Molecular Biology Commons^™

Nmr Analyses Show Tcdd Elicits Differences In Hepatic Metabolism In Female C57bl/6 Mice And Sprague-Dawley Rats, Meghan Katherine Makley

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TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) elicits tissue-, sex-, and species-specific effects. This study compares the hepatic response to an oral dose of TCDD in immature ovariectomized (i.o.) C57BL/6 mice (30 µg/kg) and i.o. Sprague-Dawley rats (10 µg/kg), at 72, 120, and 168 h post-dose. Hepatic lipid extracts were analyzed by ¹³C and ³¹P NMR, and aqueous extracts by ¹H and ³¹P NMR.

Consistent with increased lipid content in mice (p≤0.05), TCDD induced increases in hepatic triacylglycerides (TAG), cholesterol, and fatty acids. Principal component analysis of ¹³C spectra show treatment groups separate in mice, but not rats. …

The Structural And Folding Characteristics Of The Plasmid-Encoded Toxin From Enteroaggregative Escherichia Coli, Patricia Scaglione

Electronic Theses and Dissertations

Plasmid-encoded toxin (Pet) from enteroaggregative Escherichia coli is a member of the autotransporter subfamily termed SPATE (serine protease autotransporters of Enterobacteriaceae). Autotransporters, which are the most common Gram-negative secreted virulence factors, contain three functional domains: an amino terminal leader sequence, a mature protein or passenger domain, and a carboxy-terminal β domain. The leader sequence targets the protein to the periplasmic space and the β domain then forms a β-barrel pore in the outer membrane of the bacterium which allows the passenger domain to enter the external milieu. In some cases the passenger domain is cleaved from the β-barrel at the …

Generation Of Recombinant Mouse Embryonic Stem Cell Lines And Theirapplication For In Vivo Bioluminiscence Imaging In The Heart, Ramana Kammili

Electronic Theses and Dissertations

Cardiovascular disease is the major cause of death in the United States, with 80 million people suffering from some form of heart disease each year. One major limitation is the inability of the heart to repair the damaged tissue. Stem cell therapy holds enormous promise to repair and regenerate the damaged myocardium, but there are many technical difficulties that must first be overcome. One such difficulty is the present lack of ability to track and assess transplanted stem cells over time in vivo. The central hypothesis of this thesis is that in vivo bioluminescence imaging is a safe and useful …

The Effects Of Leptin And Thyroid Hormone On Metabolism And Lipid Trafficking In The Liver And Adipose Tissue Of Ob/Ob Mice, Candace Michelle Reno

Theses Digitization Project

The purpose of this project was to study how the key metabolic hormones, insulin, leptin, and thyroid hormone alter metabolic pathways and lipid and glucose trafficking in order to find possible therapies for treatment for obesity and its complications.

Distinct Phospho-Forms Of Cortactin Differentially Regulate Actin Polymerization And Focal Adhesions, Anne E. Kruchten, Eugene W. Krueger, Yu Wang, Mark A. Mcniven

Faculty Publications

Cortactin is an actin-binding protein that is overexpressed in many cancers and is a substrate for both tyrosine and serine/threonine kinases. Tyrosine phosphorylation of cortactin has been observed to increase cell motility and invasion in vivo, although it has been reported to have both positive and negative effects on actin polymerization in vitro. In contrast, serine phosphorylation of cortactin has been shown to stimulate actin assembly in vitro. Currently, the effects of cortactin serine phosphorylation on cell migration are unclear, and furthermore, how the distinct phospho-forms of cortactin may differentially contribute to cell migration has not been directly compared. Therefore, …

Bmp Signaling Goes Posttranscriptional In A Microrna Sort Of Way, Catherine A. Reinke, Richard W. Carthew

Faculty Publications

Aberrant microRNA (miRNA) expression correlates with human diseases such as cardiac disorders and cancer. Treatment of such disorders using miRNA-targeted therapeutics requires a thorough understanding of miRNA regulation in vivo. A recent paper in Nature by Davis et al. expands our understanding of miRNA biogenesis and maturation, elucidating a mechanism by which extracellular signaling directs cell differentiation via posttranscriptional regulation of miRNA expression.

The Caenorhabditis Globin Gene Family Reveals Extensive Nematode-Specific Radiation And Diversification, David Hoogewijs, Sasha De Henau, Sylvia Dewilde, Luc Moens, Marjolein Couvreur, Gaetan Borgonie, Serge N. Vinogradov, Scott W. Roy, Jacques R. Vanfleteren

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Globin isoforms with variant properties and functions have been found in the pseudocoel, body wall and cuticle of various nematode species and even in the eyespots of the insect-parasite Mermis nigrescens. In fact, much higher levels of complexity exist, as shown by recent whole genome analysis studies. In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles.

