Digital Commons Network^™

Morphine Enhances Hiv-1sf162-Mediated Neuron Death And Delays Recovery Of Injured Neurites, Ruturaj R. Masvekar, Nazira El-Hage, Kurt F. Hauser, Pamela E. Knapp

Anatomy and Neurobiology Publications

HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, …

Post-Acute Brain Injury Urinary Signature: A New Resource For Molecular Diagnostics, Andrew K. Ottens, Jillian E. Stafflinger, Hailey E. Griffin, Richard D. Kunz, David X. Cifu, Janet P. Niemeier

Anatomy and Neurobiology Publications

Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress particularly in cerebrospinal fluid with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop in part due to restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multifactorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for …

Live Cell Interferometry Quantifies Dynamics Of Biomass Partitioning During Cytokinesis, Thomas A. Zangle, Michael A. Teitell, Jason Reed

Physics Publications

The equal partitioning of cell mass between daughters is the usual and expected outcome of cytokinesis for self-renewing cells. However, most studies of partitioning during cell division have focused on daughter cell shape symmetry or segregation of chromosomes. Here, we use live cell interferometry (LCI) to quantify the partitioning of daughter cell mass during and following cytokinesis. We use adherent and non-adherent mouse fibroblast and mouse and human lymphocyte cell lines as models and show that, on average, mass asymmetries present at the time of cleavage furrow formation persist through cytokinesis. The addition of multiple cytoskeleton-disrupting agents leads to increased …

Memo Has A Novel Role In S1p Signaling And Crucial For Vascular Development, Shunya Kondo, Alessia Bottos, Jeremy Allegood, Regis Masson, Francisca G. Maurer, Christel Genoud, Patrick Kaeser, Andrea Huwiler, Masato Murakami, Sarah Spiegel, Nancy E. Hynes

Biochemistry and Molecular Biology Publications

Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate (S1P) signaling. S1P is a bioactive phospholipid produced in response to multiple stimuli, which regulates many cellular processes. S1P is secreted to the extracellular milieu where it exerts its function by binding a family of G-protein coupled receptors (S1PRs), causing their activation in an autocrine or paracrine manner. The process, termed cell-autonomous S1PR signaling, …

Otitis Media In Sperm-Associated Antigen 6 (Spag6)-Deficient Mice, Xiaofei Li, Lei Xu, Jianfeng Li, Boqin Li, Xiaohui Bai, Jerome F. Strauss Iii, Zhibing Zhang, Haibo Wang

Biochemistry and Molecular Biology Publications

Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential …

Contrasting Influences Of Drosophila White/Mini-White On Ethanol Sensitivity In Two Different Behavioral Assays, Robin F. Chan, Carol Atkinson Lewellyn, Jacqueline M. Deloyht, Kristyn Sennett, Scarlett Coffman, Matthew Hewitt, Jill C. Bettinger, John M. Warrick, Mike Grotewiel

Human and Molecular Genetics Publications

Background

The fruit fly Drosophila melanogaster has been used extensively to investigate genetic mechanisms of ethanol-related behaviors. Many past studies in flies, including studies from our laboratory, have manipulated gene expression using transposons carrying the genetic-phenotypic marker mini-white, a derivative of the endogenous gene white. Whether the mini-white transgenic marker or the endogenous white gene influence behavioral responses to acute ethanol exposure in flies has not been systematically investigated.

Methods

We manipulated mini-white and white expression via (i) transposons marked with mini-white, (ii) RNAi against mini-white and white and (iii) a null allele of white. We assessed ethanol sensitivity and …

Reassessing The Impact Of Smoking On Preeclampsia/Eclampsia: Are There Age And Racial Differences?, Jen Jen Chang, Jerome F. Strauss, Jonathan P. Deshazo, Fidelma B. Rigby, David P. Chelmow, George A. Macones

Obstetrics and Gynecology Publications

Objective

To investigate the association between cigarette use during pregnancy and pregnancy-induced hypertension/preeclampsia/eclampsia (PIH) by maternal race/ethnicity and age.

