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Sex Differences In The Drinking Response To Angiotensin Ii (Angii): Effect Of Body Weight, Jessica Santollo, Ann-Marie Torregrossa, Derek Daniels Jul 2017

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 …


The Implications Of Eco-Evolutionary Processes For The Emergence Of Marine Plankton Community Biogeography, Boris Sauterey, Ben Ward, Jonathan Rault, Chris Bowler, David Claessen Jul 2017

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 …


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 Jul 2017

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 …


Black Lives, Sacred Humanity, And The Racialization Of Nature, Or Why America Needs Religious Naturalism Today, Carol W. White Jul 2017

Black Lives, Sacred Humanity, And The Racialization Of Nature, Or Why America Needs Religious Naturalism Today, Carol W. White

Faculty Journal Articles

Embedded in persistent representations of people of African descent as inferior beings or subpar humans are problematic notions of animality, race, and nature in the U.S., or a lethal combination of intimately conjoined white supremacy and species supremacy. Confronting these processes is a model of African American religious naturalism, which presupposes human animals’ deep, inextricable homology with each other and with other natural processes. Building on the ideas of Anna J. Cooper, W. E. B. du Bois, and James Baldwin, this model of religious naturalism emphasizes humans as sacred centers of value and distinct movements of nature itself where deep …


Animal Models Of Rheumatoid Pain: Experimental Systems And Insights., Bradford D Fischer, Adeshina Adeyemo, Michael E O'Leary, Andrea Bottaro Jun 2017

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 …


Nlrp9b Inflammasome Restricts Rotavirus Infection In Intestinal Epithelial Cells, Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah Palm, Richard Flavell Jun 2017

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 …


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 Jun 2017

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 Jun 2017

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


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 Jun 2017

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 Jun 2017

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 …


Bcl11b And Combinatorial Resolution Of Cell Fate In The T-Cell Gene Regulatory Network., William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg Jun 2017

Bcl11b And Combinatorial Resolution Of Cell Fate In The T-Cell Gene Regulatory Network., William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg

Articles, Abstracts, and Reports

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment …


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 Jun 2017

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 Jun 2017

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 …


Insect Immunity Varies Idiosyncratically During Overwintering., Laura V Ferguson, Brent J Sinclair Jun 2017

Insect Immunity Varies Idiosyncratically During Overwintering., Laura V Ferguson, Brent J Sinclair

Biology Publications

Overwintering insects face multiple stressors, including pathogen and parasite pressures that shift with seasons. However, we know little of how the insect immune system fluctuates with season, particularly in the overwintering period. To understand how immune activity changes across autumn, winter, and spring, we tracked immune activity of three temperate insects that overwinter as larvae: a weevil (Curculio sp., Coleoptera), gallfly (Eurosta solidaginis, Diptera), and larvae of the lepidopteran Pyrrharctia isabella. We measured baseline circulating hemocyte numbers, phenoloxidase activity, and humoral antimicrobial activity, as well as survival of fungal infection and melanization response at 12°C and 25°C to capture any …


Ginseng And Obesity: Observations And Understanding In Cultured Cells, Animals And Humans, Longyun Zhang, Carlos Virgous, Hongwei Si Jun 2017

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 Jun 2017

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 …


C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm Jun 2017

C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …


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 Jun 2017

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 …


Variation In Dna Methylation Is Not Consistently Reflected By Sociality In Hymenoptera, Karl M. Glastad, Samuel V. Arsenault, Kim L. Vertacnik, Scott M. Geib, Sasha Kay, Bryan N. Danforth, Sandra M. Rehan, Catherine R. Linnen, Sarah D. Kocher, Brendan G. Hunt Jun 2017

Variation In Dna Methylation Is Not Consistently Reflected By Sociality In Hymenoptera, Karl M. Glastad, Samuel V. Arsenault, Kim L. Vertacnik, Scott M. Geib, Sasha Kay, Bryan N. Danforth, Sandra M. Rehan, Catherine R. Linnen, Sarah D. Kocher, Brendan G. Hunt

Biology Faculty Publications

Changes in gene regulation that underlie phenotypic evolution can be encoded directly in the DNA sequence or mediated by chromatin modifications such as DNA methylation. It has been hypothesized that the evolution of eusocial division of labor is associated with enhanced gene regulatory potential, which may include expansions in DNA methylation in the genomes of Hymenoptera (bees, ants, wasps, and sawflies). Recently, this hypothesis garnered support from analyses of a commonly used metric to estimate DNA methylation in silico, CpG content. Here, we test this hypothesis using direct, nucleotide-level measures of DNA methylation across nine species of Hymenoptera. In doing …


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 Jun 2017

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 Jun 2017

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 Jun 2017

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 May 2017

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 May 2017

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 …


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 May 2017

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 …


Ccr4 Is A Determinant Of Melanoma Brain Metastasis., Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz May 2017

Ccr4 Is A Determinant Of Melanoma Brain Metastasis., Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz

Articles, Abstracts, and Reports

We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients. Notably, the expression of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages …


Hibernator And Non-Hibernator Responses To Acute Changes In Water Intake, Sydni S. Andruskiewicz May 2017

Hibernator And Non-Hibernator Responses To Acute Changes In Water Intake, Sydni S. Andruskiewicz

All College Thesis Program, 2016-2019

Hibernating animals undergo dramatic changes in metabolic rates during torpor. One of most notable changes in these animals is the ability to maintain blood pressure and perfuse certain organs. Consequentially, blood perfusion to the kidneys is greatly decreased and the ability to concentrate urine halts. However, about once a week, torpor is interrupted and the animal becomes active to rewarm itself about once a week. This activity induces rapid regeneration of the extracellular osmotic gradient of the kidney, and allows urine to be concentrated. Nonetheless, regaining the extracellular osmotic gradient creates a potentially fatal consequence to the kidney cells. To …


Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim May 2017

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …


Are Cdi Systems Multicolored, Facultative, Helping Greenbeards?, Elizabeth S. Danka, Erin C. Garcia, Peggy A. Cotter May 2017

Are Cdi Systems Multicolored, Facultative, Helping Greenbeards?, Elizabeth S. Danka, Erin C. Garcia, Peggy A. Cotter

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Competitive and cooperative interactions between organisms, including bacteria, can significantly impact the composition of a community and the fitness of its members, as well as the fitness of their hosts when communities are living on or within other organisms. Understanding the underlying mechanisms is critical to the development of strategies to control microbiological communities that impact animal and plant health and also for understanding the evolution of social behaviors, which has been challenging for evolutionary biologists. Contact-dependent growth inhibition (CDI) is a phenomenon defined by the delivery of a protein toxin to the cytoplasm of neighboring bacteria upon cell–cell contact, …


A Discussion Regarding Various Animals' Abilities To Make Music And Move Rhythmically To Songs, Emilie R. Bufford May 2017

A Discussion Regarding Various Animals' Abilities To Make Music And Move Rhythmically To Songs, Emilie R. Bufford

Capstone Projects and Master's Theses

This project involves exploring the presence of music and rhythmic abilities in specific animal species. The main subjects are whales, sea lions, gorillas, elephants, birds, and mice. The goal of this project was to compare their abilities to those of humans, and overall, determine whether such abilities are considered musical. Cases where animals demonstrate the ability, both learned and innate, to move to a beat are analyzed, along with animals who demonstrate musical vocal abilities naturally in the wild. The previously unknown frequencies of whales, mice, and elephants, are brought to light. These findings bring up the possibility of even …