Digital Commons Network^™

Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi

Center for Environmental and Systems Biochemistry Faculty Publications

Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different …

Cyclin D1 Restrains Oncogene-Induced Autophagy By Regulating The Ampk-Lkb1 Signaling Axis., Mathew C. Casimiro, Gabriele Disante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Timothy G. Pestell, Sara Bisetto, Marco A. Velasco-Velázquez, Xuanmao Jiao, Zhiping Li, Christine M. Kusminski, Erin L. Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E. Scherer, Richard Pestell

Department of Cancer Biology Faculty Papers

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 …

Proteogenomic Analysis Of The Total And Surface-Exposed Proteomes Of Plasmodium Vivax Salivary Gland Sporozoites., Kristian E Swearingen, Scott E Lindner, Erika L Flannery, Ashley M Vaughan, Robert D Morrison, Rapatbhorn Patrapuvich, Cristian Koepfli, Ivo Muller, Aaron Jex, Robert L Moritz, Stefan H I Kappe, Jetsumon Sattabongkot, Sebastian A Mikolajczak

Articles, Abstracts, and Reports

Plasmodium falciparum and Plasmodium vivax cause the majority of human malaria cases. Research efforts predominantly focus on P. falciparum because of the clinical severity of infection and associated mortality rates. However, P. vivax malaria affects more people in a wider global range. Furthermore, unlike P. falciparum, P. vivax can persist in the liver as dormant hypnozoites that can be activated weeks to years after primary infection, causing relapse of symptomatic blood stages. This feature makes P. vivax unique and difficult to eliminate with the standard tools of vector control and treatment of symptomatic blood stage infection with antimalarial drugs. Infection …

Targeting Antioxidant Enzyme Expression As A Therapeutic Strategy For Ischemic Stroke, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

During ischemic stroke, neurons and glia are subjected to damage during the acute and neuroinflammatory phases of injury. Production of reactive oxygen species (ROS) from calcium dysregulation in neural cells and the invasion of activated immune cells are responsible for stroke-induced neurodegeneration. Scientists have failed thus far to identify antioxidant-based drugs that can enhance neural cell survival and improve recovery after stroke. However, several groups have demonstrated success in protecting against stroke by increasing expression of antioxidant enzymes in neural cells. These enzymes, which include but are not limited to enzymes in the glutathione peroxidase, catalase, and superoxide dismutase families, …

Sex Differences In The Drinking Response To Angiotensin Ii (Angii): Effect Of Body Weight, Jessica Santollo, Ann-Marie Torregrossa, Derek Daniels

Biology Faculty Publications

Sex differences in fluid intake stimulated by angiotensin II (AngII) have been reported, but the direction of the differences is inconsistent. To resolve these discrepancies, we measured water intake by male and female rats given AngII. Males drank more than females, but when intake was normalized to body weight, the sex difference was reversed. Weight-matched males and females, however, had no difference in intake. Using a linear mixed model analysis, we found that intake was influenced by weight, sex, and AngII dose. We used linear regression to disentangle these effects further. Comparison of regression coefficients revealed sex and weight differences …

A Phase Iii, Randomized, Multi-Center, Double Blind, Placebo Controlled Study Of Safety And Efficacy Of Lofexidine For Relief Of Symptoms In Individuals Undergoing Inpatient Opioid Withdrawal, Charles W. Gorodetzky, Sharon L. Walsh, Peter R. Martin, Andrew J. Saxon, Kristen L. Gullo, Kousick Biswas

Center on Drug and Alcohol Research Faculty Publications

Background: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine.

Methods: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; …

Pioglitazone Treatment Following Spinal Cord Injury Maintains Acute Mitochondrial Integrity And Increases Chronic Tissue Sparing And Functional Recovery, Samir P. Patel, David H. Cox, Jenna L. Gollihue, William M. Bailey, Werner J. Geldenhuys, John C. Gensel, Patrick G. Sullivan, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

Pioglitazone is an FDA-approved PPAR-γ agonist drug used to for treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice. Mice received either vehicle or pioglitazone (10 mg/kg) at either 15 min or 3 hr after injury (75 kDyn at …

The Implications Of Eco-Evolutionary Processes For The Emergence Of Marine Plankton Community Biogeography, Boris Sauterey, Ben Ward, Jonathan Rault, Chris Bowler, David Claessen

Entomology Faculty Publications

Models of community assembly have been used to illustrate how the many functionally diverse species that compose plankton food webs can coexist. However, the evolutionary processes leading to the emergence of plankton food webs and their interplay with migratory processes and spatial heterogeneity are yet to be explored. We study the eco-evolutionary dynamics of a modeled plankton community structured in both size and space and physiologically constrained by empirical data. We demonstrate that a complex yet ecologically and evolutionarily stable size-structured food web can emerge from an initial set of two monomorphic phytoplankton and zooplankton populations. We also show that …

Animal Models Of Rheumatoid Pain: Experimental Systems And Insights., Bradford D Fischer, Adeshina Adeyemo, Michael E O'Leary, Andrea Bottaro