Methods

This retrospective cohort study was based on the U.S. 2010 natality data. Our study sample included U.S. women who delivered singleton pregnancies between 20 and 44 weeks of gestation without major fetal anomalies in 2010 (n = 3,113,164). Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios and the corresponding 95% confidence intervals.

Results

We observed that the association between maternal smoking and PIH varied by maternal race/ethnicity and age. Compared with non-smokers, reduced odds of …

Sperm-Associated Antigen 6 (Spag6) Deficiency And Defects In Ciliogenesis And Cilia Function: Polarity, Density, And Beat, Maria E. Teves, Patrick R. Sears, Wei Li, Zhengang Zhang, Waixing Tang, Lauren Van Reesema, Richard M. Costanzo, C. William Davis, Michael R. Knowles, Jerome F. Strauss Iii, Zhibing Zhang

Obstetrics and Gynecology Publications

SPAG6, an axoneme central apparatus protein, is essential for function of ependymal cell cilia and sperm flagella. A significant number of Spag6-deficient mice die with hydrocephalus, and surviving males are sterile because of sperm motility defects. In further exploring the ciliary dysfunction in Spag6-null mice, we discovered that cilia beat frequency was significantly reduced in tracheal epithelial cells, and that the beat was not synchronized. There was also a significant reduction in cilia density in both brain ependymal and trachea epithelial cells, and cilia arrays were disorganized. The orientation of basal feet, which determines the direction of axoneme …

Unique Cytokine Signature In The Plasma Of Patients With Fibromyalgia, Jamie Sturgill, Elizabeth Mcgee, Victoria Menzies

School of Nursing Publications

Fibromyalgia (FMS) is a chronic pain syndrome with a complex but poorly understood pathogenesis affecting approximately 10 million adults in the United States. The lack of a clear etiology of FMS has limited the effective diagnosis and treatment of this debilitating condition. The objective of this secondary data analysis was to examine plasma cytokine levels in women with FMS using the Bio-Plex Human Cytokine 17-plex Assay. Post hoc analysis of plasma cytokine levels was performed to evaluate patterns that were not specified a priori. Upon examination, patients with FMS exhibited a marked reduction in cytokines such as IL-4, IL-5, and …

Guided Imagery For Stress And Symptom Management In Pregnant African American Women, Nancy Jallo, R. Jeanne Ruiz, R. K. Elswick Jr., Elise French

School of Nursing Publications

The purpose of this study was to evaluate the efficacy of a guided imagery (GI) intervention for stress reduction in pregnant African American women beginning early in the second trimester. This prospective longitudinal study of 72 women used a randomized controlled experimental design with two groups conducted over 12 weeks. The intervention was a CD with 4 professionally recorded tracts designed and sequenced to influence study variables. Participants in both GI and usual care (UC) completed measures and donated 5 cc of blood at baseline, 8 weeks and 12 weeks. Participants also completed a daily stress scale. A mixed-effects linear …

Adaptation Of An Evidence-Based Intervention To Promote Colorectal Cancer Screening: A Quasi-Experimental Study, Shin-Ping Tu, Alan Chun, Yutaka Yasui, Alan Kuniyuki, Mei-Po Yip, Vicky Taylor, Roshan Bastani

Internal Medicine Publications

Background To accelerate the translation of research findings into practice for underserved populations, we investigated the adaptation of an evidence-based intervention (EBI), designed to increase colorectal cancer (CRC) screening in one limited English-proficient (LEP) population (Chinese), for another LEP group (Vietnamese) with overlapping cultural and health beliefs.

Methods Guided by Diffusion of Innovations Theory, we adapted the EBI to achieve greater reach. Core elements of the adapted intervention included: small media (a DVD and pamphlet) translated into Vietnamese from Chinese; medical assistants distributing the small media instead of a health educator; and presentations on CRC screening to the medical assistants. …

Phase I Safety Trial Of Intravenous Ascorbic Acid In Patients With Severe Sepsis, Alpha A. Fowler, Aamer A. Syed, Shelley Knowlson, Robin Sculthorpe, Don Farthing, Christine Dewilde, Christine A. Farthing, Terri L. Larus, Erika Martin, Donald F. Brophy, Seema Gupta, Bernard J. Fisher, Ramesh Natarajan

Internal Medicine Publications

Background Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.

