The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
Klebsiella pneumoniae capsular polysaccharide (CPS) antigen was evaluated for their capability to increase immune responses. And, CPS neutralizing antibodies were approved as the main response to vaccination in many disease. Therefore, killed Stapthylococcus aureus bacteria was employed to evaluate K. pneumoniae CPS adjuvanticity. The mice groups were immunized (orally, intra-peritoneally and by swab skin)with a dose of (25μl of formalin killed S. aureus (1.5 x 108) with a CPS at dose 175μl/kg at a conc.50 μg/ml) vaccination occurred in first day then recurrent vaccination as booster dose beyond seven days. After first 7 days, the results revealed elevation of IL2,4,10,12 and IgG levels occurred mainly in oral and swab skin groups, an
... Show MoreA total of 320 samples of vaginal swabs was obtained from women complaining of vaginal infection and attending two hospitals in Al-Sader city, Baghdad, namely Ibn AlBaladi Hospital for Pediatrics and Gynecology and Fatimat Al-Zahraa Hospital for Obstetrics in Al-Habibia district during the period from Desember 1997 till July 1998. Results of direct smear and culture showed that Trichomonas vaginalis infection occurred in 19.1%, in addition to some microorganisms. The most common infection was by Candida spp. (24.7%), followed by Gardnerella vaginalis (13.8%) and Staph. aureus (10.9%). Infection with Escherichia coli, Klebsiella spp. and Prote
... Show MoreKlebsiella pneumoniae is one of common hospital-acquired bacteria causing nosocomial pneumonia, urinary tract infections, and intra-abdominal infections. The aim of this study is investigating the Modulation effect of Zinc Oxide nanoparticles (ZnO NPs) against multidrug resistant K. pneumonia which was isolated from Respiratory Tract Infections (RTIs). The results of isolation and characterization of bacterial specimens showed that 20.81% of RTIs were Klebsiella pneumoniae. The strongest isolate showed resistant for most usable antibiotics selected. Simultaneously, ZnO NPs were produced by an aqueous extract of Green Tea leaves as a reducing and stabilizer agent. The Ultraviolet-Visible (UV-Vis) spectrum was indicated a successful produc
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Abstract
The goal of the research is to diagnose some of the negative phenomena which was discovered through the period from (2010 to 2014) as determined by the national strategy to eliminate the corruption which was set out by the joint council of the corruption elimination in Iraq. And to measure the gap in applying the legal rules by the administration, concerning the misconducts and felonies upon the state employments made by the state employee and how far they are applied in the studied sample and to show the nature of the rules and their importance and their role when they are applied in scientific and expertise manner. And to encourage the offices of the general supervisors to adhere to them which will lead t
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The research deals with financial and supplies support from the rulers and governors of the
Arab cities and Islamic regions to the poor of common people and the poor of their own . The
Islamic Arab community was characterized , since the prophet's era , with great humanistic
features that formed the cultural characteristic which organized individual's economic life .
The prophet , senior Muslims and the rich cared a lot about this side . There was a large
variation in the degrees of wealth and poverty in the Muslim Arab community as a heritage
from the pve – Islamic society where there is no concern about helping the needy and poor .
Thus , the research sheds light on the different forms of help offered by rulers a
The charge species plays a vital role in changing the field in direct current discharge (DC). This article introduces a numerical modeling in one dimension of the inner electrode diameter of oxygen-fed negative corona discharge in coaxial electrodes geometry. The properties of negative corona plasma in a concentric cylindrical electrodes (wire-cylinder) were simulated by COMSOL Multiphysics software. Various diameters of negative corona electrode, namely 0.01, 0.025, 0.05, 0.075, and 0.125 mm, were applied, where the diameter of the outer cylindrical electrode was taken as 15 mm. The model was run at atmospheric pressure and the applied negative voltage was
-10 KV. Moreover, oxygen gas was used to fill the inter-electrodes dist
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The treasury bills one internal government debt instruments in iraq that were used to finance temporary deficits in the government budget, There fore the government resorted to issuing for the purpose of providing liquidity, As well as to invest in productive progects, After that it was financing the budget deficit by the monetary authovity of the central baalpennek [the new cash velease] which led to negative effects on the Iraqi econome, Thus we find that the treasury transfers have formed alarge proportion of the gross domestic government debt to finance the deficit ayear ago 2003. &nbs
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Abstract
The aim of the research is to introduce the international standards of the Supreme audit Institutions, as well as the role of these standards in achieving administrative reform and improving the performance of the Supreme audit Institutions and the performance of the economic units under its control.
In order to achieve the objectives of the research, a questionnaire was designed from two main axes that included a number of questions addressed to a number of officials and employees of the Supreme Audit Institutions and its affiliated bodies on the role of applying the international standards of the Supreme Audit Institutions in achieving administrative re
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Abstract
The research has discussed the public relations as dependent variable of its branch dimensions( confidence , commitment, control and satisfaction ) and the governmental service quality as independent variable of its branch dimensions (response, dependency, emphasis, tangibility and sympathy), and the research problem has represented by weakness of service quality presented to the customers dealing with company, which is observed via field co-existence of the researcher, where he observe that the quality presented in the company services, are inappropriate with the customers expectations level, also there is weakness of attention and recognition by the