Molecular Biology Commons^™

Bone Morphogenetic Protein-7 Attenuates Inflammation And Apoptosis And Improves Cardiac Function In Diabetes, Princess Urbina

Electronic Theses and Dissertations

Bone Morphogenetic Protein-7 (BMP-7) belongs to the transforming growth factor-β (TGFβ) family of cytokines has is known to have potent anti-inflammatory properties. It has been used in patients to treat osteoporosis clinically and has been reported to treat diabetic nephropathy in murine models. Moreover, studies show that inflammation is up-regulated in patients with pre-diabetes (PD). We, therefore, hypothesize that the administration of BMP-7 will attenuate inflammation in the heart of Streptozotocin (STZ)-induced PD mice. In this study, we divided C57Bl/6 mice into three groups: CONTROL, PD, and PD+BMP-7. CONTROL mice received intraperitoneal (i.p.) injections of Sodium Citrate Buffer while PD …

Guilty Or Not Guilty: Can Dna Help Prove Guilt Or Innocence?, Suzanne Eckstein

The Science Journal of the Lander College of Arts and Sciences

Throughout our history, science was always on the front lines for discovery and exploration. Science is used as an investigative tool by the human race to figure out all the mysteries of the universe. The discovery of DNA was tremendous, providing each human being with their own unique genetic identity - no longer would an individual be genetically confused with another. DNA fingerprinting, in particular, has changed the world. In the 1980's the legal system began using DNA fingerprinting to help establish the guilt of an indicted criminal. DNA (besides for fingerprints) is the only way to confirm scientifically if …

Cell Type Difference In Influenza A Viral Mrna Nuclear Export, Sean William Larsen

Theses Digitization Project

The focus of this thesis research was to clarify the role of host Nxf1 in influenza viral mRNA nuclear export. This study aims to define the nuclear mRNA export pathways of influenza viral mRNA. If viral mRNAs are discovered to utilize neither known mRNA nuclear export pathway this would indicate the mRNA exports via undefined mRNA nuclear export pathway. This might be an atypical pathway not utilized by many host mRNAs and thus might reveal novel antiviral target. 293T (Human embryonic kidney cells) and A549 (Human lung epithelial) cells were purchased from ATCC American Tissue Culture Collection.

Dopaminergic Modulation Of Glutamate Signaling In Caenorhabditis Elegans, Melvin Suman Baidya

Theses Digitization Project

This study investigates how DA (dopamine) modulates GLU (glutamate) signaling at the interneuron level of the C. elegans avoidance circuit in response to the noxious chemical 1-octanol. Many neural processes involved in addiction, exhibit cellular mechanisms using the neurotransmitters dopamine and glutamate along with their intracellular and genomic targets.

The Influence Of Ubiquitin-Related Modifier Protein Urm1 On Prion Formation, Jacob Beaver

Bridges: A Journal of Student Research

Prions are infectious proteins that are autocatalyzing (formed by altering a regular protein into the structurally different prion form), and are associated with many neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Bovine Spongiform encephalopathy (or Mad Cow disease). This experiment tested the effect of three different plasmids—pH317, pER62, and pMP46—on prion formation in both wild-type and Urm1 deletion mutants in the yeast Saccharomyces cerevisiae. The proposed hypothesis was over-expression of the Ure2 prion forming protein would increase the frequency of prion formation, as well as yield less sustainable prion amyloids (or prion aggregations) that are easier to cure. Another …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Identification Of Potential Lead Antimalarial Compounds From Marine Microbial Extracts, Abigail Carbonell

HIM 1990-2015

Malaria, caused by the parasite Plasmodium falciparum, has a long history as a global health threat. The vector-borne disease causes millions of deaths yearly, especially in developing countries with tropical climates that facilitate transmission. Compounding the problem is the emergence of drug-resistant strains due to overuse of outdated treatments. New compounds with antiplasmodial activity are needed to be developed as effective drugs against malaria. The hypothesis for this project is that marine microorganisms have a high likelihood of yielding novel antiplasmodial chemotypes because of their high diversity, which has not yet been explored for antimalarial development. In this project, microbes …

Elucidating The Role Of Dopamine In The Avoidance Response Of Caenorhabditis Elegans Utilizing Microfluidics, Patricia Frances Turturro

Theses Digitization Project

This study looks at dopamine modulation of ASH neurons, which are part of the avoidance circuit of C. elegans, and their response to water soluble stimuli. Because nematodes such as Caenorhabditis elegans utilize dopamine at the molecular and cellular level in much the same way as mammals, they offer researchers a unique opportunity to study the mechanisms of dopamine signaling.

