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 reveal the role of financial analysis in rationalizing the investor decision on the Iraqi stock Exchange market, by studying the relationship and impact techniques and methods of financial analysis on the decisions of investors in the market. The most important techniques and methods discussed in this study were: analysis (financial ratios analysis, comparison of financial statements analysis, cash flow statement analysis) for companies listed in the Iraqi stock Exchange market. The researcher adopted the analytical descriptive method which depends on the collection of data on the phenomenon and its interpretation. The questionnaire wa
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In this paper, we present a study of examples of writings that are known in the science of Semitic research compared to the texts (Jewish-Arab, Samaritan-Arabic) written in Hebrew script and texts from the Bible. We try to explain the role of these literary works in Islamic history and civilization, as one of the most important documents are the writings (Gniza), which contributed to provide a full presentation on life in the Islamic community in all aspects of life, especially religious activity and showed the sincere relationship in dealing with the other under tolerance The University of Cambridge has prepared Islamic documents and kept them in separate boxes and presented them to researchers to convey the Islamic heritage written by
... Show MoreThe current research aims to measure the impact of the skills of human resources management professionals in information technology in Iraqi private banks, as the skills of human resources management professionals constitute the modern trend of banks' interest in employees with outstanding performance, and the presence of information technology in banks is a prerequisite for dealing with the huge amount of data. And converting it into information to support the decision-maker in light of a complex environment, and the field research problem was the presence of a clear lack of interest in the skills of human resource management professionals and the weak adoption of information technology, which was reflected negatively on the compet
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According to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c
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Abstract:
In its theoretical farm, the research adobet the subject of human resource management strategies and the cognitive skills. It comes as result of the rapid development which considers it human resource. as main axis in organization , the research in includes ,connective analysis , between human resource management strategies and cognitive skills which is considers one of the new concept that should be studied widly so that the organization can be able recognize it as concept and type and its importance for people in the organization.The study method was descriptive and analytics , it identified collation of hypothesis which were by statist too
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This review focuses on conservation agriculture (CA) and its effects on increasing the soil’s resistance to erosion. CA involves minimum soil disturbance (minimum tillage/ no-till), diversified crop rotation, and maintenance of the soil cover to increase soil fertility and reduce erosion. CA reduces soil loss by up to 90% and water erosion by approximately 50 to 70% from runoff as it increases the health of the soil, yield of crops, and water-retention capacity of the soil by incorporating soil organic matter and promoting biodiversity. Crop rotation prevents the replenishment and depletion of soil nutrients by atmospheric fixation of nitrogen/biological nitrogen fixation. Controlled traffic farming (CTF) is a new strategy in which travel
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This research aims at highlighting the strategic role of human resource development in developing competitive advantage in light of the great challenges and rapid changes witnessed in recent years in the business world. The human element is the main engine of the organization's resources, especially when it possesses the skill quality and cognitive abilities commensurate with the nature of work. Therefore, this research focuses on the importance of human resources development strategy in contemporary organizations and reviews the summary of literature and theoretical foundations related to human resources development, as well as various philosophical concepts related to the competitive advantage and to indicate the important role
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The financial market plays an important role in influencing the economic sectors, including the private industrial sector, through the provision of capital and transfer from savers to investors for the purpose of establishing or expanding projects. Therefore, the financial market is one of the important tools in stimulating the economy in general and the industrial sector in particular, Through the inclusion of industrial companies in the financial market and the introduction of industrial shares to the public, and then provide the necessary funding to stimulate the private industrial sector, Iraq is one of the oil-dependent countries on the oil sector mainly, which lacks industrial production, which is from Are the sectors that
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Toxoplasmosis is the term for infection and disease in man and animal caused by a parasite called Toxoplasma gondii. The more susceptible to infect with toxoplasmosis is the Diabetic patients, due to low level of immunity response. The aim of current study is to investigate the immune status of diabetes mellitus type 2. One hundred and seventy five samples of both diabetes mellitus type 2patients and controls which had been tested by ELISA technique to detect anti-Toxoplasma Abs (IgG and IgM). The positive toxoplasmosis samples were tested to detect the level of TNF alpha and MIG. Results for all samples clarified that seronegative for IgM antibodies while 53 (53%) diabetic patients were seropositive for IgG antibodies and for toxoplasmosis
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