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 research aims to identify the relationship between spatial ability and the physical structure of concepts to the students of the Faculty of Education for Pure Sciences / Ibn al-Haitham، research involved students from the third class / morning study for the year 2011/2012 totaling (98) male and female students ،distributed into three groups which were selected randomly . The number of students (26 males and females) represented research sample after excluding repeaters and absentees، the research included two tests ; one test of spatial ability، which included (20) items and other test the physical structure of concepts، which included (12) items distributed into four domains ، the first (linking b
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The research aims to understand the psychological status of and the feeling of loneliness of the trainees (recently released detainees) participating in the training and rehabilitation courses held in the Technical College - Baghdad. The study was conducted on a specimen of (23) trainees. An open questionnaire was adopted which included one question that was ( What was your feeling psychologically and socially before taking part in the training course?) , also the feeling of loneliness Scale , designed by ( Russel,Peplau, Cutrona /University of California Los Angeles ) was implemented after the courses .
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The aim of the current research is to recognizing the impact of mind and informational strategy on the achievement with the second intermediate students in the grammar of arabic language, the researcher used a partial-set experimental design and intentionally selected a sample out of the second intermediate class from (AL- Markazya Intermediate school) in the district of Hilla, affiliated which belongs to General Directorate of Babylon Education in the year (2020-2021) for applying the experiment. The sample was composed of (50) students, (25) ones for each group, the experimental group and normal one. The researcher balanced between the two groups in various changes including: (the chronological age counted by months, the academic achie
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The aim of the research is to demonstrate the importance of leadership empowerment in its dimensions (knowledge, participation in decision-making, incentives, trust between the leader and subordinate, delegation of authority and communication) and its impact on enhancing the effectiveness of the company in its dimensions Represented by (achievement of objectives, quality of insurance service, adaptation to work environment and job satisfaction), by adopting the questionnaire as a main tool in collecting data from officials in the National Insurance Company, numbering (56) surveyed in job sites (section manager, division official and unit official) Their answers were analyzed using the SPSS statistical program in calculating the a
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The aim of the current research is to identify the Effect of the alternative evaluation strategy on the achievement of fourth-grade female students in the subject of biology. The researchers adopted the zero hypothesis to prove the research objectives, which is there is no statistically significant difference at the level (0.05) between the average scores of the experimental group who study according to the alternative evaluation strategy and the average scores of the control group who study in accordance with the traditional method. The researchers selected the experimental partial adjustment design of the experimental and control groups with the post-test. The researchers intentionally selected (Al-fed
... Show MoreThe scholars differed very much in determining the grammatical doctrine of Ibn Qaysan. It was said that he confused between the two sects and took the two groups(1) and that he took from Abu Abbas the fox and Abu al-Abbas almabrd(2).He was descended from the two sheikhs almbrad and fox(3), This research to find out his grammatical opinions in the tools and grammatical words that appeared in the Book of Resonance of Multiplication to the many reported by Ibn Hayyan in it, he has seen the books of Ibn Kisan did not reach us.
The collection of these opinions and analysis is important for the scholars. Because the books of Ibn Kaysan specialized in grammar have lost their most important, the books that are similar to the book of Ibn al-Ha
The follower to study the markets in the Islamic Mashreq (Iraq, Persia and the country of Ma
Behind the river for the period from the reign of the Prophet Muhammad until the end of the Islamic era) to find that there
A remarkable development in the pattern, shape, planning and privatization of markets
Islamic cities and places are the main conditions for their existence, which is the mosque of the mosque
And markets, and these markets have evolved from being a space in which there are no building and no ceilings to shade them in
The places of sale and purchase to specialized markets classified according to the materials and goods produced in them
This would facilitate the task of supervising it by the market factor and
The study aims at diagnosing the importance of environmental analysis (external, industrial and internal) in the organization's strategy for the development of public organizations. The theoretical problem derived from the existence of a knowledge gap for studies and research that dealt with the variables of the study. Three public organizations were selected as the study society (the Civil Defense Directorate, the Directorate of Nationality, Passports and Residency, the General Traffic Directorate). The sample of the study was a sample of (215) managers (managers, department managers, Analysis of the data and hypothesis testing using the appropriate statistical tools, Pearson, the simple and multiple regression coefficient to te
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