay

Dissertations and Theses (Open Access)

Cyclin E is altered or overexpressed in approximately one-third of tumors from patients with invasive breast cancer and is a powerful independent predictor for survival in women with stage I-III breast cancer. Full-length cyclin E (EL) is post-translationally cleaved into two low-molecular-weight isoforms, LMW-E (T1) and LMW-E (T2). LMW-E have been shown to exhibit greater binding affinity for cyclin-dependent kinase 2 (CDK2) , cyclin dependent kinase inhibitors (CKIs), p21 and p27, but are resistant to p21 and p27 inhibition. In addition, transgenic mice expressing LMW-E have increased mammary tumor development and metastasis compared to EL transgenic mice. Therefore, LMW-E are …

Understanding The Role Of Sumoylation In Regulating Lkb1 Function, Joan W. Ritho

Dissertations and Theses (Open Access)

Energy homeostasis in a cell is critical for its survival during metabolic stress. Liver kinase B1 (LKB1), one of the key regulators of cellular energy balance, was initially discovered as a tumor suppressor mutated in patients with Peutz-Jeghers syndrome. Germline mutations in LKB1 predispose patients to develop several benign and malignant tumors including gastrointestinal and lung cancers. In 2003, several groups demonstrated that LKB1is a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), directly associating it with the regulation of energy balance in cells. During energy stress, LKB1 phosphorylates AMPK at threonine 172 (T172) resulting in AMPK …

Actions Of Pi3k-Delta Inhibitor, Idelalisib, And Its Combination With Bendamustine In Chronic Lymphocytic Leukemia, Prexy Modi

Dissertations and Theses (Open Access)

Class I phosphatidylinositol 3-kinase isoforms (α, β, δ, and γ) play a major role in cancer cell growth and survival. PI3K α and β are most studied. PI3K pathway is highly dysregulated in many cancers and aberrant PI3K signaling is associated with oncogene mutations and disease progression in solid tumors and in hematologic malignancies.

Chronic lymphocytic leukemia (CLL) is driven by B-cell receptor (BCR) signaling that promotes B-cell proliferation and survival. PI3K is a critical node in BCR pathway and PI3Kδ has a pivotal role in B-cell development and maintenance and this isoform is over-expressed in many B-cell malignancies, including …

Activating The Msh2/Msh6 Apoptotic Pathway In Cancer Cells Using Non-Reserpine Compounds, Jacob M. Mauceri

Honors College Theses

DNA mismatch repair (MMR) is a system that is highly conserved in both prokaryotes and eukaryotes. The heterodimeric protein MutSα and a suite of associated proteins are essential in the recognition and repair of DNA afflicted with mispaired bases and short insertion/deletion loops, but are also implicated in funneling damaged cells towards apoptosis via a key conformational change in a subunit of the MutSα complex. This conformation can be bound specifically by the small molecule reserpine. Molecular dynamics modeling and virtual screening were used to identify additional small molecule novel ligands with the predicted ability to selectively bind this “death” …

The Fossil Record Of Phenotypic Integration And Modularity: A Deep-Time Perspective On Developmental And Evolutionary Dynamics, Anjali Goswami, Wendy J. Binder, Julie Meachen, Robin O'Keefe

Biological Sciences Faculty Research

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because …

Developmental Toxicity Of Tetrakis (Hydromethyl) Phosphonium Chloride (Thpc) In Zebrafish (Danio Rerio) Embryos, Lan L. Nguyen

Honors College Theses

Tetrakis (hydromethyl) phosphonium chloride (THPC) is a tetrakis (hydromethyl) phosphonium salt commonly used by the textile industry and is polymerized onto cotton fabrics to provide a flame-retardant finish. Traces of THPC were found in the Ogeechee River, a 294 mile-long black river in Georgia, and could have been a toxin contributing to the mass killing of aquatic animals in May 2011. THPC has been known to be carcinogenic and cause other systemic toxicity in various mammalian animals. However given that the chemical is mostly discharged in natural waters, the environmental impact of the discharge on water quality and there by …

