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 aims to study the influence of organizational power on the achievement of entrepreneurship for business organizations. It is an analytical study of the views of a sample of managers in the Iraqi Ministry of Education. The research highlights the contribution that can be made from the knowledge of the theory of business organizations in achieving organizational success. The organizational power of the organization contributes to achieving entrepreneurship in the business environment and achieving a competitive position in the work environment. The research dealt with two variables: the first is the independent variable, the organizational power in its dimensions (Expend Power, Structural Power, Prestige Power). And t
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Abstract
Oil is considered a commodity and is still an important and prominent role in drawing and shaping the Iraqi economic scene. The revenues generated from the export of oil are considered the main source of the general budget in cash flows.
Since the revenues consist of quantity and price and the latter is an external factor which is difficult to predict, The effect of any commodity on its price, which is proven in the theory of micro-economic, but it is observed through the research that the response is slow, which means not to take advantage of the rise in prices, by increasing the quantity exported, the result of several facto
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The research aims to identify the most important variables affecting shooting from jumping high and compare them for the two foot the weak and strong, where the researchers adopted the descriptive method, and the sample was chosen by the intentional method, which consists of (4) players from the Iraqi Sports Army Club, where these variables were studied and their impact on The accuracy of aiming at the two men, and the researchers concluded that most of the players have more accuracy in aiming at the strong leg than at the weak leg, which leads to the loss of many real opportunities during the match because of the players changing the situation or wasting the available opportunity when the position of correction is an opportunity for the w
... Show MoreThis study aims to explore the relationship between the degree of application of digital leadership and the development of administrative work at the University of Tabuk. It further aims to examine the presence of statistically significant differences between the average responses of faculty members and employees at the University of Tabuk regarding the study axes that are attributed to the following variables: (scientific rank, gender, and job), the study used the descriptive approach in its correlative style, and the questionnaire was used as a tool for data collection, as it was applied to a simple random of (310) members of the faculty and staff. University of Tabuk. The results showed that the degree of digital leadership applicatio
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This study aims to recognize the process of using computer in publicschools in Ma`an governorate in terms of hardware, capabilities, and teachers usage. It also aims to identify the most important obstacles those schools face from a teachers perspective.
The study sample consists of (150) teachers from different disciplines. The researcher prepared two questionnaires related to the research pivotal, then presented to a group of arbitrators to be used in this final form. The data was analyzed statistically and the study concluded that there is a shortage in the computer services provided to teachers, and there is a w
... Show MoreIn this research want to make analysis for some indicators and it's classifications that related with the teaching process and the scientific level for graduate studies in the university by using analysis of variance for ranked data for repeated measurements instead of the ordinary analysis of variance . We reach many conclusions for the
important classifications for each indicator that has affected on the teaching process. &nb
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The discus throwing event is one of the complex events in athletics, and it is characterized by a performance method that depends on the principle of mechanical moments and requires high explosive capabilities of the thrower in addition to some physical specifications,which depends effectively and effectively on the biomechanical aspects in generating large moments during rotation. The importance of the research is highlighted by the interest in athletics, especially the effectiveness of the discus throw and the continuation of its development process, the importance of kinetic analysis in revealing the most important weaknesses and strengths of shooters, and the importance of explosive power And the moments generated in the rotation of the
... Show MoreBackground: Normal occlusal features of primary dentition are crucial for normal development of the permanent dentition. Breastfeeding is an important factor for both general and dental health of children. Aim: The aim of the present study is to assess the impact of the breastfeeding duration on the prevalence of normal occlusal features of the primary dentition among preschool children in Baghdad. Materials and Methods: The sample was 630 Iraqi children (270- boys, 360 girls), aged 3-5 years selected from four kindergartens in Baghdad city. The study was carried out through questionnaire and clinical examination. Normal occlusal features were examined as the presence or absence of interincisive spaces (IS) and primate spaces (PS), termi
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(2)
The research aims to know the effectiveness of a training program based on multiple intelligence theory in developing literary thinking among students of the Arabic Language Department at Ibn Rushd School of Humanities and to achieve the goal of research, the Safaris Research Institute, and the research community of Arabic language students in the Faculty of Education the third section of Arabic Language: The research sample consists of (71) students. Divided into (35) students in the experimental group and (36) students in the control group, the researcher balanced between the two groups with variables (intelligence, testing of tribal literary thinking, and time age in months), and after using the T-test for two independent samples, the
... Show MoreThis research aims at identifying the level of quality of University environment according to the viewpoint of female students taking the College of Sciences for Woman an example, as represented in the college units as registration unit and the unit of students' affairs, the curricula, instructors, study halls, the college library, scientific labs, computer access, stationary and photocopying services, health care center, the unit of artistic, cultural and sportive activity, the canteen, the college gardens, college buildings and equipment and bathrooms. To achieve the objectives of the research, the researcher prepared a questionnaire to identify the viewpoints of female students concerning the extent of the availability of the standards o
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