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Evolution Of The Vertebrate Claudin Gene Family: Insights From A Basal Vertebrate, The Sea Lamprey, Christian Mukendi, Nicholas Dean, Rushil Lala, Jeramiah J. Smith, Marianne E Bronner, Natalya V. Nikitina Jan 2016

Evolution Of The Vertebrate Claudin Gene Family: Insights From A Basal Vertebrate, The Sea Lamprey, Christian Mukendi, Nicholas Dean, Rushil Lala, Jeramiah J. Smith, Marianne E Bronner, Natalya V. Nikitina

Biology Faculty Publications

Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of …


Clinically Relevant Behavioral Endpoints In A Recurrent Nitroglycerin Migraine Model In Rats, Kenneth J. Sufka, Stephanie M. Staszko, Ainslee P. Johnson, Morgan E. Davis, Rachel E. Davis, Todd A. Smitherman Jan 2016

Clinically Relevant Behavioral Endpoints In A Recurrent Nitroglycerin Migraine Model In Rats, Kenneth J. Sufka, Stephanie M. Staszko, Ainslee P. Johnson, Morgan E. Davis, Rachel E. Davis, Todd A. Smitherman

Faculty Publications

BACKGROUND: This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. METHODS: Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, …


Free Tilly?: Legal Personhood For Animals And The Intersectionality Of The Civil & Animal Rights Movements, Becky Boyle Jan 2016

Free Tilly?: Legal Personhood For Animals And The Intersectionality Of The Civil & Animal Rights Movements, Becky Boyle

Indiana Journal of Law and Social Equality

No abstract provided.


The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose Jan 2016

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …


Effect Of Anthelminthic Treatment On Helminth Infection And Related Anaemia Among School-Age Children In Northwestern Ethiopia, Yonas Yimam, Abraham Degarege, Berhanu Erko Jan 2016

Effect Of Anthelminthic Treatment On Helminth Infection And Related Anaemia Among School-Age Children In Northwestern Ethiopia, Yonas Yimam, Abraham Degarege, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Information about improvements in the health status of population at-risk of helminth infection after anthelminthic treatment helps to evaluate the effectiveness of the large scale deworming program. The objectives of this study were to assess the impact of anthelminthic treatment on the prevalence and intensity of intestinal helminth infection, haemoglobin level and prevalence of anaemia among school-age children.

METHODS: A total of 403 children attending Tikur Wuha Elementary School in Jiga, northwestern Ethiopia were enrolled in this study between February and March 2011. Formol-ether concentration and Kato-Katz methods were used to examine stool for intestinal helminth infections at baseline …


Epidemiology Of Plasmodium And Helminth Coinfection And Possible Reasons For Heterogeneity, Abraham Degarege, Berhanu Erko Jan 2016

Epidemiology Of Plasmodium And Helminth Coinfection And Possible Reasons For Heterogeneity, Abraham Degarege, Berhanu Erko

Journal Articles: Epidemiology

Understanding the impact of helminth infections on clinical malaria is useful for designing effective malaria control strategies. Plenty of epidemiological studies have been conducted to unravel the nature of interactions between Plasmodium and helminth infection. Careful broad summarization of the existing literature suggests that Schistosoma mansoni and hookworm infections may increase the risk of clinical malaria and associated morbidities, but Trichuris trichiura infection is not associated with the occurrence of clinical malaria and related outcomes. However, findings about effect of Ascaris lumbricoides and Schistosoma haematobium infection on clinical malaria are contradictory. Furthermore, the nature of relationship of helminth infection with …


Cns Plasticity In Injury And Disease, Brandon A. Miller, John C. Gensel, Michael S. Beattie Jan 2016

Cns Plasticity In Injury And Disease, Brandon A. Miller, John C. Gensel, Michael S. Beattie

Spinal Cord and Brain Injury Research Center Faculty Publications

No abstract provided.


