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 research aims to test the correlation relationships between wise leadership, and the business model, and to demonstrate its influence (wise leadership) on the business model. Therefore, two main hypotheses were put forward. The research was applied to a sample consisting of (87) managers and deputy managers, some of them are members on the board of directors of the researched company. The questionnaire was adopted as a basic tool for collecting data, in addition to personal interviews. A number of statistical methods were used to analyze the data and obtain results. The researcher showed a set of results, including: There is a significant correlation between wise leadership and business model. There is an influence of wise leadership on
... Show MoreBackground: Preterm labor and related prematurity are predisposing factors that increase perinatal morbidity and mortality. Acute phase reactants are inflammatory markers which are positive and negative reactants explained by the reaction of reactants to the subclinical infection that are commonly associated with preterm labor. Objectives: To assess the role of acute phase reactants in pregnant women with preterm delivery. Patients and method: A case control study conducted in Gynecological Department of Baghdad Teaching Hospital from 1st February 2021 to 30th October 2021, on one hundred pregnant women with gestational age (28weeks - 36weeks+6days) who attended outpatient clinic; fifty pregnant women with established preterm labor
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The Voluntary Obedience has great importance for the modern taxes systems and its management and this is meant the taxpayer whom in charge to pay of his taxes obligations voluntarily , he is very known of himself whereas he prepared his finishing accountings and present them as samples prepared by taxes management and settle the tax sum directly according to specified income , which has an impact to find end to tax evasion as result lead to increase the tax income and achieve the justice for the taxpayer and the state treasury
Osteoporosis is a systemic disease of the skeleton, characterized by low bone mass and alteration in the micro-architecture of the bone tissue that lead to an increase in brittleness with the ensuing predisposition to bone fracture. Global statistics shows that women are more exposed to this disease than men and in particular at menopause. This study was designed to evaluate the use of some bone markers: serum osteocalcin (Ost), alkaline phosphatase (ALP), as bone formation markers, also parathyroid hormone (PTH), calcium and inorganic phosphate level, for the assessment of patients with osteoporosis and to evaluate their role in monitoring of several types of therapeutic interventions (such as bisphosphonates, hormonal replacement thera
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This study is concerned with the reality of total quality management and its role in achieving the excellence performance of the employees of the Institute of Technology / Baghdad, excellence performance is described by the extent to which the organization is able to invest the effort of the human resource to achieve its Objectives by adopting the principles of Total Quality Management (TQM) according to some of its basic dimensions in proportion to the reality and Possibilities Institute, the aim is to study to know the reality of total quality management ,and indicate the levels of excellence performance in the Institute of Technology / Baghdad,
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The purpose of the research is to study the impact of knowledge management (personalization and coding strategy) in achieving strategic excellence in the environment of Iraqi private banks, and the descriptive and analytical research approach has been adopted, so the researcher adopted positive philosophy according to the deductive approach for the purpose of deriving the first research hypothesis from the theoretical side and the research reached a group of The most important results are that the personalization strategy has made great progress in its ability to influence strategic superiority as a responsive variable, as the civil bank departments were successful in employing the changes that occurred in the personalization str
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Moisture-induced damage is a serious problem that severely impairs asphaltic pavement and affects road serviceability. This study examined numerous variables in asphalt concrete mixtures to assess their impact on moisture damage resistance. Mix design parameters such as the asphalt content (AC) and aggregate passing sieve No. 4 (PNo. 4) were considered as variables during this study. Additionally, hydrated lime (HL) was utilized as a partial substitute for limestone dust (LS) filler at 1.5% by weight of the aggregate in asphalt concrete mixtures for the surface layer. This study also investigated the potential enhancement of traditional asphalt binders and mixtures by adding nano-additives, specifically nano-silica oxide (NS) and na
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Small and Medium Enterprises (SMEs) in Iraq have experienced low performance due to the limited usage of accounting information systems (AIS) and the inability to exploit knowledge of management capabilities (KMC). These deficiencies have led to competitive pressures in the marketplace that have adversely affected their sales and production. This study investigates the role of AIS in terms of operation support, knowledge support, regulatory support, and the role of KMC, including knowledge acquisition, knowledge transfer, and knowledge utilized to enhance organizational performance in Iraqi SMEs. The target population was managers and owners in SMEs using AIS in Iraq’s cities. A non-probability purposive sampling technique was use
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As population growth increases the demand for crops increases and their quality improves, and it becomes necessary to find innovative and modern solutions to enhance production. In this context, artificial intelligence plays a pivotal role in developing new technologies to improve crop sorting and increase agricultural yields. The present review discusses the main differences between manual and mechanical potato harvesting, explaining the advantages and disadvantages of each method. Manual harvesting is highlighted as a traditional method that allows for greater precision in handling the crop, but it requires more time and effort. In contrast, mechanical harvesting provides greater efficiency and speed in the process, but it may damage some
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Parasitic diseases can affect infection with COVID-19 obviously, as protective agents, or by reducing severity of this viral infection. This current review mentions the common symptoms between human parasites and symptoms of COVID-19, and explains the mechanism actions of parasites, which may prevent or reduce severity of this viral infection. Pre-existing parasitic infections provide prohibition against pathogenicity of COVID-19, by altering the balance of gut microbiota that can vary the immune response to this virus infection.
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