Biochemistry, Biophysics, and Structural Biology Commons^™

Stress Management In Cyst-Forming Free-Living Protists: Programmed Cell Death And/Or Encystment, Naveed Ahmed Khan, Junaid Iqbal, Ruqaiyyah Siddiqui

Department of Biological & Biomedical Sciences

In the face of harsh conditions and given a choice, a cell may (i) undergo programmed cell death, (ii) transform into a cancer cell, or (iii) enclose itself into a cyst form. In metazoans, the available evidence suggests that cellular machinery exists only to execute or avoid programmed cell death, while the ability to form a cyst was either lost or never developed. For cyst-forming free-living protists, here we pose the question whether the ability to encyst was gained at the expense of the programmed cell death or both functions coexist to counter unfavorable environmental conditions with mutually exclusive phenotypes.

Pcdh19 Expression In Normal And Regenerating Adult Zebrafish Retinas, Kristin N. Forkapa Ms.

Williams Honors College, Honors Research Projects

My Honors Research Project will test the function of the N-cadherin molecule on the zebrafish optic nerve regeneration. N-cadherin is a member of the cadherin superfamily. Cadherins are cell adhesion molecules important for animal development and maintenance of adult structures. Unlike mammals, fish and amphibians have the ability to regenerate their optic nerve after damages. Molecular mechanisms underlying the optic nerve regeneration are still under intense investigation. Studies in Dr. Liu’s laboratory showed that expression of several cadherins, including N-cadherin, was greatly increased during adult zebrafish optic nerve regeneration, suggesting that cadherins may be involved in the optic nerve regeneration …

Isolation Of Microbial Nrps And Pks Gene Clusters For Natural Product Isolation, Danielle N. O'Hara

Honors Theses

Greater than 99% of microbes living in the environment are uncultivable due to their complex nutrient and temperature requirements for growth. These microorganisms present a potential source of natural products that could be developed for biotechnological and pharmaceutical uses. Microorganisms with phosphopantetheinyl transferase (PPTase) activity are of high interest due to the role PPTase plays in activating non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters. These gene clusters produce multi-enzymatic, multi-domain megasynthases that produce complex natural products utilized by the host organism for selective advantages. This study isolated genomic DNA from soil samples collected from the University of …

Dna Aptamers Selected Against Wild-Type Helix 69 Ribosomal Rna And Their Implications In Combating Antibiotic Resistance, Sakina Miriam Hill

Wayne State University Dissertations

Outbreaks of advanced antibiotic-resistant strains of microbes have hastened the need to identify new viable molecular targets for the development of novel anti-infectives. For this purpose, helix 69 (H69, or m3a 19-nucleotide (nt) hairpin motif that is highly conserved throughout phylogeny and rich in modified nucleotides, including pseudouridine () and 3-methylpseudouridine (m3) was chosen as a potential target. Helix 69, which is located in domain IV of Escherichia coli 23S ribosomal RNA (rRNA), undergoes conformational changes when in close proximity to the decoding region of 16S rRNA and transfer RNAs (tRNAs) in the peptidyl-transferase center (PTC). Functionally, the exact biological …

Evaluation Of Intestinal Microbial Diversity And A New Antibiotic Regimen In Crohn's Disease Patients, Karel Alcedo

Electronic Theses and Dissertations

Crohn's disease (CD) is a chronic granulomatous inflammatory bowel disease involving Mycobacterium avium subspecies paratuberculosis (MAP). Other microorganisms such as adherent-invasive Escherichia coli (AIEC) have also been proposed in CD association. To date, only one study investigated both MAP and AIEC simultaneously using peripheral blood but not in affected intestinal tissues. A standardized and effective antibiotic therapy against MAP and/or AIEC is needed for better treatment. Three antibiotic drugs – Clarithromycin (CLA), Rifabutin (RIF), and Clofazimine (CLO) have been used to treat CD patients suspected with MAP infection. However, the outcome has been controversial. The treatment dosage is high, the …

Genetically-Programmed Suicide Of Adrenergic Cells In The Mouse Leads To Severe Left Ventricular Dysfunction, Impaired Weight Gain, And Symptoms Of Neurological Dysfunction, Aaron Owji

Electronic Theses and Dissertations

Phenylethanolamine-N-methyltransferase (Pnmt) catalyzes the conversion of noradrenaline to adrenaline and is the last enzyme in the catecholamine biosynthetic pathway. Pnmt serves as a marker for adrenergic cells, and lineage-tracing experiments have identified the embryonic heart and hindbrain region as the first sites of Pnmt expression in the mouse. Pnmt expression in the heart occurs before the adrenal glands have formed and prior to sympathetic innervation, suggesting that the heart is the first site of catecholamine production in the mouse. The function of these Pnmt+ cells in heart development remains unclear. In the present study, we test the hypothesis that (i) …

