Physiology Commons^™

Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan

Theses and Dissertations

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

The Relationship Between Heart Rate Variability, Shooting Experience, And Tactical Pistol Performance, Andrew Gerard Thompson

Human Movement Studies & Special Education Theses & Dissertations

PURPOSE: At rest and during a tactical pistol competition classifier, heart rate variability (HRV) time-domain, high frequency (HF), low frequency (LF), total power (TP), and inter-beat-interval (IBI) measurements were examined in 28, healthy subjects (37 ± 11 yr old, 180 ± 7 cm, 90.6 ± 16.9 kg) for correlations to performance. METHODS: Resting measurements were taken supine in a quiet, dimmed room, during metronomic breathing. The shooting task consisted of three stages, comprised of several strings each. The strings were initiated by a starting buzzer and involved several tactical maneuvers, including holster draws, engaging multiple targets, firing on the move, …

Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan

Department of Molecular Physiology and Biophysics Faculty Papers

Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase-1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat-stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail-safe mechanism. However, discovery of C-kinase-activated PP1 inhibitor, Mr of 17 kDa (CPI-17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting …

Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin

Physiology Faculty Publications

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.

Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.

Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …

Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander

Department of Animal Science: Faculty Publications

Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favorable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes …

Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

No abstract provided.

Genomics Of Mature And Immature Olfactory Sensory Neurons, Melissa D. Nickell, Patrick Breheny, Arnold J. Stromberg, Timothy S. Mcclintock

Physiology Faculty Publications

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein …

Membrane Properties Involved In Calcium-Stimulated Microparticle Release From The Plasma Membranes Of S49 Lymphoma Cells, Lauryl Elizabeth Campbell

Theses and Dissertations

The mechanism of microparticle shedding from the plasma membrane of calcium-loaded cells has been investigated in erythrocytes and platelets. Recent studies have revealed the physiological and clinical importance of microparticle release from nucleated cells such as lymphocytes and endothelium. The experiments of this study were designed to address whether simple mechanisms discovered in platelets and erythrocytes also apply to the more complex nucleated cells. Four such mechanisms were addressed: potassium efflux, transbilayer phosphatidylserine migration, cytoskeleton degradation, and membrane lipid order. The rate and amount of microparticle release in the presence of a calcium ionophore, ionomycin, was assayed by light scatter …

Green Tea Extract Protects Against Fibrogenesis Associated With Nonalcoholic Fatty Liver Disease In Diet-Induced Obese Rats, Allyson M. Bower

Master's Theses

No abstract provided.

Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim

Theses and Dissertations

The human dopamine transporter (hDAT) provides the primary mechanism for dopamine clearance in synapses and thus facilitates the regulation of dopaminergic functions in cognition and reward. It is the molecular target of many centrally-active agents including amphetamines and cocaine. Therefore, an understanding of hDAT function and its modulation by these therapeutic drugs and drugs of abuse can provide insight into the mechanisms of abuse and addiction. In the presented studies, hDAT is tagged with a hexahistidine construct and heterologously expressed in Xenopus laevis oocytes. The plasma membranes are isolated, solubilized, and applied to a Nickel affinity column to obtain purified …

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.

Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Jason E. Podrabsky, Michael A. Menze, Steven C. Hand

Faculty Research & Creative Activity

Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in …

Long-Term Survival Of Anoxia Despite Rapid Atp Decline In Embryos Of The Annual Killifish Austrofundulus Limnaeus., Jason Podrabsky, Michael Menze, Steven Hand

Faculty and Staff Scholarship

Embryos of the annual killifish Austrofundulus limnaeus can survive for months in the complete absence of oxygen. Survival of anoxia is associated with entry into a state of metabolic dormancy known as diapause. However, extreme tolerance of anoxia is retained for several days of post-diapause development. Rates of heat dissipation in diapause II and 4 days post-diapause II embryos were measured under aerobic conditions and during the transition into anoxia. Phosphorylated adenylate compounds were quantified in embryos during entry into anoxia and after 12 hr of aerobic recovery. Rates of heat dissipation were not affected by exposure to anoxia in …

Peripheral Nerve Injury Increases Glutamate-Evoked Calcium Mobilization In Adult Spinal Cord Neurons, Suzanne Doolen, Camille B. Blake, Bret N. Smith, Bradley K. Taylor

Physiology Faculty Publications

BACKGROUND: Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of …

Physical Activity Behaviour Of Paediatric Patients With Type 1 Diabetes, Freya Macmillan, Alison Kirk, Nanette Mutrie

International Journal of Exercise Science: Conference Proceedings

Type 1 diabetes is a common chronic condition in children and young people and its prevalence is increasing worldwide. Paediatric patients with Type 1 diabetes can have poorer health and overall quality of life than their non-diabetic peers and some studies suggest that they may be less active than their non-diabetic peers. Regular physical activity has many potential health benefits for any young person but can also benefit areas of health specifically important for those with Type 1 diabetes. In addition being regularly active can reduce the risk of developing diabetic complications. Promoting physical activity participation in this population is …

