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https://www.readbyqxmd.com/read/28822816/genetically-modified-rabies-virus-vectored-ebola-virus-disease-vaccines-are-safe-and-induce-efficacious-immune-responses-in-mice-and-dogs
#1
Lei Shuai, Xijun Wang, Zhiyuan Wen, Jinying Ge, Jinliang Wang, Dandan Zhao, Zhigao Bu
Ebola viruses (EBOVs) are zoonotic pathogens that cause EBOV disease (EVD) with high case fatality in humans. Currently, EVD vaccines are still under development in several countries. Here, we generated two recombinant rabies viruses (RABVs), rERAG333E/ZGP and rERAG333E/SGP, expressing the Zaire EBOV glycoprotein (ZGP) or Sudan EBOV glycoprotein (SGP) gene based on a modified ERA vaccine strain (rERAG333E) vector platform. The recombinant RABVs retained growth properties similar to those of the vector virus in BSR cell culture and efficiently expressed ZGP or SGP...
August 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28776445/inhibition-of-dengue-virus-replication-by-novel-inhibitors-of-rna-dependent-rna-polymerase-and-protease-activities
#2
Sveva Pelliccia, Yu-Hsuan Wu, Antonio Coluccia, Giuseppe La Regina, Chin-Kai Tseng, Valeria Famiglini, Domiziana Masci, John Hiscott, Jin-Ching Lee, Romano Silvestri
Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes - NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28737909/inhibitory-kappa-b-kinase-%C3%AE-ikk%C3%AE-inhibitors-that-recapitulate-their-selectivity-in-cells-against-isoform-related-biomarkers
#3
Nahoum G Anthony, Jessica Baiget, Giacomo Berretta, Marie Boyd, David Breen, Joanne Edwards, Carly Gamble, Alexander I Gray, Alan L Harvey, Sophia Hatziieremia, Ka Ho Ho, Judith K Huggan, Stuart Lang, Sabin Llona-Minguez, Jia Lin Luo, Kathryn McIntosh, Andrew Paul, Robin J Plevin, Murray N Robertson, Rebecca Scott, Colin J Suckling, Oliver B Sutcliffe, Louise C Young, Simon P Mackay
IKKβ plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKKα in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKKβ, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKKα over IKKβ. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKKα. We demonstrate effective target engagement and selectivity with IKKα in U2OS cells through inhibition of IKKα-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKKβ-dependent IKappa-Bα loss in the canonical pathway...
August 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646221/aberrant-activation-of-the-human-sex-determining-gene-in-early-embryonic-development-results-in-postnatal-growth-retardation-and-lethality-in-mice
#4
Tatsuo Kido, Zhaoyu Sun, Yun-Fai Chris Lau
Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY(ON)) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622871/a-spike-specific-whole-porcine-antibody-isolated-from-a-porcine-b-cell-that-neutralizes-both-genogroup-1-and-2-pedv-strains
#5
Fang Fu, Lin Li, Lingling Shan, Beibei Yang, Hongyan Shi, Jiaoer Zhang, Hongfeng Wang, Li Feng, Pinghuang Liu
Porcine epidemic diarrhea (PED), caused by an alpha coronavirus, is a highly contagious disease and causes high morbidity and mortality in suckling piglets. Isolating PEDV neutralizing antibodies from porcine B cells is critical to elucidate the development of PEDV neutralizing antibodies and the protective mechanism of PEDV infection. Here, we described the isolation of a PEDV-neutralizing antibody from the B cell of a vaccinated pig. The antibody, named PC10, was demonstrated to target the conformational epitope of PEDV spike protein, specifically bind to the infected cells of PEDV genogroup 1 and 2 strains, and potently neutralize PEDV infection...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28595631/isolation-of-tibet-orbivirus-from-culicoides-and-associated-infections-in-livestock-in-yunnan-china
#6
Jinglin Wang, Huachun Li, Yuwen He, Yang Zhou, Aiguo Xin, Defang Liao, Jinxin Meng
BACKGROUND: Culicoides-borne orbiviruses, such as bluetongue virus (BTV) and African horse sickness virus (AHSV), are important pathogens that cause animal epidemic diseases leading to significant loss of domestic animals. This study was conducted to identify Culicoides-borne arboviruses and to investigate the associated infections in local livestock in Yunnan, China. METHODS: Culicoides were collected overnight in Mangshi City using light traps during August 2013...
