Systems and Integrative Physiology Commons^™

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

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

Dissertations and 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 …

Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, …

Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in …

Co-Modulation Masking Release Begins In The Auditory Periphery, Kareem R. Hussein, Agudemu Borjigan, Mark Sayles

The Summer Undergraduate Research Fellowship (SURF) Symposium

Understanding speech in noisy environments can be difficult, especially for people with hearing loss. The background noise can cover up the sounds of interest. Normally, the auditory system works to alleviate this problem by tagging and then cancelling the noise. Our experiments are aimed at understanding the mechanism of this noise cancellation process. We hypothesize that non-linear signal processing in the mammalian cochlea (the most peripheral part of the auditory system) is the basis of noise cancellation. To test this hypothesis, we measured the responses of auditory-nerve fibers (ANFs) to sounds embedded in background noise with different statistical properties. ANFs …

H2s And Homocysteine Control A Novel Feedback Regulation Of Cystathionine Beta Synthase And Cystathionine Gamma Lyase In Cardiomyocytes., Shyam Sundar Nandi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Hydrogen sulfide (H2S), a cardioprotective gas, is endogenously produced from homocysteine by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) enzymes. However, effect of H2S or homocysteine on CBS and CSE expression, and cross-talk between CBS and CSE are unclear. We hypothesize that homocysteine and H2S regulate CBS and CSE expressions in a dose dependent manner in cardiomyocytes, and CBS deficiency induces cardiac CSE expression. To test the hypothesis, we treated murine atrial HL1 cardiomyocytes with increasing doses of homocysteine or Na2S/GYY4137, a H2S donor, and measured the levels of CBS and CSE. We found that homocysteine upregulates CSE …

Can Cone Signals In The Wild Be Predicted From The Past?, David H. Foster, Iván Marín-Franch

MODVIS Workshop

In the natural world, the past is usually a good guide to the future. If light from the sun and sky is blue earlier in the day and yellow now, then it is likely to be more yellow later, as the sun's elevation decreases. But is the light reflected from a scene into the eye as predictable as the light incident upon the scene, especially when lighting changes are not just spectral but include changes in local shadows and mutual reflections? The aim of this work was to test the predictability of cone photoreceptor signals in the wild over the …

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 …

Diabetic Cardiomyopathy: An Immunometabolic Perspective., Paras K. Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K. Bandyopadhyay, Kaushik K. Patel, Sushil K. Mahata

Journal Articles: Cellular & Integrative Physiology

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) …

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic …

On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case

Journal Articles: Cellular & Integrative Physiology

The field of free radical biology originated with the discovery of superoxide dismutase (SOD) in 1969. Over the last 5 decades, a plethora of research has been performed in species ranging from bacteria to mammals that has elucidated the molecular reaction, subcellular location, and specific isoforms of SOD. However, while humans have only begun to study this class of enzymes over the past 50 years, it has been estimated that these enzymes have existed for billions of years, and may be some of the original enzymes found in primitive life. As life evolved over this expanse of time, these enzymes …

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Williams Honors College, Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency …

The Effect Of Cold On The Physiology Of Drosophila Larva Heart And On Synaptic Transmission At Crayfish Neuromuscular Junctions, Yuechen Zhu

Theses and Dissertations--Biology

Ectothermic animals are susceptible to temperature changes such as cold shock with seasons. To survive through a cold shock, ectotherms have developed unique strategies. My interest is focusing on the physiological function of during cold shock and prolonged cold exposure in the fruit fly (Drosophila melanogaster) and crayfish (Procambarus clarkii). I used Drosophila melanogaster as a model system to investigate cardiac function in response to modulators (serotonin, acetylcholine, octopamine, dopamine and a cocktail of modulators) in acute cold shock and chronic cold shock conditions as possible mechanism to regulate heart rate in the cold. To examine if the dampened heart …

Diabetes-Induced Expression And Regulation Of Glp-1 Levels By Bile Acid Receptors (Tgr5 & Fxr), Joseph R. Spengler

Theses and Dissertations

Diabetes Mellitus has continued to drastically affect the health of the world and many complications can prove fatal. As long as this metabolic disease persist, research discoveries will need to continue to be made so that patient outcomes and healthcare are dramatically enhanced. In recent years, GLP-1 has been the topic of conversation for diabetes research, due to its promising effects in promoting insulin sensitivity. Furthermore, bile acids and their receptors (TGR5 & FXR) have shown promise in their actions in the regulation of GLP-1, and thus glucose homeostasis. Here we have shown the detection and increased expression of TGR5 …