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 area around the Suez Canal has been chosen particularly Sinai to implement the new Suez Canal project parallel to the original 72-km-long channel due to the importance of the commercial site of the Arab Republic of Egypt, competing with shipping lanes, to accommodate the increasing maritime traffic passing through the Suez canal, and to provide special services for trade world and reduce the economic cost of marine trip. The establishment of six tunnels for automobile and railway transport to Sinai The cost of the establishment of this new channel and the establishment of the tunnels about (2.8) billion, of which 4 billion cost of the new channel. Project implementation period is one year. The new proj
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Drilling solutions can be considered as an intricate mixture comprising of number of chemical additives which aid specific needs such as controlling the rheological properties and reducing corrosion. Inhibitors are substances that are added in small concentrations to corrosive environment to decrease the corrosion. Their applications can be found in drilling equipments. The effect of adding Zinc Sulphate and Carboxymethyl Cellulose to study their influence on the corrosion of carbon steel in Bentonite mud has been evaluated using Weight Loss Technique. This study focuses on determining rheological properties and corrosion characteristics. Results show CMC and ZnSO4 work as inhibitors when added to the Bentonite with inhibition
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The Results of Theoretical Studies and Experiment of Advanced Economies , Have Been Proven That Investment Expenditure Is Not The Only Factor And The Main Source of Production Growth, But Efficient Using Of The Fixed Assets Is More Important In This Process, All That Depends On Groups of Factors Called The Non-Investment Economic Growth, That Are Un-bodied Technical Progress With Organizational Nature.
It's Distinguished Features That it has An Influence on The Production Growth Without Any Large Additional Investment Expenditure Or Any Additional Increment in Inputs And That Can Not Be Reached Without Activating The Factors of Non-Investment Economic Growth, Which is Still Affecting Negatively In T
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This research aims to analyze the effect between letter of credit opening and implementation procedures which considered one of the most important Foreign services submitted by bank institutions to their customers on Time contracted time limit commitment contract by some Iraqi commercial banks, descriptive analytical method used in This research The questionnaires designed a tool main research to gather information to get to know the effect , Seventy questionnaire forms were distributed, sixty seven forms were analyzable , The answers were analyzed by the arithmetic mean and standard deviation and test the level of influence between variables simple linear regression. The result showe
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The study included general survey of some districts of Iraq in order to determinate new distribution areas for 33 species of the genus salvia L. ,new collections obtained , new locations for many species recorded. Observed specimens in most Iraqi herbaria were studies and identified. ,the flowering period were also studied
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bjective researcher through this research to Put a theoretical framework to strategic orientation the center on the market in the business and the diagnosis and interpretation of the nature of the link between relationships and influencing strategic orientation dimensions Almtmthelh organizations (Entrepreneurial Orientation, market Orientation, Interaction Orientation) and the performance of the Iraqi Private Banks The research community and the level of dimensional and through the use of scale (Balanced Scorecard) Bmnzawradtha the four, the test of this research in the Iraqi banking sector (Gulf Commercial Bank
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The research aims to shed light on the role of SAIs and the nature of their work, with the definition of the concept of quality reports and to clarify the reality of quality in the FBSA reports, the researchers reached to conclusions, including: The quality of the SAI reports is a requirement seeks to achieve any regulatory system in order to develop audit work output of the form in which its impact is reflected positively on the performance of the entities controlled, and researchers gave a set of recommendations, including: the need to increase community awareness of the importance of the FBSA Supervisory reports through conferences, seminars and workshops and that FBSA to follow-up reports, and check the quality continuously to the fa
... Show MoreThe Nuclear structure of 110-116Cd isotopes was studied theoretically in the framework of the interacting boson model of IBM-l and IBM-2. The properties of the lowest mixed symmetry states such as the 1+, 2+ and 3+ levels produced by the IBM-2 model in the vibrational-limit U(5) of Cd - isotopes are studied in details. This analysis shows that the character of mixed symmetry of 2+ is shared between and states in 110-114Cd – isotopes, the large shar goes to s, while in isotope, the state is declared as a mixed symmetry state without sharing. This identification is confirmed by the percentage of F-spin contribution. The electromagnetic properties of E2 and Ml operators were investigated and the results were analyzed. Various
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