June 8, 2017: Virology Journal
https://www.readbyqxmd.com/read/28490801/dendritic-cells-provide-a-therapeutic-target-for-synthetic-small-molecule-analogues-of-the-parasitic-worm-product-es-62
#7
Felicity E Lumb, James Doonan, Kara S Bell, Miguel A Pineda, Marlene Corbet, Colin J Suckling, Margaret M Harnett, William Harnett
ES-62, a glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae, subverts host immune responses towards anti-inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC). The PC dictates that ES-62 exhibits protection in murine models of inflammatory disease and hence a library of drug-like PC-based small molecule analogues (SMAs) was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF-κB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28390725/comparison-of-a-commercially-available-oral-nutritional-supplement-and-intravenous-fluid-therapy-for-dehydration-in-dairy-calves
#8
Jared D Taylor, Merel Rodenburg, Timothy A Snider
Calf scours is a primary cause of morbidity and mortality in the dairy industry. Effective treatments are needed to minimize death, maximize welfare, and maintain growth and productivity. The objective of this trial was to compare the efficacy of a commercially available nutritional supplement (Diaque, Boehringer-Ingelheim Vetmedica Inc., St. Joseph, MO) and i.v. lactated Ringer's solution (LRS) in rehydrating, preventing acidemia, and correcting electrolyte imbalances in an experimental model for calf scours...
April 5, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28381581/cell-attachment-domains-of-the-porcine-epidemic-diarrhea-virus-spike-protein-are-key-targets-of-neutralizing-antibodies
#9
Chunhua Li, Wentao Li, Eduardo Lucio de Esesarte, Hongbo Guo, Paul van den Elzen, Eduard Aarts, Erwin van den Born, Peter J M Rottier, Berend-Jan Bosch
Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs, resulting in significant economic losses to the swine industry worldwide. Current vaccination approaches against this emerging coronavirus are only partially effective, though natural infection protects pigs against reinfection and provides lactogenic immunity to suckling piglets. The viral spike (S) glycoprotein, responsible for receptor binding and cell entry, is the major target for neutralizing antibodies. However, knowledge of antibody epitopes, their nature and location in the spike structure, and the mechanisms by which the antibodies interfere with infection is scarce...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28219768/copper-therapy-reduces-intravascular-hemolysis-and-derepresses-ferroportin-in-mice-with-mosaic-mutation-atp7a-mo-ms-an-implication-for-copper-mediated-regulation-of-the-slc40a1-gene-expression
#10
Małgorzata Lenartowicz, Rafał R Starzyński, Aneta Jończy, Robert Staroń, Justyna Antoniuk, Wojciech Krzeptowski, Paweł Grzmil, Aleksandra Bednarz, Olga Pierzchała, Mateusz Ogórek, Zenon Rajfur, Zbigniew Baster, Paweł Lipiński
Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis...
February 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28179596/nephron-wilms-tumor-1-wt1-and-synaptopodin-expression-in-developing-podocytes-of-mice
#11
Takashi Kato, Shinya Mizuno
Newborn mouse glomeruli are still immature with a morphological feature of an early capillary loop stage, but infant mice do not manifest proteinuria. Little is known about the molecular mechanism whereby infant mice are resistant to proteinuria. Nephrin and synaptopodin are crucial for slit diaphragm and foot process (FP) formation for avoiding proteinuria. Nephrin tyrosine phosphorylation means a transient biological signaling required for FP repair or extension during nephrotic disease. Using an immunohistochemical technique, we examined the natural course of nephrin, Wilms' tumor-1 (WT1) and synaptopodin at 16...
August 5, 2017: Experimental Animals
https://www.readbyqxmd.com/read/27790431/the-role-of-vibrio-cholerae-haemagglutinin-protease-hap-in-extra-intestinal-infection
#12
Amit Ghosh, Hemanta Koley, Amit Pal
INTRODUCTION: Based on the diversity of surface O antigen Vibrio cholerae can be classified into 206 serogroups. Vibrio cholerae is the causative agent of cholera and extra intestinal infections like, septicemia, wound infection and haemorrhagic reactions. Pathogenic factors of V. cholerae extra-intestinal infection are yet to be explored. AIM: To identify the pathogenic factor associated with V. cholerae extra-intestinal infection. MATERIALS AND METHODS: This study was carried out between April, 2007 to October 2007 in National Institute of Cholera and Enteric Diseases (NICED)...
September 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27581990/sindbis-virus-can-exploit-a-host-antiviral-protein-to-evade-immune-surveillance
#13
Xinlu Wang, Melody M H Li, Jing Zhao, Shenglan Li, Margaret R MacDonald, Charles M Rice, Xiang Gao, Guangxia Gao
Viral infection induces production of type I interferons (IFNs), which stimulate the expression of a variety of antiviral factors to inhibit viral replication. To establish effective infection, viruses need to develop strategies to evade the immune responses. A neurovirulent Sindbis virus strain with neuroinvasive properties (SVNI) causes lethal encephalitis in mice, and its replication in cultured cells is inhibited by the zinc finger antiviral protein (ZAP), a host factor that specifically inhibits the replication of certain viruses by binding to the viral mRNAs, repressing the translation of target mRNA, and promoting the degradation of target mRNA...