Methods Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed …

Cxcr4 Inhibition Ameliorates Severe Obliterative Pulmonary Hypertension And Accumulation Of C-Kit+ Cells In Rats, Daniela Farkas, Donatas Kraskauskas, Jennifer Drake, Aysar A. Alhussini, Vita Kraskauskiene, Harm J. Bogaard, Carlyne D. Cool, Norbert F. Voelkel, Laszlo Farkas

Internal Medicine Publications

Successful curative treatment of severe pulmonary arterial hypertension with luminal obliteration will require a thorough understanding of the mechanism underlying the development and progression of pulmonary vascular lesions. But the cells that obliterate the pulmonary arterial lumen in severe pulmonary arterial hypertension are incompletely characterized. The goal of our study was to evaluate whether inhibition of CXC chemokine receptor 4 will prevent the accumulation of c-kit+ cells and severe pulmonary arterial hypertension. We detected c-kit+­ cells expressing endothelial (von Willebrand Factor) or smooth muscle cell/myofibroblast (α-smooth muscle actin) markers in pulmonary arterial lesions of SU5416/chronic hypoxia rats. We found increased …

Mechanisms Of Cftr Functional Variants That Impair Regulated Bicarbonate Permeation And Increase Risk For Pancreatitis But Not For Cystic Fibrosis, Jessica Larusch, Jinsei Jung, Ignacio J. General, Michele D. Lewis, Hyun W. Park, Randall E. Brand, Andres Gelrud, Michelle A. Anderson, Peter A. Banks, Darwin Conwell, Christopher Lawrence, Joseph Romagnuolo, John Baillie, Samer Alkaade, Gregory Cote, Timothy B. Gradner, Stephen T. Amann, Adam Slivka, Bimaljit Sandhu, Amy Aloe, Michelle L. Kienholz, Dhiraj Yadav, M. Michael Barmada, Ivet Bahar, Min G. Lee, David C. Whitcomb

Internal Medicine Publications

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas …

Oral Supplementation With Non-Absorbable Antibiotics Or Curcumin Attenuates Western Diet-Induced Atherosclerosis And Glucose Intolerance In Ldlr−/− Mice – Role Of Intestinal Permeability And Macrophage Activation, Siddhartha S. Ghosh, Jinghua Bie, Jing Wang, Shobha Ghosh

Internal Medicine Publications

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet …

Virginia Commonwealth University Undergraduate Bulletin [2014], Virginia Commonwealth University

VCU Bulletins

Undergraduate bulletin for Virginia Commonwealth University for the academic year 2014-2015. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for undergraduate programs.

Inhibition Of The Mdm2 E3 Ligase Induces Apoptosis And Autophagy In Wild-Type And Mutant P53 Models Of Multiple Myeloma, And Acts Synergistically With Abt-737, Dongmin Gu, Shuhong Wang, Isere Kuiatse, Hua Wang, Jin He, Yun Dai, Richard J. Jones, Chad C. Bjorklund, Jing Yang, Steven Grant, Robert Z. Orlowski

Massey Comprehensive Cancer Center Publications

Intracellular proteolytic pathways have been validated as rational targets in multiple myeloma with the approval of two proteasome inhibitors in this disease, and with the finding that immunomodulatory agents work through an E3 ubiquitin ligase containing Cereblon. Another E3 ligase that could be a rational target is the murine double minute (MDM) 2 protein, which plays a role in p53 turnover. A novel inhibitor of this complex, MI-63, was found to induce apoptosis in p53 wild-type myeloma models in association with activation of a p53-mediated cell death program. MI-63 overcame adhesion-mediated drug resistance, showed anti-tumor activity in vivo, enhanced …

