Medicine and Health Sciences Commons^™

Cryptorchidism And Infertility In Rats With Targeted Disruption Of The Adamts16 Locus, Shakila Abdul-Majeed, Blair Mell, Surya M. Nauli, Bina Joe

Pharmacy Faculty Articles and Research

A Disintegrin And Metalloproteinase with ThromboSpondin motifs16 (ADAMTS-16) is a member of a family of metalloproteinases. Using a novel zinc-finger nuclease based gene-edited rat model harboring a targeted mutation of the Adamts16 locus, we previously reported this gene to be linked to blood pressure regulation. Here we document our observation with this model that Adamts16 is essential for normal development of the testis. Absence of Adamts16 in the homozygous Adamts16(mutant) males resulted in cryptorchidism and male sterility. Heterozygous Adamts16(mutant) males were normal, indicating that this is a recessive trait. Testes of homozygous Adamts16(mutant) males were significantly smaller with significant histological …

Profiling Thiol Metabolites And Quantification Of Cellular Glutathione Using Ft-Icr-Ms Spectrometry, Sadakatali S. Gori, Pawel Lorkiewicz, Daniel S. Ehringer, Alex C. Belshoff, Richard M. Higashi, Teresa W-M Fan, Michael H. Nantz

Toxicology and Cancer Biology Faculty Publications

We describe preparation and use of the quaternary ammonium-based α-iodoacetamide QDE and its isotopologue *QDE as reagents for chemoselective derivatization of cellular thiols. Direct addition of the reagents to live cells followed by adduct extraction into n-butanol and analysis by FT-ICR-MS provided a registry of matched isotope peaks from which molecular formulae of thiol metabolites were derived. Acidification to pH 4 during cell lysis and adduct formation further improves the chemoselectivity for thiol derivatization. Examination of A549 human lung adenocarcinoma cells using this approach revealed cysteine, cysteinylglycine, glutathione, and homocysteine as principal thiol metabolites as well as the sulfinic acid …

Determination Of Corrosion Inhibitor Lubricity Improver In Jet Fuel By Liquid Chromatography-Electrospray Ionization Mass Spectrometry, David W. Johnson, Milissa Flake, Ryan Adams

Chemistry Faculty Publications

Military jet fuel (JP-8) is very similar to commercial jet fuel (Jet A) except for the presence of three additives, fuel system icing inhibitor, corrosion inhibitor–lubricity improver (CI-LI), and antistatic additive, which are added to improve characteristics of JP-8. Of particular interest is the CI-LI additive; the most common active ingredient is a dimer of linoleic acid. This article focuses on quantification of the active ingredient in the CI-LI additive by liquid chromatography–mass spectrometry (LC–MS). This method will allow the determination of CI-LI content in military jet fuel samples.

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

Small-Molecule Probes Targeting The Viral Ppxy-Host Nedd4 Interface Block Egress Of A Broad Range Of Rna Viruses., Ziying Han, Jianhong Lu, Yuliang Liu, Benjamin Davis, Michael S Lee, Mark A Olson, Gordon Ruthel, Bruce D Freedman, Matthias J. Schnell, Jay E Wrobel, Allen B Reitz, Ronald N Harty

Department of Microbiology and Immunology Faculty Papers

Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system, …

Systemic Hematogenous Maintenance Of Memory Inflation By Mcmv Infection., Corinne J Smith, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, …

A Likelihood Approach To Estimate The Number Of Co-Infections, Kristian A. Schneider, Ananias A. Escalante

Harold W. Manter Laboratory of Parasitology: Library Materials

Article abstract:

The number of co-infections of a pathogen (multiplicity of infection or MOI) is a relevant parameter in epidemiology as it relates to transmission intensity. Notably, such quantities can be built into a metric in the context of disease control and prevention. Having applications to malaria in mind, we develop here a maximum-likelihood (ML) framework to estimate the quantities of interest at low computational and no additional costs to study designs or data collection. We show how the ML estimate for the quantities of interest and corresponding confidence-regions are obtained from multiple genetic loci. Assuming specifically that infections are …

