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Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert Jan 2013

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” …


Thrombospondin-1 Signaling Through Cd47 Inhibits Self-Renewal By Regulating C-Myc And Other Stem Cell Transcription Factors, Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein, Chengyu Liu, Abdel G. Elkahloun, Michael L. Pendrak, Alina Nicolae, Satya P. Singh, Zuqin Nie, David Levens, Jeffrey S. Isenberg, David D. Roberts Jan 2013

Thrombospondin-1 Signaling Through Cd47 Inhibits Self-Renewal By Regulating C-Myc And Other Stem Cell Transcription Factors, Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein, Chengyu Liu, Abdel G. Elkahloun, Michael L. Pendrak, Alina Nicolae, Satya P. Singh, Zuqin Nie, David Levens, Jeffrey S. Isenberg, David D. Roberts

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, …


Cd56negcd16+ Nk Cells Are Activated Mature Nk Cells With Impaired Effector Function During Hiv-1 Infection, Jeffrey M. Milush, Sandra López-Vergès, Vanessa A. York, Steven G. Deeks, Jeffrey N. Martin, Frederick M. Hecht, Lewis L. Lanier, Douglas F. Nixon Jan 2013

Cd56negcd16+ Nk Cells Are Activated Mature Nk Cells With Impaired Effector Function During Hiv-1 Infection, Jeffrey M. Milush, Sandra López-Vergès, Vanessa A. York, Steven G. Deeks, Jeffrey N. Martin, Frederick M. Hecht, Lewis L. Lanier, Douglas F. Nixon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: A subset of CD3(neg)CD56(neg)CD16⁺ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.

RESULTS: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16⁺ cells are a heterogeneous population comprised of CD7⁺ NK cells and CD7(neg) non-classical myeloid cells. CD7⁺CD56(neg)CD16⁺ NK cells are significantly expanded in HIV-1 infection. CD7⁺CD56(neg)CD16⁺ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to …


Understanding The Anatomy Of Dystonia: Determinants Of Penetrance And Phenotype, R. P. Lerner, M. Niethammer, D. Eidelberg Jan 2013

Understanding The Anatomy Of Dystonia: Determinants Of Penetrance And Phenotype, R. P. Lerner, M. Niethammer, D. Eidelberg

Journal Articles

No abstract provided.


Association Between The Luteinizing Hormone/Chorionic Gonadotropin Receptor (Lhcgr) Rs4073366 Polymorphism And Ovarian Hyperstimulation Syndrome During Controlled Ovarian Hyperstimulation, Travis J. O'Brien, Mariah M. Kalmin, Arthur F. Harralson, Adam M. Clark, Ian Gindoff, Samuel J. Simmens, David Frankfurter, Paul Gindoff Jan 2013

Association Between The Luteinizing Hormone/Chorionic Gonadotropin Receptor (Lhcgr) Rs4073366 Polymorphism And Ovarian Hyperstimulation Syndrome During Controlled Ovarian Hyperstimulation, Travis J. O'Brien, Mariah M. Kalmin, Arthur F. Harralson, Adam M. Clark, Ian Gindoff, Samuel J. Simmens, David Frankfurter, Paul Gindoff

Pharmacology and Physiology Faculty Publications

Background

The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH).

Methods

This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced. We also investigated a polymorphism (rs4073366 G > C) that was 142 bp frominsLQ. The association of the insLQ and rs4073366 alleles and outcome to COH (number of mature follicles, …


The Expanding Genomic Landscape Of Autism: Discovering The 'Forest' Beyond The 'Trees', Valerie Wailin Hu Jan 2013

The Expanding Genomic Landscape Of Autism: Discovering The 'Forest' Beyond The 'Trees', Valerie Wailin Hu

Biochemistry and Molecular Medicine Faculty Publications

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by significant deficits in reciprocal social interactions, impaired communication, and restricted, repetitive behaviors. Because ASDs are among the most heritable of neuropsychiatric disorders, much of autism research has focused on the search for genetic variants in protein-coding genes (i.e., the "trees"). However, no single gene can account for more than 1% of the cases of ASD. Yet, genome-wide association studies have often identified statistically significant associations of genetic variations in regions of DNA that do not code for proteins (i.e., intergenic regions). There is increasing evidence that such noncoding regions are actively …


