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.
Abstract
Nowadays, the adoption of economic unity on the accuracy of financial reporting is very important. Economic units need accurate financial reporting to be more competitive and to improve the performance. Management can also achieve financial information in real time through the application of ERP systems. This system will facilitate management to access the most up-to-date information such as planning, monitoring and evaluating the business processes of the organization to be more effective.
On the practical side, the Enterprise Resource Planning (ERP) system was applied to the General Company for Vegetable Oils to demonstrate a course in enhancing the accuracy of financial reporting.
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Objective: The aim of this study is to determine the role of spiral Computerized Tomography in the diagnosis and
detection the types of stroke.
Methodology: One hundred sixty two patients (162) (99 males and 63 females) their ages ranging from (13 – 80)
year, all of them are suffering from stroke. They were collected randomly from spiral Computerized Tomography
unit in Baquba Teaching hospital during the period from November / 2010 to December / 2011 .All the patients
were examined clinically and then done spiral Computerized Tomography examination.
Results : The results of this study showed that the stroke effected different age groups and both sex but males is
more affected than the females .The results of spiral
Allah created the human from clay and made the system of marriage between male
and female as a reason for life continuity and human staying. This system produced an
organization called (the society) which is defined as a group lived in limited time and place.
Islam put fundamental and conditions of the righteous society in the Holy Quran and
prophetic sunna. Islam also put the solutions for problems (if they got) , naturally, these
problems may happened because of the nature of the life.
The problem of the research is summarized by that the problems of the society
enlarged in our Islamic society more than time ago. In the same time , some solution are
imported from west and east and from scientist and ignorant wit
Abstract
The goal of this research is to know the quality of working life and its impact on the level of the organizational sense of alienation among a sample of teaching Anbar University in the center of Baghdad. Find and seek to achieve a number of cognitive and practical goals.
Where the quality of work life constitutes one of the main sources to enable organizations of excellence in light of the volatile environment, as is one of alienation regulatory organizations avoid the phenomena that occur because of their negative effects on performance and thus achieve their goals. The most research problem in question the existence of the main deficiencies in the application of the concepts of organiz
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Abstract
Digital repositories are considered one of the integrated collaborative educational environments that help every researcher interested in developing the education and educational process. The learning resources provided by the repositories are suitable for every researcher, so digital information can be stored and exchanged by ensuring the participation and cooperation of researchers, teachers, and those who are interested, as well as curricula experts, teachers, and students, to exchange each other’s experiences in constantly updating that information as a reason for developing their performance in education. This reveals the importance of the role of educational digital institutions by providing and
... Show MoreThe study aimed to identify the role of the teacher in confronting intellectual extremism in high school students, and identify the differences of statistical significance in the role of teacher in confronting intellectual extremism in secondary school students according to gender variable (males, females) and the duration of service (less than 5 years more than 5 years), the sample was consisted of (100) teachers with (50) male and (50) female in the city of Bayaa, Dora and Sadiya, the measure of intellectual extremism was applied by the researcher, and the study reached a role of the teacher in facing the intellectual extremism at Secondary school students, and the existence of differences of statistical significance in the role
... Show MoreObjectives: The main objective of this study is to examine the crucial role that Russian writers and intellectuals played in catalyzing the 1905 Revolution in Russia. Specifically, the study sought to analyze how their literary works, philosophical ideas, and political writings challenged Tsarist autocracy, depicted the suffering of the masses, and inspired opposition movements. The study aimed to highlight the defiant writings that contributed to the rise of political figures and the eventual overthrow of the repressive regime. Methods: The historical narrative and analytical methods were employed, conducting a comparative analysis of prominent works by renowned authors such as Tolstoy, Gorky, and Chekhov. This analysis focused on
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The phenomenon of the social movements of researchers, based on the scope of their influence on political events, and the nature of the wide role played, and its ability to influence, through its activities and various activities and various. It has practiced its activities through new and non-traditional peaceful means, with clear slogans and specific objectives. And was able to mobilize activists from different strata of the Iraqi people, and its categories and social strata. As the demands focused on freedoms, rights, dignity and social justice