Cooper Medical School of Rowan University Departmental Research

Severe chronic pain is one of the hallmarks and most debilitating manifestations of inflammatory arthritis. It represents a significant problem in the clinical management of patients with common chronic inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies. The functional links between peripheral inflammatory signals and the establishment of the neuroadaptive mechanisms acting in nociceptors and in the central nervous system in the establishment of chronic and neuropathic pain are still poorly understood, representing an area of intense study and translational priority. Several well-established inducible and spontaneous animal models are available to study the onset, progression and chronicization …

Cib2 Interacts With Tmc1 And Tmc2 And Is Essential For Mechanotransduction In Auditory Hair Cells, Arnaud P. J. Giese, Yi-Quan Tang, Ghanshyam P. Sinha, Michael R. Bowl, Adam C. Goldring, Andrew Parker, Mary J. Freeman, Steve D. M. Brown, Saima Riazuddin, Robert Fettiplace, William R. Schafer, Gregory I. Frolenkov, Zubair M. Ahmed

Physiology Faculty Publications

Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of …

Nlrp9b Inflammasome Restricts Rotavirus Infection In Intestinal Epithelial Cells, Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah Palm, Richard Flavell

NYMC Faculty Publications

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our …

Degenerative Changes Of The Canine Cervical Spine After Discectomy Procedures, An In Vivo Study., Peter Grunert, Yu Moriguchi, Brian P Grossbard, Rodolfo J Ricart Arbona, Lawrence J Bonassar, Roger Härtl

Articles, Abstracts, and Reports

BACKGROUND: Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo.

RESULTS: Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II …

A Direct In Vivo Comparison Of The Melanocortin Monovalent Agonist Ac-His-Dphe-Arg-Trp-Nh2 Versus The Bivalent Agonist Ac-His-Dphe-Arg-Trp-Pedg20-His-Dphe-Arg-Trp-Nh2: A Bivalent Advantage, Cody J Lensing, Danielle N Adank, Stacey L Wilber, Katie T Freeman, Sathya M Schnell, Robert Charles Speth, Adam T Zarth, Carrie Haskell-Luevano

Faculty Articles

Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro, however studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH₂, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH₂ on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an anti-obesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm. Treatment with CJL-1-87 significantly decreased food intake compared to CJL-1-14 or saline (50% less intake 2 to 8 hours after …

Ca2+-Permeable Ampars Mediate Glutamatergic Transmission And Excitotoxic Damage At The Hair Cell Ribbon Synapse, Joy Y. Sebe, Soyoun Cho, Lavinia Sheets, Mark A. Rutherford, Henrique Von Gersdorff, David W. Raible

Open Access Publications

We report functional and structural evidence for GluA2-lacking Ca

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

A Linkage Map For The Newt Notophthalmus Viridescens: Insights In Vertebrate Genome And Chromosome Evolution, Melissa C. Keinath, S. Randal Voss, Panagiotis A. Tsonis, Jeramiah J. Smith

Biology Faculty Publications

Genetic linkage maps are fundamental resources that enable diverse genetic and genomic approaches, including quantitative trait locus (QTL) analyses and comparative studies of genome evolution. It is straightforward to build linkage maps for species that are amenable to laboratory culture and genetic crossing designs, and that have relatively small genomes and few chromosomes. It is more difficult to generate linkage maps for species that do not meet these criteria. Here, we introduce a method to rapidly build linkage maps for salamanders, which are known for their enormous genome sizes. As proof of principle, we developed a linkage map with thousands …

Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ca²⁺ is a ubiquitous intracellular messenger that controls diverse cellular functions but can become toxic and cause cell death. Selective control of specific targets depends on spatiotemporal patterning of the calcium signal and decoding it by multiple, tunable, and often strategically positioned Ca²⁺-sensing elements. Ca²⁺ is detected by specialized motifs on proteins that have been biochemically characterized decades ago. However, the field of Ca²⁺ sensing has been reenergized by recent progress in fluorescent technology, genetics, and cryo-EM. These approaches exposed local Ca²⁺-sensing mechanisms inside organelles and at the organellar interfaces, revealed how Ca …

Nfatc2 Modulates Microglial Activation In The Aβpp/Ps1 Mouse Model Of Alzheimer's Disease, Gunjan D. Manocha, Atreyi Ghatak, Kendra L. Puig, Susan D. Kraner, Christopher M. Norris, Colin K. Combs

Pharmacology and Nutritional Sciences Faculty Publications

Alzheimer’s disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide. We observed that the NFATc2 isoform was the most highly expressed in murine microglia cultures, and inhibition or …

Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg

Faculty Articles

Resistance to angiotensin II (Ang II)–induced hypertension in T-cell–deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1^−/−-M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6.Rag1^−/−-M and male wild-type littermates. Moreover, there were no differences in the time course or magnitude increase …

Ginseng And Obesity: Observations And Understanding In Cultured Cells, Animals And Humans, Longyun Zhang, Carlos Virgous, Hongwei Si