Results

In the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi …

A Phylogenomic Profile Of Hemerythrins, The Nonheme Diiron Binding Respiratory Proteins, Xavier Bailly, Stefano Vanin, Christine Chabasse, Kenji Mizuguchi, Serge N. Vinogradov

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Hemerythrins, are the non-heme, diiron binding respiratory proteins of brachiopods, priapulids and sipunculans; they are also found in annelids and bacteria, where their functions have not been fully elucidated.

Results

A search for putative Hrs in the genomes of 43 archaea, 444 bacteria and 135 eukaryotes, revealed their presence in 3 archaea, 118 bacteria, several fungi, one apicomplexan, a heterolobosan, a cnidarian and several annelids. About a fourth of the Hr sequences were identified as N- or C-terminal domains of chimeric, chemotactic gene regulators. The function of the remaining single domain bacterial Hrs remains to be determined. In …

Offsprings Of Hypertensive Parents Have Higher Blood Pressure And Bmi, Syed Faraz Kazim, Muhammad Bilal Salman, Akbar Jaleel Zubairi, Aisha Afzal, Usman Ahmad, Philippe M Frossard

Department of Biological & Biomedical Sciences

No abstract provided.

Il-21 Limits Peripheral Lymphocyte Numbers Through T Cell Homeostatic Mechanisms., Shrimati Datta, Nora E. Sarvetnick

Journal Articles: Regenerative Medicine

BACKGROUND: IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents.

METHODOLOGY/PRINCIPAL FINDINGS: To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non-autoimmune C57BL/6 and autoimmune NOD mice. Our data indicate that IL-21R knockout C57BL/6 and NOD mice show increased size of their lymphocyte population and decreased homeostatic proliferation. In addition, our experimental results demonstrate that IL-21 inhibits T cell survival. These data suggest that IL-21 acts …

History Of The Department Of Biochemistry And Molecular Biology, Gene A. Homandberg

UND Departmental Histories

This departmental history was written on the occasion of the UND Quasquicentennial in 2008.

Characterizing The Dynamics And Functional Role Of Site-Specific Phosphorylation Of G Protein-Coupled Receptors, John M. Busillo

Full-Text Theses & Dissertations

Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) and the subsequent recruitment of arrestin is a well-established paradigm that initiates the process known as desensitization. However, an emerging theme in GPCR regulation is the possibility of differential regulation dictated by the phosphorylation pattern elicited by the different members of the GRK family. Therefore, we have used small interfering RNA-mediated knock down of the GRKs and arrestins in an attempt to better understand how phosphorylation regulates the activity and signaling of the M3 muscarinic acetylcholine receptor (M3 mAChR) and CXCR4, two receptors endogenously expressed in HEK293 cells.

Using a …

Improved Constrained Global Optimization For Estimating Molecular Structure From Atomic Distances, Terri Marie Grant

Mathematics & Statistics Theses & Dissertations

Determination of molecular structure is commonly posed as a nonlinear optimization problem. The objective functions rely on a vast amount of structural data. As a result, the objective functions are most often nonconvex, nonsmooth, and possess many local minima. Furthermore, introduction of additional structural data into the objective function creates barriers in finding the global minimum, causes additional computational issues associated with evaluating the function, and makes physical constraint enforcement intractable. To combat the computational problems associated with standard nonlinear optimization formulations, Williams et al. (2001) proposed an atom-based optimization, referred to as GNOMAD, which complements a simple interatomic distance …

7Β-Hydroxy­Artemisinin, Paulo B. Carvalho, Bo Liu, Yunshan Wu, John S. Williamson, Mitchell A. Avery

Office for Research Publications and Presentations

Crystals of the title compound [systematic name: (3R,6R,7S,8aR,9R,12aR)-7-hydr­oxy-3,6,9-trimethyl­octa­hydro-3,12-ep­oxy[1,2]dioxepino[4,3-i]isochromen-10(3H)-one], C₁₅H₂₂O₆, were obtained from microbial transformation of artemisinin by a culture of Cunninghamella elegans. The stereochemistry of the compound is consistent with the spectroscopic findings in previously published works. A weak O—H⋯O hydrogen bond occurs in the crystal structure, together with intermolecular C—H⋯O hydrogen bonds.

