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.
Background and aim: Pseudomonas putida is a non-capsulated, rod-shaped, oxidative, gram-negative Bacterium. The aim of the study was to isolate the pathogenic P. putida from a cow with respiratory infection and to evaluate pharmacodynamics indices of cinnamon oil against isolated bacteria in order to determine its the in vitro antibacterial efficacy for the first time in Iraq. Materials and methods: divided into two parts: first part involved the isolation and identification of pathogenic P. putida from cow with respiratory infection, swab samples were cultured on different media and examined microscopically. Results: The isolates were identified based on the production of pyoverdine dye on nutrient agar, beta-hemolysis on blood aga
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The research tackles the nature of relationship between the Orthodox Church and the state in the Russian Federation. At the beginning of the nineties of the last century, the church had been performed a different role in its relationship with the state, and it had an effect over the internal and foreign policies for the Russian Federation. In political history of Russia, the church’s existence became an evident too much in comparing with the previous historical period, starting with the educational and political system, whether through a symbolic participating roles as what happened in the inauguration ceremony to take over responsibility of the head of state or taking actual roles such as influencing on the process of holding elections d
... Show MoreBrucella melitensis isolates were obtained from human infections , and milk which obtained from aborted sheep at Mosul city vicinity . One isolate from each source was used in carrying out this study. Brucella liquid culture was added to sheep milk at 2.5 % for treatments . To first treatment 2 % of yoghurt starter ( Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarius subsp. thermophilus ( 1: 1 ) ) . Second treatment was carried out without addition of yoghurt starter but the pH was lowered using lactic acid in pattern similar to first treatment . Third treatment was similar to the first treatment but contained buffer to alleviate the reduction in pH , which reduced to 6.1 in comparison to 4.9 of the first treatment .
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The research aims to develop alternatives to transportation at the entrance to the Educational City (University of Baghdad) during the morning and evening peaks, which result from of the traffic congestion at the entrances to the educational city (the University of Baghdad), and affects the emotional, functional, and social performance of the whole city, and leads to hotbeds of confluence and congestion at the entrances in the morning and evening peaks. This movement was measured on the ground for pedestrians and vehicles. Some criteria were adopted to determine the density of road length to the area and density of roads for the number of users and the rate of the area served by roads. The research reviews the experiences of some
... Show MoreThis research attempts to evaluate the role of the information system by highlighting its importance in providing date and information to the tax administration the process of tax accounting for those who are subject to income tax whether they are individuals or companies where the effective information system provides accurate and reliable information in a timely manner.
At the theoretical part of the research, the research approaches the problem of the research represented in that whether the information system, applied in the General Commission for Taxes, is capable of achieving its role in reducing the phenomenon of tax evasion. The existence of a set of things which in the Commission may lead to increase tax evasion by taxpa
... Show MoreThis article discusses the change of values in urban family, because of various communication media and modern technologies as one of the most important factors affecting the changing family values in urban areas, this means becoming part of urban life. And focuses on the family in urban areas, for the privacy of the social, economic, demographic and cultural help to this effect, and because cities are the most friction and interaction with modern technologies.
There are certain dates in the history of nations that have their effects on them ,and the 25th of January 2011 is considered one of them in the history of the state of Egypt .Since this date Egypt has passed through many events that led to changes in the political life and its actors . New rolls has arisen for actors that didn't take part in the political life before so clearly ,like the military establishment which started to practice more prominent political roll, till it became the most important actor in the political life of Egypt .This establishment tried to institutionalize its roll through constitutional means ,considering that controlling the authority is the only alternative to safeguard the state which we are trying to study
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ABSTRACT This article examines the concepts of "discourse" and "political discourse" from the point of view of various researchers and linguists. The main linguistic features characteristic of political discourse are also presented. The term "discourse" is used in various scientific disciplines such as philosophy, linguistics, political science, anthropology, sociology, etc. However, there is no unambiguous definition of this term that unites all situations of its use today.
This study is concerned look at the role of satellite channels in the dissemination of
consumer culture that has become part of our everyday lives , which is a dangerous
phenomenon on society , so the study is aimed at introducing the concept of consumer culture
and the risks to individuals , which conducted a field study on a sample of students from the
University of Baghdad, as they represent an important category of the society they are a class
of young people to get to know the impact of satellite television on them through their various
programs and serials, films and ads may develop consumer culture they have , including in
respect of ideas and information , where the questionnaire was developed to ensure diffe