Cell and Developmental Biology Commons^™

Rapid Adaptation Of Dopamine D2 Receptor Responses In The Brain And Blood Following Acute Ethanol, Ryan J. Folsom

Theses and Dissertations

Dopamine (DA) D2 receptor expression parallels DA levels in the brain and these autoreceptors have been shown to be modulated by long-term ethanol exposure. We have previously demonstrated that ventral tegmental area (VTA) GABA neurons also express D2 autoreceptors (D2R), and that DA and D2R agonists markedly enhance the excitability of VTA GABA neurons, opposite to their well-known auto-receptor inhibition of DA neurons. Most importantly, D2R antagonists block ethanol inhibition of VTA GABA neurons and D2R expression in VTA GABA neurons down-regulates with chronic ethanol, as others have shown for whole VTA D2R expression. The aim of this study was …

Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore

Theses and Dissertations

Skeletal muscle has the ability to increase in size (hypertrophy) after resistance is placed upon it. This hypertrophy is marked by significant upregulation of the mammalian target of rapamycin (mTOR) and its downstream targets. The upstream kinases, protein kinase B (also known as Akt) and AMP-activated protein kinase (AMPK), are two of the many regulators of the mTOR pathway. Recent studies suggest that the widely consumed neuroactive compound caffeine could potentially inhibit mTOR by acting through Akt and/or AMPK. The purpose of this thesis was to: 1) determine if caffeine can inhibit the mTOR pathway and ultimately attenuate skeletal muscle …

Chlorovirus Skp1 And Core Ankyrin-Repeat Protein Interplay And Mimicry Of Cellular Ubiquitin Ligase Machinery, Eric Andrew Noel

School of Biological Sciences: Dissertations, Theses, and Student Research

The ubiquitin-proteasome system is a common target of several unrelated viruses that have evolved convergent strategies to redirect host ubiquitin machinery to serve their own needs. Members of the genus Chlorovirus, a group of large dsDNA viruses that infect certain freshwater chlorella-like green algae, encode a conserved Skp1 homolog and ankyrin-repeat (ANK) proteins, some of which contain C-terminal domains characteristic of cellular F-boxes or related viral PRANC domains. These observations suggested that this unique combination of chlorovirus proteins either interact with or imitate the key components of the SCF (Skp1-Cul1-F-box) ubiquitin ligases. Using mass spectrometry, we identified two functional …

The Role Of The N-Terminus On The Enzymatic Activity Of Dutpase From Dictyostelium Discoideum, Kyle C. Varon

School of Biological Sciences: Dissertations, Theses, and Student Research

The enzyme deoxyuridine triphosphatase (dUTPase) (EC 3.6.1.23) converts dUTP to dUMP, thus shifting the dUTP to dUMP ratio in the cell. The molecule dUTP is subject to mis-incorporation into DNA due to lack of distinguishing by DNA polymerase. Uracil incorporation can be repaired with base excision repair mechanisms but may create overwhelming DNA strand breaks proving to be detrimental to the cell. Most dUTPases of eukaryotes are homotrimeric and contain five highly conserved motifs responsible for catalysis and substrate binding. Many dUTPases of eukaryotes possess a leading and core region in their sequence. The core region is composed of the …

Localization And Functional Analysis Of Dictyostelium Discoideum Gtpases, Rabs And Rab2, Katherine V. Maringer

Theses and Dissertations

Dictyostelium discoideum is a simple eukaryotic amoeba that has proven useful in studying various aspects of endosomal and lysosomal membrane trafficking, as well as development. The Rab family of small molecular weight GTPases has been implemented in several cellular processes to include various vesicle trafficking roles, cell-cell signaling, and development. This study focuses on the localization and function of two Dictyostelium GTPases, RabS, and Rab2 which we hypothesized to both localize to the Golgi, and the contractile vacuole system. Expression of GFP-tagged DdRab2, and DdRabS proteins revealed similar localization to ER-Golgi membranes as well as the contractile vacuole system. Microscopic …

Characterization Of Secondhand Smoke (Shs) And Materno-Fetal Interactions In Receptors For Advanced Glycation End-Products (Rage)-Targeted Mice, Duane Ray Winden

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are pattern recognition receptors of the immunoglobulin superfamily highly expressed in the lung. Likely functions include the modulation of pulmonary inflammation during disease. However, the contributions of RAGE in the developing lung in cases where secondhand smoke (SHS) exposure occurs are unknown. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, we exposed gestating dams to a controlled dose of SHS during the last four critical days of in utero lung morphogenesis. We discovered that both maternal and fetal lungs respond to SHS by up-regulating RAGE. Exposed fetuses were markedly …

Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina

Seton Hall University Dissertations and Theses (ETDs)

The cancer epidemic continues to afflict millions of humans world-wide each year and despite a renewed hope with the development of new and improved forms of therapy, a cure for cancer remains an elusive goal. This is partly related to the rise of resilient forms of tumors that have evolved with resistance towards conventional chemotherapy and radiation treatments. Moreover, these non-specific therapeutic regimens are highly toxic, leading to severe immunosuppressive effects which poisons the body and compromises the road towards remission. In an effort to mitigate these limitations, cancer-targeting approaches are currently experiencing a renaissance in the translation of new …

Phenotypic Variation In The Model Organism, Danio Rerio, Rachel D. Champaigne, Kim H. Brown

Student Research Symposium

Model organisms are used to study evolutionary conserved traits. Zebrafish (Danio rerio) are used a model organism because of their highly fecundity, external fertilization, and robust nature, making them highly adaptable to environmental and genetic variation. In an effort to limit data variation that lies outside of topic interest, phenotypic measures of variation must be performed, understood, and taken into consideration for future studies. A common measurement of phenotypic variation in fish is in the maximum (Ucrit) swimming speeds. Inter and intra-strain variation in zebrafish Ucrit swimming speeds will be observed in a swim tunnel. Baseline values will …

