Medicine and Health Sciences Commons^™

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations & Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …

Self And Microbiota-Derived Epitopes Induce Cd4⁺ T Cell Anergy And Conversion Into Cd4⁺Foxp3⁺ Regulatory Cells, Michal P. Kuczma, Edyta A. Szurek, Anna Cebula, Vu L. Ngo, Maciej Pietrzak, Piotr Kraj, Timothy L. Denning, Leszek Ignatowicz

Biological Sciences Faculty Publications

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4⁺CD44⁺Foxp3⁻CD73⁺FR4⁺ anergic (Tan) cells expands the CD4⁺Foxp3⁺ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila …

Elucidating The Effects Of Glucose Toxicity On Tauopathy And Aging, Lukas Fluitt

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Diabetes patients are at higher risk of contracting an age-related neurodegenerative disease such as Alzheimer’s disease (AD). However, the mechanisms which link these diseases are poorly understood. We hypothesize that glucose and elevated levels of the glycolysis by product advanced glycation end-products (AGEs), may be involved. AGEs accumulate with age and are elevated in both diabetic and AD patients. Diabetes is a metabolic disorder for which consumption of sugar-rich diets is a major risk factor and is central to etiology in the vast majority of cases.

We show that transgenic C. elegans expressing wild type (WT) human tau fed a …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …

Hdl Subclass Proteomic Analysis And Functional Implication Of Protein Dynamic Change During Hdl Maturation, Yuling Zhang, Scott M. Gordon, Hang Xi, Seungbum Choi, Merlin Abner Paz, Runlu Sun, William Yang, Jason Saredy, Mohsin Khan, Alan Thomas Remaley, Jing-Feng Wang, Xiaofeng Yang, Hong Wang

Saha Cardiovascular Research Center Faculty Publications

Recent clinical trials reported that increasing high-density lipoprotein-cholesterol (HDL-C) levels does not improve cardiovascular outcomes. We hypothesize that HDL proteome dynamics determine HDL cardioprotective functions. In this study, we characterized proteome profiles in HDL subclasses and established their functional connection. Mouse plasma was fractionized by fast protein liquid chromatography, examined for protein, cholesterial, phospholipid and trigliceride content. Small, medium and large (S/M/L)-HDL subclasseses were collected for proteomic analysis by mass spectrometry. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL) were identified and grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). Eleven …

Exercise To The Rescue: An Analysis Of Altered Metabolic Gene Regulation Post-Exercise In Lean And Obese Individuals, Brandon Mudd

Mahurin Honors College Capstone Experience/Thesis Projects

The skeletal muscle of obese individuals exhibits a depressed ability to metabolize fats. Exercise training is thought to rescue this dampened ability to metabolize fats; mediated by a coordinated increase in the expression of a network of genes that regulate metabolism and fuel utilization. The purpose of this study is to determine the exercise-induced regulation of metabolically important genes in lean and obese individuals. Muscle biopsies (one pre-exercise/baseline and one immediately post-exercise) were obtained from 4 lean (BF% 24.4 ± 5.5; 23.5 yrs ± 1.9) and 13 obese (BF% 39.7 ± 2.4; 26.1 yrs ± 2.3), age-matched, relatively young subjects, …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations & Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …