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.
Background: The immune system of the oral cavity suffers alterations due to fixed orthodontic treatment which act as potent stimulus for oral secretory immunity. The aims of this study are to estimate the effect of fixed orthodontic appliance on the level of salivary sIgA at different time intervals, and to verify the gender difference. Materials and method: The patient's history, clinical examination, and fixed orthodontic appliances were placed for 30 Iraqi orthodontic adult patients had class II division 1 and/ or class I malocclusion (15 males and 15 females) aged 18-25 years old. The unstimulated whole saliva was collected from each sample immediately before wearing fixed appliance (control group T0 as base line), and after 2 weeks (T1
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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 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
Most of the world is seeking attention to the agricultural sector, which occupies a distinguished economic center, including Iraq, it is no wonder that the focus is on this sector, especially in developing countries. Descriptive analysis of the sample tables of wheat and barley crops in Iraq showed that adherence to the principles and rules of total quality, including modern irrigation methods (irrigated) has a significant impact in increasing productivity, reducing costs and improving quality compared to traditional irrigation methods, so it became necessary to take agricultural economic units All procedures and means that will help in the application of the rules of total quality to promote the reality of wheat and barley cultivation in I
... 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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Municipalities.
Abstract
The purpose of this research is to measure the impact of regulatory flexibility dimensions (formal and authoritarian procedures) to achieve response to the requirements of high performance dimensions (the effective recruitment, intensive training, motivate employees, participation of workers) in the general municipal Directorate as one of the directorates of the Ministry of Municipalities and Public Works. For the purpose of this measure it has been selected sample composed of 88 individuals from the research community represents the levels of assistant general manager of department heads and managers of people and some of the staff to answer the questionnaire prepared for the purpose Hama
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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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On of the direct causes which led to the global financial crisis 2008 is decrease or collapse in liquidity of large financial institutions which is reflected on investments of a considerable number of institutions and persons.
This study aim's through out its three sections to explain the disclosure level of financial institutions which affected by Financial Crisis from liquidity information which explained in the statement of cash flow according to Timeliness and Completeness.
The study concluded an important result the company of research sample was disclosure in Timeliness and Completeness from all of accounting information is related in liquidity or that related in result of operations and financial position. The more
... Show MoreThis paper aims at the fact that most organizations today suffer from a waste of time, effort, and cost, and they have difficulty in achieving the best performance situations and compete strongly. The researcher distributed 108 questionnaires as a statistical analyzable sample society where the sample intentionally consists of general managers, department head, and division head. The questionnaire was formulated according to the Likert scale. The use of personal interviews and observations are additional tools for data collection and a number of statistical methods is used for data analysis such as simple regression and correlation coefficient (Pearson). One of the most prominent conclusions is that the company has adequate and c
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