Digital Commons Network^™

Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth

Wayne State University Dissertations

Cooperative reactivity of bimettalics can be is observed in many different areas of chemistry and have been increasingly investigated because of the advantageous reactivity when compared to the corresponding mononuclear systems. The focus of my dissertation is on (1) investigation of the homobimetallic cooperativity in lactide polymerization catalysis; (2) investigation of the heterobimetallic cooperativity in the biomimetic studies of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme in order to make a functional model of its active site.

Three new main group bis(alkoxide) complexes Mg(OR)2(THF)2, Zn(Cl)(μ2-OR)2Li(THF) and In(OR)2(μ2-Cl)2Li(THF)2 featuring bulky alkoxide [OCtBu2Ph] were synthesized serve as metal alkoxide precursors for bimetallic lactide …

The Role Of Alström Syndrome 1 (Alms1) In Hypertension, Salt Sensitivity And Metabolic Syndrome, Keyona Nicole King-Medina

Wayne State University Dissertations

In humans, inactivating mutations in the Alström syndrome 1 (ALMS1) gene cause obesity, insulin resistance and hypertension (metabolic syndrome). More so, SNPs in the ALMS1 gene have been associated with kidney disease and cardiovascular disease. The

mechanisms causing these alterations are unclear. We recently found that the ALMS1 is expressed in the kidney thick ascending limb (TAL) where it mediates endocytosis of the renal Na/K/2Cl cotransporter termed NKCC2. To study the role of ALMS1 in renal

physiology we generated ALMS1 knockout (KO) rats in a Dahl salt-sensitive genetic background via zinc-finger nuclease targeting. We previously found that the amount of …

Methionine Sulfoximine: A Novel Anti Inflammatory Agent, Tyler Peters

Wayne State University Dissertations

ABSTRACT

METHIONINE SULFOXIMINE: A NOVEL ANTI-INFLAMMATORY AGENT

by

TYLER J. PETERS

October 2018

Advisor: William Brusilow

Major: Biochemistry and Molecular Biology

Degree: Doctor of Philosophy

The glutamine synthetase inhibitor methionine sulfoximine (MSO), shown previously to prevent death caused by an inflammatory liver response in mice, was tested on in vitro production of cytokines by mouse peritoneal macrophages triggered with lipopolysaccharide (LPS). MSO significantly reduced the production of Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha (TNFα) at 4 and 6 hours after LPS-treatment. This reduction did not result from decreased transcription of IL-6 and TNFα genes, and therefore appeared to …

Chchd10, A Novel Bi-Organellar Regulator Of Cellular Metabolism: Implications In Neurodegeneration, Neeraja Purandare

Wayne State University Dissertations

CHCHD10 (Coiled-coil Helix Coiled-coil Helix Domain containing protein 10) and MNRR1 (Mitochondrial Nuclear Retrograde Regulator 1, also known as CHCHD2), have been shown by us to be stress regulators of mitochondrial function that act both in the mitochondria and in the nucleus. Both are members of the twin CX9C family, but CHCHD10 in particular, has been found in mutant form to be linked to a myriad of neurodegenerative conditions. In mitochondria, both activate cytochrome c oxidase (COX) whereas in the nucleus, both act as transcription regulators of a subset of genes that contain a 13-bp sequence termed as the oxygen …

The Exploration Of Characteristics Of Akkermansia Muciniphila, And Evaluation Of Its Probiotic Effects On Diabetes By Using C57bl/6 Mouse Model, Jiangqi Tang

Wayne State University Dissertations

THE EXPLORATION OF CHARACTERISTICS OF AKKERMANSIA MUCINIPHILA, AND EVALUATION OF ITS PROBIOTIC EFFECTS ON DIABETES BY USING C57BL/6 MOUSE MODEL

by

JIANGQI TANG

December 2018

Advisor: Dr. Kai-Lin Catherine Jen

Major: Nutrition and food science

Degree: Doctor of Philosophy

The prevalence of type 2 diabetes (T2D) is increasing continuously worldwide. The incidence of T2D is highly correlated with poor diet, physical inactivity and occurrence of obesity. Recent studies reported possible interaction between T2D and gut microbiome, which revealed different composition of gut microbiome. A specific strain Akkermansia muciniphila (A. muciniphila) was reported with significantly lower abundance even prior to the …

Qualitative Change Detection Approach For Preventive Therapies, Cristina Mitrea

Wayne State University Dissertations

Currently, most diseases are diagnosed only after disease-associated changes have occurred. In this PhD dissertation, we propose a paradigm shift from treating the disease to maintaining the healthy state. The proposed approach is able to identify when systemic qualitative changes in biological systems happen, thus opening the possibility of therapeutic interventions before the occurrence of symptoms. The change detection method exploits knowledge from biological networks and longitudinal data using a system impact analysis approach. This approach is validated on eight datasets, for seven different model organisms and eight biological phenomena. On these data, our proposed method performs well, consistently identifying …