Molecular Biology Commons^™

Knockdown Of Kiaa0319 Reduces Dendritic Spine Density, Daniel Young Kim

Honors Scholar Theses

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Generation Of An Fsh Inducible Inh-[Alpha]-Flag-Gg-Icer I[Gamma] Ovarian Specific Gene Construct, Goce Bogdanoski

Theses, Dissertations and Culminating Projects

Avian animal models have led to many essential discoveries in molecular biology and biochemistry, including the discovery of vitamins, the chemistry behind vision and the development of transgenic hens as natural bioreactors for pharmaceutically relevant proteins. Hyperovulation in domesticated hens is considered a highly desirable genetic trait, a feature that has been explored in multiple studies and remains the focus of many biotech companies. Unlocking the molecular mechanism that controls ovulation may provide a basis for development in new reproductive technologies.

Previous research done on rodents provided data and identified a single transcription factor, the Inducible cAMP Early Repressor (ICER), …

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Characterization Of The Catalytic Mechanism Of The Carboxyltransferase Component Of Escherichia Coli Acetyl-Coa Carboxylase Leading To Rational Inhibitor Identification And The Development Of Enzymatic Mimics, Nabil K. Thalji

Honors Capstones

No abstract provided.

The Membrane Interface Of Chloroplast Signal Recognition Particle-Dependent Protein Targeting, Naomi Jane Marty

Graduate Theses and Dissertations

A novel signal recognition particle (SRP) found in the chloroplast (cpSRP) works in combination with the cpSRP receptor, cpFtsY, to facilitate the post-translational targeting of a family of nuclear-encoded thylakoid proteins to the Alb3 translocase in thylakoid membranes. Work here focused on understanding events at the membrane that take place to ensure targeting of the cpSRP-dependent substrate to Alb3. Specifically, we sought to understand the structural and functional role of membrane binding by cpFtsY, a protein that exhibits the ability to partition between the membrane (thylakoid) and soluble (stroma) phase during protein targeting. We also sought to understand whether a …

Understanding The Role Of Histones During Chromosome Segregation: A Study Of The Effects Of Histone Gene Dosage In Saccharomyces Cerevisiae, Rebecca Leigh Danforth

Graduate Theses and Dissertations

Chromatin plays a role in all cellular functions that involve DNA. These include, but are not limited to replication, recombination, transcription, and chromosome segregation. Chromosome segregation is an extremely well conserved cellular process and is essential for maintaining the genetic integrity of a cell. There is very strong evidence indicating that chromatin structure is critical for maintaining the fidelity of chromosome transmission, but its specific role(s) in this process remains unclear. Chromatin is comprised of arrays of nucleosomes that serve to compact DNA. These nucleosomes consist of 146 bp of DNA that is wrapped around a histone octamer; two each …

The Zinc Finger Protein Zn72d And Dead Box Helicase Belle Interact And Control Maleless Mrna And Protein Levels, Kathleen A. Worringer, Feixia Chu, Barbara Panning

Molecular, Cellular & Biomedical Sciences

Background: The Male Specific Lethal (MSL) complex is enriched on the single X chromosome in male Drosophila cells and functions to upregulate X-linked gene expression and equalize X-linked gene dosage with XX females. The zinc finger protein Zn72D is required for productive splicing of the maleless (mle) transcript, which encodes an essential subunit of the MSL complex. In the absence of Zn72D, MLE levels are decreased, and as a result, the MSL complex no longer localizes to the X chromosome and dosage compensation is disrupted. To understand the Molecular basis of Zn72D function, we identified proteins that interact with Zn72D. …

Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu

Theses and Dissertations in Biomedical Sciences

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new …

Study Of The Dna Damage Complexes Within The Htlv-1 Tax Oncoprotein Interactome, Sidi Mehdi Belgnaoui

Theses and Dissertations in Biomedical Sciences

Human T-cell leukemia virus type 1 (HTLV-1) is a transforming retrovirus that can give rise to adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax is a virally encoded oncoprotein that is involved in HTLV-1 mediated cellular transformation. It has been hypothesized that Tax induces genomic instability via repression of the cellular DNA damage repair response. Our laboratory has previously shown that the interaction between Tax and various proteins involved in the DNA-damage response pathway impairs the ability of these proteins to mount an efficient repair response. As part of these observations, we proposed that Tax induces …

Characterization Of Antibiotic Resistance In Vibrio Cholerae Isolated From Ships' Ballast And Other Environmental Sources, Frank Kornegay Thomson Iii

