Medicine and Health Sciences Commons^™

Sound The (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide Pgpp, Areej Malik, Megan A. Hept, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been …

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …

Pulmonary Capillary Recruitment And Distention In Mammalian Lungs: Species Similarities, David Langleben, Benjamin D. Fox, Stylianos E. Orfanos, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We …

Effect Of Exercise Volume On Hdl-Cholesterol: A 7-Year Case Study, David P. Swain

Human Movement Sciences & Special Education Faculty Publications

Introduction: While exercise is known to increase HDL-cholesterol, it is not known if larger exercise volumes produce larger increases in HDL. However, the range of exercise volumes used in most training studies is limited. This report presents a case study of a middle-aged male who engaged in large variations of exercise volume over 7 years while frequently measuring HDL. The purpose was to determine if large increases in exercise volume were associated with larger increases in HDL than previously reported.

Methods: The subject maintained detailed logs of his main form of exercise, bicycling. These logs were analyzed to determine the …

The Effect Of Tackling Training On Head Accelerations In Youth American Football, Eric Schussler, Richard J. Jagacinski, Susan E. White, Ajit M. Chaudhari, John A. Buford, James A. Onate

Rehabilitation Sciences Faculty Publications

Background: Many organizations have introduced frameworks to reduce the incidence of football related concussions through proper equipment fitting, coach education, and alteration of tackling technique.

Purpose: The purpose of this study was to examine the effects of training in a vertical, head up tackling style on the number of head accelerations experienced while tackling in a controlled laboratory situation. The authors hypothesized that training in a head up tackling technique would reduce the severity of head acceleration experienced by participants.

Design: Controlled Laboratory Study.

Methods: Twenty-four participants (11.5 ± 0.6 years old, 60.5 ± 2.2 in, 110 ± 18.4 lbs.) …

Mitochondrial Function Assessed By 31p Mrs And Bold Mri In Non-Obese Type 2 Diabetic Rats, Yuchi Liu, Xunbai Mei, Jielei Li, Nicola Lai, Xin Yu

Electrical & Computer Engineering Faculty Publications

The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). ³¹P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. ³¹P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation. The time constant of phosphocreatine recovery, an index of mitochondrial oxidative capacity, …

Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Charalampos Birmpas, Nektarios Barabutis, Betsy W. Gregory, Mary Ann Clemens, Joseph R. Newton, David Fulton, John D. Catravas

Bioelectrics Publications

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation …

Physical Activity/Exercise And Diabetes: A Position Statement Of The American Diabetes Association, Sheri R. Colberg, Ronald J. Sigal, Jane E. Yardley, Michael C. Riddell, David W. Dunstan, Paddy C. Dempsey

Human Movement Sciences & Special Education Faculty Publications

The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes.

Physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity. Exercise improves blood glucose control in type 2 diabetes, reduces cardiovascular risk factors, contributes to weight loss, and …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Biological Sciences Faculty Publications

Background -Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results-Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate-albumin and transendothelial electrical resistance of human umbilical vein …

Histone Deacetylase Inhibitors Prevent Pulmonary Endothelial Hyperpermeability And Acute Lung Injury By Regulating Heat Shock Protein 90 Function, Atul D. Joshi, Nektarios Barabutis, Charalampos Birmpas, Christiana Dimitropoulou, Gagan Thangjam, Mary Cherian-Shaw, John Dennison, John D. Catravas

Bioelectrics Publications

Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and restores transendothelial permeability. Hyperacetylation of Hsp90, as by inhibitors of histone deacetylase (HDAC), suppresses its chaperone function and mimics the effects of Hsp90 inhibitors. In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 …

Bracing Of The Trunk And Neck Has A Differential Effect On Head Control During Gait, S. Morrison, D. M. Russell, K. Kelleran, M. L. Walker

Rehabilitation Sciences Faculty Publications

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk …

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

Medical Diagnostics & Translational Sciences Faculty Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

The Big Blue Test: Effects Of 14 Minutes Of Physical Activity On Blood Glucose Levels, Sheri R. Colberg, Manuel J. Hernandez

Human Movement Sciences & Special Education Faculty Publications

[First paragraph] For most with diabetes, physical activity has a blood glucose lowering effect (1). Hypoglycemia (i.e., blood glucose < 65 mg/dL) resulting from exercise is a concern, particularly for insulin users (2).

Blood Glucose Responses To Type, Intensity, Duration, And Timing Of Exercise, Sheri R. Colberg, Manuel J. Hernandez, Fatima Shahzad

Human Movement Sciences & Special Education Faculty Publications

[First Paragraph] The Big Blue Test (BBT) is an annual initiative by the Diabetes Hands Foundation to raise awareness of the importance of physical activity in managing diabetes. Individuals with diabetes voluntarily exercise and record self-monitored blood glucose levels. During the 2012 BBT, 5,157 diabetic participants (~90% insulin users) anonymously entered exercise type, intensity, duration, time elapsed since last meal, and blood glucose readings before and after one or more bouts of exercise separately through www.BigBlueTest.org or an Iphone app.

