Biochemistry, Biophysics, and Structural Biology Commons^™

Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers

Electronic Thesis and Dissertation Repository

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations & Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

Cellular Mechanisms Of Ionoregulation In The Gill Of Japanese Medaka And Rainbow Trout, Rebecca Jo Bollinger

Graduate Theses and Dissertations

Euryhaline fishes are capable of adapting to a wide range of salinities such as freshwater, brackish water or seawater. Through the combined effort of the gill, kidney and intestine, they are able to osmoregulate to maintain a constant internal hydromineral balance. As the gill is in direct contact with the external environment, it is continuously working to maintain ion and acid/base balance, gas exchange and eliminate nitrogenous waste. Fish in freshwater are subjected to osmotic water gain and diffusional ion loss across the gill and experience the opposite in seawater. Therefore, the gill exhibits extreme plasticity when experiencing a change …

Removal Of Endocrine Disrupting Compounds Using Membrane Bioreactor, Mohanad Ali Abdulsahib Kamaz

Graduate Theses and Dissertations

The presence of endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhAC) such as pesticides, personal care products, antibiotics and pharmaceutical compounds, in sewage, industrial, and domestic waters has extensively become the major concern for health and environmental organizations. These compounds have the ability to interact with mammalian endocrine system and disrupting their functions. The traditional activated sludge processes are designed to degrade solids, organic carbon and nitrogen loading. Although several treatment steps in a wastewater treatment plant can contribute to partial removal of EDCs, effective removal has been a challenge due to their resistant chemical and biological degradation and …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

Dissertations & Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of histone …

The Chondrocyte Channelome: A Novel Ion Channel Candidate In The Pathogenesis Of Pectus Deformities, Anthony J. Asmar

Biological Sciences Theses & Dissertations

Costal cartilage is a type of rod-like hyaline cartilage connecting the ribs to the sternum. The chest wall deformities pectus excavatum (PE) and pectus carinatum (PC) involve displacement of the sternum causing a depression or protrusion of the chest. There is little knowledge about costal cartilage and pectus deformities with much of its understanding based on assumptions from articular cartilage. Chondrocytes are subjected to a constantly changing environment with fluctuations in pH and osmolarity. Ion channels detect these changes and in turn regulate proliferation, differentiation, and extracellular matrix production. Using ion channel qPCR arrays, we produced expression profiles for normal, …

The Mechanistic Requirements Of Passive H+ Import Through The Na, K-Atpase, Kevin S. Stanley

Theses and Dissertations

This work focuses on the elucidation of the mechanism of passive proton import through the Na,K-ATPase. This enzyme uses the energy in ATP hydrolysis to exchange three intracellular Na+ for two extracellular K+ to maintain ion gradients within the cell, and while in the absence of physiological external Na+ and K+, the phosphorylated externally open (E2P) conformation passively imports protons, generating an inward current (IH). Chapter one reports on the effects of intracellular cations and nucleotides to shift the Na,K-ATPase into the E2P conformation. We identified that a combination of either internal Na+ and ATP or K+ and Pi. In …

Divergent Responses Of Larval And Juvenile Blue Mussels To Low Salinity Exposure, Melissa A. May

Electronic Theses and Dissertations

In this study, we compared the osmotic stress response of larval and juvenile blue mussels (Mytilus edulis) at the transcriptomic, metabolomic, and whole organism levels. Blue mussels inhabit coastal areas, where they face climate-induced reductions in nearshore salinity. Despite their ecological and economic importance, scientists do not fully understand the underlying transcriptomic and cellular mechanisms of the osmotic stress response in blue mussels or how the ability to respond to stress changes throughout development. Blue mussels spend the first weeks of life developing through several larval stages in the plankton. These early life history stages are more vulnerable …

Characterization Of Andrenocortical Tissue Morphology, Histology, And Steroid Synthesis Among Finetooth (Carcharhinus Isodon), Blacktip (Carcharhinus Limbatus), Atlantic Sharpnose (Rhizoprionodon Terraenovae), And Bonnethead (Sphyrna Tiburo) Sharks, Danielle Elizabeth Bailey

