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 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
... Show MoreThe 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 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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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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Background: Preterm labor and related prematurity are predisposing factors that increase perinatal morbidity and mortality. Acute phase reactants are inflammatory markers which are positive and negative reactants explained by the reaction of reactants to the subclinical infection that are commonly associated with preterm labor. Objectives: To assess the role of acute phase reactants in pregnant women with preterm delivery. Patients and method: A case control study conducted in Gynecological Department of Baghdad Teaching Hospital from 1st February 2021 to 30th October 2021, on one hundred pregnant women with gestational age (28weeks - 36weeks+6days) who attended outpatient clinic; fifty pregnant women with established preterm labor
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The purpose of the research is to study the impact of knowledge management (personalization and coding strategy) in achieving strategic excellence in the environment of Iraqi private banks, and the descriptive and analytical research approach has been adopted, so the researcher adopted positive philosophy according to the deductive approach for the purpose of deriving the first research hypothesis from the theoretical side and the research reached a group of The most important results are that the personalization strategy has made great progress in its ability to influence strategic superiority as a responsive variable, as the civil bank departments were successful in employing the changes that occurred in the personalization str
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As population growth increases the demand for crops increases and their quality improves, and it becomes necessary to find innovative and modern solutions to enhance production. In this context, artificial intelligence plays a pivotal role in developing new technologies to improve crop sorting and increase agricultural yields. The present review discusses the main differences between manual and mechanical potato harvesting, explaining the advantages and disadvantages of each method. Manual harvesting is highlighted as a traditional method that allows for greater precision in handling the crop, but it requires more time and effort. In contrast, mechanical harvesting provides greater efficiency and speed in the process, but it may damage some
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Small and Medium Enterprises (SMEs) in Iraq have experienced low performance due to the limited usage of accounting information systems (AIS) and the inability to exploit knowledge of management capabilities (KMC). These deficiencies have led to competitive pressures in the marketplace that have adversely affected their sales and production. This study investigates the role of AIS in terms of operation support, knowledge support, regulatory support, and the role of KMC, including knowledge acquisition, knowledge transfer, and knowledge utilized to enhance organizational performance in Iraqi SMEs. The target population was managers and owners in SMEs using AIS in Iraq’s cities. A non-probability purposive sampling technique was use
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The researcher aims to Diagnose the reality of research variables, strategic leadership and decision support systems, and their impact on crisis management in the General Company for Steel Industries because of their important role in preventing crises and reducing their occurrence for the research company in particular and other companies in general affiliated with the Ministry of Industry and Minerals, as well as clarifying theoretical concepts of research variables As it included the answer to questions related to the research problem, including (Is there an impact of the strategic leadership in managing crises if decision support systems are used), and the researcher adopted the descriptive and analytical approach in its comp
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