Differential Expression Of Proteins Involved In Vldl Trafficking Causes Reduced Vldl Secretion In Male Ames Dwarf Mice, Faisal Ahmed Moinuddin

Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) have been recorded as the number one cause of death worldwide, accounting for 32% of total deaths annually. More than two-thirds of all CVD cases are associated with atherosclerosis, which is the accumulation of fats and other substances causing plaque formation in the interior walls of major arteries. This leads to narrowing of the lumen and hardening of the arteries, ultimately resulting in angina, heart attack and/or stroke. Studies have shown that the pathogenesis of atherosclerosis and associated CVDs is strongly linked to elevated secretion of liver-specific lipoproteins called very-low-density-lipoprotein (VLDL). VLDLs are crucial lipoproteins responsible for …

Increased Body Mass Index May Lead To Hyperferritinemia Irrespective Of Body Iron Stores, Faiza Alam, Abdul Shakoor Memon, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Objective: Obesity causes subclinical inflammation which results in the secretion of various bioactive peptides that are key players in metabolic regulation of iron homeostasis. We sought to establish correlation of one such peptide (ferritin) with marker of subclinical inflammation (CRP) in various BMI.
Methods: Total 150 subjects between the ages of 20-60 years were included in the cross-sectional study conducted at Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, Pakistan. Body Mass Index (BMI) was calculated by weight (kg) /height (m(2)). The given values were used as reference for Group A: normal weight (18.0-22.9 kg/m2), Group B: overweight …

Prevalence Of Obesity And Overweight, Its Clinical Markers And Associated Factors In A High Risk South-Asian Population, Faridah Amin, Syeda Sadia Fatima, Najmul Islam, Anwar H. Gilani

Department of Biological & Biomedical Sciences

Background: Obesity is a global epidemic, which is a risk factor for cardiovascular diseases and metabolic abnormalities. It is measured by body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), body fat (BF) distribution and abdominal fat mass, each having its own merits and limitations. Variability in body composition between ethnic groups in South-Asians is significant and may not be truly reflected by BMI alone, which may result in misclassification. This study therefore, aims to determine the frequency of obesity, body fat composition and distribution, in a high risk population of an urban slum of Karachi, Pakistan. This survey …

How Pakistan's Media Spreads The Message About Reproductive And Sexual Health, Syed H. Abidi, Muhammad Raees, Syed Ali

Department of Biological & Biomedical Sciences

Abstract, issue, and pagination are not provided by the author/publisher

Interaction Forces And Reaction Kinetics Of Ligand-Cell Receptor Systems Using Atomic Force Microscopy, Anwesha Sarkar

Wayne State University Dissertations

Atomic Force Microscopy (AFM) provides superior imaging resolution and the ability to measure forces at the nanoscale. It is an important tool for studying a wide range of bio-molecular samples from proteins, DNA to living cells. We developed AFM measurement procedures to measure protein interactions on live cells at the single molecular level. These measurements can be interpreted by using proper statistical approaches and can yield important parameters about ligand-receptor interactions on live cells. However, the standard theory for analyzing rupture force data does not fit the experimental rupture force histograms. Most of the experimental measurements of rupture force data …

Cardiolipin Regulates Mitophagy Through The Pkc Pathway, Zheni Shen

Wayne State University Dissertations

Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is important for cardiovascular health. Perturbation of CL metabolism is implicated in cardiovascular disease (CVD). The link between CL and CVD may be explained by the physiological roles of CL in pathways that are cardioprotective, such as autophagy/mitophagy and the mitogen-activated protein kinase (MAPK) pathways. My dissertation work focuses on elucidating how CL influences mitophagy and MAPK pathways.

crd1Δ was synthetically lethal/sick with the general autophagy mutants atg8Δ, atg18Δ and mitophagy mutant atg32Δ, suggesting that autophagy/mitophagy may be deficient in cells lacking CL. Microscopic examination of mitophagy revealed decreased translocation of GFP-tagged …

Regulation Of Cxcr4 Intracellular Trafficking By Ubiquitin, Justine Elizabeth Kennedy

Dissertations

G protein-coupled receptor (GPCR) sorting into the degradative pathway is important for attenuating signaling. Perturbations in this process can manifest in a variety of diseases. Upon agonist activation of the chemokine receptor CXCR4, a GPCR, it is rapidly ubiquitinated, internalized to endosomes and sorted for degradation in lysosomes via the endosomal sorting complex required for transport (ESCRT) pathway. This process culminates in attenuation of CXCR4 signaling. CXCR4 overexpression and increased CXCR4 signaling have been associated with several pathologies including immune deficiency disorders and over 23 cancers. Yet the mechanisms governing the regulation of CXCR4 signaling remain elusive.