Repositioning Of Drugs Using Open-Access Data Portal Dtome: A Test Case With Probenecid (Review), Mohammad U. Ahmed, Dylan J. Bennett, Tze-Chen Hsieh, Barbara B. Doonan, Saba Ahmed, Joseph M. Wu Jan 2016

Repositioning Of Drugs Using Open-Access Data Portal Dtome: A Test Case With Probenecid (Review), Mohammad U. Ahmed, Dylan J. Bennett, Tze-Chen Hsieh, Barbara B. Doonan, Saba Ahmed, Joseph M. Wu

NYMC Faculty Publications

The one gene-one enzyme hypothesis, first introduced by Beadle and Tatum in the 1940s and based on their genetic analysis and observation of phenotype changes in Neurospora crassa challenged by various experimental conditions, has witnessed significant advances in recent decades. Much of our understanding of the association between genes and their phenotype expression has benefited from the completion of the human genome project, and has shown continual transformation guided by the effort directed at the annotation and characterization of human genes. Similarly, the idea of one drug‑one primary disease indication that traditionally has been the benchmark for the labeling and …


Coordination Of Rna Polymerase Ii Pausing And 3' End Processing Factor Recruitment With Alternative Polyadenylation, Becky Fusby, Soojin Kim, Benjamin Erickson, Hyunmin Kim, Martha L. Peterson, David L Bentley Jan 2016

Coordination Of Rna Polymerase Ii Pausing And 3' End Processing Factor Recruitment With Alternative Polyadenylation, Becky Fusby, Soojin Kim, Benjamin Erickson, Hyunmin Kim, Martha L. Peterson, David L Bentley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2 residues of its heptad repeats (YS2PTSPS). The function of cotranscriptional events in the selection of alternative poly(A) sites is poorly understood. We investigated Pol II pausing, CTD Ser2 phosphorylation, and processing factor CstF recruitment at wild-type and mutant IgM transgenes that use alternative poly(A) sites to produce mRNAs encoding the secreted and membrane-bound forms of …


Vector Competence Of American Mosquitoes For Three Strains Of Zika Virus, James Weger-Lucarelli, Claudia Rückert, Nunya Chotiwan, Chilinh Nguyen, Selene M. Garcia Luna, Joseph R. Fauver, Brian D. Foy, Rushika Perera, William C. Black, Rebekah C. Kading, Gregory D. Ebel Jan 2016

Vector Competence Of American Mosquitoes For Three Strains Of Zika Virus, James Weger-Lucarelli, Claudia Rückert, Nunya Chotiwan, Chilinh Nguyen, Selene M. Garcia Luna, Joseph R. Fauver, Brian D. Foy, Rushika Perera, William C. Black, Rebekah C. Kading, Gregory D. Ebel

Journal Articles: Epidemiology

In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness …


Sglt2 Inhibitor Therapy Improves Blood Glucose But Does Not Prevent Diabetic Bone Disease In Diabetic Dba/2j Male Mice, Kathryn M. Thrailkill, R. Clay Bunn, Jeffry S. Nyman, Mallikarjuna R. Rettiganti, Gael E. Cockrell, Elizabeth C. Wahl, Sasidhar Uppuganti, Charles K. Lumpkin, John L. Fowlkes Jan 2016

Sglt2 Inhibitor Therapy Improves Blood Glucose But Does Not Prevent Diabetic Bone Disease In Diabetic Dba/2j Male Mice, Kathryn M. Thrailkill, R. Clay Bunn, Jeffry S. Nyman, Mallikarjuna R. Rettiganti, Gael E. Cockrell, Elizabeth C. Wahl, Sasidhar Uppuganti, Charles K. Lumpkin, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by …


Dog Walking Among Adolescents: Correlates And Contribution To Physical Activity., Jessa K. Engelberg, Jordan A. Carlson, Terry L. Conway, Kelli L. Cain, Brian E. Saelens, Karen Glanz, Lawrence D. Frank, James F. Sallis Jan 2016

Dog Walking Among Adolescents: Correlates And Contribution To Physical Activity., Jessa K. Engelberg, Jordan A. Carlson, Terry L. Conway, Kelli L. Cain, Brian E. Saelens, Karen Glanz, Lawrence D. Frank, James F. Sallis

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To assess the association of dog walking with adolescents' moderate-to-vigorous physical activity (MVPA) and body mass index (BMI), and identify correlates of dog walking.

