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 current research aims to identify the effect of the proposed strategy in accordance with realistic mathematics on the achievement and mathematical Interrelation of third Intermediate students. Two samples were tested from the middle third grade in a school affiliated with the General Directorate of Baghdad- Rusafa, the first for the academic year (2022-2021). The experimental group is (30) students taught according to the proposed strategy, and the control group is (30) students based on the traditional method. To achieve the research objective, the researchers developed a test for achievement consisting of (30) items and a test of sports interconnection composed of (20) items. The results of the stu
... Show MoreThe reality of the field of construction projects in Iraq refers to needing for the development of performance in order to improve quality and reduce defects and errors and to control the time and cost, so there is needing for the application of effective methods in this area, one of the methods that can be applied in this area is the manner of Six Sigma. This research aims to enhance the performance and quality improvement for the construction projects by improving performance in the work of the implementation of the concrete structure depending on the Six Sigma methodology, and for the purpose of achieving the aim of the research, the researcher firstly depends on the theoretical study that include the concepts of qual
... Show MoreThis study aims to identify both the importance of using (LinkedIn) and its drawbacks for researchers and specialists in the field of information and knowledge technologies. The study relied mainly on the statistical method (analytical method) from the collection of data tools (questionnaire) that was distributed electronically (Google Forms) to the sample community of (55) instructors. The feedback received illustrates that (46) instructors among those who participated in the questionnaire subscribed to (LinkedIn) and the rest did not. Their data was analyzed statistically, and the general arithmetic mean and the hypothetical mean was extracted for them to achieve the objectives of the study and prove their hypotheses. The site positively
... Show MoreThe Current research aims to identify ( the effect of Carin model in the achievement of the first intermediate Grade Students and their Reflective Thinking in physics Subject ) the researcher selected the experimental design with a partial adjust , The research sample consisted of ( 47 ) Students with ( 23 ) Students in the experimental group and ( 24 ) Students in the control group , The two groups rewarded in the variables chronological age in months , Reflective Thinking and the degrees in physics in the first course. The researcher coined the purposes of behavioral which belong to chapter fifth, sixth, and seventh of physics books scheduled of the school year ( 2015-2016 ) and prepared appropriate lesson plans for the two experimenta
... Show Moreيهدف هذا البحث الى التطرق الى صورة العربي كما يعرضها ادب اليافعين العبري في رواية " نادية " للكاتبة العبرية " كاليلا رون فيدر " . والتي تعد من الاديبات العبريات اللواتي تطرقن بصورة مباشرة الى موضوع ما خلف الجدار ، والصراع العربي – الإسرائيلي وانعكاساته على المجتمع الإسرائيلي بصورة عامة والمجتمع العربي بصورة خاصة . ينقسم هذا البحث إلى ثلاثة فصول، تطرق الفصل الأول إلى "ادب اليافعين"، و تاريخه ، مميزاته والفئ
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يعد الاقتصاد الياباني احد اكبر الاقتصادات الرأسمالية المتقدمة ويحتل المرتبة الثالثة بعد الاقتصاد الأمريكي واقتصاد الاتحاد الاوربي من حيث حجم الناتج المحلي الإجمالي والذي يكاد يقترب من (5) تريليون دولار سنويا.
لقد ادت التطورات المتلاحقة التي شهدها الاقتصاد العالمي وخاصة في حقل التمويل الدولي خلال العشرين سنة الاخيرة الى تصاعد وارتفاع في حجم وحركه رؤوس الاموال الدولية على اوسع نطاق بحيث ا
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The research dealt with the subject of measuring the competitive performance of the National Insurance Company and some of its branches (Basra, Ninwa, Kirkuk and Babil), Depending on the Revenue Growth Index at the activity level, and the Revealed Comparative Advantage Index RCAIAt the branch level,To measure the competitiveness of the company And some branches, As the problem of research in the lack of adoption by some companies in the insurance service sector on scientific indicators to measure their competitive performance, The aims of the research is to measure the competitiveness of the National Insurance Company, as well as the competitiveness of its branches according to the scientific method, One of the main Conclusions of the re
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The aim of the current study is to identify the effectiveness of cognitive conflict strategy in comprehending reading among literary fifth students in literature and literature texts. The researcher uses experimental method with partial control. The sample consisted of (80) students distributed into control and experimental groups. The scientific material, the behavioral goals, the teaching plans, and the instrument of the research have been prepared (reading comprehension test) by the researcher.
The instrument's validity and reliability have been calculated and then applied to the sample. After treating the data statistically by using SPSS, the results have revealed that there is a statistically significant difference at the si
... Show MoreOne of the most important elements of achieving food security is livestock, which is an essential element in the agricultural sector, and is one of the state support sectors. Animal production (sheep) ranked an important position in this sector due to the economic advantages that are available when rearing. Moreover, the success and development of sheep breeding depend on several factors, including financial return and achieving profitability. The study aims to identify the phenomenon size of random slaughter as a problem, which spread in Baghdad and its causes and the factors that influencing its development. As well as, the possibility of applying the idea of amobile slaughterhouse to reduce this phenomen
... Show MoreThe sports field is one of the fields that are concerned with the various methods and methods because of their positive impact on the development of actual training, the investment of the exerted effort in time, and through the follow-up of the researcher in the field and academic field, I noticed that there is a weakness in explosive ability, which affects performance and skill level during training and competition Therefore, the researcher decided to prepare maximum physical exertion exercises according to the anaerobic threshold as a principle of development in many physical and skill variables because good physical performance leads to reaching the best achievements and since the skill of shooting by jumping high - either constitutes a
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