Medical Physiology Commons^™

Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP3 receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca2+ coupling, IP3Rs …

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …

Ctpathway: A Crosstalk-Based Pathway Enrichment Analysis Method For Cancer Research, Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-E Huang, Fei Hou, Christine M. Eischen, Wei Jiang

Department of Cancer Biology Faculty Papers

Background: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in …

The Effects Of Alcohol Consumption On Metabolic Factors In The Alive-Ex Study Participants, Meva Beganovic, Stefany D. Primeaux

Medical Student Research Poster Symposium

Alcohol consumption among people living with HIV (PLWH) is common and increases the risk for metabolic disorders such as insulin resistance and diabetes. Adiponectin is an adipokine, produced in adipocytes, that protects against insulin resistance by increasing insulin sensitivity and thus may play a preventative role against the development of metabolic disease. Previous studies have demonstrated an inconsistency regarding the impact of alcohol consumption on adiponectin levels. In a cross-sectional analysis of participants enrolled in the ALIVE-Ex Study, we did not find a significant relationship between at-risk alcohol use, as measured by Alcohol Use Disorders Identification Test (AUDIT) score, in …

Translational Investigation Of Sex Differences In Alcohol Analgesic Efficacy: Comparison Across Preclinical And Clinical Domains, Sumin Lee, Noor Alrashed, Erin Davis, Jessica A. Cucinello-Ragland, Patricia E. Molina, Scott Edwards

Medical Student Research Poster Symposium

Although chronic pain affects over 220 million Americans and significantly contributes to both the development and maintenance of alcohol use disorder (AUD), there is an alarming gap in knowledge regarding the mechanisms underlying the anti-nociceptive effects of alcohol. The goals of the current project were to: 1) relate self-reported pain rating in people living with HIV (PLWH) and 2) investigate neuroadaptations in the phosphorylation status of excitatory and inhibitory protein markers produced by alcohol in the central amygdala (CeA) and the insula in an animal model of chronic inflammatory pain. Towards our first goal, we asked participants in the New …

The Effect Of Nicotine Inhalation On Taste Receptor Gene Expression And Fungiform Papillae Density, Chloe Sterling, Jolie Primeaux, Jason Gardner, Stefany Primeaux

Medical Student Research Poster Symposium

BACKGROUND: Smoking is one of many acquired causes of smell and taste disorders. The effect on taste may be due to cigarette smoke causing a gustatory disturbance through changing the form, quantity, and vascularization of taste buds. Nicotine’s negative impact on taste buds is elicited through aversive sensory effects like oral irritation and pain as well as bitter taste. Taste buds are located on fungiform, circumvallate, and foliate papillae found on the tongue. Taste receptor cells can be stimulated by one of five basic taste qualities, which are sweet, bitter, umami (savory), salty, and sour. More recently, fat has been …

The Characterization Of Rodent Diet Influences On Ethanol Consumption In Mice, Selby White, Franciely Paliarin, Evan Dore, Cameron Gabriel, Rajani Maiya

Medical Student Research Poster Symposium

The gut-brain axis is a distinct, yet uncharacterized tract of the nervous system that provides direct communication between the myenteric and the central nervous systems. The gut-brain axis is implicated in numerous underlying pathological phenomena, such as depression, Parkinson’s disease, and autoimmune disorders. Signaling along the gut-brain axis is primarily mediated by the Vagus nerve, which projects to the Nucleus Tractus Solitarius (NTS). From the NTS, projections link to higher order brain structures, namely reward regions, such as the paraventricular nucleus of the hypothalamus, Locus Coeruleus and the Prefrontal cortex. Alcohol Use Disorder is a complex and widespread disease with …

Chronic Binge Alcohol Impairs Myoblast Differentiation: Role Of Microrna-206, Peter Bergeaux, Brianna Bourgeois, Patricia E. Molina, Liz Simon

Medical Student Research Poster Symposium

Background: With recent advances in antiretroviral therapy, people living with HIV (PLWH) now have a near-normal life expectancy. As such, PLWH experience aging-related comorbidities, such as metabolic disorders and frailty earlier in life than the general population. At-risk alcohol use is twice as likely in PLWH compared to the general population and alcoholic myopathy occurs in 40- 60% of people with an alcohol use disorder. Previous studies demonstrate that chronic binge alcohol (CBA) in simian immunodeficiency virus (SIV)-infected rhesus macaques causes decreased myoblast differentiation and downregulation of microRNA-206 (miR-206) in skeletal muscle. Additionally, lower miR-206 expression is associated with increased …

The Role Of Traf3ip2 In The Progression Of Alcoholic Cardiomyopathy, Nicholas R. Harris, Joshua M. Edavettal, Jason D. Gardner

Medical Student Research Poster Symposium

Alcoholic Cardiomyopathy (ACM) manifests in humans after excessive alcohol consumption and is characterized by ventricular dilation and cardiac function impairment. Previous studies have identified deterioration of mitochondrial homeostasis, increased oxidative stress, and inflammation as mechanisms of ACM development. However, little is known of the molecular mechanism of ACM. Here, we focus on the role of TRAF3IP2, a proinflammatory cytoplasmic adapter protein, in the pathogenesis of ACM. Previous work suggests TRAF3IP2 is a master regulator of inflammation; thus, being a potential therapeutic target. In this study, we used a mouse model of chronic plus binge alcohol feeding described by the NIAAA. …

Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto

Department of Cancer Biology Faculty Papers

Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …

Stones, Bones, And Groans With Cancerous Overtones - A Rare Case Of Diffuse Large B Cell Lymphoma Presenting As Hypercalcemia, Evan Becker, Caitlyn Moss, Steve Chung

Advances in Clinical Medical Research and Healthcare Delivery

Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that can present in a variety of ways including fever, weight loss, weakness, and drenching night sweats. Uncommonly, hypercalcemia of malignancy can be associated with DLBCL through multiple mechanisms that include synthesis of parathyroid hormone related peptide (PTHrP) or elevated calcitriol levels. It is estimated that hypercalcemia in the setting of DLBCL is present in 18% of newly diagnosed cases. This report details a case of an 80-year-old man with history of chronic anemia and CKD stage 3b that presented with weakness, decreased oral intake, and self-reported weight …

A Case Of Intractable Hyperhidrosis In Spinal Cord Injury: Role Of Stellate Ganglion Block, Soun Sheen, Hemant Kalia, Victoria Kung

Advances in Clinical Medical Research and Healthcare Delivery

Objective:

Autonomic dysreflexia (AD) in spinal cord injury (SCI) can present as hyperhidrosis due to sudomotor dysfunction. Hyperhidrosis can also occur without an identifiable etiology. There are no standard treatment guidelines for refractory hyperhidrosis in the setting of persistent noxious stimulation. Stellate ganglion blockade may prevent hyperhidrosis by inhibiting profound sympathetic surge and vasoconstriction.

Case:

58-year-old female with C7 ASIA-A quadriplegia was admitted to the hospital for episodes of profuse sweating in the setting of autonomic dysreflexia secondary to underlying T7-8 discitis. Despite conservative treatment of discitis, patient continued experience 50-60 episodes of profuse sweating daily. Stellate ganglion block was …

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Are We Compulsively Chasing Rainbows?, Olivier George, Serge H. Ahmed, Nicholas W. Gilpin

School of Medicine Faculty Publications

No abstract provided.

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …