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 importance of government Expenditure policy in economy come from its role leading to the mitigation and adjustment of fluctuations in macroeconomic variables caused by imbalance between aggregate demand and aggregate supply, It is associated with the efficient management of government Expenditure to reinforcement the relationship between government Expenditure and the overall economic system .
Regarding the Iraqi economy,the increasing in financial rentier after the political change in 2003 has led to finance the budgets Characterized by consumption,The government Expenditure employed to encourage government employment in services jobs, and find different channels for the distribution of
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The study consisted in the development and use of a practical method to detect and
monitor, analyze and produce maps of changes in land use and land cover in the district of
Mahmudiya in Baghdad during the period 1990-2007 using the applications of remote sensing
techniques and with the assisstant of geographic information systems (GIS),as a valuable
contribution to land degradation studies.
This study is based maiuly on the processing on two subsets of landsat5 TM images picked up
in August 1990 and 2007 respectively in order to facilitate comparision and were thengeometrically and radiometrcally calibrated ,to used for digital classification purposes using
maximum liklihoods classification or six spectral bands of
Is a high degree of economic freedom an important part in the development of the economies of developing countries in the last decade of the twentieth century and the beginning of the twentieth century and the atheist. This is because a test subject (deltoid analysis of the relationship between the degree of economic freedom and foreign trade of selected developing countries for the period
( 1990 -2005) to determine the degree of economic freedom in foreign trade promotion in Singapore and Turkey. The research recommends a number of recommendations, the most important is the responsibility of the Ministry of Planning in Iraq that is providing the necessary data for the Fraser Institute, the aim of increasing cooperation
This research aims to identify the effectiveness of counseling by using the technique of self-talkin developing the habits of mind among middle school students by testing important hypotheses, and choosing the experimental design for the two groups (experimental - control). The classification of "Costa & Kallick" was adopted to measure the habits of the mind, and the scale consisted of (64) items, and after confirming the psychometric properties of the scale, the researcher applied it to the research sample (487) students from middle school students. One of the students who got the lowest marks after answering the scale. purpose of applying the experiment. He divided them into two groups, one of them is experimental (10) students, as
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Abstract
The study aims to find out the degree of practicing professional leadership of the faculty’s deans, deputies, and heads of the scientific divisions at Al-Qaseem University. The study has adopted the descriptive analytical method. To achieve the objective of the study, the researcher developed a questionnaire consisting of (45) items distributed to six fields that were applied to a sample of (116) faculty deans, deputies, and the head of division at Al-Qaseem University. The results showed there is a high practicing degree of the study sample individuals of the professional leadership on the questionnaire’s fields as a whole, strategic thinking field came at the first rank, while the innovation, creat
... Show MoreThis research sheds light on those discrepancies in the use of ornaments, adornment and perfumes, as well as the art of cosmetics, in two important civilizations, namely, the Mesopotamian civilization as the earlier civilization, and the civilization of Yemen, which represents the first Arab civilization. Through the foregoing, our research includes two topics, the first topic included the history of the use of decorations, ornaments and perfumes in the civilization of Mesopotamia, while the second topic included the study of ornaments, adornment and cosmetic art in the ancient civilization of Yemen. And then the research came out with a number of conclusions that the researcher considers very important to highlight the differences and f
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The goal of current research is to identify the difficulties in the application of modern physics in the middle schools of the province of Baghdad schools from the perspective of teachers of physics trends, sample search of (127) teachers, Karkh Third Directorate, and use Researcher questionnaire data collection tool after applying it to teachers who have experience (5) years and more after confirmation of the validity and reliability of the scale (the tool) researcher has used the averages for the purpose of interpreting the results. the results showed that the difficulties have been in the order following: (difficulties related educational environment of modern trends of teaching, curriculum-related dif
... Show MoreThe current research aims to identify: 1. The level of mathematical construct among the Department of Mathematics students in the colleges of education and basic education. 2. The level of effective mathematical operations in both sides of the brain at the Department of Mathematics students in the colleges of education and basic education. 3. The strength and direction of the correlation between the mathematical construct and effective mathematical operations on both sides of the brain at the Department of Mathematics students in the colleges of Education and Basic Education. To investigate the research objectives, the researcher formulated zero-main hypothesis for each aim and from the same hypothesis, three sub-zero hypotheses are deri
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