Outcomes Of Third-Year Pharmacy Students Using Technology For Instruction In An Infectious Diseases Elective Course, Joanna Headley, Pharmd, Candidate 2015, Bhavik Shah, Pharmd, Bcps, Aahivp, Jason J. Schafer, Pharmd, Mph, Bcps, Aahivp

College of Pharmacy Faculty Papers

BACKGROUND

• The use of technology both inside and outside the classroom is integral to the facilitation of pharmacy students’ learning.¹

• Technology is allowing education to restructure classroom time for something other than simple transmission of factual information and to adopt an evidence-based approach to instructional innovation and reform.¹

• Pharmacy colleges and schools should incorporate technologies that students frequently use and that positively impact learning.²

• Limited assessment of the impact of technology on student performance is available including teaching and learning from peers.^1,2

• An infectious diseases elective course developed at the Jefferson School of Pharmacy incorporated the …

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A New Reinforced Fibrin Collagen Glycosaminoglycan Material To Resist Tissue Contraction In Heart Valves, Claire Brougham, Gerard Cooney, Stefan Jockenhoevel, Thomas Flanagan, Fergal O'Brien

Conference Papers

A crosslinked, multicomponent scaffold of collagen, GAG and fibrin has been characterised for heart valve applications. Fibrin gels reinforced with a 0.75% collagen, 0.044% GAG scaffolds can resist VSMC induced contraction significantly more than fibrin-only gels, while allowing cell proliferation and maintaining excellent cell viability. This improvement in structural integrity may facilitate the use of fibrin based materials for heart valve tissue engineering.

The Regulator Of G Protein Signaling (Rgs) Domain Of G Protein-Coupled Receptor Kinase 5 (Grk5) Regulates Plasma Membrane Localization And Function., Hua Xu, Xiaoshan Jiang, Ke Shen, Christopher C. Fischer, Philip B Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs at the plasma membrane (PM). Here GRK5/GRK4 chimeras and point mutations in GRK5 identify a short sequence within the regulator of G protein signaling (RGS) domain in GRK5 that is critical for GRK5 PM localization. This region of the RGS domain of GRK5 coincides with a region of GRK6 and GRK1 shown to form a hydrophobic dimeric interface (HDI) in crystal structures. Coimmunoprecipitation (coIP) and acceptor photobleaching fluorescence resonance energy transfer assays show that expressed GRK5 self-associates in cells, whereas GRK5-M165E/F166E (GRK5-EE), containing hydrophilic mutations in the HDI region of …

Time Course Of Cocaine-Induced Behavioral And Neurochemical Plasticity, Victoria Lutgen, Linghai Kong, Kristen S. Kau, Aric Madayag, John Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Factors that result in augmented reinstatement, including increased withdrawal period duration and high levels of cocaine consumption, may provide insight into relapse vulnerability. The neural basis of augmented reinstatement may arise from more pronounced changes in plasticity required for reinstatement and/or the emergence of plasticity expressed only during a specific withdrawal period or under specific intake conditions. In this study, we examined the impact of withdrawal period duration and cocaine intake on the magnitude of cocaine-primed reinstatement and extracellular glutamate in the nucleus accumbens, which has been shown to be required for cocaine-primed reinstatement. Rats were assigned to self-administer under …

Characterization Of Primary Care Clinicians’ Use Of Genomic And Pharmacogenomic Testing, Brian Stello Md, Heather Bittner-Fagan Md, Mph, Christopher V. Chambers Md, Melanie B. Johnson Mpa, Geoffrey Mills Md, Phd, Michael P. Rosenthal Md, Kyle Shaak Bs

Department of Family Medicine

No abstract provided.

Crohn’S Disease Linked Polymorphisms Associated With Autophagy Contribute To Th17 Cell Induction Through Increasing The Expression Of Il-1Β And Tnf-Α, Daniel Clayton Morse

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Genome wide association studies (GWAS) have linked polymorphisms in autophagy genes to Crohn’s Disease (CD). Interestingly, recent studies have shown that defective autophagy leads to increased levels of the cytokines IL-1b and TNF-a, which play a critical role in Th17 cell differentiation. This is significant because CD is marked by a Th17 cell mediated inflammatory response. This article examines the manners in which defective expression of autophagy linked proteins, can indirectly amplify and sustain Th17 cell induction through increasing the production of Th17 positively differentiating cytokines (IL-1b and TNF-a) and decreasing the production of a Th17 down regulating cytokine, IL-10.