METHODS/DESIGN: Participants were 12-17year-olds (n=925) from the Baltimore, MD and Seattle, WA regions. Differences in accelerometer-assessed minutes/day of MVPA and self-reported BMI (percentile) were compared among adolescents (1) without a dog (n=441) and those with a dog who (2) did (≥1days/week, n=300) or (3) did not (n=184) walk it. Correlates of (1) dog walking (any vs. none) among adolescents with dogs (n=484), and (2) days/week of dog walking among dog walkers (n=300) were investigated. Potential …


Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan Jan 2016

Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan

Journal Articles: Pediatrics

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array …


Assessment Of Clarias Gariepinus As A Biological Control Agent Against Mosquito Larvae, Buze Chala, Berhanu Erko, Abebe Animut, Abraham Degarege, Beyene Petros Jan 2016

Assessment Of Clarias Gariepinus As A Biological Control Agent Against Mosquito Larvae, Buze Chala, Berhanu Erko, Abebe Animut, Abraham Degarege, Beyene Petros

Journal Articles: Epidemiology

BACKGROUND: The emergence and spread of insecticide resistant mosquitoes renewed interest in investigating the use of larvivorous fish as a biological control agent. The potential of Clarias gariepinus fish in controlling Anopheles arabiensis and culicine larvae was assessed under laboratory and semi-field conditions.

RESULTS: Small size (15-20 cm) C. gariepinus fish consumed greater number of mosquito larvae than the large size fish (25-40 cm) in the multivariate regression model (β = 13.36, 95 % CI = 4.57, 22.15). The Anopheles larvae consumed was greater in number than the culicines larvae consumed by the fish (β = 12.10, 95 % CI …


Spermatogenesis Drives Rapid Gene Creation And Masculinization Of The X Chromosome In Stalk-Eyed Flies (Diopsidae), Richard H. Baker, Apurva Narechania, Rob Desalle, Philip M. Johns, Josephiine A. Reinhardt, Gerald S. Wilkinson Jan 2016

Spermatogenesis Drives Rapid Gene Creation And Masculinization Of The X Chromosome In Stalk-Eyed Flies (Diopsidae), Richard H. Baker, Apurva Narechania, Rob Desalle, Philip M. Johns, Josephiine A. Reinhardt, Gerald S. Wilkinson

Biology

Throughout their evolutionary history, genomes acquire new genetic material that facilitates phenotypic innovation and diversification. Developmental processes associated with reproduction are particularly likely to involve novel genes. Abundant gene creation impacts the evolution of chromosomal gene content and general regulatory mechanisms such as dosage compensation. Numerous studies in model organisms have found complex and, at times contradictory, relationships among these genomic attributes highlighting the need to examine these patterns in other systems characterized by abundant sexual selection. Therefore, we examined the association among novel gene creation, tissue-specific gene expression, and chromosomal gene content within stalk-eyed flies. Flies in this family …


High Level Fluoroquinolone Resistance In Escherichia Coli Isolatedfrom Animals In Turkey Is Due To Multiple Mechanisms, Pinar Şahi̇ntürk, Erdem Arslan, Esra Büyükcangaz, Songül Sonal, Ayşi̇n Şen, Fi̇gen Ersoy, Mark A. Webber, Laura Jv. Piddock, Murat Cengi̇z Jan 2016

High Level Fluoroquinolone Resistance In Escherichia Coli Isolatedfrom Animals In Turkey Is Due To Multiple Mechanisms, Pinar Şahi̇ntürk, Erdem Arslan, Esra Büyükcangaz, Songül Sonal, Ayşi̇n Şen, Fi̇gen Ersoy, Mark A. Webber, Laura Jv. Piddock, Murat Cengi̇z

Turkish Journal of Veterinary & Animal Sciences

The aim of this study was to determine the molecular mechanisms of fluoroquinolone resistance in E. Coli isolated from cattle, goats, sheep, cats, and dogs in Turkey. Twenty nonreplicate E. Coli isolates (chosen on the basis of RAPD pattern) from food-producing animals were selected for the study. To identify phenotypic differences between isolates, the sum of the MIC values of 14 antimicrobials was calculated; values ranged from 565 to 2520 μg/mL, indicating the diversity in antimicrobial resistance present in the panel of isolates. PCR and qRT-PCR were used to characterize the presence and expression levels of known molecular mechanisms of …


Palmitate-Induced Changes In Energy Demand Cause Reallocation Of Atp Supply In Rat And Human Skeletal Muscle Cells., Raid B. Nisr, Charles Affourtit Jan 2016