Early Alzheimer's And Parkinson's Disease Pathology In Urban Children: Friend Versus Foe Responses—It Is Time To Face The Evidence, Lilian Calderón-Garcidueñas, Maricela Franco-Lira, Antonieta Mora-Tiscareño, Humberto Medina-Cortina, Ricardo Torres-Jardon, Michael Kavanaugh Jan 2013

Early Alzheimer's And Parkinson's Disease Pathology In Urban Children: Friend Versus Foe Responses—It Is Time To Face The Evidence, Lilian Calderón-Garcidueñas, Maricela Franco-Lira, Antonieta Mora-Tiscareño, Humberto Medina-Cortina, Ricardo Torres-Jardon, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascularrelated sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPrc), alpha-synuclein, and beta-amyloid could …


Exposure To Urban Air Pollution And Bone Health In Clinically Healthy Six-Year-Old Children, Lilian Calderón-Garcidueñas, Antonieta Mora-Tiscareño, Maricela Franco-Lira, Ricardo Torres-Jardon, Bernardo Pena-Cruz, Carolina Palacios-López, Hongtu Zhu, Linglong Kong, Nicolas Mendoza-Mendoza, Hortencia Montesinoscorrea, Lina Romero, Gildardo Valencia-Salazar, Michael Kavanaugh, Silvestre Frenk Jan 2013

Exposure To Urban Air Pollution And Bone Health In Clinically Healthy Six-Year-Old Children, Lilian Calderón-Garcidueñas, Antonieta Mora-Tiscareño, Maricela Franco-Lira, Ricardo Torres-Jardon, Bernardo Pena-Cruz, Carolina Palacios-López, Hongtu Zhu, Linglong Kong, Nicolas Mendoza-Mendoza, Hortencia Montesinoscorrea, Lina Romero, Gildardo Valencia-Salazar, Michael Kavanaugh, Silvestre Frenk

Biomedical and Pharmaceutical Sciences Faculty Publications

Air pollution induces systemic inflammation, as well as respiratory, myocardial and brain inflammation in children. Peak bone mass is influenced by environmental factors. We tested the hypothesis that six-year-olds with lifetime exposures to urban air pollution will have alterations in inflammatory markers and bone mineral density (BMD) as opposed to low-polluted city residents when matched for BMI, breast feeding history, skin phototype, age, sex and socioeconomic status. This pilot study included 20 children from Mexico City (MC) (6.17 years ± 0.63 years) and 15 controls (6.27 years ± 0.76 years). We performed full paediatric examinations, a history of outdoor exposures, …


Novel Dicarboxylate Selectivity In An Insect Glutamate Transporter Homolog, Hui Wang, Avi M. Rascoe, David Charles Holley, Eric Gouaux, Michael Kavanaugh Jan 2013

Novel Dicarboxylate Selectivity In An Insect Glutamate Transporter Homolog, Hui Wang, Avi M. Rascoe, David Charles Holley, Eric Gouaux, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Mammals express seven transporters from the SLC1 (solute carrier 1) gene family, including five acidic amino acid transporters (EAAT1-5) and two neutral amino acid transporters (ASCT1-2). In contrast, insects of the order Diptera possess only two SLC1 genes. In this work we show that in the mosquito Culex quinquefasciatus, a carrier of West Nile virus, one of its two SLC1 EAAT-like genes encodes a transporter that displays an unusual selectivity for dicarboxylic acids over acidic amino acids. In eukaryotes, dicarboxylic acid uptake has been previously thought to be mediated exclusively by transporters outside the SLC1 family. The dicarboxylate selectivity was …


Brain Immune Interactions And Air Pollution: Macrophage Inhibitory Factor (Mif), Prion Cellular Protein (Prpc), Interleukin-6 (Il-6), Interleukin 1 Receptor Antagonist (Il-1ra), And Interleukin-2 (Il-2) In Cerebrospinal Fluid And Mif In Serum Differentiate Urban Children Exposed To Severe Vs. Low Air Pollution, Lilian Calderón-Garcidueñas, Janet V. Cross, Maricela Franco-Lira, Mariana Aragón-Flores, Michael Kavanaugh, Ricardo Torres-Jardon, Chih-Kai Chao, Charles Thompson, Jing Chang, Hongtu Zhu, Amedeo D'Angiulli Jan 2013

Brain Immune Interactions And Air Pollution: Macrophage Inhibitory Factor (Mif), Prion Cellular Protein (Prpc), Interleukin-6 (Il-6), Interleukin 1 Receptor Antagonist (Il-1ra), And Interleukin-2 (Il-2) In Cerebrospinal Fluid And Mif In Serum Differentiate Urban Children Exposed To Severe Vs. Low Air Pollution, Lilian Calderón-Garcidueñas, Janet V. Cross, Maricela Franco-Lira, Mariana Aragón-Flores, Michael Kavanaugh, Ricardo Torres-Jardon, Chih-Kai Chao, Charles Thompson, Jing Chang, Hongtu Zhu, Amedeo D'Angiulli

Biomedical and Pharmaceutical Sciences Faculty Publications

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile …


Plasma Soluble Thrombomodulin And Soluble Endothelial Protein C Receptor Levels In Colorectal Cancer Patients, Serap Ünal Ti̇lki̇, Hüseyi̇n Engi̇n, Ayla Gökmen, Cemi̇l Bi̇li̇r, Yücel Üstündağ Jan 2013

Plasma Soluble Thrombomodulin And Soluble Endothelial Protein C Receptor Levels In Colorectal Cancer Patients, Serap Ünal Ti̇lki̇, Hüseyi̇n Engi̇n, Ayla Gökmen, Cemi̇l Bi̇li̇r, Yücel Üstündağ

Turkish Journal of Medical Sciences

Thrombomodulin (TM) and endothelial protein C receptor (EPCR) are 2 transmembrane proteins that are thought to play an important role in cancer. We aimed to discover whether these 2 proteins are prognostic indicators in colorectal cancer. Materials and methods: Plasma TM and EPCR levels were measured using the ELISA method in 50 patients in different tumor stages that had been recently diagnosed with colorectal cancer and in a healthy control group of 50 people. Results: In colorectal cancer patients, higher plasma TM (21.3 ± 22.8 ng/mL, 13.2 ± 16.2 ng/mL, P = 0.010) and plasma EPCR levels (149.9 ± 79.6, …


Polymorphisms In Abc Transporters (Abca1 And Abcc8) In Metabolic Syndrome, Orhan Değer, Yunus Emre Yandi, Mi̇hri̇ban Ayvaz, Ci̇hangi̇r Erem, Ari̇f Bayram Hacihasanoğlu Jan 2013

Polymorphisms In Abc Transporters (Abca1 And Abcc8) In Metabolic Syndrome, Orhan Değer, Yunus Emre Yandi, Mi̇hri̇ban Ayvaz, Ci̇hangi̇r Erem, Ari̇f Bayram Hacihasanoğlu

Turkish Journal of Medical Sciences

To identify important single nucleotide polymorphisms (SNPs) in the ABCA1 and ABCC8 (SUR1) genes and determine if they are associated with metabolic syndorome (MetS). Materials and methods: Fifty-eight subjects fulfilling all 5 MetS criteria were chosen from 4809 subjects who participated in our screening study (Trabzon MetS study). Forty-three subjects who did not fulfill any MetS criteria were chosen as the control group. Genotyping of the samples after DNA isolation was performed by direct sequencing. For SNP analysis, exons 7, 15, 19, 36, 41, and 49 for ABCA1 and exons 16 and 18 for ABCC8 were selected. Results: The most …


Alfacalcidol Suppresses Α-Receptor–Mediated Vasoconstriction Via An Endothelium Dependent Mechanism, İsmai̇l Ün, Aki̇f Hakan Kurt, Ali̇ Batuş, Kansu Büyükafşar Jan 2013

Alfacalcidol Suppresses Α-Receptor–Mediated Vasoconstriction Via An Endothelium Dependent Mechanism, İsmai̇l Ün, Aki̇f Hakan Kurt, Ali̇ Batuş, Kansu Büyükafşar

Turkish Journal of Medical Sciences

Vitamin D level could be related to blood pressure and cardiovascular health. However, the direct suppressor effect of vitamin D on vascular contraction has not yet been explored. Therefore, the effects of alfacalcidol (1\alpha-hydroxyvitamin D_3) and calcitriol (1\alpha,25-dihydroxyvitamin D_3) on contractions induced by phenylephrine (10^{-8} to 10^{-5} M) in mice aorta were investigated. Materials and methods: Arterial rings were suspended in isolated organ chambers filled with Krebs bicarbonate solution gassed with 95% O_2 and 5% CO_2 maintained at 37 °C. Tissue responses were recorded isometrically with a force transducer and displayed on an acquisition system. Alfacalcidol and calcitriol were applied …


The Effect Of Combined Treatment Of Alpha-Tocopherol, Ascorbic Acid, And Pyridoxine With Nmda Blocker Memantine On Penicillin-Induced Epileptiform Activity In Rats, Duygu Aydin, Mehmet Yildirim, Mustafa Ayyildiz, Erdal Ağar Jan 2013

The Effect Of Combined Treatment Of Alpha-Tocopherol, Ascorbic Acid, And Pyridoxine With Nmda Blocker Memantine On Penicillin-Induced Epileptiform Activity In Rats, Duygu Aydin, Mehmet Yildirim, Mustafa Ayyildiz, Erdal Ağar

Turkish Journal of Medical Sciences

To evaluate the effects of coadministration of vitamins alpha-tocopherol, ascorbic acid, and pyridoxine with memantine on a penicillin-induced experimental epilepsy model in rats so as to clarify the eventual interaction between these vitamins and the N-methyl-D-aspartate (NMDA) system. Materials and methods: The epileptic focus was produced by intracortical penicillin G potassium injection. The effects of intraperitoneal injections of memantine, memantine + alpha-tocopherol, memantine + ascorbic acid, and memantine + pyridoxine combinations on epileptiform activity were evaluated in electrocorticogram recordings. Results: The antiepileptiform effects appeared earlier in all memantine and vitamin coadministrated groups compared to the memantine-alone group, but the difference …


The Outcomes Of The Pregnancies Of Lactating Women, Özlem Şengül, Ahmet Akin Si̇vaslioğlu, Mahmut Kuntay Kokanali, Işik Üstüner, Ayşe Fi̇li̇z Avşar Jan 2013

The Outcomes Of The Pregnancies Of Lactating Women, Özlem Şengül, Ahmet Akin Si̇vaslioğlu, Mahmut Kuntay Kokanali, Işik Üstüner, Ayşe Fi̇li̇z Avşar

Turkish Journal of Medical Sciences

To evaluate the outcomes of pregnancies occurring during lactation. Materials and methods: Sixty-one women who had interpregnancy intervals of 2 years were evaluated. Group 1 included 39 pregnancies of lactating women. Group 2 included 22 pregnancies of women who ceased lactation before conception. The groups were compared for gestational weight gain, birth weight, and obstetric complications. Results: The birth weights of the subsequent pregnancies of the first group were statistically lower than the second group (3086.6 ± 379.2 versus 3386.8 ± 388.1 g, P = 0.006). There was no statistically significant difference in obstetric complications observed between the 2 groups …


The Effects Of Acetyl Shikonin Isolated From Onosma Armeniacum On Oxidative Stress In Ethanol-Induced Ulcer Model Of Rats, Aysun Toker, Fati̇h Akçay, Hülya Aksoy, Hali̇s Süleyman, Ufuk Özgen, Havva Erdem Jan 2013

The Effects Of Acetyl Shikonin Isolated From Onosma Armeniacum On Oxidative Stress In Ethanol-Induced Ulcer Model Of Rats, Aysun Toker, Fati̇h Akçay, Hülya Aksoy, Hali̇s Süleyman, Ufuk Özgen, Havva Erdem