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Application Of Nuclear Magnetic Resonance Based Metabolomics To Study The Central Metabolism Of Staphylococci, Bo Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

Metabolomics studies the collection of small molecules (metabolites) involved in enzymatically catalyzed reactions, cell signaling and cellular structure. Perturbations in metabolite concentrations have been used to reflect the activity of corresponding enzymes or proteins. Nuclear magnetic resonance (NMR) spectroscopy is a well-known approach for the structure determination of biological macromolecules. Alternatively, NMR has recently been established as a valuable tool of metabolomics, in which NMR spectral signals correlate small molecules with cellular activities. This has been accomplished through the chemometric analysis of high-throughput one dimensional ¹H spectra (metabolic fingerprinting) and quantitative metabolite identification based on two dimensional ¹H, …

Identification Of Cd24 As A Cancer Stem Cell Marker In Human Nasopharyngeal Carcinoma, Chun-Hung Yang, Hui-Ling Wang, Yi-Sheng Lin, K. P. Shravan Kumar, Hung-Chi Lin, Chih-Jung Chang, Chia-Chen Lu, Tsung-Teng Huang, Jan Martel, David M. Ojcius, Yu-Sun Chang, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24⁺ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24⁺ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged …

A Retrospective Chart Review To Determine Proper Stress Test Utilization In Low Risk Chest Pain Patients, Yassir Nawaz Md, Bilal Ayub Md

Department of Medicine

No abstract provided.

Accurate Murmur Recognition By Cardiologists – Premature Requiem Or Phoenix Rising?, Yassir Nawaz Md, Matthew W. Martinez Md, Michael J. Barrett Md

Department of Medicine

No abstract provided.

Correlating Periodontal Disease And Cardiovascular Disease: A Comparative Study Of Research Methodology, Alexandra Hensen

Honors Theses

This meta-analysis compares and contrasts three types of population-based research methodology currently used to analyze correlations between Periodontal disease and Cardiovascular disease, the most wide spread diseases in the Western industrialized world. The three studies that were analyzed in this thesis include: "Gender Differences in the Relationship Between Periodontal Disease, Tooth Loss, and Atherosclerosis," published in the Journal of Stroke and Cerebrovascular Diseases (2013), this was a cross-sectional population-based study; "Periodontal Disease and Mortality in Type 2 Diabetes" published in Diabetes Care (2005), this was a longitudinal population-based study; and "Identification of a Shared Genetic Susceptibility Locus for Coronary Heart …

A Central Role For Carbon-Overflow Pathways In The Modulation Of Bacterial Cell Death., Vinai Chittezham Thomas, Marat Sadykov, Sujata S. Chaudhari, Joselyn Jones, Jennifer L. Endres, Todd J. Widhelm, Jong-Sam Ahn, Randeep S. Jawa, Matthew C. Zimmerman, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux …

Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder

Dartmouth Scholarship

Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these …

Overt Responses During Covert Orienting., Brian D Corneil, Douglas P Munoz

Brain and Mind Institute Researchers' Publications

A distributed network of cortical and subcortical brain areas controls our oculomotor behavior. This network includes the superior colliculus (SC), which coordinates an ancient visual grasp reflex via outputs that ramify widely within the brainstem and spinal cord, accessing saccadic and other premotor and autonomic circuits. In this Review, we discuss recent results correlating subliminal SC activity in the absence of saccades with diverse components of the visual grasp reflex, including neck and limb muscle recruitment, pupil dilation, and microsaccade propensity. Such subtle manifestations of covert orienting are accessible in the motor periphery and may provide the next generation of …

Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …

Age-Associated Increases In Fkbp51 Facilitate Tau Neurotoxicity, Laura J. Blair

USF Tampa Graduate Theses and Dissertations

Tau is a protein which regulates microtubule stability and is heavily involved in axonal transport. This stability is dynamically controlled in part by over 40 phosphorylation sites across the tau protein which allows for binding and release from the microtubules. However, if abnormal hyperphosphorylation occurs, tau dissociates from the microtubules. Once released, the microtubules become unstable and the aberrant tau mislocalizes from the axon to the somatodendric compartment, where it aggregates. These aggregates are made of many pathological forms of tau including oligomeric species, paired helical filaments, and neurofibrillary tangles, all of which have associated toxicities. Tau pathology is a …

Investigating The Viability Of Two Stenotrophomonas Maltophilia Isolates After Air-Drying, Samantha Lane, Joanna Brooke

DePaul Discoveries

Abstract

Stenotrophomonas maltophilia is a water-borne infectious bacterium that is found in both clinical (hospitals) and non-clinical environments. This human pathogen is commonly recovered from respiratory tract infections. A recent study at a hospital in Taiwan suggested that dry patient charts can serve as a vehicle of transmission of this bacterium⁷. As S. maltophilia is not commonly isolated from dry surfaces, this current study tested the hypothesis that this pathogen can remain viable for some time on a dry surface. This study was designed to determine how long S. maltophilia could remain viable after air-drying by observing …

New Clues To Understanding Hiv Nonprogressors: Low Cholesterol Blocks Hiv Trans Infection, Vinayaka R. Prasad, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A small percentage of HIV-infected subjects (2 to 15%) are able to control disease progression for many years without antiretroviral therapy. Years of intense studies of virologic and immunologic mechanisms of disease control in such individuals yielded a number of possible host genes that could be responsible for the preservation of immune functions, from immune surveillance genes, chemokines, or their receptors to anti-HIV restriction factors. A recent mBiopaper by Rappocciolo et al. (G. Rappocciolo, M. Jais, P. Piazza, T. A. Reinhart, S. J. Berendam, L. Garcia-Exposito, P. Gupta, and C. R. Rinaldo, mBio 5:e01031-13, 2014) describes another potential factor …

White-Tailed Deer Are A Biotic Filter During Community Assembly, Reducing Species And Phylogenetic Diversity, Danielle R. Begley-Miller, Andrew L. Hipp, Bethany H. Brown, Marlene Hahn, Thomas P. Rooney

Biological Sciences Faculty Publications

Community assembly entails a filtering process, where species found in a local community are those that can pass through environmental (abiotic) and biotic filters and successfully compete. Previous research has demonstrated the ability of white-tailed deer (Odocoileus virginianus) to reduce species diversity and favour browse-tolerant plant communities. In this study, we expand on our previous work by investigating deer as a possible biotic filter altering local plant community assembly. We used replicated 23-year-old deer exclosures to experimentally assess the effects of deer on species diversity (H′), richness (SR), phylogenetic community structure and phylogenetic diversity in paired …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Acute Sterol O-Acyltransferase 2 (Soat2) Knockdown Rapidly Mobilizes Hepatic Cholesterol For Fecal Excretion, Stephanie M. Marshall, Anthony D Gromovsky, Kathryn L. Kelley, Matthew A. Davis, Martha D. Wilson, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Lawrence L. Rudel, J. Mark Brown, Ryan E. Temel

Saha Cardiovascular Research Center Faculty Publications

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting …

Genome-Wide Analysis Of Regulatory Proteases Sequences Identified Through Bioinformatics Data Mining In Taenia Solium, Hong-Bin Yan, Zhong-Zi Lou, Li Li, Paul J. Brindley, Yadong Zheng, Xuenong Luo, Junling Hou, Aijiang Guo, Wan-Zhong Jia, Xuepeng Cai

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Cysticercosis remains a major neglected tropical disease of humanity in many regions, especially in sub-Saharan Africa, Central America and elsewhere. Owing to the emerging drug resistance and the inability of current drugs to prevent re-infection, identification of novel vaccines and chemotherapeutic agents against Taenia solium and related helminth pathogens is a public health priority. The T. solium genome and the predicted proteome were reported recently, providing a wealth of information from which new interventional targets might be identified. In order to characterize and classify the entire repertoire of protease-encoding genes of T. solium, which act fundamental biological roles in …