Translational Medical Research Commons^™

Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …

Systematic Control Of Aged Skeletal Muscle Following High-Intensity Stretch-Shortening Contraction Exercise Training: Epigenomic Regulation And Signaling Factors Underpinning Adaptation, Marshall Alan Naimo Jr.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sarcopenia, the age-related decline in skeletal muscle mass, results in a loss of strength and functional capacity, which subsequently increases the risk of disease, disability, frailty, and all-cause mortality. Exercise is known to be an efficacious paradigm for improving health and attenuating or preventing many chronic diseases. For the previous two decades, our laboratory has established an in vivo rodent dynamometer model to explore the effects of various skeletal muscle training paradigms following stretch-shortening contractions (SSCs).The responses tohigh-intensity resistance-type exercise training (RTET) using this physiological model ranges from adaptation, characterized by enhanced skeletal muscle performance along with increased muscle mass, …

Behavioral And Anti-Inflammatory Effects Of Magl Inhibition In A Mouse Model Of Inflammatory Arthritis, Floyd Franklin Steele Iii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cannabinoids have analgesic and anti-inflammatory properties. For example, in preclinical models of acute inflammatory pain, cannabinoid receptor subtype 2 (i.e., CB_2, Table 1) agonists decrease paw inflammation and resulting pain. Yet, the anti-inflammatory properties of cannabinoid receptor manipulation in chronic inflammatory pain states are unknown. Monoacylglycerol lipase (MAGL) is the primary catabolic enzyme of the endocannabinoid (i.e., endogenous cannabinoid ligand) 2-arachidonoyl glycerol (i.e., 2-AG). Compounds that inhibit MAGL indirectly increase tissue levels of 2-AG by preventing its catabolism. MAGL inhibitors demonstrate efficacy in acute models of inflammatory/rheumatic disease. Thus, in this study, the MAGL inhibitor JZL184 was tested …

A Study Of Gastrointestinal Pathophysiology, Emily Minor

Graduate Theses, Dissertations, and Problem Reports (ETD)

Though the duodenum is the primary site of iron absorption, the colon also contains iron transporters and participates in iron absorption. The purpose of this study was to characterize colonic iron absorption in control patients and those with ulcerative colitis (UC), a disease that frequently results in iron deficiency. Using RT-qPCR and western blot analysis, we found that colonic expression of the apical iron importer, divalent metal transporter 1 (DMT1), is equal to duodenal expression. However, colonic expression of ferroportin 1 (FPN1), an iron exporter, is only about one-quarter that of the duodenum. Patients with active ulcerative colitis were found …

Translational Insights Into The Genetic Etiology Of Mental Health Disorders: Examining Risk Factor Models, Neuroimaging, And Current Dissemination Practices, Jessica L. Bourdon

Theses and Dissertations

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a …

Targeted Therapies For Ewsr1-Fli1 Translocated Ewing Family Of Tumors, Daniel A.R. Heisey

Theses and Dissertations

The EWSR1-FLI1 t(11;22)(q24;q12) translocation is the pathognomonic genomic alteration in 85% of the Ewing Family of Tumors (EWFT) a malignancy of the bone and the surrounding tissue, predominantly affecting children and adolescents. This translocation results in the formation of a chimeric oncoprotein which acts as an aberrant transcription factor that is currently not pharmaceutically druggable, driving the need for more effective targeted therapies. The EWSR1-FLI1 translocation induces a variety of changes including dysregulation of the epigenome and altered gene expression to drive tumorigenesis, and consequently contributes to the hypersensitivity of EWFT to several classes of chemotherapeutics. We sought to exploit …