The Role Of Cardiolipin In Iron Homeostasis And Glutathione Metabolism, Vinay A. Patil

Wayne State University Dissertations

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays a critical role in mitochondrial bioenergetic functions. Inside the mitochondria, CL is a critical target of mitochondrial generated reactive oxygen species (ROS) and regulates signaling events related to apoptosis and aging. CL deficiency causes perturbation of signaling pathways outside the mitochondria, including the PKC-Slt2 cell integrity pathway and the high osmolarity glycerol (HOG) pathway, and is a key player in the cross-talk between the mitochondria and the vacuole. The importance of CL in human health is underscored by the observation that perturbation of CL …

Defending Your Dna: Combating Threats Both Foreign And Domestic, James Mcisaac

Undergraduate Review

We are under constant assault from forces capable of damaging our DNA. The genetic code of DNA is made up of four nucleotides: adenine (A) which bonds with thymine (T) and guanine (G) which bonds with cytosine (C). If something happens to upset this normal pairing or the nucleotides themselves, our body must spring to action and respond to the damage. When damage to nucleotides prevents the normal replication machinery from doing its job, enzymes like the Y-family polymerases are called in. A special mechanism allows them to identify damage and insert the correct nucleotide or bypass the lesion to …

Screening Of Quantum Dots For Toxicity On The Growth And Viability Of Escherichia Coli, Jeremy Tharkur

Electronic Theses and Dissertations

Heavy metal (HM) containing quantum dots (Qdots) are increasingly used in commercial products due to their unique electronic, optoelectronic, optical and magnetic properties. Once disposed to the landfill, environmental weathering is likely to compromise HM Qdot integrity, leading to release of heavy metal ions. To minimize any negative environmental impact of HM Qdots, there is an increasing demand for developing HM free or environmentally-friendly surface modified HM Qdot alternatives. In this study, synthesis of HM free ZnS:Mn/ZnS and surface modified HM CdS:Mn/ZnS Qdots (using N-acetylcysteine, NAC, and Dihydrolipoic acid, DHLA) and their potential toxicity assessment using E. coli as a …

Is Breakdown Of Fatty Acid Peroxides Involved In The Induction Of Apolipoprotein A1?, Rajat Gupta

Electronic Theses and Dissertations

Over the past few years the number of deaths caused due to cardiovascular diseases has been increasing and is of major concern. In the United States, 75% of cardiovascular-related deaths have been attributed to atherosclerosis. Western diets containing large quantities of peroxidized lipids are considered atherogenic. Heated oil in the form of fried food brings high levels of peroxidized fat and its decomposition products in the diet. Peroxidized lipids are known to increase the susceptibility of serum lipoproteins to undergo oxidation, thereby contributing to the progression of atherosclerosis. The intestinal cells are responsible for the absorption of dietary fatty acid …

Identification Of Epithelial Stromal Interaction 1 And Epidermal Growth Factor Receptor As Novel Kruppel-Like Factor 8 Targets In Promoting Breast Cancer Progression, Tianshu Li

Electronic Theses and Dissertations

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 …

Polymeric Nanocarriers And Their Oral Inhalation Formulations For The Regional Delivery Of Nucleic Acids To The Lungs, Denise Santos Conti

Wayne State University Dissertations

Gene therapy has attracted attention in the fields of medicine, pharmacy, and bionanotechnology due to the potential for treating a large number of medically relevant diseases. Oral inhalation (OI) is a promising route for the administration of therapeutics, including small molecules and biomacromolecules, such as nucleotides, peptides, and proteins, to (locally) and through (systemically) the lungs. The use of OI is especially attractive for the delivery of nucleic acids as it provides a direct and non-invasive route for targeting the lungs. Pressurized metered-dose inhalers (pMDIs), are the most commonly used OI in treatment of lung diseases and are thus promising …

Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya

Dissertations

The ErbB-2 gene is amplified and the resulting protein product overexpressed in 15-30% of breast tumors, and associated with aggressive behavior and poor overall survival. Currently, there are two FDA approved therapies targeting ErbB-2 for the treatment of ErbB-2 positive breast cancer: trastuzumab, a humanized monoclonal antibody is directed against the extracellular domain of ErbB-2 and lapatinib, a dual EGFR/ErbB-2 tyrosine kinase inhibitor. Unfortunately, anti-ErbB-2 therapy resistance remains a major problem in metastatic breast cancer. Our data suggested that gene amplification or overexpression of ErbB-2 inhibits Notch-1 transcriptional activity and trastuzumab or lapatinib increased