OES Theses and Dissertations

Ships' ballast has been implicated as a vector in the dispersal of invasive species into new environments. Numerous cases have been documented for the introduction of macroorganisms via ballasting operations, but what is less known is the role of ballast water and residuals in the spread of potentially harmful microbes, especially with reference to novel genotypes. Of particular interest are the genes encoding for various forms of antibiotic resistance, many of which are carried on mobile genetic elements. A four-year sampling effort has yielded over 300 putative isolates of Vibrio cholerae from ships' ballast tanks and various environmental sources, of …

Role Of The Human Cytomegalovirus Ie2 Protein On Transcriptional Regulation Of Viral Promoters, Siabhon Michelle Harris

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous pathogen able to cause severe mortality and morbidity in immuno-compromised individuals. Successful infection by HCMV is dependent on expression of viral genes essential for replication. Immediate early (IE) gene products are the first subset of viral genes to be expressed during infection and function as key transcriptional regulators. IE2 is one the most predominantly expressed IE proteins and is essential for HCMV infection. IE2 transactivates several viral promoters, including those of the essential viral DNA polymerase (UL54) and UL112-113 gene regions. IE2 is also able to autoregulate is own expression and repress expression of …

Interdependent Regulation Of Cytomegalovirus Proteins In Complex, Lisa L. Bolin

Theses and Dissertations in Biomedical Sciences

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes significant morbidity and mortality in the immune compromised. Using the mutine cytomegalovirus (MCMV) model, we identified two genes, M140 and M141, which are determinants of macrophage tropism. Monocytes/macrophages are a critical cell type for cytomegalovirus (CMV) pathogenesis as sites of viral latency and by supporting viral replication and disseminating virus throughout the body. We previously found that the localization of the M140/M141 gene products (pM140/pM141) is different when the proteins are co-expressed as compared to their individual expression. When the proteins are individually expressed pM141 localizes diffusely throughout the cytoplasm and, …

Resampling And Editing Of Mischarged Trna Prior To Translation Elongation, Jiqiang Ling, Byung Ran So, Srujana S. Yadavalli, Hervé Roy, Shinichiro Shoji, Kurt Fredrick, Karin Musier-Forsyth, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Faithful translation of the genetic code depends on the GTPase EF-Tu delivering correctly charged aminoacyl-tRNAs to the ribosome for pairing with cognate codons. The accurate coupling of cognate amino acids and tRNAs by the aminoacyl-tRNA synthetases is achieved through a combination of substrate specificity and product editing. Once released by aminoacyl-tRNA synthetases, both cognate and near-cognate aminoacyl-tRNAs were considered to be committed to ribosomal protein synthesis through their association with EF-Tu. Here we show instead that aminoacyl-tRNAs in ternary complex with EF-Tu•GTP can readily dissociate and rebind to aminoacyl-tRNA synthetases. For mischarged species, this allows resampling by the product editing …

Molecular Coevolution Of Pacific Northwest Hantaviruses And Their Host, The Deer Mouse, Peromyscus Maniculatus, Philip Darren Jones

Dissertations and Theses

Sin Nombre virus (SNV, family Bunyaviridae, genus Hantavirus), hosted by the deer mouse, Peromyscus maniculatus (family Cricetidae, Subfamily Neotominae), is the primary etiological agent of Hantavirus pulmonary syndrome (HPS) in the western United States. HPS, with known pathogenicity only to humans and for which there is no cure or prophylaxis, affects the epithelium of the lungs by making the capillaries leaky, thereby resulting in bilateral infiltrates, and eventually leading to respiratory failure and death by drowning in approximately 38% of hospitalized patients.

In the Americas, Peromyscus has been co-evolving with hantaviruses for approximately 12–20 million years, since the first …

Adaptation Of The Bacterial Membrane To Changing Environments Using Aminoacylated Phospholipids, Hervé Roy, Kiley Dare, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fine‐tuning of the biophysical properties of biological membranes is essential for adaptation of cells to changing environments. For instance, to lower the negative charge of the lipid bilayer, certain bacteria add lysine to phosphatidylglycerol (PG) converting the net negative charge of PG (−1) to a net positive charge in Lys‐PG (+1). Reducing the net negative charge of the bacterial cell wall is a common strategy used by bacteria to resist cationic antimicrobial peptides (CAMPs) secreted by other microbes or produced by the innate immune system of a host organism. The article by Klein et al. in the current issue of …

Microscopic Analysis Of Sympathetic And Parasympathetic Distribution, Terminal Morphology, And Interaction In Whole-Mount Atria, Scott Harden

Electronic Theses and Dissertations

The sympathetic (SNS) and parasympathetic (PSNS) branches of the autonomic nervous system (ANS) innervate the heart, exerting excitatory and inhibitory influences (respectively) over cardiac functions (heart rate, AV conduction velocity, and contractility). However, the distribution and structure of SNS and PSNS innervation has not yet been well studied. Detailed characterization of the distributional organization and structural morphology of the SNS and PSNS in normal states is essential to the study of pathological autonomic remodeling. The present study utilized double immunohistochemical labeling techniques to examine tyrosine hydroxylase (TH) immunoreactive (IR) SNS and vesicular acetylcholine transporter (VAChT) IR PSNS axons and terminal …

