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The Role Of Biomaterial Substrate In Stem Cell Fate Determination, Zhenjie Liu

Wayne State University Dissertations

The physical cues, which included topography, stiffness, and mechanical forces, can influence the stem cell renewal, differentiation, and maturation in vivo and in vitro. The nano-topography of the ECM can stimulate the neural differentiation of the stem cells, while the micro-topography of the ECM can guide the neurite outgrowth. However, the role and functional size of the micro- and nano-topography in the stem cell fate determination is not clear yet. To study this aim, two biomaterial based aligned fiber platforms (ACMFP and ASMFP) were designed, fabrication and evaluated to cover the micro-, submicro-, and nano-fiber topography, which used to study …

A Multispecies Perspective Into Dietary Genetic Adaptations And Ancient Migration In The Peruvian Andes, Kelsey Jorgensen

Wayne State University Dissertations

Successful adaptation to the high-elevation Andes would have required both cultural and biological adaptations by early human populations. These past adaptations continue to shape the evolutionary outcomes of both humans and non-human species today. A multispecies perspective was used to examine how humans and non-human creatures, specifically insects, were shaped by past human adaptations. This dissertation asked two primary questions: 1) Given the importance and evolutionary history of potato consumption in the Peruvian Andes, is a genetic adaptation to better digest potato starch detectable in present-day Peruvians? and 2) Using the Andean Potato Weevil (APW) phylogeny as a proxy, what …

Identifying Biologically Relevant Mechanisms And Biomarkers Using Novel Bioinformatics Methods, Samer Hanoudi

Wayne State University Dissertations

There is a tremendous need to analyze molecular and patient clinical data to identify biomarkers, biological mechanisms, or to simply classify samples accurately. Issues such as: i) limited tools to diagnose many diseases, ii) not considering biological interactions, or iii) damaged DNA samples could cause a challenge in identifying valuable insights. In this work, I try to address these issues by developing different bioinformatic frameworks.First, I present three frameworks to identify i) Sarcoidosis biomarkers, ii) Tuberculosis biomarkers and iii) Cystic fibrosis (CF) biomarkers. I identified Sarcoidosis biomarkers I applied them to classify Sarcoidosis samples from non-Sarcoidosis (healthy controls, Tuberculosis, and …

The Probiotic Effect Of Clostridium Cochlearium Is Associated With Significant Change In Short-Chain Fatty Acid Metabolism And Gut Microbiota, Qing Ai

Wayne State University Dissertations

The prevalence of obesity is rising steadily across the world, which increases the risk of many metabolic diseases and life-threatening illnesses. A specific strain, Clostridium cochlearium (C. cochlearium), reported as a butyrate producer, could have potential probiotic effects against obesity. The objective of this study was to evaluate the effects of dietary supplementation of C. cochlearium on a high-fat diet-induced obese (DIO) mouse model. The 16S rRNA sequencing of mice gut microbiome was performed at the end of the experimental period to identify the changes in gut microbial composition, investigate possible functional genes, and elucidate potential mechanisms. Thirty-six C57BL/6 6-8 …

Health And Nutrition Status Of Hemodialysis Patients During Ramadan In Saudi Arabia., Bayan Mansour Tashkandi

Wayne State University Dissertations

During Ramadan R month, Muslims abstain from eating, drinking, and medication from sunrise to sunset, and this causes some changes in their lifestyle and often eating habits (quantity and quality). These changes could lead to affect their health and nutritional status. Among Hemodialysis (HD) patients, malnutrition is common, and it is associated with mortality. Some HD patients opt to fast R which could have an impact on their nutritional and health status. Thus, the primary objective of this study was to document nutritional changes before, during, and after Ramadan on biochemical and health parameters in HD patients. A prospective cohort …

Substrate Profiling Of The Epigenetic Erasers Hdac1 And Lsd1, Herath Mudiyansela Gedara Kavinda Eranga Herath

Wayne State University Dissertations

Regulators of chromatin structure have emerged as a key driver of transcriptional responses inside the cell. Two such groups of regulators, histone writers and erasers; the proteins, that add or remove histone post translational modifications (PTMs), have become the central players in chromatin structure. Thus, the aberrant expression of writers and erasures is a hallmark in human diseases. For example, overexpression of the erasures histone deacetylase1 (HDAC1) and lysine specific demethylase1 (LSD1) had been reported in many cancers. Currently, HDAC inhibitors have been used successfully for cancer treatment and several inhibitors targeting LSD1 are in clinical trial. To date, apart …

Therapeutic Dual-Targeting Of Cytosolic And Mitochondrial One-Carbon Metabolism, Aamod Sanjeev Dekhne