Effect Of Gamma Radiation On Growth And Mycotoxins Production Of Alternaria Alternata, Danny Karlet

Anatomy and Cell Biology Publications

The ubiquitous genus Alternaria contains many species that are able to invade cereals, oleaginous plants and other crops. Alternaria alternata is considered one of the most important species and can produce several mycotoxins under favourable conditions of temperature and humidity, including the economically important toxins: alternariol (AOH) and alternariol monomethyl ether (AME). The aim of this study was to evaluate the radio-sensitivity of Alternaria alternata spores through different gamma radiation doses. A. alternata growth and the production of AOH and AME were then analyzed. After fungal irradiation with 2 kGy, 5 kGy and 7 kGy, the spores were suspended with …

Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop

Open Access Dissertations

The correct development of different organisms requires the precise timing of genes important for development transitions. Organisms have recruited ATP-dependent chromatin remodelers to ensure the correct timing of gene expression during developmental transitions. Here I show how different CHD ATP-dependent chromatin remodelers regulate developmental transitions of different organisms. I show that PICKLE not only promotes H3K27me3 during development to repress developmental genes but also is targeted to these genes. The association of PICKLE to these genes suggests that both repression and H3K27me3 levels is a direct action of PICKLE on these loci. Using zebrafish as a model system, I show …

The Evolutionary Origination And Diversification Of A Dimorphic Gene Regulatory Network Through Parallel Innovations In Cis And Trans, Eric M. Camino, John C. Butts, Alison J. Ordway, Jordan E. Vellky, Mark Rebeiz, Thomas M. Williams

Biology Faculty Publications

The origination and diversification of morphological characteristics represents a key problem in understanding the evolution of development. Morphological traits result from gene regulatory networks (GRNs) that form a web of transcription factors, which regulate multiple cis-regulatory element (CRE) sequences to control the coordinated expression of differentiation genes. The formation and modification of GRNs must ultimately be understood at the level of individual regulatory linkages (i.e., transcription factor binding sites within CREs) that constitute the network. Here, we investigate how elements within a network originated and diversified to generate a broad range of abdominal pigmentation phenotypes among Sophophora fruit flies. …

Cell Type-Specific Responses To Wingless, Hedgehog And Decapentaplegic Are Essential For Patterning Early Eye-Antenna Disc In Drosophila, Jong-Hoon Won, Orkhon Tsogtbartarr, Wonseok Son, Amit Singh, Kwang-Wook Choi, Kyung-Ok Cho

Biology Faculty Publications

The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered epithelia, from which most head structures are derived. Secreted morphogens like Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early patterning of ead, but the underlying mechanisms are still largely unknown. To understand how these morphogens function in the ead of early larval stages, we used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant eads. We found that the ead immediately after hatching was crescent-shaped with the Bolwig’s nerve at the ventral edge, suggesting that it consists of dorsal domain. In a subsequent …

Plasma Activated Air Mediates Gene Transfer, Chelsea M. Edelblute

Biological Sciences Theses & Dissertations

Cold plasma is produced when strong applied electric fields accelerate free electrons, which dissociate, excite, or ionize gaseous molecules [1]. The deposition of ions from the plasma source is dependent on power generation, input gas composition, and gas flow rate. In the presence of reactive species, the membrane of eukaryotic cells is compromised allowing for otherwise impermeant molecules, such as DNA, to enter the inner-cell milieu [2].