Live Cell Interferometry Quantifies Dynamics Of Biomass Partitioning During Cytokinesis, Thomas A. Zangle, Michael A. Teitell, Jason Reed

Massey Comprehensive Cancer Center Publications

The equal partitioning of cell mass between daughters is the usual and expected outcome of cytokinesis for self-renewing cells. However, most studies of partitioning during cell division have focused on daughter cell shape symmetry or segregation of chromosomes. Here, we use live cell interferometry (LCI) to quantify the partitioning of daughter cell mass during and following cytokinesis. We use adherent and non-adherent mouse fibroblast and mouse and human lymphocyte cell lines as models and show that, on average, mass asymmetries present at the time of cleavage furrow formation persist through cytokinesis. The addition of multiple cytoskeleton-disrupting agents leads to increased …

Adjuvant Exemestane With Ovarian Suppression In Premenopausal Breast Cancer, Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer Jr., Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer, Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis

Massey Comprehensive Cancer Center Publications

BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was …

Crystal Structures Of Influenza A Virus Matrix Protein M1: Variations On A Theme, Martin K. Safo, Faik N. Musayev, Philip D. Mosier, Qibing Zhou, Hang Xie, Umesh R. Desai

Medicinal Chemistry Publications

Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1's multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N1-165-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly …

Bioinformatics And Biomedical Informatics, Kayvan Najarian, Rachid Deriche, Mark A. Kon, Nina S. T. Hirata

Computer Science Publications

No abstract provided.

Regional And Scale-Specific Effects Of Land Use On Amphibian Diversity [Poster], James R. Vonesh, David Marsh, J. J. Apodaca, Karen H. Beard, Jane M. Bell, Christine Bozarth, Derrick Carper, Julie Charbonnier, Bradley J. Cosentino, Andreia Dantas, Elizabeth A. Forys, Miranda Foster, Jaquelyn General, Kristen S. Genet, Macie Hanneken, Kyle Hess, Shane Hill, Faisal Iqbal, Kara Jones, Nancy E. Karraker, Eran Kilpatrick, Tom A. Langen, James Langford, Katherine Lauer, Alison J. Mccarthy, Joseph Neale, Saumya Patel, Austin Patton, Cherie Southwick, Nathaniel Stearrett, Nick Steijn, Mohammad Tasleem, Joseph Taylor

Biology Presentations

Background/Question/Methods

Habitat loss and degradation influence amphibian distributions and are important drivers of population declines. Our previous research demonstrated that road disturbance, development and wetland area consistently influence amphibian richness across regions of the U.S. Here, we examined the relative importance of these factors in different regions and at multiple spatial scales. Understanding the scales at which habitat disturbance may be affecting amphibian distributions is important for conservation planning. Specifically, we asked: 1) Over what spatial scales do distinct landscape features affect amphibian richness? and 2) Do road types (non-rural and rural) have similar effects on amphibian richness? This is …

Arabidopsis Transcriptome Analysis Reveals Key Roles Of Melatonin In Plant Defense Systems, Sarah Weeda, Na Zhang, Xiaolei Zhao, Grace Ndip, Yangdong Guo, Gregory A. Buck, Conggui Fu, Shuxin Ren

Study of Biological Complexity Publications

Melatonin is a ubiquitous molecule and exists across kingdoms including plant species. Studies on melatonin in plants have mainly focused on its physiological influence on growth and development, and on its biosynthesis. Much less attention has been drawn to its affect on genome-wide gene expression. To comprehensively investigate the role(s) of melatonin at the genomics level, we utilized mRNA-seq technology to analyze Arabidopsis plants subjected to a 16-hour 100 pM (low) and 1 mM (high) melatonin treatment. The expression profiles were analyzed to identify differentially expressed genes. 100 pM melatonin treatment significantly affected the expression of only 81 genes with …

Identification Of Novel Regulatory Cholesterol Metabolite, 5-Cholesten, 3Β,25-Diol, Disulfate, Shunlin Ren, Jin Koung Kim, Genta Kakiyama, Daniel Rodriguez-Agudo, William M. Pandak, Hae-Ki Min, Yanxia Ning

VCU Health Publications

Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3β, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages …

A Metagenomic Assessment Of The Bacteria Associated With Lucilia Sericata And Lucilia Cuprina (Diptera: Calliphoridae), Baneshwar Singh, Tawni L. Crippen, Longyu Zheng, Andrew T. Fields, Ziniu Yu, Qun Ma, Thomas K. Wood, Scot E. Dowd, Micah Flores, Jeffery K. Tomberlin, Aaron M. Tarone

Forensic Science Publications

Lucilia Robineau-Desvoidy (Diptera: Calliphoridae) is a blow fly genus of forensic, medical, veterinary, and agricultural importance. This genus is also famous because of its beneficial uses in maggot debridement therapy (MDT). Although the genus is of considerable economic importance, our knowledge about microbes associated with these flies and how these bacteria are horizontally and trans-generationally transmitted is limited. In this study, we characterized bacteria associated with different life stages of Lucilia sericata (Meigen) and Lucilia cuprina(Wiedemann) and in the salivary gland of L. sericata by using 16S rDNA 454 pyrosequencing. Bacteria associated with the salivary gland of …

Neuropathological Responses To Chronic Nmda In Rats Are Worsened By Dietary N-3 Pufa Deprivation But Are Not Ameliorated By Fish Oil Supplementation, Vasken L. Keleshian, Matthew Kellom, Hyung-Wook Kim, Ameer Y. Taha, Yewon Cheon, Miki Igarashi, Stanley I. Rapoport, Jagadeesh S. Rao

Anatomy and Neurobiology Publications

Background

Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.

Methods

Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose …

Impaired Bone Formation In Pdia3 Deficient Mice, Yun Wang, Alexandr Nizkorodov, Kelsie Riemenschneider, Christopher S. D. Lee, Rene Olivares-Navarrete, Zvi Schwartz, Barbara D. Boyan

Biomedical Engineering Publications

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3) mediates 1α,25(OH)2D3initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/− heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality.Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis …

Rock Inhibitor Is Not Required For Embryoid Body Formation From Singularized Human Embryonic Stem Cells, Giuseppe Pettinato, Wendy S. Vanden Berg-Foels, Ning Zhang, Xuejun Wen

Biomedical Engineering Publications

We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from …

Sjl Mice Infected With Acanthamoeba Castellanii Develop Central Nervous System Autoimmunity Through The Generation Of Cross-Reactive T Cells For Myelin Antigens, Chandirasegaran Massilamany, Francine Marciano-Cabral, Bruno Da Rocha-Azevedo, Melissa Jamerson, Arunakumar Gangaplara, David Steffen, Rana Zabad, Zsolt Illes, Raymond A. Sobel, Jay Reddy

Microbiology and Immunology Publications

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139–151 and myelin basic protein 89–101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139–151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139–151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, …

Reduction Of The Hiv Protease Inhibitor-Induced Er Stress And Inflammatory Response By Raltegravir In Macrophages, Xiaoxuan Zhang, Risheng Cao, Ruping Liu, Renping Zhao, Yi Huang, Emily C. Gurley, Phillip B. Hylemon, William M. Pandak, Guangji Wang, Luyong Zhang, Xiaokun Li, Huiping Zhou

Microbiology and Immunology Publications

Background

HIV protease inhibitor (PI), the core component of highly active antiretroviral treatment (HAART) for HIV infection, has been implicated in HAART-associated cardiovascular complications. Our previous studies have demonstrated that activation of endoplasmic reticulum (ER) stress is linked to HIV PI-induced inflammation and foam cell formation in macrophages. Raltegravir is a first-in-its-class HIV integrase inhibitor, the newest class of anti-HIV agents. We have recently reported that raltegravir has less hepatic toxicity and could prevent HIV PI-induced dysregulation of hepatic lipid metabolism by inhibiting ER stress. However, little information is available as to whether raltegravir would also prevent HIV PI-induced inflammatory …