Human Sciences Faculty Research

Ginseng, a traditional medical herb, has been reported having beneficial effects in fatigue, heart diseases, diabetes, immune function and erectile dysfunction. In recent years, increasing investigations have been conducted on ginseng in preventing and treating of obesity, one of the major worldwide escalating public health concerns. However, the effect and the relevant mechanisms behind how ginseng works as an antiobesity treatment are still controversial. In this review, we briefly discussed the chemical structures, metabolism and pharmacokinetics of ginseng and its major bioactive components ginsenosides. The major focus is on the antiobesity effects and the physiological, cellular and molecular mechanisms of …

A Comparison Of Nucleosome Organization In Drosophila Cell Lines, Rebecca L. Martin, John Maiorano, Greg J. Beitel, John F. Marko, Graham Mcvicker, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Changes in the distribution of nucleosomes along the genome influence chromatin structure and impact gene expression by modulating the accessibility of DNA to transcriptional machinery. However, the role of genome-wide nucleosome positioning in gene expression and in maintaining differentiated cell states remains poorly understood. Drosophila melanogastercell lines represent distinct tissue types and exhibit cell-type specific gene expression profiles. They thus could provide a useful tool for investigating cell-type specific nucleosome organization of an organism’s genome. To evaluate this possibility, we compared genome-wide nucleosome positioning and occupancy in five different Drosophila tissue-specific cell lines, and in reconstituted chromatin, and then …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

Peripheral Administration Of The Soluble Tnf Inhibitor Xpro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, And Rescues Impaired Long-Term Potentiation In 5xfad Mice, Kathryn P. Macpherson, Pradoldej Sompol, George T. Kannarkat, Jianjun Chang, Lindsey Sniffen, Mary E. Wildner, Christopher M. Norris, Malú G. Tansey

Sanders-Brown Center on Aging Faculty Publications

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer’s disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII …

Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has …

Simulating Within-Vector Generation Of The Malaria Parasite Diversity, Lauren M. Childs, Olivia F. Prosper

Mathematics Faculty Publications

Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken. To examine the role that vector biology plays in modulating parasite diversity, we develop a two-part model framework …

A Consensus Definitive Classification Of Scavenger Receptors And Their Roles In Health And Disease, Mercy R Prabhudas, Cynthia L Baldwin, Paul L Bollyky, Dawn M E Bowdish, Kurt Drickamer, Maria Febbraio, Joachim Herz, Lester Kobzik, Monty Krieger, John Loike, Benita Mcvicker, Terry K Means, Soren K Moestrup, Steven R Post, Tatsuya Sawamura, Samuel Silverstein, Robert Charles Speth, Janice C Telfer, Geoffrey M Thiele, Xiang-Yang Wang, Samuel D Wright, Joseph El Khoury

Faculty Articles

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and …

The Effects Of Nicotine In The Neonatal Quinpirole Rodent Model Of Psychosis: Neural Plasticity Mechanisms And Nicotinic Receptor Changes, Daniel J. Peterson, W. Drew Gill, John M. Dose, Donald B. Hoover, James R. Pauly, Elizabeth D. Cummins, Katherine C. Burgess, Russell W. Brown

Pharmaceutical Sciences Faculty Publications

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given …

Single-Trait And Multi-Trait Genome-Wide Association Analyses Identify Novel Loci For Blood Pressure In African-Ancestry Populations, Jingjing Liang, Thu H. Le, Digna R. Velez Edwards, Bamidele O. Tayo, Kyle J. Gaulton, Jennifer A. Smith, Yingchang Lu, Richard A. Jensen, Guanjie Chen, Lisa R. Yanek, Karen Schwander, Salman M. Tajuddin, Tamar Sofer, Wonji Kim, James Kayima, Colin A. Mckenzie, Ervin Fox, Michael A. Nalls, J. Hunter Young, Yan V. Sun, Jacqueline M. Lane, Sylvia Cechova, Jie Zhou, Hua Tang, Myriam Fornage, Solomon K. Musani, Heming Wang, Juyoung Lee, Adebowale Adeyemo, Albert W. Dreisbach, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10⁻⁸) for either systolic and …

A Serosurvey Of Selected Cystogenic Coccidia In Spanish Equids: First Detection Of Anti-Besnoitia Spp. Specific Antibodies In Europe, Daniel Gutiérrez-Expósito, Ignacio García-Bocanegra, Daniel K. Howe, Antonio Arenas-Montes, Michelle R. Yeargan, Sallyanne L. Ness, Luis M Ortega-Mora, G. Álvarez-García

Veterinary Science Faculty Publications

Background: Equine besnoitiosis, caused by Besnoitia bennetti, and equine protozoal myeloencephalitis (EPM), caused by Sarcocystis neurona and Neospora hughesi are relevant equine diseases in the Americas that have been scarcely studied in Europe. Thus, a serosurvey of these cystogenic coccidia was carried out in Southern Spain. A cross-sectional study was performed and serum samples from horses (n = 553), donkeys (n = 85) and mules (n = 83) were included. An in-house enzyme-linked immunosorbent assay (ELISA) was employed to identify a Besnoitia spp. infection and positive results were confirmed by an a posteriori western blot. For Neospora …