The Expression Of Mkrn1, An E3 Ubiquitin Ligase For Telomerase Reverse Transcriptase, Is Induced With Differentiation Therapy In Leukemia, Jose Salvatico

Electronic Theses and Dissertations

Telomeres are important structural and functional components of chromosomes, serving to provide stability and enabling full replication of the chromosomes. However, a shortening of the telomeres occurs with each cell division that can be fixed by a polymerase activity provided by telomerase, preventing this loss which would otherwise eventually lead to chromosome end-to-end fusions, senescence and cell death. The telomerase activity is present in stem cells and germ line cells, but absent or barely noticeable in adult somatic cells. However, in approximately 80-90% of transformed somatic cells the telomerase activity is recovered, resulting in a "telomerase positive phenotype". This phenotype …

Understanding The Physical Properties That Control Protein Crystallization By Analysis Of Largescale Experimental Data, W. Nicholson Price Ii, Yang Chen, Samuel K. Handelman, Helen Neely, Philip Manor, Richard Karlin, Rajesh Nair, Jinfeng Liu, Michael Baran, John Everett, Saichiu N. Tong, Farhad Forouhar, Swarup S. Swaminathan, Thomas Acton, Rong Xiao, Joseph R. Luft, Angela Lauricella, George T. Detitta, Burkhard Rost, Gaetano T. Montelione, John T. Hunt

Law Faculty Scholarship

Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of …

Alpha-Msh Regulated Cell Signaling In Pancreatic Alpha Cells, Liang Liang

Electronic Theses and Dissertations

Peripheral injection of α-MSH promotes glucagon secretion in POMC knockout mice, suggesting the role of α-MSH in regulation of pancreatic α cells. However, the underlying mechanisms remain unknown. This study investigated the stimulatory effect of α-MSH on mice pancreatic α cell line αTC1-6 cells in cell signaling pathway as well as glucagon secretion. In normal level of glucose, application of α-MSH stimulated Ltype Ca2+ current induced Ca2+ induced Ca2+ release (CICR) and membrane hyperpolarization. Increase of [cAMP]c was also observed when α-MSH was applied with IBMX. Acute hypoglycemia-induced CICR via N- and L-type Ca2+ channels was overridden by typical α-MSH …

Minimotif Miner 2nd Release: A Database And Web System For Motif Search, Sanguthevar Rajasekaran, Sudha Balla, Patrick R. Gradie, Michael R. Gryk, Krishna Kadaveru, Vamsi Kundeti, Mark W. Maciejewski, Tian Mi, Nicholas Rubino, Jay Vyas, Martin R. Schiller

Life Sciences Faculty Research

Minimotif Miner (MnM) consists of a minimotif database and a web-based application that enables prediction of motif-based functions in user-supplied protein queries. We have revised MnM by expanding the database more than 10-fold to approximately 5000 motifs and standardized the motif function definitions. The web-application user interface has been redeveloped with new features including improved navigation, screencast-driven help, support for alias names and expanded SNP analysis. A sample analysis of prion shows how MnM 2 can be used.

Alterations In Gene Expression And Sensitivity To Genotoxic Stress Following Hdmx Or Hdm2 Knockdown In Human Tumor Cells Harboring Wild-Type P53, Katherine Heminger, Michael P. Markey, Meldrick Mpagi, Steven J. Berberich

Biochemistry and Molecular Biology Faculty Publications

While half of all human tumors possess p53 mutations, inactivation of wild-type p53 can also occur through a variety of mechanisms that do not involve p53 gene mutation or deletion. Our laboratory has been interested in tumor cells possessing wild-type p53 protein and elevated levels of HdmX and/or Hdm2, two critical negative regulators of p53 function. In this study we utilized RNAi to knockdown HdmX or Hdm2 in MCF7 human breast cancer cells, which harbor wild-type p53 and elevated levels of HdmX and Hdm2 then examined gene expression changes and effects on cell growth. Cell cycle and growth assays confirmed …

The Evolution Of Opioid/Orphanin Receptors In Chordates, Jazalle Deshaun Mcclendon

Electronic Theses and Dissertations

The interest in the opioid/orphanin gene family stems from functional similarities that these peptides have to the narcotic opium. Opiates have been extensively studied because of their analgesic properties; however, the reason that these plant products can affect the human central nervous system was a mystery until the discovery of opiate-like peptides. The endogenous opioid peptides are well understood today because they have been fully cloned and characterized in several different organisms including lower chordates. On the other hand, the opioid/orphanin receptors have not been fully cloned or characterized in lower chordates; therefore, to better understand the past and present …

