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.
At different stages of the evolution of the modern Iraqi state ears last century did not receive the industrial sectors importance in great domestic production (GDP) and that the limited resources available in the initial stage and the dominance of public sector industry in the late stage , so the continued decline in the contribution of the private industrial sector in GDP , and this is why imbalance in the labor market and reduced demand for manpower in this sector despite the high rates of labor supply and the various skills and levels of investments, their human and the different geographical distribution , and direction of labor to other economic sectors most requested of the l
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This study aims to highlight the role of financial control in the development of government performance through the use of "GFS" system and its application in the service of government units, which will help them in how to use financial resources efficiently through the quality of accounting information provided by this system in the financial statements that reflect the predictability in that fiscal policy of the state through government programs and activities fee as well as to identify weaknesses and address them quickly in order to avoid wastage and loss of public money, which leads to the possibility of utilization of available financial resources of the state to effectively and efficiently, has been reached that the failure of gove
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The current research aims to determine the role of strategic leadership in achieving organizational excellence. In this context the sample of the research consist of 123 managers .The research problem can be summarized as {what is the role of strategic leadership in achieving organizational excellence}which resulted in a number of sub-questions and its goal was to explain the theoretical philosophy and intellectual expositions of this variables because of they are vital variables imposed by the current situation. To achieve research objectives we had use the questionnaire as a tool to collect data and information after verifying the validity and dependency of the measures. A number of statistical techniques and tools had been use
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This purpose of the research is to test liquidity ratios to assess bank liquidity risks represented by liquidity ratios (current assets / current liabilities, current assets / total deposits, current assets / total assets, cash credit / total deposits, liquidity coverage ratio LCR, net stable financing ratio NSFR). This research involves evaluating these risks in banks via these ratios, and reveal the most important means used to solve these risks, including the capital adequacy ratio under the Basel II decisions and for selected period (2017-2019).The research reached the most important conclusion, which is the bank sample did not fall into bank liquidity risks throughout the years of research. Tracking specific ratio with adequ
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The main objective of the central bank is to achieve price stability and target in fractionates. Therefore, the bank sought to use modern tools and policies in order to reduce the negative effects of the accumulation of foreign reserves represented by monetary sterilization, similar to developed and developing countries alike, but with different available tools that are possible and imposed by the local financial and monetary environments, such as the window for buying and selling foreign currency, open market operations and deposit facilities. And lending existing. Because any in crease in the monetary base resulting from the accumulation of foreign reserves will affect price stability directly due to the consumer nature of the
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The present study was designed to indicate the influence of the feeding plate on the nutritional and general health problems of the isolated cleft palate infants. For this study fourteen infants were taken, their ages between one day to one week, refered from cosmetic surgery and palate center to cleft lip and palate rehabilitation center in institute of technical medical / Baghdad for feeding plate purpose . Four infants put them as normal group; all those infants were subjected during (6th) month to evaluate the body weight, feeding problem and the respiratory infection. According to tables and figures this study showed a gradual improvement in nutritional problem including (feeding problem, body weight) and health problem (such as respir
... Show MoreThe research aimed to identify the level of job security, the level of sports institutional performance, and the relationship, contribution and impact of job security to sports institutional performance from the point of view of workers in the Iraqi Ministry of Youth and Sports. The descriptive approach was adopted in the manner of correlational relationships on a sample of (400) individuals who were randomly selected by (33.333%) of the employees working in the institutions at the headquarters of the Ministry of Youth and Sports, amounting to a total of (2293) individuals for the sports season (2022-2023), and they are naturally distributed among (13) main institutions in the formations of the headquarters of this ministry, and after adopt
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