Palmitate-Induced Changes In Energy Demand Cause Reallocation Of Atp Supply In Rat And Human Skeletal Muscle Cells., Raid B. Nisr, Charles Affourtit

School of Biomedical Sciences

Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes because skeletal muscle energy metabolism is mostly controlled by ATP demand. Probing the bioenergetics of rat and human myoblasts in real time we show here that the saturated fatty acid palmitate lowers the rate and coupling efficiency of oxidative phosphorylation under conditions it causes insulin resistance. Stearate affects the bioenergetic parameters …


Neural Crest Cell-Autonomous Roles Of Fibronectin In Cardiovascular Development., Xia Wang, Sophie Astrof Jan 2016

Neural Crest Cell-Autonomous Roles Of Fibronectin In Cardiovascular Development., Xia Wang, Sophie Astrof

Department of Medicine Faculty Papers

The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into …


Co-Creaturely Associates Or Peers? The Nature Of Animals As Portrayed In Isaiah, A. Rahel Wells Jan 2016

Co-Creaturely Associates Or Peers? The Nature Of Animals As Portrayed In Isaiah, A. Rahel Wells

Faculty Publications

No abstract provided.


Gotta Catch 'Em All, Jennifer Lynn Lombardi Jan 2016

Gotta Catch 'Em All, Jennifer Lynn Lombardi

LSU Master's Theses

The ability to imagine is essential to shaping who we are, and is an important part of our humanity. Children have the ability to use aspects of their environment as their playthings, becoming the characters in their world through their sense of imagination. We lose this ability as we grow, leaving us with only memories and sentimentality. I have come to realize that my art is an expression of the longing and search to regain that ability to become fused with my imagination and my environment. I allow myself to become lost in a world of fantasy once more, and …


Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel Jan 2016

Local Corticotropin Releasing Hormone (Crh) Signals To Its Receptor Crhr1 During Postnatal Development Of The Mouse Olfactory Bulb, Isabella Garcia, Paramjit K Bhullar, Burak Tepe, Joshua Ortiz-Guzman, Longwen Huang, Alexander M Herman, Lesley Chaboub, Benjamin Deneen, Nicholas J Justice, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related …


Framework For Hyperspectral Image Processing And Quantification For Cancer Detection During Animal Tumor Surgery, Guolan Lu, Dongsheng Wang, Xulei Qin, Luma Halig, Susan Muller, Hongzheng Zhang, Amy Chen, Brian W. Pogue, Zhuo G. Chen Dec 2015

Framework For Hyperspectral Image Processing And Quantification For Cancer Detection During Animal Tumor Surgery, Guolan Lu, Dongsheng Wang, Xulei Qin, Luma Halig, Susan Muller, Hongzheng Zhang, Amy Chen, Brian W. Pogue, Zhuo G. Chen

Dartmouth Scholarship

Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, …


The Interrelationships Of Placental Mammals And The Limits Of Phylogenetic Inference, James E. Tarver, Mario Dos Reis, Siavash Mirarab, Raymond J. J. Moran, Sean Parker, Joseph E. O'Reilly, Benjamin L. King, Mary J. O'Connell, Robert J. Asher, Tandy Warnow, Kevin J. Peterson, Philip C.J. Donoghue, Davide Pisani Dec 2015

The Interrelationships Of Placental Mammals And The Limits Of Phylogenetic Inference, James E. Tarver, Mario Dos Reis, Siavash Mirarab, Raymond J. J. Moran, Sean Parker, Joseph E. O'Reilly, Benjamin L. King, Mary J. O'Connell, Robert J. Asher, Tandy Warnow, Kevin J. Peterson, Philip C.J. Donoghue, Davide Pisani

Dartmouth Scholarship

Placental mammals comprise three principal clades: Afrotheria (e.g., elephants and tenrecs), Xenarthra (e.g., armadillos and sloths), and Boreoeutheria (all other placental mammals), the relationships among which are the subject of controversy and a touchstone for debate on the limits of phylogenetic inference. Previous analyses have found support for all three hypotheses, leading some to conclude that this phylogenetic problem might be impossible to resolve due to the compounded effects of incomplete lineage sorting (ILS) and a rapid radiation. Here we show, using a genome scale nucleotide data set, microRNAs, and the reanalysis of the three largest previously published amino acid …


Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman Dec 2015

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …


Intravacuolar Membranes Regulate Cd8 T Cell Recognition Of Membrane-Bound Toxoplasma Gondii Protective Antigen, Jodie Lopez, Amina Bittame, Céline Massera, Virginie Vasseur, Gregory Effantin, Anne Valat, Celia Buaillon, Sophie Allart, Barbara A. Fox, Leah M. Rommereim, David J. Bzik Dec 2015

Intravacuolar Membranes Regulate Cd8 T Cell Recognition Of Membrane-Bound Toxoplasma Gondii Protective Antigen, Jodie Lopez, Amina Bittame, Céline Massera, Virginie Vasseur, Gregory Effantin, Anne Valat, Celia Buaillon, Sophie Allart, Barbara A. Fox, Leah M. Rommereim, David J. Bzik

Dartmouth Scholarship

Apicomplexa parasites such as Toxoplasma gondii target effectors to and across the boundary of their parasitophorous vacuole (PV), resulting in host cell subversion and potential presentation by MHC class I molecules for CD8 T cell recognition. The host-parasite interface comprises the PV limiting membrane and a highly curved, membranous intravacuolar network (IVN) of uncertain function. Here, using a cell-free minimal system, we dissect how membrane tubules are shaped by the parasite effectors GRA2 and GRA6. We show that membrane association regulates access of the GRA6 protective antigen to the MHC I pathway in infected cells. Although insertion of GRA6 in …


Nucleus Accumbens Deep Brain Stimulation In A Rat Model Of Binge Eating, W. T. Doucette, J. Y. Khokhar, A. I. Green Dec 2015

Nucleus Accumbens Deep Brain Stimulation In A Rat Model Of Binge Eating, W. T. Doucette, J. Y. Khokhar, A. I. Green

Dartmouth Scholarship

Binge eating (BE) is a difficult-to-treat behavior with high relapse rates, thus complicating several disorders including obesity. In this study, we tested the effects of high-frequency deep brain stimulation (DBS) in a rodent model of BE. We hypothesized that BE rats receiving high-frequency DBS in the nucleus accumbens (NAc) core would have reduced binge sizes compared with sham stimulation in both a 'chronic BE' model as well as in a 'relapse to chronic BE' model. Male Sprague-Dawley rats (N=18) were implanted with stimulating electrodes in bilateral NAc core, and they received either active stimulation (N=12) or sham stimulation (N=6) for …


Possible Synergistic Effects Of Thymol And Nicotine Against Crithidia Bombi Parasitism In Bumble Bees, Olivia Masi Biller, Lynn S. Adler, Rebecca E. Irwin, Caitlin Mcallister, Evan C. Palmer-Young Dec 2015

Possible Synergistic Effects Of Thymol And Nicotine Against Crithidia Bombi Parasitism In Bumble Bees, Olivia Masi Biller, Lynn S. Adler, Rebecca E. Irwin, Caitlin Mcallister, Evan C. Palmer-Young

Dartmouth Scholarship

Floral nectar contains secondary compounds with antimicrobial properties that can affect not only plant-pollinator interactions, but also interactions between pollinators and their parasites. Although recent work has shown that consumption of plant secondary compounds can reduce pollinator parasite loads, little is known about the effects of dosage or compound combinations. We used the generalist pollinator Bombus impatiens and its obligate gut parasite Crithidia bombi to study the effects of nectar chemistry on host-parasite interactions. In two experiments we tested (1) whether the secondary compounds thymol and nicotine act synergistically to reduce parasitism, and (2) whether dietary thymol concentration affects parasite …


Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava Dec 2015

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …


Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo Dec 2015

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …


Functional Analysis Of The Unique Cytochrome P450 Of The Liver Fluke Opisthorchis Felineus., Mariya Y. Pakharukova, Valentin A. Vavilin, Banchob Sripa, Thewarach Laha, Paul J. Brindley, Viatcheslav A. Mordvinov Dec 2015

Functional Analysis Of The Unique Cytochrome P450 Of The Liver Fluke Opisthorchis Felineus., Mariya Y. Pakharukova, Valentin A. Vavilin, Banchob Sripa, Thewarach Laha, Paul J. Brindley, Viatcheslav A. Mordvinov

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered …