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Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger Aug 2018

Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger

Internal Medicine Faculty Publications

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. …


Correlates Of Not Using Antiretroviral Therapy Among Transwomen Living With Hiv: The Unique Role Of Personal Competence, Richard A. Crosby, Laura F. Salazar, Brandon J. Hill Aug 2018

Correlates Of Not Using Antiretroviral Therapy Among Transwomen Living With Hiv: The Unique Role Of Personal Competence, Richard A. Crosby, Laura F. Salazar, Brandon J. Hill

Health, Behavior & Society Faculty Publications

Purpose: This study tested three psychosocial measures for their potential to serve as counseling goals for promoting ART to transgender women living with HIV (TWLH).

Methods: Among 69 TWLH, 17.4% were not taking ART; these volunteers were compared to the remainder using multivariate regression analyses.

Results: Only one psychosocial measure achieved significance: Personal Competence (Adjusted Odds Ratio = 0.80, 95% CI = 0.67–0.97, P = 0.02). Because this was a continuous measure, assessed on a 7-point scale, the protective adjusted odds ratio of 0.80 represents a 20% reduction in the odds of not taking ART for each unit of increase …


Bee Attractiveness Data, Bernadette Maria Mach, Daniel A. Potter Aug 2018

Bee Attractiveness Data, Bernadette Maria Mach, Daniel A. Potter

Entomology Research Data

Urban and suburban landscapes can be refuges for biodiversity of bees and other pollinators. Public awareness of declining pollinator populations has increased interest in growing plants that provide floral resources for bees. Various publications and websites list “bee-friendly” plants, but such lists are rarely based on empirical data, nor do they emphasize flowering trees and shrubs, which are a major component of urban landscapes. We quantified bee visitation to 72 species of flowering woody landscape plants across 373 urban and suburban sites in Kentucky and southern Ohio, USA, sampling and identifying the bee assemblages associated with 45 of the most …


Lake Regionalization And Diatom Metacommunity Structuring In Tropical South America, Xavier Benito, Sherilyn C. Fritz, Miriam Steinitz-Kannan, Maria I. Vélez, Michael M. Mcglue Aug 2018

Lake Regionalization And Diatom Metacommunity Structuring In Tropical South America, Xavier Benito, Sherilyn C. Fritz, Miriam Steinitz-Kannan, Maria I. Vélez, Michael M. Mcglue

Earth and Environmental Sciences Faculty Publications

Lakes and their topological distribution across Earth's surface impose ecological and evolutionary constraints on aquatic metacommunities. In this study, we group similar lake ecosystems as metacommunity units influencing diatom community structure. We assembled a database of 195 lakes from the tropical Andes and adjacent lowlands (8°N–30°S and 58–79°W) with associated environmental predictors to examine diatom metacommunity patterns at two different levels: taxon and functional (deconstructed species matrix by ecological guilds). We also derived spatial variables that inherently assessed the relative role of dispersal. Using complementary multivariate statistical techniques (principal component analysis, cluster analysis, nonmetric multidimensional scaling, Procrustes, variance partitioning), we …


Bee Assemblages Data, Bernadette Maria Mach, Daniel A. Potter Aug 2018

Bee Assemblages Data, Bernadette Maria Mach, Daniel A. Potter

Entomology Research Data

Urban and suburban landscapes can be refuges for biodiversity of bees and other pollinators. Public awareness of declining pollinator populations has increased interest in growing plants that provide floral resources for bees. Various publications and websites list “bee-friendly” plants, but such lists are rarely based on empirical data, nor do they emphasize flowering trees and shrubs, which are a major component of urban landscapes. We quantified bee visitation to 72 species of flowering woody landscape plants across 373 urban and suburban sites in Kentucky and southern Ohio, USA, sampling and identifying the bee assemblages associated with 45 of the most …


Targeting The Mitochondrial Permeability Transition Pore In Traumatic Central Nervous System Injury, Joe E. Springer, Pareshkumar Prajapati, Patrick G. Sullivan Aug 2018

Targeting The Mitochondrial Permeability Transition Pore In Traumatic Central Nervous System Injury, Joe E. Springer, Pareshkumar Prajapati, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

The mitochondrion serves many functions in the central nervous system (CNS) and other organs beyond the well-recognized role of adenosine triphosphate (ATP) production. This includes calcium-dependent cell signaling, regulation of gene expression, synthesis and release of cytotoxic reactive oxygen species, and the release of cytochrome c and other apoptotic cell death factors. Traumatic injury to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial function. One consequence of compromised mitochondrial function is induction of the mitochondrial permeability transition (mPT) state due to formation of the cyclosporine A sensitive permeability transition pore (mPTP). In this mini-review, …


A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford Aug 2018

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …


Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo Aug 2018

Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, …


An Electromyography Study Of Muscular Endurance During The Posterior Shoulder Endurance Test, Neil A. Evans, Emily Dressler, Timothy L. Uhl Aug 2018

An Electromyography Study Of Muscular Endurance During The Posterior Shoulder Endurance Test, Neil A. Evans, Emily Dressler, Timothy L. Uhl

Physical Therapy Faculty Publications

The primary purpose was to determine if there is a difference between the median frequency slopes of 5 posterior shoulder muscles during the initial portion of the Posterior Shoulder Endurance Test (PSET) at the 90° and 135° shoulder abduction positions. Fifty-five healthy volunteers (31 females) participated. The median frequency of the posterior deltoid (PD), upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and infraspinatus (INF) was measured during the PSET at 90° and 135° of shoulder abduction. External torque of 13 ± 1 Nm was used for females and 21 ± 1 Nm for males. A fixed effect multi-variable …


Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin Aug 2018

Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated …


Managing Herbicide Resistance: Listening To The Perspectives Of Practitioners. Procedures For Conducting Listening Sessions And An Evaluation Of The Process, Jill Schroeder, Michael Barrett, David R. Shaw, Amy B. Asmus, Harold Coble, David Ervin, Raymond A. Jussaume Jr., Micheal D. K. Owen, Ian Burke, Cody F. Creech, A. Stanley Culpepper, William S. Curran, Darrin M. Dodds, Todd A. Gaines, Jeffrey L. Gunsolus, Bradley D. Hanson, Prashant Jha, Annie E. Klodd, Andrew R. Kniss, Ramon G. Leon, Sandra Mcdonald, Don W. Morishita, Brian J. Schutte, Christy L. Sprague, Phillip W. Stahlman, Larry E. Steckel, Mark J. Vangessel Aug 2018

Managing Herbicide Resistance: Listening To The Perspectives Of Practitioners. Procedures For Conducting Listening Sessions And An Evaluation Of The Process, Jill Schroeder, Michael Barrett, David R. Shaw, Amy B. Asmus, Harold Coble, David Ervin, Raymond A. Jussaume Jr., Micheal D. K. Owen, Ian Burke, Cody F. Creech, A. Stanley Culpepper, William S. Curran, Darrin M. Dodds, Todd A. Gaines, Jeffrey L. Gunsolus, Bradley D. Hanson, Prashant Jha, Annie E. Klodd, Andrew R. Kniss, Ramon G. Leon, Sandra Mcdonald, Don W. Morishita, Brian J. Schutte, Christy L. Sprague, Phillip W. Stahlman, Larry E. Steckel, Mark J. Vangessel

Plant and Soil Sciences Faculty Publications

Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting …


Plant And Microbial Responses To Repeated Cu(Oh)2 Nanopesticide Exposures Under Different Fertilization Levels In An Agro-Ecosystem, Marie Simonin, Benjamin P. Colman, Weiyi Tang, Jonathan D. Judy, Steven M. Anderson, Christina M. Bergemann, Jennifer D. Rocca, Jason M. Unrine, Nicolas Cassar, Emily S. Bernhardt Jul 2018

Plant And Microbial Responses To Repeated Cu(Oh)2 Nanopesticide Exposures Under Different Fertilization Levels In An Agro-Ecosystem, Marie Simonin, Benjamin P. Colman, Weiyi Tang, Jonathan D. Judy, Steven M. Anderson, Christina M. Bergemann, Jennifer D. Rocca, Jason M. Unrine, Nicolas Cassar, Emily S. Bernhardt

Plant and Soil Sciences Faculty Publications

The environmental fate and potential impacts of nanopesticides on agroecosystems under realistic agricultural conditions are poorly understood. As a result, the benefits and risks of these novel formulations compared to the conventional products are currently unclear. Here, we examined the effects of repeated realistic exposures of the Cu(OH)2 nanopesticide, Kocide 3000, on simulated agricultural pastureland in an outdoor mesocosm experiment over 1 year. The Kocide applications were performed alongside three different mineral fertilization levels (Ambient, Low, and High) to assess the environmental impacts of this nanopesticide under low-input or conventional farming scenarios. The effects of Kocide over time were …


Genome-Wide Atlas Of Alternative Polyadenylation In The Forage Legume Red Clover, Manohar Chakrabarti, Randy D. Dinkins, Arthur G. Hunt Jul 2018

Genome-Wide Atlas Of Alternative Polyadenylation In The Forage Legume Red Clover, Manohar Chakrabarti, Randy D. Dinkins, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Studies on prevalence and significance of alternative polyadenylation (APA) in plants have been so far limited mostly to the model plants. Here, a genome-wide analysis of APA was carried out in different tissue types in the non-model forage legume red clover (Trifolium pratense L). A profile of poly(A) sites in different tissue types was generated using so-called ‘poly(A)-tag sequencing’ (PATseq) approach. Our analysis revealed tissue-wise dynamics of usage of poly(A) sites located at different genomic locations. We also identified poly(A) sites and underlying genes displaying APA in different tissues. Functional categories enriched in groups of genes manifesting APA between …


Horse Y Chromosome Assembly Displays Unique Evolutionary Features And Putative Stallion Fertility Genes, Jan E. Janečka, Brian W. Davis, Sharmila Ghosh, Nandina Paria, Pranab J. Das, Ludovic Orlando, Mikkel Schubert, Martin K. Nielsen, Tom A. E. Stout, Wesley Brashear, Gang Li, Charles D. Johnson, Richard P. Metz, Al Muatasim Al Zadjali, Charles C. Love, Dickson D. Varner, Daniel W. Bellott, William J. Murphy, Bhanu P. Chowdhary, Terje Raudsepp Jul 2018

Horse Y Chromosome Assembly Displays Unique Evolutionary Features And Putative Stallion Fertility Genes, Jan E. Janečka, Brian W. Davis, Sharmila Ghosh, Nandina Paria, Pranab J. Das, Ludovic Orlando, Mikkel Schubert, Martin K. Nielsen, Tom A. E. Stout, Wesley Brashear, Gang Li, Charles D. Johnson, Richard P. Metz, Al Muatasim Al Zadjali, Charles C. Love, Dickson D. Varner, Daniel W. Bellott, William J. Murphy, Bhanu P. Chowdhary, Terje Raudsepp

Veterinary Science Faculty Publications

Dynamic evolutionary processes and complex structure make the Y chromosome among the most diverse and least understood regions in mammalian genomes. Here, we present an annotated assembly of the male specific region of the horse Y chromosome (eMSY), representing the first comprehensive Y assembly in odd-toed ungulates. The eMSY comprises single-copy, equine specific multi-copy, PAR transposed, and novel ampliconic sequence classes. The eMSY gene density approaches that of autosomes with the highest number of retained X–Y gametologs recorded in eutherians, in addition to novel Y-born and transposed genes. Horse, donkey and mule testis RNAseq reveals several candidate genes for stallion …


Gut Inflammatory Diseases, Infection, And Nutrition, Helieh S. Oz, Sung-Ling Yeh, Amedeo Amedei Jul 2018

Gut Inflammatory Diseases, Infection, And Nutrition, Helieh S. Oz, Sung-Ling Yeh, Amedeo Amedei

Internal Medicine Faculty Publications

No abstract provided.


Select Biomarkers On The Day Of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes At 2-Year Follow-Up: A Pilot Study, Christian Lattermann, Caitlin E. -W. Conley, Darren L. Johnson, Emily K. Reinke, Laura J. Huston, Janet L. Huebner, Ching-Heng Chou, Virginia B. Kraus, Kurt P. Spindler, Cale A. Jacobs Jul 2018

Select Biomarkers On The Day Of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes At 2-Year Follow-Up: A Pilot Study, Christian Lattermann, Caitlin E. -W. Conley, Darren L. Johnson, Emily K. Reinke, Laura J. Huston, Janet L. Huebner, Ching-Heng Chou, Virginia B. Kraus, Kurt P. Spindler, Cale A. Jacobs

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. Inflammatory and chondrodegenerative biomarkers have been associated with both pain and the progression of osteoarthritis; however, it remains unclear if preoperative biomarkers differ for patients with inferior postoperative outcomes. Hypothesis/Purpose. The purpose of this pilot study was to compare biomarkers collected on the day of ACL reconstruction between patients with "good" or "poor" 2-year postoperative outcomes. We hypothesized that inflammatory cytokines and chondrodegenerative biomarker concentrations would be significantly greater in patients with poorer outcomes. Study Design. Prospective cohort design. Methods. 22 …


Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield Jul 2018

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …


Cross Photoreaction Of Glyoxylic And Pyruvic Acids In Model Aqueous Aerosol, Sha-Sha Xia, Alexis J. Eugene, Marcelo I. Guzman Jul 2018

Cross Photoreaction Of Glyoxylic And Pyruvic Acids In Model Aqueous Aerosol, Sha-Sha Xia, Alexis J. Eugene, Marcelo I. Guzman

Chemistry Faculty Publications

Aerosols of variable composition, size, and shape are associated with public health concerns as well as with light-particle interactions that play a role in the energy balance of the atmosphere. Photochemical reactions of 2-oxocarboxylic acids in the aqueous phase are now known to contribute to the total secondary organic aerosol (SOA) budget. This work explores the cross reaction of glyoxylic acid (GA) and pyruvic acid (PA) in water, the two most abundant 2-oxocarboxylic acids in the atmosphere, under solar irradiation and dark thermal aging steps. During irradiation, PA and GA are excited and initiate proton-coupled electron transfer or hydrogen abstraction …


Stable Isotope-Resolved Metabolomics Shows Metabolic Resistance To Anti-Cancer Selenite In 3d Spheroids Versus 2d Cell Cultures, Teresa W. -M. Fan, Salim S. El-Amouri, Jessica K. A. Macedo, Qing Jun Wang, Huan Song, Teresa Cassel, Andrew N. Lane Jul 2018

Stable Isotope-Resolved Metabolomics Shows Metabolic Resistance To Anti-Cancer Selenite In 3d Spheroids Versus 2d Cell Cultures, Teresa W. -M. Fan, Salim S. El-Amouri, Jessica K. A. Macedo, Qing Jun Wang, Huan Song, Teresa Cassel, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Conventional two-dimensional (2D) cell cultures are grown on rigid plastic substrates with unrealistic concentration gradients of O2, nutrients, and treatment agents. More importantly, 2D cultures lack cell–cell and cell–extracellular matrix (ECM) interactions, which are critical for regulating cell behavior and functions. There are several three-dimensional (3D) cell culture systems such as Matrigel, hydrogels, micropatterned plates, and hanging drop that overcome these drawbacks but they suffer from technical challenges including long spheroid formation times, difficult handling for high throughput assays, and/or matrix contamination for metabolic studies. Magnetic 3D bioprinting (M3DB) can circumvent these issues by utilizing nanoparticles that enable …


Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris Jul 2018

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca2+ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca2+/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca2+ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …


Grp78 Is A Targetable Receptor On Cancer And Stromal Cells, Nathalia Araujo, Nikhil Hebbar, Vivek M. Rangnekar Jul 2018

Grp78 Is A Targetable Receptor On Cancer And Stromal Cells, Nathalia Araujo, Nikhil Hebbar, Vivek M. Rangnekar

Toxicology and Cancer Biology Faculty Publications

No abstract provided.


Cysteine Modifiers Suggest An Allosteric Inhibitory Site On The Cal Pdz Domain, Yu Zhao, Patrick R. Cushing, David C. Smithson, Maria Pellegrini, Alexandre A. Pletnev, Sahar Al-Ayyoubi, Andrew V. Grassetti, Scott A. Gerber, R. Kiplin Guy, Dean R. Madden Jul 2018

Cysteine Modifiers Suggest An Allosteric Inhibitory Site On The Cal Pdz Domain, Yu Zhao, Patrick R. Cushing, David C. Smithson, Maria Pellegrini, Alexandre A. Pletnev, Sahar Al-Ayyoubi, Andrew V. Grassetti, Scott A. Gerber, R. Kiplin Guy, Dean R. Madden

Pharmaceutical Sciences Faculty Publications

Protein–protein interactions have become attractive targets for both experimental and therapeutic interventions. The PSD-95/Dlg1/ZO-1 (PDZ) domain is found in a large family of eukaryotic scaffold proteins that plays important roles in intracellular trafficking and localization of many target proteins. Here, we seek inhibitors of the PDZ protein that facilitates post-endocytic degradation of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR): the CFTR-associated ligand (CAL). We develop and validate biochemical screens and identify methyl-3,4-dephostatin (MD) and its analog ethyl-3,4-dephostatin (ED) as CAL PDZ inhibitors. Depending on conditions, MD can bind either covalently or non-covalently. Crystallographic and NMR data confirm that MD …


Artificial Gravity As A Countermeasure To The Cardiovascular Deconditioning Of Spaceflight: Gender Perspectives, Joyce M. Evans, Charles F. Knapp, Nandu Goswami Jul 2018

Artificial Gravity As A Countermeasure To The Cardiovascular Deconditioning Of Spaceflight: Gender Perspectives, Joyce M. Evans, Charles F. Knapp, Nandu Goswami

Biomedical Engineering Faculty Publications

Space flight-induced physiological deconditioning resulting from decreased gravitational input, decreased plasma volume, and disruption of regulatory mechanisms is a significant problem in returning astronauts as well as in normal aging. Here we review effects of a promising countermeasure on cardiovascular systems of healthy men and women undergoing Earth-based models of space-flight. This countermeasure is produced by a centrifuge and called artificial gravity (AG). Numerous studies have determined that AG improves orthostatic tolerance (as assessed by various protocols) of healthy ambulatory men, of men deconditioned by bed rest or by immersion (both wet and dry) and, in one case, following spaceflight. …


A Cross-Sectional Study Of The Use And Effectiveness Of The Individual Development Plan Among Doctoral Students, Nathan L. Vanderford, Teresa M. Evans, L. Todd Weiss, Lindsay Bira, Jazmin Beltran-Gastelum Jul 2018

A Cross-Sectional Study Of The Use And Effectiveness Of The Individual Development Plan Among Doctoral Students, Nathan L. Vanderford, Teresa M. Evans, L. Todd Weiss, Lindsay Bira, Jazmin Beltran-Gastelum

Toxicology and Cancer Biology Faculty Publications

Background: The Individual Development Plan (IDP) was introduced as a tool to aid in career planning for doctoral trainees. Despite the National Institutes of Health and academic institutions creating policies that mandate the use of IDPs, little information exists regarding the use and effectiveness of the career planning tool.
Methods: We conducted a multi-institutional, online survey to measure IDP use and effectiveness. The survey was distributed to potential respondents via social media and direct email. IDP survey questions were formatted using a five-point Likert scale (strongly agree, agree, neutral, disagree and strongly disagree). For data analysis purposes, responses were grouped …


High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb Jul 2018

High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1β (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and …


Periodic Catatonia Marked By Hypercortisolemia And Exacerbated By The Menses: A Case Report And Literature Review, Samantha Zwiebel, Alejandro G. Villasante Tezanos, Jose De Leon Jul 2018

Periodic Catatonia Marked By Hypercortisolemia And Exacerbated By The Menses: A Case Report And Literature Review, Samantha Zwiebel, Alejandro G. Villasante Tezanos, Jose De Leon

Psychiatry Faculty Publications

Kahlbaum first described catatonia; later Kraepelin, Gjessing, and Leonhard each defined periodic catatonia differently. A 48-year-old female with catatonia, whose grandmother probably died from it, was prospectively followed for >4 years in a US psychiatric state hospital. Through 4 catatonic episodes (one lasting 17 months) there were menstrual exacerbations of catatonia and increases in 4 biological variables: (1) creatine kinase (CK) up to 4,920 U/L, (2) lactate dehydrogenase (LDH) up to 424 U/L, (3) late afternoon cortisol levels up to 28.0 mcg/dL, and (4) white blood cell (WBC) counts up to 24,200/mm3 with neutrophilia without infections. Records from 17 …


