Life Sciences Commons^™

Distinct Roles For Free Fatty Acid Receptor 3 (Ffar3) In Vagal And Spinal Afferents Regulating Energy Balance And Glucose Homeostasis, Tyler M. Cook

Dissertations

energy balance, glucose homeostasis, gut-brain axis, microbiome, nutrient sensing, satiety

The Role Of Gut Microbiome And Scfa Butyrate In The Development Of Obesity Associated Pre-Hfpef, Jomana Hatahet

Dissertations

No abstract provided.

The Role Of Glycogen Synthase Kinase 3 Β (Gsk-3Β) At The Cardiac Myofilament, Marisa Jean Stachowski

Dissertations

Altered kinase activity and localization is gaining appreciation as a mechanism contributing to cardiovascular disease. Previous work suggests that the kinase glycogen synthase kinase 3 β (GSK-3β) regulates contractile function of the myofilament, but this work was performed in vitro. The goal of this work was to investigate GSK-3β’s in vivo role in regulating myofilament function, the mechanisms involved, and the translational relevance in disease. GSK-3β’s myofilament localization was confirmed in wild type mouse and human tissue via western blot of myofilament enriched tissue and immunofluorescence. These experiments also revealed that GSK-3β phosphorylated at Y216 binds to the z-disc. We …

The Role Of The Co-Chaperone Protein Bcl-2-Associated Athanogene 3 (Bag3) At The Cardiomyocyte Sarcomere, Thomas Gwynn Martin

Dissertations

The co-chaperone protein Bcl-2-associated athanogene-3 (BAG3) is a central mediator of cellular protein quality control through autophagy. In the heart, decreased BAG3 activity through mutation or decreased expression are linked to dilated cardiomyopathy (DCM). Unfortunately, though clinical data indicates BAG3 mutations are a definitive cause of DCM, few mechanistic studies had been performed to decipher the fundamental role of BAG3 in cardiomyocytes. However, several studies suggested BAG3 was involved in maintenance of the sarcomere, the molecular contractile structure in muscle cells. The goals of this dissertation were to: 1. Determine the functional significance of BAG3 for the sarcomere, 2. Identify …

Behavioral Ecology And Physiological Health Of Managed Populations Of Juvenile Blanding's Turtles (Emydoidea Blandingii) In Urban Wetlands, Armand Andre' Cann

Master's Theses

Substantial threats to reptile species biodiversity have become apparent in the last few decades. This is partly caused by significant losses in grasslands and their associate prairie-wetland ecosystems. One Midwestern prairie-wetland species, Blanding's Turtles (Emydoidea blandingii), are at risk of extirpation due to habitat loss, fragmentation, and increased predator populations. Consequently, significant head-starting efforts, a form of reintroduction conservation using captive-reared and then released turtles, have been conducted to recover populations of E. blandingii in northeastern Illinois. However, the success of these programs both locally and range-wide have not been fully quantified. Unfortunately, many approaches to guaging success involve long-term …

Estrogen Regulation Of Mir-9-5p And Mir-9-3p Stability And Localization In The Aging Female Brain, Chun Kim

Dissertations

In females, levels of estrogens fluctuate across the lifespan and rapidly decline during menopause. Hormone replacement therapy (HRT) has been introduced as a clinical alternative to replenish systemic levels of 17β-estradiol (E2), the primary estrogen in circulation. However, studies from the Women's Health Initiative revealed a critical period immediately following the onset of menopause where HRT is efficacious. Here, we identified the differential regulation of miRNAs, small non-coding RNAs that inhibit translation, as a potential mechanism for this temporal switch in estrogen action. Specifically, early - but not late - E2 administration following ovariectomy in a rat model of menopause …

Adolescent Binge Alcohol Exposure Effects On Heart Structure And Function, Lizhuo Ai

Master's Theses

More than 5 million underage Americans report binge drinking at least once per month. While the effects of alcohol consumption on the adult heart have been well studied, the impact to the adolescent heart is almost entirely unknown. Adolescents primarily consume alcohol in a binge pattern, which elevates blood alcohol content (BAC) to 0.08 g/dL within 2 hours. During adolescence the body grows rapidly, and the heart must also grow by cellular hypertrophy to meet this increasing demand. Our goal was to determine the impact of adolescent binge alcohol exposure on the heart, using an outbred rat model. This thesis …