Molecular Characterization Of Trypanosoma Cruzi And Shed Vesicle Components Involved In Host Immunomodulation And Cell Invasion, Ernesto Satoshi Nakayasu

Open Access Theses & Dissertations

Chagas disease caused by Trypanosoma cruzi is a devastating infectious disease with millions of cases in Latin America, and recently became a public health concern in United States and Europe. Although many efforts have been made for the development of an effective immunotherapy, currently there is no human vaccine for Chagas disease. Thus, the treatment is based only on two drugs that have limited efficacy and in some cases present severe side effects. One restriction for the rational approach to develop new therapies against this disease is the limited information about the proteins, glycolipids and protein posttranslational modifications expressed by …

Immuno-Opioid Interaction A Potential Connection, Linda Staikos-Byrne

Seton Hall University Dissertations and Theses (ETDs)

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Regulated Expression Of Adenoviral Vectors-Based Gene Therapies: Therapeutic Expression Of Toxins And Immune-Modulators, James Curtin, Marianela Candolfi, Mariana Puntel, Weidong Xiong, Akm Ghulam Muhammad, Kurt Kroeger, Sonali Mondkar, Chunyan Liu, Niyati Bondale, Pedro Lowenstein, Maria Castro

Articles

Regulatable promoter systems allow gene expression to be tightly controlled in vivo. This is highly desirable for the development of safe, efficacious adenoviral vectors that can be used to treat human diseases in the clinic. Ideally, regulatable cassettes should have minimal gene expression in the "OFF" state, and expression should quickly reach therapeutic levels in the "ON" state. In addition, the components of regulatable cassettes should be non-toxic at physiological concentrations and should not be immunogenic, especially when treating chronic illness that requires long-lasting gene expression. In this chapter, we will describe in detail protocols to develop and validate first …

Identification Of Lactic Acid Bacteria In Michigan Cherry Wines, Emily Henk, Margaret Dietrich, Terri Weese

Student Summer Scholars Manuscripts

Many factors contribute to the final flavor of wine. One factor is malolactic fermentation, during which lactic acid bacteria (LAB) transform the harsh tasting malic acid into a more drinkable lactic acid in grape wine. The role of LAB in the production of cherry wine is completely unknown. The goal of this study is to identify the species of LAB in cherry wine and compare them to those found in grape wines. Bacteria from cherry wine were grown on general media plates and plates fortified with malic acid, which may provide optimal growing conditions for the LAB. To identify the …

Transcriptional Regulation Of Lamb3 By P53, Meghna Jani

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The p53 tumor-suppressor plays a very important role in the prevention of cancer and it is known that about 50% of all human tumors possess p53 mutations. Although mutations in p53 are most prevalent in human cancers, inactivation of wild-type p53 occurs through many different mechanisms that are independent of p53 mutation or deletion. In an effort to determine novel p53 target genes, our lab employed a microarray method in which p53 was re-activated by RNAi mediated knockdown of Hdm2 and HdmX in MCF7 human breast cancer cell line, harboring wild-type p53 and elevated levels of Hdm2 and HdmX. Gene …

Ancient Dna Identification Of Early 20th Century Simian T-Cell Leukemia Virus Type 1, Sebastien Calvignac, Jean-Michel Terme, Shannon M. Hensley, Pierre Jalinot, Alex D. Greenwood, Catherine Hanni

Biological Sciences Faculty Publications

The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to …

Validation Of A Custom-Made Microarray To Study Human Intestinal Microflora, Harshavardhan Kenche

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Intestinal microflora refers to all the different species of bacteria that reside in the human gut and is an important organ of the human body because almost all the digestive reactions of the host occur in the intestine. The bacteria of the intestine play a key role in this process by supplementing the intestine with various enzymes and proteins that are required for the digestive process. At the same time, these bacteria were shown to be implicated in a variety of gastrointestinal disorders like Irritable Bowel Syndrome, Inflammatory Bowel Disorder and Gastrointestinal Cancer, but with the current knowledge about the …

Giardia Lamblia: Genomic And Molecular Analyses Of Flippase, Diana Leticia Villazana-Kretzer

Open Access Theses & Dissertations

Giardia lamblia, is an intestinal protozoan parasite responsible as a major cause of water-borne intestinal infection in humans (giardiasis). It has been proposed earlier that Giardia has limited lipid synThesis ability and therefore relies on preformed lipid molecules from outside sources. It has also been proposed that lipids are taken up through passive and active transport, and giardial flippasse play a significant role in this process. This study describes the identification and characterization of a putative homologue of flippase gene from Giardia. Flippase is an enzyme that functions as a trans-bilayer transport system facilitating the flip flop diffusion of phospholipids …

Mdm2 Amplification In Nih3t3l1 Preadipocytes Leads To Mdm2 Elevation In Terminal Adipogenesis, Vaughn Litteral

