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 paper presents the syntactic dimension of ditransitive verbs in terms of the universal theory of Role and Reference Grammar (RRG). This theory is syntactic in nature, but it also covers the semantic as well as the pragmatic aspects of any linguistic phenomenon. It assumes a universal framework through which syntactic constructions can be analyzed. However, the morphological structure that each language enjoys renders the universal treatment more complicated and can question the universal nature of such a theory. In this paper, an attempt is made to check if the universal tenet of the theory is maintained over two typologically different languages: English and Arabic in respect of the way that double-object constructions (DOCs)
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The objective of this research to analyze the effectiveness of monetary policy in achieving economic stability and growth for the period 2004-2011 ،This period of time saw a fundamental shift in monetary policy after the issuing new law the Central Bank of the full independence of the monetary authority ،This is Prompt the monetary authority to bring about a change in the philosophy and objectives and the tools used to achieve the desired goals ،Which give them the ability to control the size of the money supply and to achieve price stability Indeed، Monetary policy has been able to achieve the golden triangle of economic stability ،Consisted of staff، exchange rate stability and low and stable general level of prices
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The present paper attempts to find out the role of developmental loans in promoting strategic crops especially the basis stemming from the problem of non - defining economic feasibility study and the negative or positive revenues of developmental loans, directed to Iraqi Agricultural sector in general and Basic strategic crops in particular which resulted in the difficulty of planning and future prediction to grant loans agriculturally directed in terms of quality and quantity and the arbitrary of distributing these loans .the strategic crops have been selected as sample of population where the sample of Basic strategic crops include wheat and barley .The paper has come to several of conclusions mainly are as follows :- the increase in n
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The follower of the needs of the users of accounting information notices the necessity of adopting faithful representation of information Hence, IASB adopted the economic substance approach as the basis for the Formulation and development of international accounting standards Therefore, this research discusses the reflection of the economic phenomenon in terms of its economic substance on the subject of measurement , And it should be consistent measurement method where the problem of research is concentrated in the fact that the economic units operating in the local environment to address events and economic phenomena according to the legal form , as appropriate With the requirements of the unified accounting sys
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Mixing this strategy with a qualitative research design and an idea known as AI-supported journalism, the paper is going to approach the requirements of how AI technologies may transform journalism content and culture in a way beyond what one anticipates; therefore, enabling more of it to reach an audience. The current research used descriptive research design to investigate the potential applications of the AI tools that mediate civilizational conversation and a structured questionnaire to media professionals. AI-driven journalism can promote peaceful cohabitation and mutual respect and thus act as a bridge between cultures, the research said. The piece even goes on to mention the need for media establishments and civil soc
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The Mediating Role of Cobit 2019 in Managing the Relationship Between Qualitative Characteristics of Accounting Information and Information Asymmetry
Abstract The results of isolation, morphological and microscopic diagnosis, Chromic Agar, Vitik technology and Bact Alert showed that the diagnosis of fungi isolated from blood samples of end-stage renal patients who did not undergo dialysis and those who underwent dialysis was 60 samples for each type. The total number of fungal isolates isolated from people who did not undergo dialysis was 26 pathogenic fungal isolates, with a percentage frequency of 43.33%. In this study, 4 genera of pathogenic fungi were identified: Candida spp, Rhodotorula spp, Cryptococcus spp. and Aspergillus spp. The number of Candida isolates reached 13 isolates, with a frequency of 50%. The results also showed that the diagnosed species from the genus Rhodotorula
... Show MoreAfter the success of the reforms Keynesian save the capitalist system from collapse and to apply the concepts of state intervention in economic activity in order to revive aggregate demand to achieve the purposes of macro-economic policies which draw their scope of economic (John Keynes) theory of effective demand, which created the new role of the state away from the classical concepts. Valley transmission role of the State of (State Guardian) to the process of state overlapping that increased and social functions have become responsible for raising the standard of living of classes with limited incomes, in particular, and the rest of the classes in general, through the expansion of the delivery of public servic
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The optical energy gap(Eopt) and the width of the tails of localized states in the band gap (?E) for Se:2%Sb thin films prepared by thermal co-evaporation method as a function of annealing temperature are studied in the photon energy range ( 1 to 5.4)eV.Se2%Sb film was found to be indirect transition with energy gap of (1.973,2.077, 2.096, 2.17) eV at annealing temperature (295,370,445,520)K respectively. The Eopt and ?E of Se:2%Sb films as a function of annealing temperature showed an increase in Eopt and a decrease in ?E with increasing the annealing temperature. This behavior may be related to structural defects and dangling bonds.
Social networking sites represent one of the modern communication technologies that have contributed to the expression of public opinion trends towards various events and crises of which security crisis is most important being characterized by its ability to influence the community life of the public. In order to recognize its role in shaping opinions of the educated class of the public that is characterized by a high level of knowledge, culture and having experience in dealing with the media. Its advantage is that they have an active audience by expressing their views on the situations, events, and news published on them as well as expressing their attitudes and sympathy with the events. So a number of questions are included in the ques
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