Functional Studies Of Novel Mosquito Stage-Specific Genes In The Malaria Parasite, Plasmodium Berghei., Kaitlyn Kiernan

Master's Theses

The development and survival of the malaria parasite Plasmodium within its mosquito vector is not very well understood. When the parasite is taken up by an Anopheles mosquito, it is exposed to digestive enzymes, reactive oxygen species, increasing pH, decreasing temperature, and a diverse microbial flora. Our lab is studying the adaptive mechanisms underlying parasite survival in this hostile environment, one of which is movement out of the midgut. In order to escape the midgut, the parasite develops into an elongated, motile form called the ookinete. I am investigating two genes, thioredoxin-like protein 1 (trxl-1) and subpellicular microtubule protein 1 …

Critical Role Of C-Jun N-Terminal Kinase Signaling In Binge Alcohol-Driven Atrial Arrhythmic Remodeling, Jiajie Yan Yan

Dissertations

Holiday Heart Syndrome (HHS) is cardiac arrhythmia induced by binge alcohol consumption, a drinking pattern affects 38 million adults in our society. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in HHS and causes significant morbidity and mortality. Despite the intensive prevention effort nationwide, the binge drinking population keeps rising. However, no effective treatment strategies are available for binge drinking induced AF due to the unknown underlying mechanisms. In this thesis, I aim to elucidate the mechanisms of binge alcohol-promoted atrial arrhythmogenicity by using a mouse model of repeated binge alcohol exposure established in the Ai Lab.

The Ai …

The Amino Terminal Region Of Cardiac Myosin Binding Protein-C Is Necessary For Cardiac Function, Thomas Lawrence Lynch

Dissertations

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that has been suggested to regulate cardiac contraction via its amino terminal (N’) region. Following ischemic injury to the heart, cMyBP-C is cleaved into a predominant N’ fragment consisting of domains C0 through C1 and the first 17 residues of the M-domain that is referred to as C0-C1f. However, the necessity of the N’-C0-C1f region of cMyBP-C in regulating cardiac function in vivo has not been elucidated. I hypothesized that the N’-C0-C1f region of cMyBP-C is critical for normal cardiac function in vivo. To test this hypothesis, transgenic (TG) mice …

Cardiac Calcium Atpase Dimerization Measured By Fluorescence Resonance Energy Transfer And Chemical Cross-Linking, Daniel Blackwell

Dissertations

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homo-oligomers that increase the catalytic rate of calcium transport. We investigated SERCA oligomerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher molecular weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer (FRET) measurements in cells transiently transfected with fluorescently-labeled SERCA2a revealed that SERCA readily forms homo-dimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation …

Regulation Of Micrornas By 17Β-Estradiol In The Aging Female Brain, Yathindar Satya Giffin-Rao

Dissertations

Hormone Therapy (HT) is used to increase the 17β-estradiol (E2) levels in women who are going through the menopausal transition to alleviate the negative symptoms associated with menopause and decrease the risk of chronic diseases. Clinical and basic science research had previously shown that HT provided protection from cognitive decline and reduced the risk of dementia. However the Women's Health Initiative (WHI) clinical trial demonstrated that HT had no beneficial effects for cognitive decline and, in some cases increased the risk of dementia in post-menopausal women. However, further analysis of WHI data showed that when HT was given to women …

L30a Mutation Of Phospholemman Mimics Effects Of Cardiac Glycosides On Isolated Cardiomyocytes, Ryan David Himes

Dissertations

In order to determine if mutations made to phospholemman (PLM) could increase PLM binding to the Na/K-ATPase (NKA) and cause positive inotropy we performed scanning mutagenesis of the transmembrane domain of PLM and measured FRET between each mutant and NKA. We observed increased binding to NKA for several PLM mutants compared to WT, including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca2+ transient compared to GFP control. Ca2+ transient amplitude was further increased by L30A PLM overexpression. L30A mutation also delayed Ca2+ extrusion and increased the duration of the cardiomyocyte contraction. …

Mechanisms Of Estrogen Receptor Alternative Splicing And The Consequences For Aging In The Female Brain, Cody Lee Shults

Dissertations

The advances in healthcare and scientific knowledge have resulted in longer life expectancies in women. These advanced ages in women now means that they are experiencing the effects of age-related changes in the body for much longer periods of time, mainly reproductive senescence, resulting in the loss of circulating ovarian hormones. The age at which menopause occurs has not changed, resulting in women now living over a third of their lives in a postmenopausal state.

