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 research studies the effectiveness of the symbol in the Iraqi monodrama texts. The methodological framework is devoted to the research problem and the need for conducting it, its importance, the purpose of research, and the definition of the most important terms. The research problem dealt with the concept of the effectiveness of the symbol, the monodrama, and the working levels of the symbol in the monodrama texts of the author, in addition to the disclosure of the artistic vision embodied by the playwright in the use of the symbol within the literary product, as well as the development of the creative process. The research problem was defined by the following question: How effective is the symbol in the Iraqi Monodrama texts?
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This study was aimed to investigate the load of bacterial contaminant in fresh meat with different types of bacteria.One handered and seven samples were collected from different regions of Baghdad . These samples included 37 of fresh beef 70 of fresh sheep meat. All samples were cultured on different selective media to identitfy of contaminated bacteria .The result revealed that The percentage of bacterial isolate from raw sheep meat were, % 23.8of StreptococcusgroupD,29.4 % of Staphylococcus aureus ,14.7 % of E.coli , %4.9of Salmonella spp, ,%3.5 of pseudomonas aeruginosa, %14.7.%14.7 of Proteus spp.% 2.1 of Listeria spp while the raw beef meat content %5.55 of Staphylococcus aureus, %8.14 of streptococcus group D , %5.18 %1.85 of E.coli,
... Show MoreEconomists agree upon the importance of exports and their positive impacts on the economic variables. Therefore، they studied policies encouraging exports and set out the instrumentalities supporting them. These instrumentalities included a combination of fiscal، monetary، commercial، production policies like the tax policy that is encouraging to the exports، exchange rates reduction، establishing commercial free zones، better production quality، fostering investment climate، and preparation of the necessary financing before the exporting process and afterwards.
This research is interested in the finding aspect amongst the instrumentalities encouraging exports which is parallel t
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The purpose of this research is to highlight the nature of the relationship between the mental abilities of decision makers and strategic orientation . The intellectual capacity of decision-makers is the cornerstone for the implementation of all the tasks and duties of the Organization and constitutes the most important of its capabilities. As a result of the sharp changes in the environment in which it operates, this organization must accurately define its strategic directions to ensure its
survival and continuity. The problem of field research was to answer a fundamental question: Is the Iraqi director aware of how to employ mental abilities in strategic direc
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This study aims at recognizing the levels of comprehension of the students of basic schools to the concepts of mathematical geometric and discovering the existing of the differences among students in the level of understanding of the concepts of mathematical geometrical which is due to the change of gender.
The sample of the study is the students of Basic schools, eight level in the basic school of Erbil city, particularly 7-8-and 9 levels in the academic year 2013-2014. The sample consists of 444 students in both genders238 males and 206 females.
The tool of the study is test sheet included 20 items of multiple choice. The items are valid since are given to a jury of expert
... Show MoreThis research is intended to high light the uses of political content in foreign Arabic / speaking websites, such as “ CNN “ and” Euro News“, The research problem stems from the main question: What is the nature of the use of the websites in the political content provided through them? A set of sub-questions that give the research aspects and aims to achieve a set of objectives , including the identification of topics that included , the political content provided through , the sample sites during the time period for analysis and determine that the study uses descriptive research based on the discovery of the researcher, describing it accurately and defining the relations between the components.
The research conducted the des
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Background/Aim There is an association between patient general health, socioeconomic status and fracture incidence. Aim of this study was to demonstrate the relation between the socioeconomic and health status and the occurrence of fractures in Al-Kindy Hospital residents. Methods A prospective cross-sectional study was performed by using data collected from fractured patients in Al-Kindy Teaching Hospital / Baghdad Orthopaedics Outpatient Clinic, between 12 December 2021 and 8 March 2022. A hundred patients aged 20 to 75 years were included in this study. The data were collected using a researcher-administered questionnaire, which included items to assess patient's socioeconomic status (accommodations, occupation, income status, level of e
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This study aims to suggest an alternative to the use of quality agricultural soil in the brick industry (Iraq). The Late Miocene claystone bed in the Injana Formation in central Iraq was targeted through the study of 18 exposed sections that were sampled by using the trench sampling method. The claystones are characterized by quartz (36.4%) followed by calcite (32.8%), quartz (36.4%) feldspar (2.6%), gypsum (1.3%) and dolomite (0.7%), kaolinite (10.5%), illite (7.7%), chlorite (6.7%), palygorskite (6.0%) and montmorillonite (0.7%). New thermal mineral phases were formed at 950°C, including diopside (62.9%), quartz (18.4%), wollastonite (8.28%), akermanite (7.6%), Anorthite (6.25%), Nosean (4.9%), gehlenite (3.75%) and Lazurite (3.1
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Researching the effects of the research and technological development contract, determining its extent and demarcating the boundaries of the obligations imposed in it, is the cornerstone of economic growth and development, because defining these obligations removes the ambiguity and conflict between interests, by stating the rights owed to each party and even trying to reconcile them, or impose protection by specifying guarantees that are compatible with the essence of the R&D contract, For the purpose of studying the subject thoroughly, we will divide this research into two sections. The first is devoted to identifying the parties to the research and technological development contract. As for the other topic, we will explain the obligation
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