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The p53 protein is a tumor suppressor protein that is mutated or non-functional in nearly all cancers. The Mdm2 protein has the ability to functionally inactivate p53 and these two proteins have been studied extensively in the context of cellular proliferation. In this study, expression of the murine double minute 2 (mdm2) gene was examined in the mouse NIH3T3L1 cell line. Under the proper conditions, the immortalized NIH3T3L1 cells have the ability to differentiate from fibroblasts to adipocytes (Green et al., 1975). This well characterized cell line provides an excellent model to study mdm2 in differentiation. While evaluating the regulation …

In Search For New P53 Regulated Genes, Meldrick Daniel Mpagi

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The p53 tumor suppressor protein has the ability to transactivate its target genes whose gene products are involved in carrying out cell cycle arrest, apoptosis, DNA repair, and senescence. Here, I report that two genes may be p53 regulated. Utilizing a microarray method to search for novel p53 target genes, I was able to identify a possible transcriptional target of p53 being solute carrier family 1a1 (SLC1a1). Along with that finding I also identified an E2F-target gene, minichromosome maintenance 10 (MCM10), as being p53 regulated. Gene expression profiling of MCF7 breast cancer cells treated with RNAi targeting Hdm2 and HdmX …

The Development Of A "Genetic Eyewitness" Profiling System For Low Template Forensic Specimens: Identification Of Novel Protein, Rna, And Dna Biomarkers, Erin Hanson

Electronic Theses and Dissertations

In many criminal investigations, valuable information regarding the physical appearance of suspected perpetrators or the time and order of events that transpired are provided by eyewitness accounts. However, the information obtained from eyewitnesses is often constrained by human recollection or subjective accounts and provides a biased description of the perpetrator's appearance or an inaccurate time line of events. Additionally, in numerous situations eyewitness accounts may not be available. An increasing reliance therefore is placed on the biological evidence recovered during criminal investigations to act as a silent witness, providing unbiased and scientific information that may aid in the resolution of …

The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis

Electronic Theses and Dissertations

Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …

Novel Functions Of Acyl-Coa Thioesterases And Acyltransferases As Auxiliary Enzymes In Peroxisomal Lipid Metabolism., Mary Hunt, Stefan Alexson

Articles

Peroxisomes are single membrane bound organelles present in almost all eukaryotic cells, and to date have been shown to contain approximately 60 identified enzymes involved in various metabolic pathways, including the oxidation of a variety of lipids. These lipids include very long-chain fatty acids, methyl branched fatty acids, prostaglandins, bile acid precursors, and xenobiotics that are either β-oxidized or α-oxidized in peroxisomes. The recent identification of several acyl-CoA thioesterases and acyltransferases in peroxisomes has revealed their various functions in acting as auxiliary enzymes in α- and β-oxidation in this organelle. To date, 9 functional acyl-CoA thioesterases and acyltransferases have been …

The Nudix Hydrolase 7 Is An Acyl-Coa Diphosphatase Involved In Regulating Peroxisomal Coenzyme A Homeostasis., Sarah-Jayne Reilly, Veronica Tillander, Rob Ofman, Stefan Alexson, Mary Hunt

Articles

Coenzyme A (CoASH) is an obligate cofactor for lipids undergoing β-oxidation in peroxisomes. Although the peroxisomal membrane appears to be impermeable to CoASH, peroxisomes contain their own pool of CoASH. It is believed that CoASH enters peroxisomes as acyl-CoAs, but it is not known how this pool is regulated. The mouse nudix hydrolase 7 (NUDT7α) was previously identified in peroxisomes as a CoAdiphosphatase, and therefore suggested to be involved in regulation of peroxisomal CoASH levels. Here we show that mouse NUDT7α mainly acts as an acyl-CoA diphosphatase, with highest activity towards medium chain acyl-CoAs, and much lower activity with CoASH. …

Maldi Mass Spectrometry Imaging For The Discovery Of Prostate Carcinoma Biomarkers, Lisa Harris Cazares

Theses and Dissertations in Biomedical Sciences

The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision …

Subcellular Localization Of Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein, Kimberly Anne Fryrear

Theses and Dissertations in Biomedical Sciences

Human T-cell Leukemia Virus Type 1 (HTLV-1) is a transforming retrovirus that gives rise to Adult T-cell Leukemia (ATL) and a variety of other subneoplastic conditions such as HTLV-Associated Myelopathy/Tropical Spastic Paraperesis (HAM/TSP). In ATL, the transformation and immortalization of T-lymphocytes has been attributed to the expression and activity of a single HTLV-1 viral protein, namely the trans-activating protein Tax. Although the exact mechanism of Tax-mediated transformation is uncertain, current studies support a model in which Tax induces genomic instability in the host cell through interference with DNA repair mechanisms, dysregulation of cell cycle progression, transcriptional activation of cellular …