Wayne State University Dissertations

One-carbon metabolism (1CM) is compartmentalized in the mitochondria and cytosol and generates a host of metabolites critical to tumor propagation. Although drug-targeting of cytosolic 1CM remains a clinically-relevant mainstay, development of clinically-useful agents targeting mitochondrial 1CM remains elusive. Of particular pharmacological interest is the mitochondrial 1CM enzyme, serine hydroxymethyltransferase2 (SHMT2). SHMT2 expression correlates with the oncogenic phenotype in lung, colon, breast, glioma, and liver cancer and, overall, is the fifth-most differentially expressed metabolic enzyme in cancer cell versus normal tissue. Despite the unequivocal oncogenic importance and therapeutic potential of SHMT2, there are no clinically relevant (i.e. active in vivo) inhibitors …

Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, Aktham H. Mestareehi

Wayne State University Dissertations

Diabetes is a group of metabolic diseases characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. Diabetes is associated with damage, dysfunction, and failure of various organs, such as the eyes, heart, kid-neys, and brain. Diabetes is mainly classified into type 1 (T1DM) and type 2 diabetes (T2D). Diabetes affects more than 34 million people in the USA (about 1 in 10) and more than 90% of diabetic patients have type 2 diabetes (T2D). Insulin resistance is a main characteristic feature of type 2 diabetes. Skeletal muscle insulin resistance is con-sidered to be the primary defect …

Characterization Of Clostridium Cochlearium As A Potential Probiotic For Obesity Management, Paba Edirisuriya

Wayne State University Dissertations

ABSTRACTCHARACTERIZATION OF CLOSTRIDIUM COCHLEARIUM AS A POTENTIAL PROBIOTIC FOR OBESITY MANAGEMENT

ByPABA EDIRISURIYA MAY 2021 Advisor: Dr. Kequan Zhou Major: Nutrition and food science Degree: Doctor of Philosophy Emerging evidence indicates that manipulation of gut microflora is a potential therapeutic approach for managing obesity. Probiotic effects on host weight reduction have repeatedly been revealed through previous studies. Clostridium cochlearium is a butyrate-producing, spore-forming bacteria that have been reported to present in the mammalian gut. Our simulated Invitro digestion model revealed that C. cochlearium could survive in the unfavorable conditions of the human gastrointestinal tract, including low pH (pH2), high bile …

Cardio-Renal Mechanisms Of Fructose-Induced Salt-Sensitive Hypertension, Peter Eric Levanovich

Wayne State University Dissertations

Dietary consumption of fructose facilitates increased intestinal fluid absorption and renal sodium reabsorption, thereby increasing fluid retention. The net result of this is a sustained increased in extracellular fluid volume that leads to states of hypervolemia and subsequent hypertension. Simultaneously, arterial pressure is being elevated by increased autonomic drive stemming from the sympathetic nervous system and various other endovascular proteins that induce vasoconstriction. Under these conditions, the addition of high dietary sodium promotes hypertension prior to the development of significant metabolic disturbances; the subtlety of which may go unnoticed by patients for prolonged periods. While much is understood regarding the …

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

Mnrr1: Understanding The Role Of A Novel Mitochondrial-Nuclear Regulator, Stephanie L. Gladyck

Wayne State University Dissertations

Mitochondria are complex organelles that generate most of the energy required to sustain life and function in metabolic and signaling pathways required to maintain cellular homeostasis. MNRR1 (mitochondrial nuclear retrograde regulator 1 or CHCHD2) is a small, bi-organellar twin CX9C protein that is emerging as an important regulator of mitochondrial function, apoptosis, and cellular stress by participating in mitochondrial-nuclear crosstalk. Our lab has previously shown that in the mitochondria, MNRR1 regulates complex IV (Cytochrome c oxidase or COX) and is able to finetune the oxidase function through phosphorylation status. We have also shown that during stress, mitochondrial MNRR1 levels deplete, …

Modulation Of Pharyngeal Health In Bacterial Diet-Dependent Survival, Deniz Sifoglu

Wayne State University Dissertations

ABSTRACT

MODULATION OF PHARYNGEAL HEALTH IN BACTERIAL DIET-DEPENDENT SURVIVAL

by

DENIZ SIFOGLU

August 2021

Advisor: Dr. Joy Alcedo Major: Biological Sciences Degree: Doctor of Philosophy Both diet and bacterial microbiome modulate insulin signaling, which regulates key physiological processes that are important for survival. However, the mechanisms through which diet and the microbiome modulate insulin signaling remain unclear. To understand these mechanisms, I turned to the nematode worm C. elegans, whose diet consists of different types of bacteria. Like humans and other animals, C. elegans has to modulate its responses to its diet and to bacteria to optimize its survival. Because …