Development And Validation Of A Predictive Model Of Acute Glucose Response To Exercise In Individuals With Type 2 Diabetes, Bryan S. Gibson, Sheri R. Colberg, Paul Poirier, Denise Maria Martins Vancea, Jason Jones, Robin Marcus

Human Movement Sciences & Special Education Faculty Publications

Background: Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes.

Design and methods: Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation. …

Aging, Neuromuscular Decline, And The Change In Physiological And Behavioral Complexity Of Upper-Limb Movement Dynamics, S. Morrison, K. M. Newell

Rehabilitation Sciences Faculty Publications

Aging is characterized by a general decline in physiological and behavioral function that has been widely interpreted within the context of the loss of complexity hypothesis. In this paper, we examine the relation between aging, neuromuscular function and physiological-behavioral complexity in the arm-hand effector system, specifically with reference to physiological tremor and isometric force production. Experimental findings reveal that the adaptive behavioral consequences of the aging-related functional decline in neurophysiological processes are less pronounced in simple motor tasks which provides support for the proposition that the motor output is influenced by both extrinsic (e.g., task related) and intrinsic (e.g., coordination, …

Dose-Dependent Thresholds Of 10-Ns Electric Pulse Induced Plasma Membrane Disruption And Cytotoxicity In Multiple Cell Lines, Bennett L. Ibey, Caleb C. Roth, Andrei G. Pakhomov, Joshua A. Bernhard, Gerald J. Wilmink, Olga N. Pakhomova

Bioelectrics Publications

In this study, we determined the LD50 (50% lethal dose) for cell death, and the ED50 (50% of cell population staining positive) for propidium (Pr) iodide uptake, and phosphatidylserine (PS) externalization for several commonly studied cell lines (HeLa, Jurkat, U937, CHO-K1, and GH3) exposed to 10-ns electric pulses (EP). We found that the LD50 varied substantially across the cell lines studied, increasing from 51 J/g for Jurkat to 1861 J/g for HeLa. PS externalized at doses equal or lower than that required for death in all cell lines ranging from 51 J/g in Jurkat, to 199 J/g in CHO-K1. Pr …

Balance Training Reduces Falls Risk In Older Individuals With Type 2 Diabetes, Steven Morrison, Sheri R. Colberg, Mita Mariano, Henri K. Parson, Arthur I. Vinik

Rehabilitation Sciences Faculty Publications

OBJECTIVE - This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS - Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program.

RESULTS - Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, …

Effects Of 8 Weeks Of Flexibility And Resistance Training In Older Adults With Type 2 Diabetes, Matthew T. Herriot, Sheri R. Colberg, Henri K. Parson, Tanja Nunnold, Aaron I. Vinik

Human Movement Sciences & Special Education Faculty Publications

(First paragraph) Flexibility is often downplayed as unimportant to fitness. However, flexibility training is imperative to maintain full range of motion (ROM) of joints, particularly in individuals with type 2 diabetes, who may experience limited joint mobility due to glycation of joint structures (1). Maladies such as “frozen shoulder” are common complaints in type 2 diabetes (2).

Laminin Potentiates Differentiation Of Pcc4uva Embryonal Carcinoma Into Neurons, T. M. Sweeney, Roy C. Ogle, C. D. Little

Medical Diagnostics & Translational Sciences Faculty Publications

The embryonal carcinoma PCC4uva differentiates into neurons in response to treatment with retinoic acid and dbcAMP. We used this in vitro model system to study the effects of laminin on early neural differentiation. Laminin substrata markedly potentiate neural differentiation of retinoic acid and dbcAMP-treated cultures. Only laminin induced more rapid neural cell body clustering, neurite growth and neurite fasciculation as compared to type IV collagen, type I collagen, and fibronectin substrata. Exogenous laminin substrata promoted greater cell attachment, cellular spreading and growth to confluence than type IV collagen, type I collagen, fibronectin and glass substrata. Laminin-induced effects were inhibited by …

Embryonic Chicken Fibroblast Collagen Binding Proteins: Distribution, Role In Substratum Adhesion, And Relationship To Integrins, Roy C. Ogle, A. Jeannette Potts, Marchall Yacoe, Charles D. Little

Medical Diagnostics & Translational Sciences Faculty Publications

Collagen binding proteins (CBP) are hydrophobic, cell surface polypeptides, isolated by collagen affinity chromatography. Antibodies to CBPs inhibit the attachment of embryonic chicken heart fibroblasts to native type I collagen fibrils in a dose-dependent manner. The CBP antibodies also induce rounding and detachment of cells adherent to a planar substratum. This process of antibody-mediated substratum detachment resulted in a clustering of CBP and cell-associated extracellular matrix at the cell surface, and the rearrangement of filamentous actin. Other functional studies showed that cells grown within a three-dimensional gel of type I collagen cannot be immunostained at the cell surface with CBP …