The major circulating estrogen produced by the ovaries, 17β-estradiol (E2), has many homeostatic effects in the body like neuroprotection and cardioprotection. Hormone replacement therapy (HT) …

Haploinsufficiency Of Cardiac Myosin Binding Protein-C In The Development Of Hypertrophic Cardiomyopathy, David Barefield

Dissertations

Heart Failure is one of the leading causes of morbidity and mortality in the human population and represents a common endpoint for several diseases including inherited cardiomyopathies. Hypertrophic Cardiomyopathy (HCM) is characterized by left ventricular wall thickening, diastolic dysfunction, and sarcomere disarray. Mutations in sarcomeric protein encoding genes have been established as causative for HCM.

The gene MYBPC3, encoding cardiac myosin binding protein-C (cMyBP-C), is the second most commonly mutated gene in HCM cases. As a majority of these mutations have been determined to result in a null allele which does not produce any protein, it is thought that haploinsufficiency …

Functional Importance Of Oxidative Post-Translational Modifications Of Ryanodine Receptor In Cardiac Sarcoplasmic Reticulum Ca2+ Handling During Oxidative Stress, Stefan R. Mazurek

Dissertations

Free ionic calcium (Ca2+) plays an essential role as a second messenger that initiates muscle contraction in the heart. Ryanodine receptor (RyR2) acts as the primary Sarcoplasmic Reticulum (SR) Ca2+ release channel in the heart. In the event that intracellular SR Ca2+ handling is compromised, both the contractility and electrical excitability of the heart can be altered. As a consequence, heart function may not be able to maintain the necessary cardiac output to meet the metabolic demand of the body.

Increased oxidation of RyR2 has been implicated in abnormal Ca2+ handling that promotes the onset and progression of cardiovascular disease. …

Serine 910 Phosphorylation Of Focal Adhesion Kinase Is Critical For Costamere Assembly, Miensheng Chu

Dissertations

Tyrosine-phosphorylated FAK is required for the hypertrophic response of cardiomyocytes to growth factors and mechanical load, but the role of FAK serine phosphorylation in this process is unknown. Endothelin-1 (ET-1; 1-100nM, 2-30min) and other hypertrophic factors induced a time- and dose-dependent increase in FAK-S910 phosphorylation in neonatal rat ventricular myocytes (NRVM). FAK-S910 phosphorylation required ET_AR-dependent activation of PKCδ and Src via parallel Raf-1→MEK1/2→ERK1/2 and MEK5→ERK5 signaling pathways. Using co-immunoprecipitation, TIRF-microscopy and FRAP, ET-1 stimulation of NRVM expressing a nonphosphorylatable, S910A-FAK mutant decreased the interaction of paxillin and vinculin within costameres. This interaction was important in stabilizing α-actinin within …

Receptor-Mediated Hypertrophic Signaling Via Protein Kinase D And Histone Deacetylase 5 In Adult Myocytes, Chia-Wei Jenny Chang

Dissertations

Hemodynamic stress and neurohumoral signaling are common causes of cardiac hypertrophy. These extrinsic stress stimuli typically act on GPCR and induce a cascade of signal transduction to re-program terminally differentiated myocytes to grow in length or width. The compensatory hypertrophic response can enhance cardiac output briefly due to increased work load. However, prolonged stress results in maladaptive changes in the heart and gradually deteriorates ventricular function to supply blood throughout the body. Sustained hypertrophic signaling can also progress toward heart failure.

