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 study titled “The role of the social media sites of Iraqi satellite channels in prioritizing the public” is a field study for the public of Dhi Qar.
The emergence of the social networking sites we are currently experiencing has undergone radical and important changes in the role of the mass media in light of the growth and rapid spread of modern technologies Or the so-called new media، which led the media organizations to create satellite channels on the social networks، which led to bypass the traditional lines between the public and media institutions with the public gain the possibility of The purpose of the research is to determine the habits and patterns of public use of the social media sites of the Iraqi satellite cha
Abstract
This study was to demonstrate the role-use planning scientific methods is disabled and little used in the planning and follow-up construction of vital projects in the province of Baghdad, including network planning methods, in order to find the optimal time to finish the project in light of the resources available and the budget set for it, in the current research has been used the most prominent network planning methods and two stylistic (CPM / PERT), was the application of the critical path method on standard-design school project (traditional) to draw Action Network according to confirmed times for the activities of the project and account his Crashing time , It was Pert technique applied to the project hemato
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Background : In order for a tooth to erupt, two obvious requirements are needed. First, there has to be alveolar bone resorption of the bone overlying the crown of the tooth such that an eruption pathway is formed. Second, resorption of bony crypt and apposition of new one, third, there has to be a biological process that will result in the tooth moving through this eruption pathway.The amniotic sac contains a considerable quantity of stem cells. These amniotic stem cells are multipotent and able to differentiate into various tissues, which may be useful for human application. Receptor activator of nuclear factor kappa B ligand (RANKL) is concentrated on bone biology, more specifically bone metabolism. RANKL plays a vital role in osteoclast
... Show MoreThe study was conducted to detect the effect of addition of 0.03, 0.06 and0.10% potassium sorbate and 0.10, 0.15, 0.20 and 0.30% sodium propionate upon the sensory properties of laboratory made biscuit. The statistical analysis of the results revealed no significant differences (P<0.05) between the propionate treatment (A,B,C,D) and between the sorbate treatment (E,F,G) and the control (H) in most sensory properties of biscuit prior to storage. Upon six month storage of biscuit made with addition of different levels of sodium propionate 20-40C (room temperature) no significant differences (P<0.05) were shown on softness, flakiness and color in comparison with the control . No significant differences (P<0.05) were also
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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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This research had been achieved using 2D seismic sections to study the presence of subsurface salty bodies in the Khashim Al-Ahmer, Galabat, Injana fields as a case study. The selected oil fields is located to the northeast of Baquba city within Diyala Governorate.
The study aims to determine the salt accumulations of the selected fields and their role in the formation of oil traps.
The interpretation of seismic data was focused on two reflectors Fatha and Jeribe Formations which belong to the lower and Middle Miocene. Structurally, Two systems of reversal faults are affecting the fields, according to seismic sections, the first represents thrust faults affected on the top part of Fatha (Red Beds &
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The impact of television has made it an essential technology that can't be dispensed with in all circumstances and situations, measuring the society's need for it. Some argue that there is no stronger media than television in introducing people of the world to each other, as it has the most powerful impact and attracts millions of viewers.
Television is deemed as the most effective tool of media as it is designed to capture both sound and image. The image, in itself, has the ability to engage and interact with our thoughts. In light of the aforementioned, it is noticeable that this interactive medium (television) has significantly evolved over the years, thanks to modern technologies that have been introduced over time. These advancem
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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