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.
Abstract :
This research aims to examine the correlation and the impact of Cultural Intelligence with their dimensions (Strategy, Knowledge, Motivation, Behavior) on Drawing Local politics and their dimensions (Empowerment, Flexibility, Organizational Justice, Local Funding) In Dhi Qar Provincial Council To determine the extent of the presence of significant statistical differences between research variables Due to the recent experiment which requires clarification of the role of the pivotal and important carried out by the provincial council in the exercise of his work in light of the diversity of cultures and the peculiarities of the local community, which may impede the provision of equal services to all those parties
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Abstract:
In its theoretical farm, the research adobet the subject of human resource management strategies and the cognitive skills. It comes as result of the rapid development which considers it human resource. as main axis in organization , the research in includes ,connective analysis , between human resource management strategies and cognitive skills which is considers one of the new concept that should be studied widly so that the organization can be able recognize it as concept and type and its importance for people in the organization.The study method was descriptive and analytics , it identified collation of hypothesis which were by statist too
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In light of the intellectual and technological progress within the current developments of time, as well as the emergence of digital tools and means of display and communication, which had a major role in the shifts of the time of globalization in various commercial and economic fields, as well as areas of transferring the design image and its stages of development to customers and the convergence of views between the customer and the interior designer, which are the most important pillars of the design process As a whole, and accordingly, there is an urgent need for a process of intellectual balance between them through digital tools from the technical side and through social media from the intellectual side. Customer comments via socia
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In Iraq, there is a limited research work exploring the clinical pharmacists' role from the point of view of other healthcare professionals. To investigate physicians' assessment of clinical pharmacy services at Baghdad hospitals, and compare junior physicians with senior physicians' point of view. The study was conducted in twelve governmental hospitals in Baghdad, Iraq. Data was collected from a sample of two hundred physicians, and through a validated, self-administered questionnaire, which comprised twenty statements in addition to a non-personal information form that precedes the questionnaire The study findings reveal a somewhat positive point of view towards clinical pharmacists' performance in Baghdad h
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chronic obstructive pulmonary disease (COPD) is a common respiratory disease with episodes of exacerbation. Variable factors including infectious pathogen can predispose for this exacerbation. The aim of this study is to evaluate the role of intestinal protozoa in COPD exacerbation. A total of 56 patients with COPD were included in this study. Patients were categorized into two groups based on the frequency of exacerbation during the last 6 months: those with ≤1 exacerbation (32 patients) and those with ≥2 exacerbations (24 patients). Stool specimens from each patient were collected two times (one week interval) examined for intestinal parasite. In univariate analysis, rural residence and parasitic infection were more common among patie
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According to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c
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This article makes it possible to verify the role of quality management in strengthening the innovation process. The first hypothesis, according to which the quality (certification ISO 9001) influences the innovation positively, is confirmed for certain innovation indicators. Another hypothesis indicates that there are the levels of quality which develop the innovation process in diverse ways. The results indicate that for some domains of innovation, the performance of innovation of enterprises that have a very increased level of quality is higher than those of enterprises with an average quality, which in return is higher than those enterprises having a low quality level. Therefore, we discovered that the difference of performance innov
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The current research aims to measure the impact of the skills of human resources management professionals in information technology in Iraqi private banks, as the skills of human resources management professionals constitute the modern trend of banks' interest in employees with outstanding performance, and the presence of information technology in banks is a prerequisite for dealing with the huge amount of data. And converting it into information to support the decision-maker in light of a complex environment, and the field research problem was the presence of a clear lack of interest in the skills of human resource management professionals and the weak adoption of information technology, which was reflected negatively on the compet
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The research aims to reveal the role of financial analysis in rationalizing the investor decision on the Iraqi stock Exchange market, by studying the relationship and impact techniques and methods of financial analysis on the decisions of investors in the market. The most important techniques and methods discussed in this study were: analysis (financial ratios analysis, comparison of financial statements analysis, cash flow statement analysis) for companies listed in the Iraqi stock Exchange market. The researcher adopted the analytical descriptive method which depends on the collection of data on the phenomenon and its interpretation. The questionnaire wa
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