Transcriptome Analysis Of Sea Lamprey Embryogenesis, Zakary Ilya Yermolenko

Seton Hall University Dissertations and Theses (ETDs)

The sea lamprey (Petromyzon marinus) has survived throughout evolution for hundreds of millions of years. It is considered an invasive species to the Great Lakes that has caused dramatic changes in the ecosystem for fish communities resulting in the collapse of a fishing industry that was previously valued at billions of dollars. Successful management of the sea lamprey is essential to a sustainable fishing industry and biodiversity. Therefore sea lamprey embryos were studied at various stages of development by growing them in a simulated habitat. RNAs from adult female ovaries and embryos at different time points during embryogenesis …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Defining The Sites Of Interaction Of The Fancd2, Fance, And Fancl Proteins, Joseph Mcclanaghan

Senior Honors Projects

Fanconi anemia (FA) is a rare genetic disease characterized by congenital defects, bone marrow failure and increased cancer susceptibility. FA is caused by mutations in any one of 16 genes. These genes encode for proteins that function in the FA-BRCA pathway to repair damaged DNA. Because of its important r­­­ole in DNA repair, this pathway is considered a major cellular tumor suppressor pathway, i.e. is critical for the prevention of cancer. Underscoring this fact, several of the FA genes - including BRCA2, BRIP1, PALB2, and RAD51C - are bona fide breast and ovarian cancer susceptibility genes.

My …

The Development Of A Comprehensive Antifungal Susceptibility Testing Assay For Vulvovaginal Candidiasis Therapy, David Hardaker

Graduate School of Biomedical Sciences Theses and Dissertations

Vulvovaginal candidiasis is the most common fungal infection of the female urogenital tract, commonly caused by Candida albicans and C. glabrata. However, treatment can be difficult when caused by non-albicans strains due to resistance to the oral antifungal drug fluconazole. The mechanism through which strains of Candida, particularly C. glabrata, develop resistance to different antifungal classes has not been completely characterized. The ergosterol biosynthesis pathway, an important component of the cell membrane, is the major target of antifungals such as fluconazole, an inhibitor of the ERG 11 gene. Current research shows that an upregulation of specific genes in C. glabrata …

Molecular Chaperone Tools For Use Against Neurodegenerative Diseases, Matthew Tinkham

Senior Honors Projects

A noted characteristic found in several neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and bovine spongiform encephalopathy, is the accumulation of amyloid plaques in the brain. Amyloid plaques contain deposits of fibrillar aggregates of misfolded proteins that disrupt normal functionality in neurons. Certain variants of these misfolded proteins are self-replicating; these self-replicating amyloids are termed prions (for infectious protein). We are interested in how protein misfolding contributes to amyloid formation and how molecular chaperone proteins can change the formation of amyloid deposits. Chaperone proteins function by catalyzing the proper folding of other proteins, the refolding of misfolded proteins, …

The Neural Correlates Of Regulating Positive And Negative Emotions In Medication-Free Major Depression, Steven G. Greening, Elizabeth A. Osuch, Peter C. Williamson, Derek G. V. Mitchell

Anatomy and Cell Biology Publications

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. …

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed using …

The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller

Student Publications & Research

CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Alendronate Alters Single Cell Gene Expression Of Cortical Osteoblast Lineage Cells During Bone Loss, Ryan Jakob Murphy

Dissertations, Masters Theses, Capstones, and Culminating Projects

The mineralized matrix of bone makes it difficult to examine specific populations of cells which are integral to the tissue using traditional molecular methods. For this study we examined single cell cortical osteoblasts derived from the femurs of C57BL/6J mice. After isolating single cells from bone, we were able to individually analyze their gene expression profiles using the quantitative polymerase chain reaction (qPCR). The mice used for the study were divided into 4 treatment groups, including ovariectomized mice (OVX) and sham surgical controls (SHAM), treated with or without the anti-resorptive bisphosphonate drug Alendronate, an effective FDA approved therapeutic for slowing …

Progesterone Signaling In Mouse Oocyte Development Via The Pgrmc1 And Pgrmc2 Receptors And The Pairbp1 Protein, Amanda M. Catchings

Renée Crown University Honors Thesis Projects - All

There are thought to be many different causes that can lead to the development of infertility in females. Many of the causes for this condition present themselves before birth, which can predetermine a woman’s fertility capability before she is even born. The complex process of germ cell development possesses possibilities for error and malfunction that can have permanent, lasting effects on a developing fetus. The process of oocyte development is initiated when primordial germ cells migrate to the embryotic gonad and begin dividing mitotically. As mitosis proceeds, the process of cytokinesis does not go to completion, which maintains the cells …

The Grass Shrimp, Palaemonetes, Pugio: Hypoxic Influences On Embryonic Development, Christensen C. Javier

UNLV Theses, Dissertations, Professional Papers, and Capstones

Grass shrimp,Palaemonetes pugio, can survive in brackish waters and estuarine ecosystems despite the frequent oscillations and fluctuations in salinity, temperature and oxygen. AdultP. pugiohave the ability to osmoregulate (Romney and Reiber 2011), change cardiac parameters to tolerate temperatures (not yet published, Mika and Reiber) and oxyregulate (Guadagnoli and Reiber 2013). Manipulation of cardiac parameters allows for these methods of regulation. However, cardiac contraction and internal convection of oxygen do not occur until later stages of embryonic development. Studies focused on these morphological and physiological advantages may provide further understanding of the regulatory mechanisms within grass shrimp embryos, larvae and adults. …