Turkish Journal of Medical Sciences

We investigated the effects of acetyl shikonin isolated from Onosma armeniacum on ethanol-induced gastric injury (ulcer) and on oxidant-antioxidant parameters in the gastric tissue of rats. Materials and methods: Eighteen albino Wistar male rats were divided into 3 different experimental groups. Group 1 (n = 6) was the control group, group 2 (n = 6) was the ethanol group, and group 3 (n = 6) was the acetyl shikonin + ethanol group. The animals in group 3 were given ethanol (1 mL, 50% v/v) 30 min after acetyl shikonin (40 mg/kg) administration by orogastric tube. Results: The lowest mean nitric …


Influence Of Exposure To Benzo[A]Pyrene On Mice Testicular Germ Cells During Spermatogenesis, Hueiwang Anna Jeng, Silvina M. Bocca Jan 2013

Influence Of Exposure To Benzo[A]Pyrene On Mice Testicular Germ Cells During Spermatogenesis, Hueiwang Anna Jeng, Silvina M. Bocca

Community & Environmental Health Faculty Publications

The objective of this study was to assess the toxicological effect of exposure to benzo(a)pyrene, B[a]P, on germ cells during spermatogenesis. Mice were exposed to B[a]P at 1, 10, 50, and 100 mg/kg/day for 30 days via oral ingestion. Germ cells, including spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatids, were recovered from testes of mice exposed to B[a]P, while mature spermatozoa were isolated from vas deferens. Reproductive organs were collected and weighed. Apoptotic response of germ cells and mature spermatozoa were qualified using the terminal deoxynucleotidyl transferase mediated deoxy-UTP nick end labeling (TUNEL) assay. B[a]P exposure at


Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco Jan 2013

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …


Evidence-Based Toxicology For The 21st Century: Opportunities And Challenges, Martin L. Stephens, Melvin E. Andersen, Richard A. Becker, Kellyn Betts, Kim Boekelheide, Ed Carney, Robert Chapin, Dennis Devlin, Suzanne C. Fitzpatrick, John R. Fowle Iii, Patricia Harlow, Thomas Hartung, Sebastian Hoffman, Michael P. Holsapple, Abigail Jacobs, Richard Judson, Olga Naidenko, Tim Pastoor, Grace Patlewicz, Andrew Rowan, Roberta Scherer, Rashid Shaikh, Ted Simon, Douglas Wolf, Joanne Zurlo Jan 2013

Evidence-Based Toxicology For The 21st Century: Opportunities And Challenges, Martin L. Stephens, Melvin E. Andersen, Richard A. Becker, Kellyn Betts, Kim Boekelheide, Ed Carney, Robert Chapin, Dennis Devlin, Suzanne C. Fitzpatrick, John R. Fowle Iii, Patricia Harlow, Thomas Hartung, Sebastian Hoffman, Michael P. Holsapple, Abigail Jacobs, Richard Judson, Olga Naidenko, Tim Pastoor, Grace Patlewicz, Andrew Rowan, Roberta Scherer, Rashid Shaikh, Ted Simon, Douglas Wolf, Joanne Zurlo

Toxicology and Animal Models in Research Collection

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that …


Fyn-Dependent Gene Networks In Acute Ethanol Sensitivity, Sean P. Farris, Michael F. Miles Jan 2013

Fyn-Dependent Gene Networks In Acute Ethanol Sensitivity, Sean P. Farris, Michael F. Miles

Pharmacology and Toxicology Publications

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex …


Contribution Of Nadph Oxidase To Membrane Cd38 Internalization And Activation In Coronary Arterial Myocytes, Ming Xu, Xiao-Xue Li, Joseph K. Ritter, Justine M. Abais, Yang Zhang, Pin-Lan Li Jan 2013

Contribution Of Nadph Oxidase To Membrane Cd38 Internalization And Activation In Coronary Arterial Myocytes, Ming Xu, Xiao-Xue Li, Joseph K. Ritter, Justine M. Abais, Yang Zhang, Pin-Lan Li

Pharmacology and Toxicology Publications

The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase …


Immunohistochemical Distribution And Gene Expression Of Transforming Growth Factor Alpha In Ovarian Tissue Of Rats Treated With Capsaicin In Puberty, Sevda Eli̇ş Yildiz, Mümtaz Nazli, Gökhan Nur Jan 2013