November 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27474493/plant-produced-crimean-congo-haemorrhagic-fever-virus-nucleoprotein-for-use-in-indirect-elisa
#14
Richard Atkinson, Felicity Burt, Edward P Rybicki, Ann E Meyers
Crimean-Congo haemorrhagic fever (CCHF) is a disease of serious public concern caused by the CCHF virus (CCHFV). Anti-CCHFV IgG in humans can be detected using ELISA with native antigen prepared from cell cultures which have been infected with virus or from brain tissue of suckling mice which have been inoculated with virus. However, the preparation of these reagents requires high biosafety levels and is expensive. A safer, more cost-effective recombinantly-produced NP reagent is desirable. Recently, plants have been shown to be a cost-effective and safe system for expression of recombinant proteins...
October 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27357720/isolation-and-characterization-of-porcine-epidemic-diarrhea-virus-associated-with-the-2014-disease-outbreak-in-mexico-case-report
#15
María Elena Trujillo-Ortega, Rolando Beltrán-Figueroa, Montserrat Elemi García-Hernández, Mireya Juárez-Ramírez, Alicia Sotomayor-González, Erika N Hernández-Villegas, José F Becerra-Hernández, Rosa Elena Sarmiento-Silva
BACKGROUND: Interest in porcine epidemic diarrhea has grown since the 2013 outbreak in the United States caused major losses, with mortality rates up to 100 % in suckling piglets. In Mexico, an outbreak of porcine epidemic diarrhea, characterized by 100 % mortality in piglets, began in March 2014 in the State of Mexico. METHODS: The aim of this study was to confirm and identify porcine epidemic diarrhea virus (PEDV) in samples from piglets with suggestive clinical signs using virological, histological, and molecular techniques...
June 29, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27313500/glycosphingolipid-gm3-is-indispensable-for-dengue-virus-genome-replication
#16
Kezhen Wang, Juanjuan Wang, Ta Sun, Gang Bian, Wen Pan, Tingting Feng, Penghua Wang, Yunsen Li, Jianfeng Dai
Dengue virus (DENV) causes the most prevalent arthropod-borne viral disease of humans worldwide. Glycosphingolipids (GSLs) are involved in virus infection by regulating various steps of viral-host interaction. However, the distinct role of GSLs during DENV infection remains unclear. In this study, we used mouse melanoma B16 cells and their GSL-deficient mutant counterpart GM95 cells to study the influence of GSLs on DENV infection. Surprisingly, GM95 cells were highly resistant to DENV infection compared with B16 cells...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27076131/generation-of-a-single-cycle-replicable-rift-valley-fever-vaccine
#17
Shin Murakami, Kaori Terasaki, Shinji Makino
Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. The virus carries a tripartite, single-stranded, and negative-sense RNA genome, designated as L, M, and S RNAs. RVFV spread can be prevented by the effective vaccination of animals and humans. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, MP-12 showed neuroinvasiveness and neurovirulence in young mice and immunodeficiency mice...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27047204/validation-of-%C3%AE-radiation-and-ultraviolet-as-a-new-inactivators-for-foot-and-mouth-disease-virus-in-comparison-with-the-traditional-methods
#18
Safy El Din Mahdy, Amr Ismail Hassanin, Wael Mossad Gamal El-Din, Ehab El-Sayed Ibrahim, Hiam Mohamed Fakhry
AIM: The present work deals with different methods for foot and mouth disease virus (FMDV) inactivation for serotypes O/pan Asia, A/Iran05, and SAT-2/2012 by heat, gamma radiation, and ultraviolet (UV) in comparison with the traditional methods and their effects on the antigenicity of viruses for production of inactivated vaccines. MATERIALS AND METHODS: FMDV types O/pan Asia, A/Iran05, and SAT-2/2012 were propagated in baby hamster kidney 21 (BHK21) and titrated then divided into five parts; the first part inactivated with heat, the second part inactivated with gamma radiation, the third part inactivated with UV light, the fourth part inactivated with binary ethylamine, and the last part inactivated with combination of binary ethylamine and formaldehyde (BEI+FA)...
September 2015: Veterinary World
https://www.readbyqxmd.com/read/27036203/s1-domain-of-the-porcine-epidemic-diarrhea-virus-spike-protein-as-a-vaccine-antigen
#19
Niraj Makadiya, Robert Brownlie, Jan van den Hurk, Nathalie Berube, Brenda Allan, Volker Gerdts, Alexander Zakhartchouk
BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows...
April 1, 2016: Virology Journal
https://www.readbyqxmd.com/read/26936988/intrinsic-excitability-differs-between-murine-hypoglossal-and-spinal-motoneurons
#20
M A Tadros, A J Fuglevand, A M Brichta, R J Callister
Motoneurons differ in the behaviors they control and their vulnerability to disease and aging. For example, brain stem motoneurons such as hypoglossal motoneurons (HMs) are involved in licking, suckling, swallowing, respiration, and vocalization. In contrast, spinal motoneurons (SMs) innervating the limbs are involved in postural and locomotor tasks requiring higher loads and lower movement velocities. Surprisingly, the properties of these two motoneuron pools have not been directly compared, even though studies on HMs predominate in the literature compared with SMs, especially for adult animals...
May 1, 2016: Journal of Neurophysiology
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