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.
This study is concerned with the comparison of the results of some tests of passing and dribbling of the basketball of tow different years between teams of chosen young players in Baghdad. Calculative methods were used namely (Arithmetic mean, Value digression and T.test for incompatible specimens). After careful calculative treatments, it has been that there were abstract or no abstract differences in the find results of chestpass, highdribble and cross-over dribble. The clubs were: (Al-Khark, Air defence, Police and Al-Adamiyah) each one separate from the other for the year (2000-2001). After all that many findings were reached such as the lack of objective valuation (periodical tests) between one sport season and the other. In the light
... Show MoreBackground: Osteoarthritis (OA) currently seems
inevitable and unavoidable for a large swath of the
population .its etiology relates to a strong ,but
complex ,non mendelian genetic basis ,combined
with mechanical and metabolic factors that cause
molecular alterations the end results of which
affect the whole joint .Glucosamine and
chondrotin sulfate alone or in combination may be
of benefit to a subgroup of individuals who have
knee pain due to OA.
Glucosamine has been shown to alter cartiage turn
over in patients with OA undergoing physical
training
Aim of the study: To find the validity of
glucosamine chondrotin sulfate in treatment of
grade 1 and 2 OA.
Methods: the sample of 280 patients
Business Ethics play a major role in explaining the behavior of those interested in the management of tourism enterprises in the field of management gains, which sometimes turn to manipulation in the specification of the service of tourism and influence in the technical characteristics at the expense of the brand and market share, as well as misleading beneficiaries about the fact that the performance of the service of tourism, may depend activities tourist dramatically when submitting and sharing various services on the types of mutual relations the framework for moral distinct, in interaction or direct contact between producers of tourism services and tourists or their beneficiaries, in order to provide comfort and recreation a
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This research shed light on the relationship between the social orientation of the marketing (interests of the Organization ,the welfare of society, satisfaction the customer) strategies competitive dimensions of (cost leadership strategy, differentiation strategy, focus and strategy), As well as to to seek to achieve a number of knowledge and applied goals, and represented the field research problem extent of interesting researched the application of social orientation and interest in achieving competitive strategy and omission of this interest in the hotels the surveyed Organization, Based on this problem, and to clarify the relationshi
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The integration of AI technologies is revolutionizing various aspects of the apparel and textile industry, from design and manufacturing to customer experience and sustainability. Through the use of artificial intelligence algorithms, workers in the apparel and textile industry can take advantage of a wealth of opportunities for innovation, efficiency and creativity.
The research aims to display the enormous potential of artificial intelligence in the clothing and textile industry through published articles related to the title of the research using the Google Scholar search engine. The research contributes to the development of the cultural thought of researchers, designers, merchants and the consumer with the importance of integ
Negotiations are distinguished in that they are an easy and simple means between the conflicting parties, and it is an effective means at the same time as the conflicting parties seek understanding on the most effective way to solve their dispute, but negotiations are not always appropriate to resolve international disputes, especially when there is a disparity in power between the negotiating countries, or when it is missing Goodwill, or even when one of the parties is absent or less flexible, and the internal circumstances of one of the conflicting countries may play a negative or positive role in the success of the negotiations, away from the influence of the role of external variables in that, a
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Abstract
The aim of the research is to clarify the requirements of the qualification of the external auditor in Iraq and the extent of their impact on the quality of the professional performance of the audit process. The research was based on analyzing the results of the questionnaire prepared for the impact of qualifications on the quality of professional performance. The researcher has reached a number of conclusions, the most important of which is that a highly qualified and unethical auditor has a greater negative impact on the quality of professional performance than those with low qualifications. The most important recommendations of the research were the need to pay
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This paper reflects the evidence of the Islamic Development Bank's role in building human and institutional capacities in Member States and assisting governments in achieving economic development. The Bank's activities in the area of capacity development are an important part in following up the economic developments, And help governments to build and formulate effective policies and institutions to implement more effective macro policies leading to better economic outcomes. It is therefore helpful to help Member States increase their resources, modernize their banking systems, establish effective legal frameworks and improve Reports on macroeconomic and financial statistics. The Bank has faced many challenges and risks tha
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The objective of this study is to enable the role of modern and advanced computerized information systems. The model or mechanism should be developed by collecting the necessary information about the taxpayers and the sources of the taxpayers' income, on the basis of which the accuracy of the inventory process will be adopted. In addition to studies related to computerized information systems and showing their importance to the tax institution. To achieve the objectives of the study and to answer its questions, the researcher relied on collecting data and information on the subject on the literature and previous studies The secondary sources, which also formed the theoretical framework of the study, were obtained either as a practical fr
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Informing means informing and informing, which is conveying information to someone and confirming his narration with it. Accordingly, information is its main content..and it has multiple means, including visual, audio and read, and it has become the dominant role in the process of socialization, and much of what we hear, read, or watch in the media is not devoid of a goal, and expresses that scientifically as “charged with values” ( Value Loaded)..Values that are: the set of beliefs that the individual holds towards things, meanings, and various aspects of activity, which direct his desires and attitudes towards them, and determine for him acceptable and unacceptable behavior, right and wrong, and all of this
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