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.
This research set to indicate the role of the opportunity cost in the overall economic development (human and social development) by selecting the most appropriate alternative for the growth of the country in exchange for sacrificing profit limits to achieve this growth and development of the country, especially in the present circumstances of the country and after studying the reality of the economic case for him, as the problem lies with don't selecting the best alternative that enhances the gross domestic product, which extends to promote overall economic development and revive the industrial and agricultural sectors, productivity is more like Impotent, versus sacrifice alternative consumption may bring more financially lucrative than
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Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin’s practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity,
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Abstract:
Purpose\The researcher paper aims to determine the impact of information technology on the job performance, for Iraq private ban as through the use of technology dimensions of job performance.
The aim of this research: this study aims to discuss the importance of information technology and its role in achieving job performance and its impact on the Iraq banking sector design/ methodology/ approach used entrance design/methodology/approach- pilot, the questionnaire was used to collect data in order to develop a model to measure reliably and correctly to the variables of information technology and job performance, and hypotheses were tested through the use of some statisti
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Abstract:
The tax is one of the elements of the general revenues of the state and contributes to covering its expenses. Taxes are imposed in most countries of the world. The tax proceeds depend on a set of factors that contribute either positively or negatively to the tax share by increasing or decreasing it. Therefore, the research aims to demonstrate the role of the tax examiner's procedures in achieving the validity of the taxable base and its reflection on the tax proceeds, as well as reviewing the tax examiner's procedures related to the tax return process. Examination and tax audit of the financial statements, as well as presenting the financial statements to an independent and i
... Show Moreفي البداية اود الاشارة الى ان فهم حقيقة الازمة هو ذو جانب فني يتعلق بالجينات الوراثية لنظام يملك في احيناته قدرة عالية على تفريخ المشتقات. هذا النظام الذي يزداد عقما وتدميرا يزداد قدرة على خلق النقود الائتمانية/المشتقات، وكلما اقتربنا اكثر من فهم هذا الجانب كلما اسقطت في ايدينا تلك التوصيفات الاكاديمية الجاهزة في نقص الرقابة والاشراف، تركيز المخاطر،....الخ التي تناولتها الكتابات الشائعة في معظم طروحات
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Abstract
This study was to demonstrate the role-use planning scientific methods is disabled and little used in the planning and follow-up construction of vital projects in the province of Baghdad, including network planning methods, in order to find the optimal time to finish the project in light of the resources available and the budget set for it, in the current research has been used the most prominent network planning methods and two stylistic (CPM / PERT), was the application of the critical path method on standard-design school project (traditional) to draw Action Network according to confirmed times for the activities of the project and account his Crashing time , It was Pert technique applied to the project hemato
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The Developing economies of countries have witnessed essential changes to words the development of tourism industry in the 21st century . in addition to adopting same of policies and strategies to grow up with the tourism sector to make it one of the important economic sector to compete the tourist cal developments in the wear .
As for the tourism sector in Iraq ,it's still afresh one , has many of elements which can be in vested ,needs a wide strategies of tourist cal in statutes and variety completive services and change of success for the locale and forgin investor ,the essential aim after this research is to prompt the national economic through the tourism industry and making concisen
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based on the importance of public relations in companies, I will discussed the issue of public relations and its role in marketing national products, given what these companies represent of great importance in terms of providing products and services to large segments of Iraqi society, which necessitated the need to search and investigate the role and importance of activities that Provides public relations in Iraqi companies in all categories( public, private and mixed).
the study tables and theirinterpretations, results and recommendations, and the studyreachedseveralresults, including the positive and the negative, the positive including the success in marketing the products by the number of companies in the Fairswhere the level of
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As long as the place in which a person lives has a meaning and temporal dimensions , memory is the main axis of these dimensions , today , city centers and old historical sectors of cities are abandoned , and began to turn into slums , the contradiction between old and historical sectors led cities to lose their identity while people lost their sense of belongingness to the old sectors where their ancestors used to live . The old city of Hilla used to have social , historical and cultural role on determining the identity . The study problem can be summarized as the ( lack of studies regarding the impact of historical memory related to Hilla old city on social and cultural mobility ) , the study hypothesis claims that the social , histori
... Show MoreProstate cancer is the commonest male cancer and the second leading cause of cancer-related death in men. Over many decades, prostate cancer detection represented a continuous challenge to urologists. Although all urologists and pathologists agree that tissue diagnosis is essential especially before commencing active surgical or radiation treatment, the best way to obtain the biopsy was always the big hurdle. The heterogenicity of the tumor pathology is very well seen in its radiological appearance. Ultrasound has been proven to be of limited sensitivity and specificity in detecting prostate cancer. However, it was the only available targeting technique for years and was used to guide biopsy needle passed transrectally or transperineally
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