CXCR4 is ubiquitinated …

Eliminating Acute Myeloid Leukemia Stem Cells By Targeting The Niche Microenviromnent: Co-Inhibition Of Tnf/Il1- Jnk And Nf-Κb, Andrew Volk

Dissertations

Leukemia Stem Cells (LSCs) from Acute Myeloid Leukemia (AML) require the activity of the transcription factor NF-kB to maintain stemness and drive tumor formation. Blocking NF-kB can preferentially eliminate LSCs in vitro with minimal effects on healthy Hematopoietic Stem and Progenitor Cells (HSPCs), making NF-kB a compelling target for anti-leukemia therapies. However, blocking NF-kB in vivo can only extend survival for a short period of time before transplanted mice succumb to the disease. I propose this is due to components of the in vivo niche supporting LSC survival and compensating for the inhibition of NF-kB.

I observed patients with partially …

Application Of Lipid Styryl Dye For Staining Intracytoplasmic Membranes In Gram-Negative Bacteria, Theodore J. Hammer

Williams Honors College, Honors Research Projects

Intracytoplasmic membranes are structures that form within cells which help facilitate a variety of different metabolic processes. This feature of intracellular membranes makes them particularly valuable for studying compartmentalization and cell dynamics in bacteria. In the past, transmission electron microscopy has been the primary method for imaging bacteria with intracytoplasmic membranes. Because transmission electron microscopy takes images of a cell in fixed slices, it’s impossible to follow a cell’s growth and development over time. Fluorescence microscopy is a particularly effective method of measurement that can combat these issues when evaluating live bacterial cells. Here, standard biochemical laboratory procedures were used …

Inhibition Of Shp2 Suppresses Mutant Egfr-Induced Lung Tumors In Transgenic Mouse Model Of Lung Adenocarcinoma, Valentina E. Schneeberger, Yuan Ren, Noreen Luetteke, Qingling Huang, Liwei Chen, Harshani R. Lawrence, Nicholas J. Lawrence, Eric B. Haura, John M. Koomen, Domenico Coppola, Jie Wu

Molecular Biosciences Faculty Publications

Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless, it is unclear if Shp2 is activated by oncogenic EGFR mutants in lung carcinoma or if inhibiting the Shp2 PTP activity can suppress EGFR mutant-induced lung adenocarcinoma. Here, we generated transgenic mice containing a doxycycline (Dox)-inducible PTP-defective Shp2 mutant (tetO-Shp2CSDA). Using the rat Clara …

The Νsaα Specific Lipoprotein Like Cluster (Lpl) Of S. Aureus Usa300 Contributes To Immune Stimulation And Invasion In Human Cells, Minh Thu Nguyen, Beatrice Kraft, Wenqi Yu, Dogan Doruk Demicrioglu, Tobias Hertlein, Marc Burian, Mathias Schmaler, Klaus Boller, Isabelle Bekeredjian-Ding, Knut Ohlsen, Birgit Schittek, Friedrich Götz

Molecular Biosciences Faculty Publications

All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted …

Regulation Of Vldl Trafficking By Orp 10, Philip A. Wessels

HIM 1990-2015

Of the challenges facing the improvement of human health, none has taken the forefront quite like the endeavor to discover novel treatments for heart disease. As heart disease has now become the leading cause of death throughout the world [1], the medical community has made incredible strides in the mission to treat atherosclerosis which is the major contributor to heart disease. Very Low Density Lipoproteins (VLDL) are secreted by the liver and subsequently converted to Low Density Lipoproteins (LDL). Many factors contribute to the narrowing of the arterial walls, however oxidized LDL is the main factor that leads to the …

Conservation Of Lipid Storage Droplet Proteins In Evolution Of Animalia, Jacob D. Bowman

Undergraduate Honors Thesis Projects

Lipolysis is a conserved pathway used by organisms for the mobilization of fatty acid (FA) out of triacylglycerol (TAG). Neutral lipids are stored in lipid-storage droplets (LSD) which are in nearly every cell of an organism. LSDs are the location of lipolysis. Perilipin proteins are lipid-droplet associated proteins. Perilipins interact with other proteins such as ATGL that breaks down TAG into FA and DAG. Because of its conservation as a whole system, this suggests that proteins of the same pathway are evolving together. This present study traces the evolutionary history of lipolysis-related proteins amongst individual organisms and classes of organisms …

Transfer Rna Comes Of Age, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

"The year the journal RNA was founded was slated by some in scientific publishing to be the year that one particular type of RNA's run in the spotlight would end. In 1995 I had recently started as a post-doc with Dieter Söll at Yale when he came into the lab to solemnly inform us all that an editor at a certain (S)cience journal had just told him “we won't be publishing any more tRNA papers.” For a post-doc who had migrated across the Atlantic for the sole purpose of furthering his career by working on tRNA this was not great …