My dissertation research focuses on the hypertrophic signaling in adult cardiac myocytes in response to neurohumoral stimuli, ET-1 and …

An Investigation Of The Phospholamban-Serca Regulatory Interaction With Fluorescence Resonance Energy Transfer, Philip Adam Bidwell

Dissertations

With Fluorescence Resonance Energy Transfer (FRET), we are able to detect changes in the structure and affinity of the PLB-SERCA regulatory complex in live cells. Using this approach, we have detected a high level of PLB-SERCA interaction even at Ca2+ concentrations known to fully relieve PLB inhibition of SERCA, suggesting that dissociation is not required for relief of inhibition. We also detect no real-time change in PLB-SERCA binding over the course of a single Ca2+ transient in paced myocytes. The effect of Ca2+ on the PLB-SERCA interaction is best described as a reduced affinity with no change in the structure …

The Role Of T-Type Calcium Channels In Vascular Smooth Muscle Cell Cycle Regulation, Abigail Prier

Master's Theses

Results from previous experiments have provided evidence for T-type channel expression in adult pulmonary artery smooth muscle cells (PASMCs) using electrophysiology and qRT-PCR. Studies have also shown that when T-type channels are blocked, either pharmacological or with small hairpin RNA targeted against T-type channel Cav3.1 subunit, mRNA levels are reduced and cell proliferation is inhibited. These results suggest a connection between T-type calcium channels and cell proliferation. In this thesis, Cav3.1 and its possible interplay with cyclin D, an early marker of the cell cycle, was investigated. The time course of cyclin D's translocation to the nucleus to begin the …

Expression And Regulation Of Osteopontin In The Diabetic Heart, Abigail Goodman

Dissertations

Diabetes leads to several alterations in cardiac structure, one of which is fibrosis of the ventricular myocardium. Myocardial fibrosis is a common underlying factor in most cardiac pathologies. Osteopontin (OPN) is a small phospho-protein that has been implicated in fibrotic tissue remodeling. In the heart, the expression of OPN protein is increased after acute and chronic pathologies. Upregulation of OPN coincides with a transition to heart failure and a direct role for OPN in the progression of diabetic cardiomyopathy to heart failure has been reported.

The overall objective of this project is to determine if OPN is upregulated in the …

Camkii-Mediated Phosphorylation Of The Inositol 1,4,5-Trisphosphate Receptor At Serine-150 Results In Decreased Channel Activity, Joshua Thomas Maxwell

Dissertations

One mechanism by which calcium is mobilized from intracellular stores is via the activation of inositol 1,4,5-trisphosphate receptors (InsP3Rs) by the second messenger, inositol 1,4,5-trisphosphate (InsP3). InsP3 is produced when certain factors bind to G protein-coupled receptors on the plasma membrane, causing activation of phospholipase C which cleaves InsP3 from its membrane tether, allowing InsP3 to diffuse through the cytoplasm to bind to its receptor. Activation of InsP3Rs leads to release of calcium into the cytoplasm of the cell, where it can activate a multitude of signal transduction cascades and a variety of local and global cellular events. One such …

Cloning And Characterization Of A Novel Ion Channel, Jung-Ha Lee

Dissertations

No abstract provided.

Physiologic Studies Of Immune Cell-Derived Peptide Modulation Of Chromaffin Cell Epinephrine Secretion, Jennifer Curran Roberts

Dissertations

No abstract provided.

Regulation Of Sarcoplasmic Reticulum Calcium Atpase (Serca2) Gene Expression In Left Ventricular Hypertrophy And Heart Failure, Ming Qi

Dissertations

No abstract provided.

Dexamethasone And Insulin Regulation Of Tumor Necrosis Factor And Interleukin 6 Production During Septic Shock, Elisabeth Lilli Hahn

Dissertations

No abstract provided.

Voltage Clamp Analysis Of Latent Pacemaker Cells Isolated From Cat Right Atrium, Zhengfeng Zhou

Dissertations

No abstract provided.

Roles Of Ion Channels In Nervous System Tumor Cell Growth, Yong Soo Lee

Dissertations

No abstract provided.

Relationship Between Intracellular Ph And Calcium Uptake In The Skeletal Muscle During Sepsis, Gin Mo

Master's Theses

No abstract provided.

The Physiology And Morphology Of Canine Intracardiac Ganglion Cells, Xiaohe Xi

Dissertations

No abstract provided.