Amino Acid Residues Implicated In The Interaction Of Melanocortin Ligands And Their Receptors: A Study Of Mc2r Selectivity, Kristopher D. Veo

Electronic Theses and Dissertations

Melanocortin receptor ligand selectivity has been a question not easily answered. The inability to functionally express melanocortin 2 receptor (MC2R) has inhibited the study of why MC2R is only stimulated by ACTH, a melanocortin hormone. With the recent discovery of the MC2R accessory protein (MRAP), creating a heterologous system is now feasible. Using a general cell line like CHO-K1 cells, which do not express endogenous MCRs, we were able to create a heterologous expression system and test the selectivity of MC2R using analog variants of ACTH(1-24). Our results indicate an amino acid requirement in the C-terminal portion of ACTH(1-24) for …

Evolution Of Gene Structure In Multicellular Eukaryotes, Maria Hester

Inquiry: The University of Arkansas Undergraduate Research Journal

We investigated the patterns of intron conservation in eukaryotes for five different genes. The genes examined were ribosomal proteins L8, S14 and S17, along with elongation factor 2B and triose phosphate isomerase. Intron conservation for S14, S17, and triose phosphate isomerase was determined for 32 species representing the major branches of multicellular eukaryotes. For 25 conserved introns 16 were phase 0, five were phase 1, and four were phase 2. Triose phosphate isomerase had five of nine conserved introns shared between plants and animals, where S14 had one of nine and S17 had one of seven. However, there were two …

A Microrna Imparts Robustness Against Environmental Fluctuation During Development, Xin Li, Justin J. Cassidy, Catherine A. Reinke, Stephen Fischboeck, Richard W. Carthew

Faculty Publications

The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila , in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found …

Lipid Uptake And Metabolism In The Parasitic Protozoan Giardia Lamblia., Mayte Yichoy

Open Access Theses & Dissertations

Giardia lamblia is a protozoan parasite that causes various intestinal syndromes, and it is a common cause of water-borne illness worldwide, both in developed and developing countries. Giardia attaches to the mucosal epithelia of the duodenum below the bile duct, where it is exposed to bile salts and dietary lipids. G. lamblia is unable to synthesize lipids de novo and must therefore scavenge necessary lipids from its extracellular environment and remodel them as needed. However, the current lipidomic analysis (presented in this Dissertation) has revealed that while the Giardia lipidome is rich in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG), …

The Impact Of Environment On Virulence Of The Pathogenic Yeast Cryptococcus Gattii, Deborah Jean Springer

Legacy Theses & Dissertations (2009 - 2024)

Four serotypes of Cryptococcus are responsible for most human and animal infections. C. gattii , serotype B and C, are the primary the causative agent of cryptococcosis in immune competent individuals whilst, C. neoformans var. neoformans serotype D, and C. neoformans var. grubii serotype A are most prevalent in immunocompromised hosts world-wide. C. gattii is recognized as a species distinct from C. neoformans based on differences in clinical manifestations, morphology, biological characteristics, and environmental niche. We used the plant model Arabidopsis thaliana plants and plant derived substrates as a model to explore C. gattii interactions in its ecological niche. C. …

A Locus-Based Paradigm For Generating Systems Biological Inferences From Large Scale Functional Genomics Datasets, Ajish Dominic George

Legacy Theses & Dissertations (2009 - 2024)

Genomics data is growing at a exponential rate. The ability to integrate new results with existing knowledge about genomic biology is rapidly becoming the limiting factor as there no universal language with which to describe genomic functional elements. To integrate and compare new and existing genomic data, we define our basic functional unit of a genome to be a locus -- a set of positional coordinates along any genome with an arbitrary amount of functional annotations attached. The locus concept enables addressing genomic elements and annotations at any level of granularity from entire swaths of chromosomes to single base-positions. We …

Opportunism And Diversity In The Lifestyle Of A Group Ii Intron, Arthur R. Beauregard

Legacy Theses & Dissertations (2009 - 2024)

Group II introns are mobile retroelements. They invade the cognate intron-minus gene in an efficient process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Retrohoming occurs by the intron RNA reverse-splicing into double-stranded DNA (dsDNA) through an endonuclease-dependent pathway. However, in retrotransposition in Lactoccocus lactis, the intron inserts predominantly into single-stranded DNA (ssDNA), in an endonuclease-independent manner. Unlike in L. lactis, in Escherichia coli the Ll.LtrB intron retrotransposes frequently into dsDNA, and the process is dependent on the endonuclease activity of the intron-encoded protein. Further, the endonuclease-dependent integrations preferentially occurred around the origin and terminus …