Immunohistochemical Distribution And Gene Expression Of Transforming Growth Factor Alpha In Ovarian Tissue Of Rats Treated With Capsaicin In Puberty, Sevda Eli̇ş Yildiz, Mümtaz Nazli, Gökhan Nur

Turkish Journal of Medical Sciences

In this study, the effects of capsaicin on the immunohistochemical distribution and gene expression of transforming growth factor alpha (TGF-\alpha) in ovarian tissue of rats at the pubertal age were examined. Materials and methods: Rats (50 days old) were divided into experimental, alimentation, and sham groups. The experimental group was injected with 1 mg/kg doses of capsaicin (10% ethanol and 1% Tween in an 80% distilled water mixture) subcutaneously every day for a period of 1 week. The alimentation group received 1 mg/kg doses of capsaicin (10% ethanol and 1% Tween in an 80% distilled water mixture). The sham group …


Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian Jan 2013

Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher A. Drummond, George Buddny, Steven T. Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph I. Shapiro Md, Jiang Tian

Biochemistry and Microbiology

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed …


Neuropsychological Outcome In Relation To Duration Of Early Orphanage Experience, Jacquelyn Marie Perry Avery Jan 2013

Neuropsychological Outcome In Relation To Duration Of Early Orphanage Experience, Jacquelyn Marie Perry Avery

Wayne State University Dissertations

In this sample of 144 children with a history of prior orphanage experience, increasing duration of institutionalization is related to decreasing performance for a number of cognitive domains, most consistently verbal measures and executive Functioning measures. The relationships with duration for measures requiring visual-spatial skills were more mixed and a visual reasoning task was found to significantly relate to duration but not a measure of visual memory or a measure of nonverbal achievement. There was little evidence to support a relationship between the duration of institutionalization and fine-motor dexterity. The strongest relationships with duration were observed for language measures followed …


Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid Jan 2013

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …


Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar Jan 2013

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …


Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee Jan 2013

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …


Studies On Bronchodilator And Cardiac Stimulant Activities Of Urginea Indica, Samra Bashir, Saima Abbas, Aslam Khan, Anwar H. Gilani Jan 2013

Studies On Bronchodilator And Cardiac Stimulant Activities Of Urginea Indica, Samra Bashir, Saima Abbas, Aslam Khan, Anwar H. Gilani

Department of Biological & Biomedical Sciences

This study was designed to evaluate bronchodilator and cardio-tonic effects of Urginea indica to provide rational for these medicinal uses. U. indica bulb extract was studied on rabbit tracheal and guinea-pig atrial preparations mounted in tissue baths under simulated physiological conditions. U. indica inhibited carbachol (1 µM) and K+ (80 mM)-induced contractions in rabbit trachea, similar to dicyclomine, suggesting the presence of anticholinergic and calcium channel blocking (CCB) mechanisms in U. indica. Anticholinergic and CCB effects of U. indica were respectively confirmed when it shifted the carbachol and Ca2+ concentration-response curves rightwards, similar to dicyclomine. U. indica (0.01-1 …


The Influence Of Gender And Aging On The Neural Circuitry Supporing Facial Emotion Processing In Adults With Major Depressive Disorder, Emily Briceno Jan 2013

The Influence Of Gender And Aging On The Neural Circuitry Supporing Facial Emotion Processing In Adults With Major Depressive Disorder, Emily Briceno

Wayne State University Dissertations

Major Depressive Disorder (MDD) is associated with decrements in facial emotion processing (FEP). Previous studies investigating the neural substrates of these decrements have often reported hyperactivity of emotion processing circuitry. Neural circuitry supporting FEP has been shown to be different between healthy men and women, and between young and elder adults. However, no prior studies have investigated how gender and aging affect emotion processing circuitry in individuals with MDD. The present study aimed to investigate the influence of gender and aging on emotion processing circuitry in MDD. One hundred-ten adults, grouped into subgroups according to MDD status, gender, and age …


Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji Jan 2013

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …