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 global trend towards the use of fair value accounting is increasing, so the current study aimed to maximize the impact of fair value application on achieving relevance and representation faithfulness of accounting information in accordance with the common conceptual framework. To achieve the objective of this study, the researcher has determined in the theoretical framework the relationship of fair value with the characteristics of relevance and representation faithfulness of accounting information and the extent of achieving these characteristics, as well as conducting a field study by preparing a questionnaire distributed to a sample of academics (50) and auditors (50) with a total number of selected participants (100) of acad
... Show MoreThis research aims to investigate the role of quality management in enhancing the efficiency and effectiveness of settling accounts tax in terms of achieving satisfaction in charge of the hand and the increase of tax revenue on the other hand, by testing the main hypothesis of the study and the sub-hypotheses in the Income and Sales Tax Department in Jordan for the period 2000-20
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In this work an enzyme linked immunosorbent assay (ELISA) technique has been used for detection of some inflammatory markers in serum of acute coronary syndrome (ACS)-Patients Admitted to the cardiac care unit (CCU) of Iraqi Centre For Heart Diseases and Ibn AlNafees Teaching Hospital. The present method includes quantitative measurement of interleukine-6 (IL-6) and C-reactive protein (CRP), as their increase during symptoms may be responsible for identifying the mechanism of myocardial damag, in addition to their best performance than other quantitative tests perhaps due to their association with atherosclerotic process that belongs to the endothelial dysfunction. Aim of this study is to estimate the prevalence and correlation of IL-6 w
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The interest in the intellectual capital and its development is a civilized necessity imposed by the requirements of the times and cannot imagine an advanced society in its potential productivity in poor efficiency of human capital, and features the work environment change permanently, putting the management of financial companies against a constant challenge toward coping with new developments in this changing environment and this is not taken unless owned by these companies qualified human resources and the provision of Culture organizers have, which manifested itself with the research problem by the following two questions:
- Did the intellectual capital value specific financial and
The present study evaluates the effects of Ginkgo biloba extract as monotherapy on the glycemic status, insulin resistance (IR), body mass index (BMI), and visceral adiposity index (VAI), in addition to the inflammatory markers, oxidative status and leptin level in patients with metabolic syndrome in comparison with metformin.
The study is a randomized, double-blind pilot study conducted during the period May to September, 2020. Fifty patients were recruited in the study and they were allocated into two groups (25 per each group): Ginkgo biloba and Metformin groups, they received (120 mg Ginkgo biloba extract/ capsule) and (500 mg Metformin/ capsule) respectively; orally as a single dose for 90 days. Blood samples were taken at z
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The Quality function deployment (QFD) tool is an important tool of total quality management because its a link between two important parts customer and production process of the product, using advanced House of quality, which contributed to provide more details about improving the product before it had a vision for the future of the product be improved. Also the identification of the two competitors (Alwazeer , Altouri) bases on the survey of retailers which they identified five competitors products (Alwazeer , Altouri , Ferry , Jif , Dina)for the product (Zahi). Then House of quality to product (Zahi) has been developed By using a Kano Model to classify of customer's requirements for the
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This research is based on monitoring the local and environmental technologies in the design of the temporary hotel units (nomadic tents) in the desert in the south of Jordan in order to air condition them in summer and winter, maintaining the Jordanian identity, that they are presented with the form and technologies of the age in order to get to the universality.
The research adopted the descriptive analytical method and the researcher conducted the analysis of SWOT specified for the analysis of the positive and negative aspects in the design of the temporary hotel units and comparing them with the case studies available in the chosen research area "the Jordanian golden triangle", through the elements of the case under study. The res
This research aims at shedding light on the concept of insurance awareness and clarifying its role on marketing insurance services of a sample of (100) employees in the National Company for Insurance. Questionnaire is used as a main instrument for collecting data and information from the sample. Their answers were analyzed by using arithmetic means, standard deviation, centesimal weight, and the correlation coefficient ( , F, t) tests .The research reached several conclusions of which:1.The sample member's response to insurance awareness and marketing insurance services factors was in the medium level.2.There was a positive relationship of a moral sign between insurance awareness and marketing insurance services, that correlation coeffic
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Abstract:
Today, the financial and banking sector is witnessing a qualitative shift thanks to financial technology services, which provide their services to many individuals and companies in quick, easy and less expensive ways compared to traditional means. Financial technology is a new form of financial science that combines financial transactions and technological skills concerned with providing financial services and improving the work environment within Banking institutions, and financial technology provides many advantages such as lower transaction costs, instant payment, and saving more time and effort in conducting banking
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