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.
Abstract:-
The approach maintenance and replacement one of techniques of operations research whom cares of the failure experienced by a lot of production lines which consist of a set of machines and equipment, which in turn exposed to the failure or work stoppages over the lifetime, which requires reducing the working time of these machines or equipment below what can or conuct maintenance process once in a while or a replacement for one part of the machine or replace one of the machines in production lines. In this research is the study of the failure s that occur in some parts of one of the machines for the General Company for Vege
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This study examines the relationships between Kuwait and the Soviet Union from 1961 to 1991, chiefly by analyzing not only the factors that drove Kuwait to form diplomatic relationships with Moscow in 1963 but also how domestic, regional, and international variables affected the development of those relationships until 1991. The study presents the analytical and historical research methods used to reach its findings. Among the findings, Kuwait’s decision to forge diplomatic relationships with Moscow in 1963 indeed seems to have been driven by domestic, regional, and international factors, including Kuwait’s geographical situation, the historical background of the relationships between Kuwait and Moscow, and the structure of t
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The researcher aims to detect the emotive equanimity in kindergartens teachers,also to uncover the anxiousness in children of kindergartens,then to detect the relationship between them,then to choose the simple random way which is about(180) teachers and children,when the twore searchers made two tools to measure the emotive equanimity and the anxiety for both teachers and children,statistical methods had been used include:(pearsons correlation coefficient,t-test for one sample,t-test for two independent samples are individuals).the researcher led to multiple results:
1-the teacher has an emotive equanimity.
2-children has no anxiousness.
The Phenomenon of Euphemism in the Translon Activity Euphemism is the replacement of a harsh word with a less harsh or more acceptable one. Most languages are affected by ideological, cultural, social, or religious perspectives which in turn would reflect different linguistic levels. On such a basis, translation is affected by its medium,i.e. language, and consequently what is acceptably expressed by a nation may not be acceptable by another. In this paper, we try to
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Abstract
Islam has been concerned with preserving and maintaining rights, so the provisions in which it is preserved are legislated. Among that is the testimony that made it a way to prove the truth and obliges its bearer to fulfill right in order to preserve the right and establish justice and prevent injustices by defying conflict, and tyranny .
And while acknowledging that divine absolute wisdom that is the cause and origin of legal rulings is sufficient, it is obligatory to abide by its provisions and imposes obedience, surrender, contentment and work in accordance with its controls.
However, the realization of the defects behind the legislation in a comprehensive way that realizes the dev
... Show MoreIn the present study, an attempt has been to develop a new water quality index (WQI) method that depends on the Iraqi specifications for drinking water (IQS 417, 2009) to assess the validity of the Euphrates River for drinking by classifying the quality of the river water at different stations along its entire reach inside the Iraqi lands. The proposed classifications by this method are: Excellent, Good, Acceptable, Poor, and Very poor. Eight water quality parameters have been selected to represent the quality of the river water these are: Ion Hydrogen Concentration (pH), Calcium (Ca), Magnesium (Mg), Sodium (Na), Chloride (Cl), Sulphate (SO_4), Nitrate (NO_3), and Total Dissolved Solids (TDS). The variation of the water quality p
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Abstract:
This study seeks to shed light on the important processes are linked to the impact of accounting information on the behavior of producer and user of information and are urging informational and informational use. That accounting as a system of accounting information and functions of the delivery of information to decision makers Under behavioral entrance to the formulation of accounting theory should be taken into account Othertlk accounting information in the behavior of the decision maker which requires an explanation of human behavior and predictable.
On the other hand that the accounting information that should be delivered to the decision maker will affect your beha
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