Robust Analysis Of Metabolic Pathways, Emily Gruber, Amy Ko, Michael Macgillvray, Miranda Sawyer

Mathematical Sciences Technical Reports (MSTR)

Flux Balance Analysis (FBA) is a widely used computational model for studying the metabolic pathways of cells and the role individual metabolites and reactions play in maintaining cell function. However, the successes of FBA have been limited by faulty biological assumptions and computational imperfections. We introduce Robust Analysis of Metabolic Pathways (RAMP) to provide a more theoretically sound and computationally accurate model of cellular metabolism. RAMP overcomes the faulty assumptions of traditional FBA by allowing deviation from steady-state and accounting for variability across a cellular culture. Computationally, RAMP more successfully predicts the lethality of gene knockouts and reduces degeneracy in …

Diffusion Barriers Of The Lateral Ventricular System, Anitha Saravanakumar

Master's Theses

Adult neurogenesis in mammalian brain has become a well-accepted phenomenon. The neural stem cells in the sub ventricular zone (SVZ) along the lateral wall of the lateral ventricle, the largest germinal center of adult neurogenesis, are maintained by the neural stem cell niche. One prominent feature of the niche is its close proximity to the cerebral spinal fluid (CSF). The role of micromolecules (such as ions, water and gases) present in the CSF and diffusing through the lateral ventricular wall and how the stem cell micro-environment is maintained is poorly understood. The cytoarchitecture of the lateral ventricular wall with a …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai

Theses and Dissertations

Head and Neck Squamous Cell Carcinoma (HNSCC) is an epithelial skin cancer of the upper aerodigestive tract, and is the sixth most common malignancy in the U.S. HNSCC patients undergoing chemotherapy commonly develop anemia, a condition in which the body lacks mature red blood cells (RBCs). Erythropoietin (EPO) is a systemically circulating hormone in the body that regulates the production of RBCs and is applied to treat anemia. Recently, several studies implicated shortened life expectancy of cancer patients by EPO administration. It may be due to an unexpected activation of survival and proliferation pathways of cancer cells by EPO because …

A Pseudo-Trna Modulates Antibiotic Resistance In Bacillus Cereus, Theresa E. Rogers, Sandro F. Ataide, Kiley Dare, Assaf Katz, Stephanie Seveau, Hervé Roy, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial genomic islands are often flanked by tRNA genes, which act as sites for the integration of foreign DNA into the host chromosome. For example, Bacillus cereus ATCC14579 contains a pathogenicity island flanked by a predicted pseudo-tRNA, tRNAOther, which does not function in translation. Deletion of tRNAOther led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding tRNAOther. This suggested that tRNAOther might be expressed as part of a larger RNA, and RACE analysis …

A Diabetic Adolescent Case Study: Use Of A Website In Combination With An Exercise Program To Increase Physical Activity, Danielle Buckley, Nicole Demilia, Stephanie Tanzi, Furong Xu, Linda S. Lamont

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 296-300, 2012. The purpose of this study was to report on the efficacy of a web-based technology support to encourage physical activity in children. This program was designed to promote physical activity and proper nutrition in the diabetic adolescent with a weekly meeting that consisted of a 30-minute educational session followed by 60-minutes of exercise. A specifically designed website was used as a support to this weekly supervised exercise program. Outcomes assessment included body mass index (BMI), muscle strength (grip strength, back and leg strength), flexibility, exercise self-efficacy, and physical activity participation (pedometer, …

Exercise Therapy For Plantar Heel Pain: A Systematic Review, Ameer A. Almubarak, Nadine Foster

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 276-289, 2012. This study aimed to review the evidence of exercise therapy in the treatment of Plantar Heel Pain. Comprehensive search strategy was conducted to identify randomized and quasi-randomized trials. The primary outcome was pain intensity; the secondary outcome was functional limitation. From an initial list of 2327 potentially relevant trials, seven trials were included. Most trials included short-term follow up only of pain and function outcomes. Narrative review revealed limited evidence that stretching exercise alone was superior to other conservative treatments; combining other conservative treatments with stretching was more effective than stretching …

Nitric Oxide And The Biological Cascades Underlying Increased Neurogenesis, Enhanced Learning Ability, And Academic Ability As An Effect Of Increased Bouts Of Physical Activity, Samuel Hunt, James W. Navalta

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 245-275, 2012. The consummate principle underlying all physiological research is corporeal adaptation at every level of the organism observed. With respect to humans, the body learns to function based on the external stimuli from the environment, beginning in the womb, throughout the developmental stages of life. Nitric Oxide (NO) appears to be the governor of the plasticity of several systems in mammals implicit in their proper development. It is the purpose of this review to describe the physiological pathways that lead to plasticity of not only the vasculature but also of the brain …

