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Browsing by Subject "Department of Integrative Biology and Physiology"

Now showing 1 - 6 of 6
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    Chronic stress shifts the phase of adrenal clock gene rhythms
    (2012-04-18) Karsten, Carley
    The hypothalamic-pituitary-adrenal (HPA) axis is characterized by a robust circadian rhythm in adrenal secretion of glucocorticoids (GC), driven in part by adrenal clock genes. The GC rhythm serves to synchronize other peripheral clocks and to maintain homeostasis. Mechanisms for entrainment of the adrenal clock remain unclear. Since stress activates the HPA axis, it is possible that entrainment of the adrenal clock and, concomitantly, glucocorticoid rhythms would be susceptible to stress. The present experiment aimed to test the hypothesis that chronic stress can alter adrenal circadian rhythms. The model of chronic subordinate stress used, consisting of daily exposure to a dominant mouse, has shown a robust metabolic phenotype in previous studies. Per2::Luc mice were used to assess rhythmic expression of the clock gene Per2. Per2::Luc mice express a luciferase reporter gene driven by the Per2 promoter, so that light output measured in tissue explants reflects PER2 expression.
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    Distribution of Renin in Rat Adipose Tissue
    (2009-04-08) Newman, Krista M.
    Obesity and hypertension are two leading international health problems of particular concern within the United States. Obesity is often a precursor to high blood pressure which is regulated in part by the renin angiotensin system (RAS). Recent studies have also implicated the RAS as a regulator of body adiposity in human and rodent models. Adipose (fat) tissue has been shown to display a fully functional RAS with the discovery of mRNA for renin, angiotensinogen, angiotensin converting enzyme (ACE) and angiotensin II receptor expression in adipocytes (fat cells). However, it is not yet known where renin is distributed within fat tissue. The aim of this study is to analyze the distribution of renin in components of fat tissue.
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    Engineering Cardiac Tissue
    (2010-04-21) Gorecki, Elizabeth
    There are currently 5.7 million Americans living with heart failure and 670,000 new cases diagnosed each year. One reason for heart failure is weakened, dead or scarred tissue on the heart as a result of myocardial infarction. Heart transplant could be a useful therapy, but the effects of rejection, the need to take immunosuppressant drugs and the dire lack of available tissue are all deterrents to transplantation. A solution to some patient’s transplant needs lies in the creation of a tissue graft that could be placed over the injured heart tissue to help repair the patient’s original heart. A graft that avoids rejection by the patient’s immune system would greatly enhance the healing process. Bioartificial tissues created with a patient’s own cells are a solution to creating a graft of heart tissue that would avoid rejection. There are many artificial products commercially available that may serve as a scaffold for tissue growth. The Taylor lab has developed a method to obtain scaffold, called extracellular matrix, from biological tissues by perfusion with a detergent to remove cellular constituents. I have been working with members of the Taylor lab to compare the growth of cardiac cells on this extracellular matrix to growth on an artificial collagen sponge, which may provide insight into the effects of native verses non-native scaffold composition on the growth of cells in vitro. This insight could help to create cardiac patches that may help to alleviate suffering and loss of life due to heart failure.
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    Methods for Replicating P188-Induced Sarcolemma Stabilization in Dystrophin-Deficient Skeletal Muscle Based on Length Kinetics
    (2024-08-30) Lie, Ethan; Quick, Joseph; Hahn, Dongwoo
    Duchenne Muscular Dystrophy (DMD) is a severe muscle-wasting disease brought about by a genetic mutation that prevents the synthesis of dystrophin, a protein necessary for myofiber cell membrane integrity. There is no known method capable of curing DMD, although many therapies have been developed to curb its symptoms and delay its progression. One such solution is the application of synthetic copolymers as a substitute for dystrophin. A recent study investigated the therapeutic possibilities of poloxamer 188 (P188), a linear, amphiphilic triblock copolymer, by observing twitch kinetics of sarcomere length in vitro (Hahn et al., 2023). They found that P188 can effectively improve contractility in dystrophic skeletal muscle. Our experiment initially aimed to follow up on this study by using a similar approach for testing bottlebrush copolymers. However, when practicing the procedure with P188, we found it difficult to replicate Hahn et al.’s results. Hence, we adjusted the methodology in various ways to determine the most accurate and precise technique before moving on to new experimental conditions. We measured length kinetics from different regions of a myofiber and used centrifugation to shorten the procedure length. Because Hahn et al. used Fura-2AM as a calcium indicator, we also tried implementing it in attempt to more accurately follow their procedure. We found that using centrifugation and measuring contractility from the myofiber’s center produces results closest to their study. Despite this, our study showed a less marked improvement in myofiber peak contraction height. Further refinement of our methods is required to improve our technique’s reliability and efficiency before we can proceed to trials with bottlebrush copolymers.
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    Quantum Mechanics/Molecular Mechanics Optimizations of Zinc Metallo- β-Lactamase Inhibitor
    (2021) Jeffy, Jeffy; Dodda, Vasudeva Reddy; Sham, Yuk; Muthyala, Ramaiah
    Metallo-β-lactamase (MBL) is a zinc-dependent enzyme that inactivates a wide range of β-lactam antibiotics. Currently, there is no FDA-approved inhibitor for overcoming MBL causing drug resistance. The Sham Lab has recently discovered analogs of 8-hydroxyquinoline (8HQ) as a low-cytotoxic, nanomolar MBL inhibitor against NDM-1 and VIM-2. The goal of the project is to apply the quantum mechanics/molecular mechanics (QM/MM) method to explore the effect of aromatic substitutions and electronic polarization on binding affinity. Additionally, in-silico combinatorial library design will afford a high throughput discovery platform to identify and optimize novel 8HQ for overcoming the antibiotic drug resistance effect of MBL
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    Thermal Comfort Ratings and Their Relationship to Body Sweat Rates and Skin Wetness
    (2009-04-08) Fink, Birgit
    Astronauts manually regulate the water temperature flowing through their cooling garments while engaged in space walks; therefore, a better understanding of the relationship between subjective perception of thermal comfort and physiological factors is crucial for effective and safe functioning in space. Subjective perception and internal/external body status are not always highly correlated. At thermal extremes, individuals become less accurate in their subjective thermal experiences, for example, some people in hypothermia feel that they are extremely hot, those with high fever report feeling very cold and begin shivering. In this study, the goal was to assess the individual’s subjective thermal experience as related to body skin wetness and sweat rates on different body zones and in different types of cooling garments. The individual’s subjective experience was considered to be an important component in identifying the optimal features of different cooling garments.