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.
The research aimed to prepare a measure of the importance of enlightenment, academic education, and applied skills for third-stage female students, including teaching methods from their point of view/College of Education and Sports Sciences/University of Baghdad/Al-Jadriyah. The researchers used descriptive description in the comprehensive research procedures, an appropriate methodology in achieving the research objectives, sufficient for interpretations, how important is the academic teacher’s knowledge of teaching methods for student learning, what are the roles that the learners have acquired from the academic teacher. The scale of importance and horror consists of 15 items. The research population includes female students of t
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This research aims to identify the role of external environment factors on the quality of educational services, from the academic point of view, where the distribution of a questionnaire to a random sample of (100) university professors, and then analyzing a model, and test the validity of this model using structural modeling (SEM) (Structural Equation Modeling).
And then test the relationships between variables using the software of Statistical Package for Social Sciences (SPSS V.18), the research found a number of conclusions, the most important conclusion is: the external environment factors has significant impact on the quality of educational services.
The study aimed to identify the effect of Total Quality Management on enhancing competitiveness through the opinions of employees of the front- rows of customer service in local Palestinian banks, the researcher adopted an analytical descriptive method through developing a special questionnaire to accomplish the study’s objectives and answer its questions. The study involved all the Palestinian local banks, with their scattered branches in West Bank. The study sample consisted of 3470 executive employees for banking services out of 4753 employees, in the rate of 73%, and the study sample reached (485) employees who were randomly selected working in the front -rows to provide services in the local Palestinian banks during the ye
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This paper is dealing with an experimental study to show the influence of the geometric characteristics of the vortex generators VG son the thickness of the boundary layer (∂) and drag coefficients (CD) of the flat plate. Vortex generators work effectively on medium and high angles of attack, since they are "hidden" under the boundary layer and practically ineffective at low angles.
The height of VGs relative to the thickness of the boundary layer enables us to study the efficacy of VGs in delaying boundary layer separation. The distance between two VGs also has an effect on the boundary layer if we take into
... Show MoreDialogue is one of the pillars of character building in the television series, through which it is possible to identify the most important characteristics and traits of the personality, in addition to its ability to reveal the most important problems at all levels. The following: (How does dialogue contribute to enhancing the traits of the alienated personality?). It therefore aims to identify the effectiveness of the dramatic dialogue in enhancing the traits of the alienated personality represented by (powerlessness, isolation, meaninglessness, objectification, non-standardization and rebellion). (The traits of the alienated character, and the second is the psychological function of the dramatic dialogue), to extract from them the main
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The military presence in the Gulf region after the British withdrawal from it in 1971 was one of the most important pillars of the American strategy to climb the ladder of global leadership, as the geostrategic features that the region enjoyed provided factors of controlling energy sources and global trade routes. The United States of America guarantees Western Europe and Japan the process of access to energy sources and the exclusion of its opponents from the region, especially the Soviet Union, and the growing American military presence in the Gulf after the invasion of Iraq in 2003. On the other hand, the region experiences many contradictions, some of which threaten its security, such as the exacerbation of disputes between its count
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