Concurrent Verbal Encouragement And Wingate Anaerobic Cycle Test Performance In Females: Athletes Vs. Non-Athletes, Dyana L. Bullinger, Christopher M. Hearon, Stacey A. Gaines, Michael L. Daniel

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 239-244, 2012. To examine the effect of concurrent verbal encouragement on the performance of the WAnT in female athletes vs. female non-athletes. College-age female subjects were recruited where ten of the subjects were intercollegiate athletes (ATH, n₁=10) and the nine were non-athletes (NON, n₂=9). The WAnT was novel to all subjects and the subjects were blinded to the study’s purpose. Prior to the experimental trials, subjects were measured for body composition and performed a familiarity WAnT trial without verbal encouragement. Subjects then performed the WAnT twice, once with concurrent …

Short Duration High-Intensity Interval Training Improves Aerobic Conditioning Of Female College Soccer Players, Andrea E. Rowan, Tannin E. Kueffner, Stasinos Stavrianeas

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 232-238, 2012. We hypothesized that High-intensity Interval Training (HIIT) is comparable to traditional endurance training for improving aerobic capacity over a 5-week training period. A VO_2max test and Yo-Yo Intermittent Recovery 1 test (Yo-Yo) were conducted by the HIIT group (Sprint Training (SPR); 5 maximal sprint efforts with 30 seconds of stimulus and 4.5 minutes of active recovery, twice weekly) and the endurance group (END; 40-min run at 80% of VO_2max, twice weekly) before and after intervention. Following initial testing, female NCAA D-III level soccer players were matched for VO …

Development And Comparison Of Two Field-Based Body Fat Prediction Equations: Nhanes 1999-2004, Michael Zanovec, Jing Wang, Carol E. O'Neil

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 223-231, 2012. Clinical guidelines define obesity in terms of excess body weight adjusted for height (i.e., bodymass index [BMI] categories) and/or gender-specific waist circumference (WC) cut-point values. Since body composition, particularly fat mass, is the most variable among individuals due to differences by gender, age, and race, and total percent body fat (%BF) can be estimated accurately using dual-energy X-ray absorptiometry (DXA), the purpose of this study was to develop and compare two field-based body fat prediction equations suitable for a nationally representative sample of the US adult population. Data were analyzed from …

Energy Drinks: Ergolytic Or Ergogenic?, Joe Sillivent, Jennifer Blevins-Mcnaughton, Kayla Peak

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 214-222, 2012. Despite the growing popularity of energy drinks, many do not realize the negative effects on the cardiovascular system. The purpose of this study was to examine the effects of energy drink ingestion on estimated VO₂max, heart rate (HR), systolic and diastolic BP (SBP and DBP, respectively), rate pressure product (RPP), and RPE at rest and during exercise. Seven healthy adults (age: 24.3 ± 3.5 yrs; body mass: = 66.0 ± 2.2 kg) participated in this randomized double blind, crossover study. Subjects ingested a placebo (PL) or Redline (RL) energy …

Validation Of Three Body Composition Techniques With A Comparison Of Ultrasound Abdominal Fat Depths Against An Octopolar Bioelectrical Impedance Device, Kelly E. Johnson, Ian A. Naccarato, Michelle A. Corder, Wendy Repovich

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 205-213, 2012. The aims of this study were to cross-validate three clinical-grade measures of body composition, using an octopolar Bioelectrical Impedance (BIA), an ultrasound analyzer (US) and Air-Displacement Plethysmography (ADP) and second to compare the US scans of total abdominal, subcutaneous and visceral fat depths (mm) against the trunk percent fat (%BF) from the octopolar BIA. Twenty-six college-aged (22.9 ± 1.35 years) men (n = 18) and women (n = 8) volunteered to participate in this study. Body composition was assessed using BIA (total and by segments), ADP and US. In addition, total …

The Effect Of Kinesio Tape® On Lower Extremity Functional Movement Screen™ Scores, Hyun Mo An, Catherine Grove Miller, Michael Mcelveen, James M. Lynch

International Journal of Exercise Science

International Journal of Exercise Science 5(3) : 196-204, 2012. The purpose was to determine if application of Kinesio Tape (KT^®) improves lower extremity scores on the Functional Movement Screen (FMS™). Individual FMS™ score assessments of 32 college students were obtained. The subjects were then randomized into treatment and control groups. The treatment group had a second FMS™ score after application of KT^® to the lower extremity while the control group had a second FMS™ score with no intervention. 16 varsity women’s basketball players and 16 non-varsity female students (Tegner Scale: 6.84 ±1.25, Age: 19±1.2, Height: 165.1±15.1cm, Weight: …