Hyperpolarization By Activation Of Halorhodopsin Results In Enhanced Synaptic Transmission: Neuromuscular Junction And Cns Circuit, Matthew Mattingly, Kristin Weineck, Jennifer Costa, Robin L. Cooper Jul 2018

Hyperpolarization By Activation Of Halorhodopsin Results In Enhanced Synaptic Transmission: Neuromuscular Junction And Cns Circuit, Matthew Mattingly, Kristin Weineck, Jennifer Costa, Robin L. Cooper

Biology Faculty Publications

Optogenetics offers a unique method to regulate the activity of select neural circuits. However, the electrophysiological consequences of targeted optogenetic manipulation upon the entire circuit remain poorly understood. Analysis of the sensory-CNS-motor circuit in Drosophila larvae expressing eHpHR and ChR2-XXL revealed unexpected patterns of excitability. Optical stimulation of motor neurons targeted to express eNpHR resulted in inhibition followed by excitation of body wall contraction with repetitive stimulation in intact larvae. In situ preparations with direct electrophysiological measures showed an increased responsiveness to excitatory synaptic activity induced by sensory stimulation within a functional neural circuit. To ensure proper function of eNpHR …


A Dose Falloff Gradient Study In Rapidarc Planning Of Lung Stereotactic Body Radiation Therapy, Ganesh Narayanasamy, Dharmin Desai, Sanjay Maraboyina, Jose Penagaricano, Robert Zwicker, Ellis Lee Johnson Jul 2018

A Dose Falloff Gradient Study In Rapidarc Planning Of Lung Stereotactic Body Radiation Therapy, Ganesh Narayanasamy, Dharmin Desai, Sanjay Maraboyina, Jose Penagaricano, Robert Zwicker, Ellis Lee Johnson

Radiation Medicine Faculty Publications

Introduction: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D2cm and R50% as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics. Materials and Methods: In this retrospective study, 41 RapidArc lung SBRT plans with 2 or 3 …


Capn5 Expression In The Healthy And Regenerating Zebrafish Retina, Cagney E. Coomer, Ann C. Morris Jul 2018

Capn5 Expression In The Healthy And Regenerating Zebrafish Retina, Cagney E. Coomer, Ann C. Morris

Biology Faculty Publications

PURPOSE. Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a devastating inherited autoimmune disease of the eye that displays features commonly seen in other eye diseases, such as retinitis pigmentosa and diabetic retinopathy. ADNIV is caused by a gain-of-function mutation in Calpain-5 (CAPN5), a calcium-dependent cysteine protease. Very little is known about the normal function of CAPN5 in the adult retina, and there are conflicting results regarding its role during mammalian embryonic development. The zebrafish (Danio rerio) is an excellent animal model for studying vertebrate development and tissue regeneration, and represents a novel model to explore the …


A Broad Spectrum Racemase In Pseudomonas Putida Kt2440 Plays A Key Role In Amino Acid Catabolism, Atanas D. Radkov, Luke A. Moe Jun 2018

A Broad Spectrum Racemase In Pseudomonas Putida Kt2440 Plays A Key Role In Amino Acid Catabolism, Atanas D. Radkov, Luke A. Moe

Plant and Soil Sciences Faculty Publications

The broad-spectrum amino acid racemase (Alr) of Pseudomonas putida KT2440 preferentially interconverts the L- and D-stereoisomers of Lys and Arg. Despite conservation of broad-spectrum racemases among bacteria, little is known regarding their physiological role. Here we explore potential functional roles for Alr in P. putida KT2440. We demonstrate through cellular fractionation that Alr enzymatic activity is found in the periplasm, consistent with its putative periplasm targeting sequence. Specific activity of Alr is highest during exponential growth, and this activity corresponds with an increased accumulation of D-Lys in the growth medium. An alr gene knockout strain (Δalr) was generated …