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.
United nation determined many basic climatic effects which affect the crust of Earth.
And the most important one is the climatic change and its effect on environmental, economic,
social, and political effects. So, the amount of rain which is considered as one of climatic
changes in Iraq should be studied.So, this research explains the factors which affect rain, its
overall average, the variation in the amounts of rain, the amount of yearly rain and variation
in both yearly and monthly rains by using standard variation and yearly fluctuation.As a
result, it is concluded that the number of rainy days doesn't mean an increase in rains amount.
And there's variation in rains amount in all study areas which is contrastive
Observed mosques with the advent of Islam under the auspices of care being the houses of God Almighty, and I like parts of the ground to him, the center of radiation spiritual, intellectual and ideological in the lives of Muslims, was the most important cultural and architectural evidence built by Muslims voicing their deep faith and serenity Aqidthm.valmsadjad better reflecting the reality of communication between the person and his Lord, because he is the most important building of permanence and survival, making it imperative designed the best visual forms both externally and internally.Mosques have been characterized in the United Arab Emirates distinct characteristics in terms of building elements of construction in general, and the
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This research deals with the case of the Iraqi joint-stock companies listed on the Iraq Stock Exchange study in terms of compliance with the requirements of IAS 33 "Earnings per share" and the research problem Alrtash concentrated in a statement the commitment of those companies the requirements of the International Standard 33, which may adversely affect the quality of financial reporting where and in particular the quality of accounting information and content of the primary and secondary characteristics make them be of interest to the decisions of its users, so the aim of this research to the statement of financial reporting earnings per share on the quality of financial reporting in listed shareholding in Iraq Stock Exchange
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This research aims to the possibility of evaluating the strategic performance of the State Board for Antiquities and Heritage (SBAH) using a balanced scorecard of four criteria (Financial, Customers, Internal Processes, and Learning and Growth). The main challenge was that the State Board use traditional evaluation in measuring employee performance, activities, and projects. Case study and field interviews methodology has been adopted in this research with a sample consisting of the Chairman of the State Board, 6 General Managers, and 7 Department Managers who are involved in evaluating the strategic performance and deciding the suitable answers on the checklists to analyze it ac
... Show MoreThe weak and strong forms are so called because it is not their lexical content that primary matter, but the role they have in the sentence. The problematic confusion, our students encounter, in recognizing and producing the correct pronunciation of weak and strong forms of the English function words is the main incentive behind conducting this study. In order to gather the data, this paper used two types of tests: a recognition test and a production test. The general results reached through the analysis of the students' answers seem to conform to the researcher's assumption: students face a critical problem in recognizing and producing correct pronunciation of the weak and strong forms of the English funct
... Show MoreThis research studies the effect of addition of some nanoparticles
(MgO, CuO) and grain size (30,40nm) on some physical properties
(impact strength, hardness and thermal conductivity) for a matrix
blend of epoxy resin with SBR rubber. Hand –Lay up method was
used to prepare the samples. All samples were immersed in water for
9 weeks.
The Results showed decreased in the values of impact strength and
hardness but increased the coefficient of thermal conductivity.
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Background: Several infectious lung diseases often develop in patients with Rheumatoid arthritis (RA), especially during immunosuppressive medication, including disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to determine the role of respiratory tract bacterial infection in RA activity. Methods: Blood and sputum samples were collected from 31 patients with RA and 12 healthy subjects as control. The bacterial isolates were isolated and identified in collected sputum by biochemical tests and Vitec 2 system. Results: In the present study, thirty-one patients with RA were compared with 12 healthy subjects. Eight patients with RA were not infected with pathogenic bacteria (RA-NIPB) (25.8%). Twenty-three RA patients wer
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Change the morphological characteristics with the change of the factors affecting it has been shown that the Tigris River has the characteristics of the morphology of the low values in terms of depth, width and perimeter wet and gradient which in turn affected the morphological and other characteristics in terms of the direction and pattern of runoff came through the study of 48 cross-section is taken of the Tigris River Year 2008 by section for each 1 km, it has been shown that the average width of the Tigris River does not exceed 221.1 meters and the average depth of 3.9 meters either wet ocean amounted to 268.9 meters and changed the cross-section area of the last section at a rate of 4594.3 square meters, and through the study turned
... Show Morethe Reception and the Creative Reaction