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 space occupied by the dialogic imperative in the language is a very wide range, as it is present in most of the speeches received by the recipient, and this is not limited to dialogues. That the literary discourse is a dialogical and fulfillment imperative, as the implication is related to the implicit connotations, as if the implication covers the indirect actions of the speech act theory.
This paper deals with the process of evaluating the performance of agricultural activity in Iraq and in particular the agricultural initiative launched by Prime Minister Nuri al-Maliki, during the period from 2008 - 2011. Where it is possible to use criteria or indicators that are fabricated by a statement on the calendar and the results of which may be by comparing planned performance with actual performance or the evaluation of the actual performance of successive periods selected. With an emphasis on the agricultural initiative is subject to the evaluation process by implementing and destinations specialized loan funds its own projects as one of the agricultural lending. With the need to co
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The importance of the research lies in preparing an experimental curriculum according to a scientific method that will contribute to the development of the special strength(endurance the strength of arms) in order to contribute to the attempt to develop the basic skills of the national team players with the goal ball for the blind As for the research problem, it lies in the weakness of the strength endurance of the national team players with the goal ball for the blind, as the research problem is clearly evident in the last minutes of the match, as well as the former studies in the field of goal ball game for the blind at the country level The research aims to prepare special exercises for endurance of strength as well as t
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This study tackles the contribution of the environmental audit in achieving the sustainability of the environmental balance in the Sudanese business environment. The study aimed at clarifying the role of environmental auditing in supporting sustainable development, and to recognize the role of environmental audit in urging businesses to abide by environmental protection. It also shows how effective the environmental audit reports are, in providing the reliable data for the concerned authorities, in order to use it in making the decisions that would help in the sustainability of the environmental balance. To achieve the goals of the study, a questionnaire was developed and distributed to the registered chartered accountants in Sud
... Show MoreThe current research deals with the study of aesthetic relations in the field of interior design and the extent to which its mechanisms achieve sensory stimulation between the internal and external spaces, to generate a continuous visual connection that is an extension of it, achieving in turn sensory stimulation for the users of those spaces. The internal and external spaces meet the desired purpose of feeling pleasure and beauty.” The current research aims to “discover the nature of aesthetic relations between the internal and external spaces and the extent to which mechanisms can achieve sensory stimulation in residential spaces.” The first topic included the concept of aesthetic relations, sensory excitement, and perception at
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The study aims to indicate the role of the agricultural initiative in building agricultural development, mediated by activation of the role of internal and external audit on agricultural initiative projects, for the purpose of meeting the challenges of abuses on agricultural land and lack of water used in agriculture and proportions of high poverty, which led to the rural people of the migration to the city and leave agriculture and livestock, and that of the main conclusions reached by the researcher. When comparing the work of the external auditing agencies (the Federal Office of Financial Supervision) on the initiative of agricultural projects with internal audit services in the Directorate of Agriculture and branches of the Agricultu
... Show MoreThe accounting information that is produced by any System a user either entering or leaving, since the needs of the users began to evolve where he became the information provided by the current reporting system that does not meet their requirements in terms of users began to demand information, more quickly, and as a result of the needs of the user accounting system and the development of information and communications technology has emerged a new system (real- time reporting system), which has the ability to produce information at the moment of data gathered, it is no longer dependent on local circumstance, but this case has become a global response where the computer has become a cornerstone of the culture of the communi
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This study aims to clarify the role of Iraqi satellite channels in spreading negative values among university youth; and the tendency of this segment to simulate the descending behaviors and pseudo-peculiar concepts of our society, which are displayed through the screens of these channels, based on the relevant media literature such as scientific references and the results of previous studies and research.
The study followed the survey methodology to examine the public based on the questionnaire as a research tool, which was distributed to a sample of male and female students of Baghdad University enrolled in the university for the academic year 2011-2012.
In order to achieve the specific objectives of this research
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Abstract
The current research aims to identify mental health and its role in promoting self-confidence and positive behavior of female university students. The researcher adopted the descriptive analytical approach in this research. The researcher depended on the availability of sources and references, literature, and previous field studies to analyze and study all aspects related to mental health and its role in promoting self-confidence and positive behavior of university students and then expand its importance and identify the areas of mental health, self-confidence, positive behavior, and university. The second chapter included the concept of mental health, the importance of the study, the most important factors of health and psyc
