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.
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The 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 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
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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 study of history has begun to become increasingly important for those interested in the field of education in general, and physical education and sports sciences in particular. It is a recent study of the past and relying on it. Therefore, studying the history of sports for people with disabilities and their development is of great importance, as it is one of the means to measure the extent of development of societies and their culture in this field. Weightlifting is a sport for people with motor disabilities, and the way to play is for the contestant to lie on the bench (ping bar) and most often the legs are tied to the bench to ensure that the hip and legs do not contribute to the lifting process with the arms, when the player grabs t
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A New Perspective About Masculinity and the Issue of Identity in Ernest Hemingway's The Old Man and The Sea and Michael Ondaatje's in The Skin of a lion
لمعرفة مدى تأثير تمرينات مهارية وفق تقنية تركيز للتفكير الجاني على الدقة الحركة وتعلم هجمة الإيقاف بالغطس للطلاب في سلاح الشيش استخدمت الباحثتان المنهج التجريبي على عينة من طلاب المرحلة الثالثة بكلية التربية البدنية وعلوم الرياضة –جامعة ديالى والتي بلغت (30) طالباً موزعين على مجموعتين التجريبية والضابطة وبعد إكمال اجراءات البحث وتطبيق الاختبارات القبلية وتنفيذ التمرينات والاختبار البعدي ومعالجة الب
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The study aims to examine the reality of preparing the Arabic language teacher for non-native speakers by presenting the experience of the Arabic Language Institute at the International University of Africa. Thus, it addresses the following questions: How is it possible to invest the long scientific experiences in proposal and experiment preperations to qualify Arabic language teachers for non-native speakers? What is the reality of preparing an Arabic language teacher at the Institute? How did the Arabic Language Institute process teacher preparation? What are the problems facing the preparation of the Arabic language teachers and the most important training mechanisms used in that Institute?What problems faced the implementation of the
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