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 study aims to identify the degree of Arabic language teachers at the secondary stage possessing the teaching competencies necessary to develop the skills of literary savor among their students from the perception of educational leaders in Bisha Province. To achieve the objectives of the study, the descriptive approach was used by adopting a comprehensive survey method. The study sample consisted of (48) school principals and Arabic language supervisors in Bisha Province who supervise the teaching of Arabic language at the secondary level in Bisha Province. The necessary data was collected using a questionnaire. The results of the study revealed that the evaluation of the study sample for the degree to which Arabic language teachers
... Show MoreThe research problem stems from a chief question: “What is the nature of the responsibility that «Al-Sabah Al-Jadeed» and «Al-Mada» Newspapers have undertaken in promoting the values of citizenship and national belonging in the society? The research aims to achieve a number of goals, including: Determining the most prominent themes that were emphasized in the opinion articles in these two newspapers within the framework of the responsibility of promoting the values of citizenship and national belonging in society, and revealing the most prominent topics that were discussed in opinion articles in the two sample newspapers regarding the promotion of the mentioned values. This research is a desc
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In the analysis of multiple linear regression, the problem of multicollinearity and auto-correlation drew the attention of many researchers, and given the appearance of these two problems together and their bad effect on the estimation, some of the researchers found new methods to address these two problems together at the same time. In this research a comparison for the performance of the Principal Components Two Parameter estimator (PCTP) and The (r-k) class estimator and the r-(k,d) class estimator by conducting a simulation study and through the results and under the mean square error (MSE) criterion to find the best way to address the two problems together. The results showed that the r-(k,d) class estimator is the best esti
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The propaganda discourse is the most widely circulated in the media and communication studies, where the interest of scholars and researchers in this field has become clear in the analysis and interpretation of the content of this discourse, to identify the intentions, purposes and objectives of the communicator activity, which exceeded the borders of states in the heated atmosphere of rivalries and political conflicts that characterize The countries of the world as a whole and for many years.
In particular, the economically and militarily developed countries (the Nordic capitalist countries) have exerted special efforts in the production of information and ideas, using advanced methods and means in all details of communication w
... Show Morehe aim of the research is to clarify the meanings and connotations of (Semitic), and to identify the peoples that fell under this name according to historical data, biblical texts and Qur’anic news. International sympathy on the one hand and on the other hand controlling the land of Palestine and giving them international legitimacy to grow their entity according to global support and sympathy with their alleged slogan (anti-Semitism), which revolves around the oppression of the Jews.
The issue of the other in the graphic design and specifically the advertising constitutes a cognitive study of the structure of the intellectual expansion in the cognitive and intellectual creative systems because of the implicit and declared embodiment it provides within the mechanisms of reading in the advertising design that appeared according to the other and through the embodiment of the textualism, the difference and the binary opposites is nothing but a reaction to the design thought and what constitutes of the manifestations of the other in advertising design. Based on the above, we review this study (Manifestations of the Other in Graphic Design) to clarify the topic through four chapters. The first chapter included the research
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This research aims to address the most recent international standard in the field of insurance contracts, the International Financial Reporting Standard (IFRS17) and the theoretical framework of the standard in addition to the most important characteristics of the standard (IFRS17), as well as to identify the paragraphs of the modern standard, with the challenges its application in general and the use of the approach (inputs - operations - outputs) to present the challenges of its application in the Iraqi environment and specifically in the environment of Iraqi insurance sector companies (government), the research is based on the main premise that the identification of the requirements for the application of the International Fin
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In this paper the method of singular value decomposition is used to estimate the ridge parameter of ridge regression estimator which is an alternative to ordinary least squares estimator when the general linear regression model suffer from near multicollinearity.
The concept of self is considered one of the important dimensions in the human personality, because feeling of self is an important characteristic in this phase from the psychological point of view.
The first source which forms the concept of self is the physical image, where the built and appearance of the body is considered among the vital matters which determine the person's image of himself/herself.
The current research aims to:
1) Identify the level of physical self concept at the kindergarten children.
2) Identify the level of psychological self concept at the kindergarten children.
3) Iden
... Show MoreMost of the theorists and researchers and also those interested in cinema and television attributed the fact of the existence of the dramatic works to the directors may be due to a historical justification. At the same time, the existence of the production world came as a result of the emergence of the production city (Hollywood). This is also a historic fact. The research would tackle all the formative truths to prove the relation and the timeline, i.e., before and after and the synergy that resulted in the existence of the dramatic works that benefited the humanity and those interested in this giving art. The objective of the research is to uncover the formative truth of the dramatic work between direction and production.
The s
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