Notch-1 transcriptional activity. Furthermore, Notch-1 is …

Significance Of Protein Interactions In Mediating Af9 Function, Bhavna Malik

Dissertations

Rearrangements of the MLL gene at chromosome band 11q23 have been associated with a heterogeneous group of lymphoid, myeloid and mixed lineage leukemias. MLL rearrangements occur approximately in 70% of infant leukemias and are also common in therapy-related leukemias where patients were previously treated with topoisomerase II inhibitors. Unfortunately, these patients have a poor prognosis. MLL gene rearrangements give rise to chimeric proteins that contain the N-terminal portion of MLL fused to the C-terminal portion of over 50 different fusion partners. The chimeric proteins cause constitutive expression of some MLL target genes such as HOXA9 and MEIS1, and enhanced proliferation …

Molecular Functions Of Mll Phd3 Binding To Its Ligands Cyp33 And H3k4me3, Gayathree Raman

Dissertations

Mixed Lineage Leukemia protein (MLL) is required for proper embryonic development, and hematopoiesis. It is a SET domain containing histone methyl transferase that trimethylates histone H3 on lysine 4 (H3K4Me3), a histone modification that correlates with active transcription. The 3rd PHD finger of MLL binds to H3K4me3. Thus MLL is a "writer" with an embedded "reader" for H3K4Me3. Cyp33 is another known ligand of MLL PHD3. Over expression of Cyp33 results in transcriptional repression of MLL target genes.

The aim of this study is to determine the biological function of MLL PHD3 binding to H3K4Me3 or Cyp33. Cyp33 binding to …

Extracellular Proteases Are Key Mediators Of Staphylococcus Aureus Virulence Via The Global Modulation Of Virulence-Determinant Stability, Stacey L. Kolar, J. Antonio Ibarra, Frances E. Rivera, Joe M. Mootz, Jessica E. Davenport, Stanley M. Stevens Jr., Alexander R. Horswill, Lindsey N. Shaw

Molecular Biosciences Faculty Publications

Staphylococcus aureus is a highly virulent and successful pathogen that causes a diverse array of diseases. Recently, an increase of severe infections in healthy subjects has been observed, caused by community-associated methicillin-resistant S. aureus (CA-MRSA). The reason for enhanced CA-MRSA virulence is unclear; however, work suggests that it results from hypersecretion of agr-regulated toxins, including secreted proteases. In this study, we explore the contribution of exo-proteases to CA-MRSA pathogenesis using a mutant lacking all 10 enzymes. We show that they are required for growth in peptide-rich environments, serum, in the presence of antimicrobial peptides (AMPs), and in human blood. …

A Transient Α-Helical Molecular Recognition Element In The Disordered N-Terminus Of The Sgs1 Helicase Is Critical For Chromosome Stability And Binding Of Top3/Rmi1, Jessica A. Kennedy, Gary W. Daughdrill, Kristina H. Schmidt

Molecular Biosciences Faculty Publications

The RecQ-like DNA helicase family is essential for the maintenance of genome stability in all organisms. Sgs1, a member of this family in Saccharomyces cerevisiae, regulates early and late steps of double-strand break repair by homologous recombination. Using nuclear magnetic resonance spectroscopy, we show that the N-terminal 125 residues of Sgs1 are disordered and contain a transient α-helix that extends from residue 25 to 38. Based on the residue-specific knowledge of transient secondary structure, we designed proline mutations to disrupt this α-helix and observed hypersensitivity to DNA damaging agents and increased frequency of genome rearrangements. In vitro binding assays …

Identification Of Proteins At Active, Stalled, And Collapsed Replication Forks Using Isolation Of Proteins On Nascent Dna (Ipond) Coupled With Mass Spectrometry, Bianca M. Sirbu, W. Hayes Mcdonald, Huzefa Dungrawala, Akosua Badu-Nkansah, Gina M. Kavanaugh, Yaoyi Chen, David L. Tabb, David Cortez

Molecular Biosciences Faculty Publications

Both DNA and chromatin need to be duplicated during each cell division cycle. Replication happens in the context of defects in the DNA template and other forms of replication stress that present challenges to both genetic and epigenetic inheritance. The replication machinery is highly regulated by replication stress responses to accomplish this goal. To identify important replication and stress response proteins, we combined isolation of proteins on nascent DNA (iPOND) with quantitative mass spectrometry. We identified 290 proteins enriched on newly replicated DNA at active, stalled, and collapsed replication forks. Approximately 16% of these proteins are known replication or DNA …