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.
Imposed on foreign oil companies from important sources in the financing of the general budget in most countries of the world income tax is considered as well as be used to achieve political, economic and social goals, and has developed the concept of the tax until it became play an important role in influencing the economic conditions of a country, and the aim of this research is to statement imposed on foreign oil companies operating in Iraq in the financing of the state budget income tax contribution, as well as clarify the contracts type contracts with these companies, which is in favor of Iraq, together with the Income Tax Law No. (19) for the year / 2010, and instructed No. (5) for the year / 2011, which organized the tax process s
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Background: presence of lingual vascular foramina and canals in the interforaminal region may increase the risk ofsurgical complications during implant placement or any surgical procedure in this area. Aim of this study is the radiological evaluation of the anatomic characteristic of the lingual foramina and their vascular canals in the anterior of the mandible using cone beam computed tomography. Materials and Methods: Prospective study including 72 Iraqi subjects (31 male and 41 female) ranging from 20 to 59 years, all subjects attended Al-Sharaa dental clinic in AL-Najaf AL-Ashraf city, scanned with CBCT from September 2016 to February 2017. Using 3dimentional and sagittal cross section to detect lingual foramina and their vascular canal
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It was found that there was a significant correlation between all tests of the mechanical and electrical activity of the heart (systolic force FC, stroke volume SV, end-diastolic volume, EF volume, and left ventricular volume during diastole LVDD) with the test of the oxygen-phosphating energy system (Markaria). - As safe (Margaria-Kalamen( It was found that there is a significant correlation between all tests of the mechanical and electrical activity of the heart (myocardial systolic force FC, stroke volume SV, end-diastolic volume EDV, and the percentage of heart pumpingEF blood, and left ventricular volume during diastole (LVDD) with the Lactational Oxygen Energy System Test (Wingate Test 30 Second(
The purpose of this paper is to identify the statistical indicators of the searched variables and identify the relationship between the cognitive learning outcome and the performance of the two mastering skills by parallel spherical standing and equilibrium on the balance beam. And the identification of the percentage of the cognitive learning outcome contribution to the performance of the two mastering skills by parallel spherical standing and the equilibrium on the balance beam. The two researchers used the descriptive approach in the survey method and the correlational relations, being the most appropriate to the nature of the research problem. The research community for the second stage students in the College of Physical Education and
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The research’s goal lies in demonstrating the impact of the Federal Financial Supervision Endowment through the process of auditing the performance of the entities subject to its audit as to improve the performance of these entities, especially if the performance audit method is one of the newly applied methods that are compatible with the standards issued by the International Organization of Financial Supervision and Accounting Institutions which is the method of auditing performance according to the performance evaluation guide for programs and policies issued by the Federal Office of Financial Supervision.
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... Show MoreThe research is trying to identify the investment portfolio risks of the insurance company and their impact, on the Profitability ratios of the company, and whether the company's scientific methods followed in the measurement of these risks, and conducted research in the National Insurance Company. by relying on its annual budget as well as the annual reports, The search dealing with these data in theoretical and practical major premise to statistically significant between to investment portfolio risk and financial performance correlation and reach a set of conclusions and recommendations which are the following.
investments include many ri
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One of the Kurdish scholars who have research on the doctrinal issues of the author of this brief message that we are about to achieve; to bring it out better and in order to preserve the Islamic heritage, and revive what can be revived after being close to death by staying in libraries here and there, out of reach of hands, carrying dust Years of forgetting and marginalization, and this letter is the papers in the door of the divorce entitled his author "Iqdar al-dream for those who did not sign divorce commoner," and the name is evident the name, and the intention of the author through writing, where he wrote it to answer some of the knowledgeable among the public at the time So they decreed that there was no divorce from commoners D w
... Show MoreThere is no doubt that the advertisement picture and the written text play a key role in the formation of the language of the communicative discourse as the main pillars of the design of commercial advertising and the main entrance for the advertising message awareness... Hence the researcher chose the title of her research (Integrative Relationship between the Picture and the Written Text in the Printed Commercial Advertisement) starting from following questions: What is the relationship between the picture and the written text in the printed commercial declaration? Is there functional, aesthetic and interactive integration between them?
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لخلاصة تشغل قضايا الهوية محور اهتمام الكثير من الباحثين والدارسين في بنية المجتمعات ومستقبل الدول, وفي كثير من الدراسات التي كتبها هؤلاء كان هناك ميل نحو دراسة الهوية وعلاقتها بحركة الدول تقدما وتراجعا ,فهناك من عزا تقدم دولة ما إلى نجاح نخبها السياسية في صناعة هوية جامعة لحالة التنوع الذي يميز مجتمعها, ويمكن ان تشير الى الولايات المتحدة الامريكية كأنموذج للنجاح في هذا الاطار.وهناك من ارجع
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The Light and the Dark is the fourth novel in a series written by Charles Percy Snow where it tackles a phase of gifted scholar and remarkable individual Roy Calvert as he search for a source of power and meaning in life to relieve his inner turmoil. The character Roy Calvert is based on Snow's friend, Charles Allbery who exposes the message the character of Roy intends to convey in a certain phase of his life and the prophecy the novel carries amid catastrophe so widespread in the thirties of the twentieth century