Master's Theses

Adrenocortical (interrenal) tissue is composed of steroidogenic cells that produce corticosteroids involved in the stress response and hydromineral balance. Previous research characterizing the elasmobranch interrenal suggests that the number of interrenal bodies that produce the single primary corticosteroid, 1a-hydroxycorticosterone (1a-OHB), varies among species. However, potential species-specific differences in the amount of interrenal tissue and major steroid products produced have been understudied. To address this critical gap in our understanding of elasmobranch biology, this study examined interrenal morphology, cell structure, steroidogenic enzyme distribution (3bHSD), and steroid production in four shark species: Finetooth Carcharhinus isodon, Blacktip Carcharhinus limbatus, Atlantic Sharpnose …

Role Of Alström Syndrome 1 (Alms1) In Nkcc2 Endocytosis, Thick Ascending Limb Function, Blood Pressure Regulation And Metabolic Function, Ankita Bachhawat Jaykumar

Wayne State University Dissertations

NaCl absorption by the Thick Ascending Limb (TAL) is mediated by the apical Na+/K+/2Cl- co-transporter, NKCC2. Increased NKCC2 activity and apical trafficking are associated to salt sensitive hypertension in rodents and humans. NKCC2 endocytosis is important for maintaining surface NKCC2 such that blocking NKCC2 endocytosis increased NKCC2 surface abundance and NKCC2-mediated NaCl reabsorption. Despite its importance, NKCC2 endocytosis has been poorly studied and a part of the reason may be attributed to the lack of availability of methods with good time resolution. Hence, we developed a method to image apical NKCC2 to monitor its endocytosis in real-time by Total Internal …

The Role Of Oxidation-Sensitive Nociception And Epigenetics In Endometriosis-Associated Pain, Kristeena Ray Wright

Theses, Dissertations and Capstones

Endometriosis is an enigmatic disease that is associated with severe symptoms and consequences such as total hysterectomy. Upwards of 10% of women of reproductive age have endometriosis, most of whom are afflicted with chronic pelvic pain and/or infertility. Despite many treatment options available to endometriosis patients, there is no cure for this condition and recurrence of symptoms is extremely common. In CHAPTER 1, we describe the mechanisms involved in endometriotic pain and the currently available treatment strategies. Our laboratory has provided evidence for the role of oxidative stress in the etiology of endometriosis and its associated pain. In this dissertation …

Rad Gtpase: Identification Of Novel Regulatory Mechanisms And A New Function In Modulation Of Bone Density And Marrow Adiposity, Catherine Nicole Kaminski Withers

Theses and Dissertations--Molecular and Cellular Biochemistry

The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates voltage-dependent calcium channel function. Given its expression in both excitable and non-excitable cell types, the control mechanisms for Rad regulation and the potential for novel functions for Rad beyond calcium channel modulation are open questions. Here we report a novel interaction between Rad and Enigma, a scaffolding protein that also binds to the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1). Overexpression of Smurf1, but not …

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Identification Of Expression And Function Of The Glucagon-Like Peptide-1 Receptor In Gastrointestinal Smooth Muscle, Alexander T. May

Theses and Dissertations

In response to ingestion of nutrients, enteroendocrine L cells secrete the incretin hormone, glucagon-like peptide-1 (GLP-1), to enhance glucose-dependent insulin release. Therapies related to GLP-1 are approved for type 2 diabetes. The GLP-1 receptor (GLP-1R) is expressed in cells of the gastrointestinal tract and elsewhere. In pancreatic beta cells, GLP-1R are coupled to the Gs/cAMP/PKA pathway. The expression and function of GLP-1R in gastrointestinal smooth muscle are not known. Aim. To test the hypothesis that GLP-1 regulates smooth muscle function by acting on GLP-1R expressed on smooth muscle. Methods. Smooth muscle cells (SMC) were isolated and cultured. Expression of GLP-1R …