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.
The analysis of the orientations of Iraqi art commodification contributed to the discovery of deliberation, which was founded in the deliberative discourse in the trends towards commodification in the Iraqi art, since the important transformations in social structures and relations produced a dictionary with new vocabulary and tools that replaced the traditions and norms that have been in circulation for a century. Deliberation and commodification have become more prevalent in the mechanics and trends of the art where the pace of change is becoming increasingly frantic towards the market. The general market for art constitutes one of the most effective phenomena within contemporary art, that there has been a proliferation of sales auctio
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The theater has live foundations that interact with all symbols and signs. It has never been far from these innovations and developments in the manner of dealing with those symbols and how and the extent of their effects on society through the world of technology because the theatrical performance contributes to its structure, a technique that is employed by designers in various technologies such as ( Music, lighting and sound effects engineer, as well as fashion designer, architecture, and modeling designer). The theater today also relied on various interactive techniques represented in the use of body language and a sign in order to communicate the meaning by forming movements, singing and dancing in order for the recipient to interact
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Background: This study aimed to find whether there is a relation between the mesio-distal crown diameters of the deciduous second molars and the permanent first molars in an Iraqi sample from Baghdad city. Material and methods: The sample consisted of 54 Iraqi children aged 8-9 years at the mixed dentition stage. The measurements included the mesio-distal crown width of the deciduous second molars and the permanent first molars on the study casts using digital sliding vernier. Results: The results revealed absence of the side difference of the widths of teeth measured. High significant gender difference was detected for the permanent first molars and the deciduous second molars except mandibular permanent first molar. On the other hand, hig
... Show MoreThis research deals with the poetic image of poets of the eighth century poetic, where they embodied the features of the religious life in which they live, and their impact on the Koranic text in the reflection of the image on their poems, where it becomes clear the ability of the poet at that stage to clarify the aesthetic components of the poetic text; Investigations, singled out the first topic: the analogy, and the second metaphorical picture, and the third: the picture.
The present study aimed to identify the therapeutic evaluation of chitosan extracted from the fungus cushroom and pure chitosan on glucose and lipid profile in the blood of 35 male rabbits with hyperlipidemia induced experimentally by cholesterol. The tests included estimation of glucose levels, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins. hyperlipidemia was induced in the male rabbits used in the study which was administered orally with cholesterol 150mg/kg body weight for a week. rabbits were divided into seven groups: control, cholesterol, pure chitosan, mushroom chitosan, cholesterol and pure chitosan, cholesterol and mushroom chitosan and cholestero
... Show Moreيعتقد البعض ان مفهوم العلم يعني الآلات والاجهزة العلمية (تقنيات التعليم) وهي لا تختلف عن مفهوم تكنولوجيا المعلومات , ويعد هذا الاعتقاد خاطئ , لان العلم هو بناء المعرفة العلمية المنظمة والتي يتم التوصل اليها عن طريق البحث العلمي , اما تكنولوجيا المعلومات فهي "التطبيقات العملية للمعرفة العلمية في مختلف المجالات ذات الفائدة المباشرة بحياة الانسان, او هي النواحي التطبيقية للعلم وما يرتبط بها من آلات واجهزة".
A field study investigated the degree of need for managers working in the directories of education to develop their skills for the exercise of administrative empowerment, and it adopted the descriptive analytical approach. The research community, was determined which consisted of 126 principals, and the sample was selected with arte of randomly Statistics and by (100%) of the research community, as the number of respondents was (126) of managers working in the directories of education. A questionnaire was built which included 40 items distributed among the fields of study. Researchers verified its validity and reliability. The research data were analyzed using software (SPSS), the questionnaire was applied in the second semester of the a
... Show MoreThe research aims to find out the impact of Lee’s cognitive strategy on the achievement of fifth-grade literary students in the module of history. The research community consists of the secondary female day schools of Al-Karkh Al-Oula Directorate General of Education. The size of the research sample comprises (45) female students of the fifth grade of the literary brunch, (21) students for the experimental group and (24) students for the control group. The researchers have chosen an experimental design with partial control to suit the current research and its goal. They used a unified tool to measure the achievement of female students, which consisted of (50) items characterized by sincerity and they extracted the stability of t
... Show MoreThe research topic (The Impact of the Compulsory Reserve on the Banks Credit-an applied research on a sample of Iraqi banks), was chosen on basis of the Iraqi private Banks attempts to increase their credit activities in hope to gain more profits.This coincided with the CBI aim to back the private banking market.It is thus apparent why the CBI issued its regulation to those banks to increase their capitals up to IDB250. On the other hand,the CBI acted as an obstacle in the way of increasing the private banks of their capitals,that is by implementing the quantitive monetary tool so called the compulsory reserve.This is why we intended to overlook at this contradictional problome
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