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.
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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This study aims to highlight the role of financial control in the development of government performance through the use of "GFS" system and its application in the service of government units, which will help them in how to use financial resources efficiently through the quality of accounting information provided by this system in the financial statements that reflect the predictability in that fiscal policy of the state through government programs and activities fee as well as to identify weaknesses and address them quickly in order to avoid wastage and loss of public money, which leads to the possibility of utilization of available financial resources of the state to effectively and efficiently, has been reached that the failure of gove
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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
At different stages of the evolution of the modern Iraqi state ears last century did not receive the industrial sectors importance in great domestic production (GDP) and that the limited resources available in the initial stage and the dominance of public sector industry in the late stage , so the continued decline in the contribution of the private industrial sector in GDP , and this is why imbalance in the labor market and reduced demand for manpower in this sector despite the high rates of labor supply and the various skills and levels of investments, their human and the different geographical distribution , and direction of labor to other economic sectors most requested of the l
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This purpose of the research is to test liquidity ratios to assess bank liquidity risks represented by liquidity ratios (current assets / current liabilities, current assets / total deposits, current assets / total assets, cash credit / total deposits, liquidity coverage ratio LCR, net stable financing ratio NSFR). This research involves evaluating these risks in banks via these ratios, and reveal the most important means used to solve these risks, including the capital adequacy ratio under the Basel II decisions and for selected period (2017-2019).The research reached the most important conclusion, which is the bank sample did not fall into bank liquidity risks throughout the years of research. Tracking specific ratio with adequ
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Neuron-derived neurotrophic factor [NENF], a human plasma neurotrophic factor, also increases neurotrophic activity in conjunction with Parkinson's disease-related proteins in Neudesin. Although Neudesin (neuron-derived neurotrophic secreted protein) is a member of the membrane-associated progesterone receptor (MAPR) protein subclass, it is not evolutionary related to the other members of the same family. The expression of Neudesin is found in both brain and spinal cord from embryonic stages to adulthood, as w Neudesin levels in Parkinson's patients with osteoporosis disease and Parkinson's patients without osteoporosis disease, as well as the relationship between Neudesin levels, Anthropometric and Clinical Features (Age, Gender, BMI) and
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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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