The efficacy of a novel cold plasma reactor based on shielded sliding discharge for the delivery of plasmid DNA was assessed. The device is entirely non-contact, wherein the plasma never directly touches the …

Phenotypic And Mutational Consequences Of Mitochondrial Etc Genetic Damage, Michael James Lue

Dissertations and Theses

Genetic mutation is the ultimate source of new phenotypic variation in populations. The importance of mutation cannot be understated, and constitutes a significant evolutionary force. Although single mutations may have little to no impact on organismal performance or fitness, when multiplied across the total number of potential sites within the genome, mutation can have a large impact. Accurate measurement of the rates, molecular mechanisms, and distributions of effects of mutations are critical for many applications of evolutionary theory. Despite the importance of both deleterious and beneficial mutations, their genome-wide patterns and phenotypic consequences are poorly understood when considering the mitochondrial …

Use And Misuse Of Material Transfer Agreements: Lessons In Proportionality From Research, Repositories, And Litigation, Tania M. Bubela, Jenilee Guebert, Amrita Mishra

Office of the Provost

Material transfer agreements exist to facilitate the exchange of materials and associated data between researchers as well as to protect the interests of the researchers and their institutions. But this dual mandate can be a source of frustration for researchers, creating administrative burdens and slowing down collaborations. We argue here that in most cases in pre-competitive research, a simple agreement would suffice; the more complex agreements and mechanisms for their negotiation should be reserved for cases where the risks posed to the institution and the potential commercial value of the research reagents is high.

Trehalose Is A Chemical Attractant In The Establishment Of Coral Symbiosis, M. Hagedorn, V. Carter, N. Zuchowicz, M. Phillips, C. Penfield, B. Shamenek, Elizabeth A. Vallen, F. W. Kleinhans, K. Peterson, M. White, P. H. Yancey

Biology Faculty Works

Coral reefs have evolved with a crucial symbiosis between photosynthetic dinoflagellates (genus Symbiodinium) and their cnidarian hosts (Scleractinians). Most coral larvae take up Symbiodinium from their environment; however, the earliest steps in this process have been elusive. Here we demonstrate that the disaccharide trehalose may be an important signal from the symbiont to potential larval hosts. Symbiodinium freshly isolated from Fungia scutaria corals constantly released trehalose (but not sucrose, maltose or glucose) into seawater, and released glycerol only in the presence of coral tissue. Spawning Fungia adults increased symbiont number in their immediate area by excreting pellets of Symbiodinium, and …

Gene Expression Patterns That Support Novel Developmental Stress Buffering In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Josiah T. Wagner, Jason E. Podrabsky

Biology Faculty Publications and Presentations

Background: The cellular signaling mechanisms and morphogenic movements involved in axis formation and gastrulation are well conserved between vertebrates. In nearly all described fish, gastrulation and the initial patterning of the embryonic axis occur concurrently with epiboly. However, annual killifish may be an exception to this norm. Annual killifish inhabit ephemeral ponds in South America and Africa and permanent populations persist by the production of stress-tolerant eggs. Early development of annual killifish is unique among vertebrates because their embryonic blastomeres disperse randomly across the yolk during epiboly and reaggregate several days later to form the embryo proper. In addition, annual …

Regulation Of Synaptogenesis By The Mirna Pathway And Fmr/P Bodies, Jacqueline Rochelle Furlong

Electronic Theses and Dissertations

Post-transcriptional regulation of mRNA is facilitated by different mechanisms, such as microRNA (miRNA) induced gene silencing or fragile X mental retardation protein (FMRP) mediated repression either independent of or acting through cytoplasmic RNA Processing bodies (P bodies). DPTP99A, Lar, and Wg have known functions during synaptogenesis and may be targets of miR-8. Here, we provide evidence that miR-8 regulates DPTP99A in vitro. Non-endogenous miR-8 expressed using an UAS driver regulates Lar. Endogenous miR-8 may regulate DPTP99A in vivo. Here we show that FMRP is capable of colocalizing with the P body components: DCP1, HPat, and Me31B, but not …

Ua94/6/15 Student / Alumni Personal Papers Wku Dorris Hutchinson, Wku Archives

WKU Archives Collection Inventories

Correspondence and publications created by and about the Dorris Hutchison during her time at Sloan-Kettering Institute.