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 upbringing of Yehuda Amichai and the conditions he lived in had a great influence on his deep sense of pain, which made him think of death and suicide. Especially after the Nazis came to power in Germany, and his emigration with his family. Amichai searched for love throughout his life, and his failure was one of the most important factors affecting his psyche, which is A deep influence that made him live in harsh and painful pains that broke him, and prevented her from achieving his ambitions in life.Dramatic texts are characterized by repetition in writing and presentation. It is a textual discourse that has two advantages, first, that it can be read as a literary text like all other literary texts, and second, that it can be consider
... Show MoreIn this study, the researcher aims to analyze the content of the physics textbook for the 3rd intermediate grade according to the criteria for designing and producing infographics, and the research community consists of the content of the physics textbook for the 3rd intermediate grade intermediate grade for the academic year 2021-2022. The researcher adopted the analysis instruments with a number of the criteria for designing and producing infographics. The results revealed randomness in the percentage of the criteria included in the content of the physics textbook for the 3rd intermediate grade, and they are not compatible with the proposed criteria by the experts also.
Excessive skewness which occurs sometimes in the data is represented as an obstacle against normal distribution. So, recent studies have witnessed activity in studying the skew-normal distribution (SND) that matches the skewness data which is regarded as a special case of the normal distribution with additional skewness parameter (α), which gives more flexibility to the normal distribution. When estimating the parameters of (SND), we face the problem of the non-linear equation and by using the method of Maximum Likelihood estimation (ML) their solutions will be inaccurate and unreliable. To solve this problem, two methods can be used that are: the genetic algorithm (GA) and the iterative reweighting algorithm (IR) based on the M
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The purpose of this study is to diagnose factors that effect Thi-Qar behavioral intention to use internet. A sample of (127) internet users of university staff was taken in the study and were analyzed by using path analyze . The study concluded that there is a set of affecting correlation. It was founded that exogenous variables (gender, income, perceived fun, perceived usefulness, Image, and ease of use) has significant effect on endogenous (behavioral intention) . The result of analysis indicated that image hopeful gained users comes first, ease of use secondly, perceived fan and perceived usefulness on (dependent variables (daily internet usage and diversity of internet usage. Implication of these result are discussed . the st
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This study aims to clarify areas of using information technology in accounting and its impact on the profession of auditors by reviewing the concept, types, areas and the importance of information technology and its implications on the audit profession as well as to clarify the extent of contribution of information technology in developing of procedures of the audit profession and what its requirement, also this study aims to enhance the theoretical side by identifying the views of a sample of auditors in Arab countries selected (Iraq, Syria, Jordan), for the extent of using of information technology in their work and level of their perception for the importance of that
The aim of this research is to identify how to employ the social imagination and its representations in the paintings of the students of the Department of Art Education. Students of the Department of Art Education in the light of this tool, and the researcher reached a number of results, the most important of which are:
1. The indicator of the social imagination in the excitement of the artist and the recipient, because the representations are embodied in forms within the painting and close to reality.
2. An artistic sample of the representational imagination and the creative imagination was found to be more than the imaginary imagination.
3. Individual symptoms related to the term.
4. The representations of the socia
The research included (the aesthetics of the sculptural formulations of swords in the Al-Kafeel Museum) four chapters. Al-Kafeel Museum.)
Within the time period: (1240 AH / (1824 and 1825) AD - 1312 AH / (1894 and 1895) AD). The second: the types of Islamic swords. The third chapter included (research procedures), and the analysis of samples from the sample (3) as a model according to the descriptive approach, and the fourth chapter dealt with (results, conclusions, recommendations, and proposals). As well as recommendations, proposals and sources.
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The objective of the current research is to identify the degree of awareness of the teachers of Arabic language with the requirements of sustainable development. The research sample consisted of (100) male and female teachers of the Arabic language. A 3-likert scale of (71) items grouped into practical and cognitive aspects, five trends for each aspect was designed by the researcher to explore the required data. The results showed that the level of awareness of teachers of the Arabic language was moderate of both the cognitive and practical aspects of sustainable education with means (1.69) and (1.48) respectively. The researcher presented a set of recommendations and suggestions.
The research aims to demonstrate the impact of governance mechanisms on the quality of financial reports in the light of the accounting disclosure for sustainable development represented in (accounting disclosure for economic development, accounting disclosure for environmental development, and accounting disclosure for social development) in a sample of banks listed in the Iraq Stock Exchange.
Governance mechanisms were measured by evaluating and analyzing the mechanisms in banks for the research sample consisting of (15) banks, based on the governance guide issued by the Central Bank, as well as the banks’ financial reports for the years 2016 -2018, and the dimensions of accounting disclosure for sust
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