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 issue of Palestinian prisoners inside the prisons of the Israeli occupation is considered
a humanitarian issue par excellence، as it affects every Palestinian family as a
result of the absence of a husband، wife or son.
Almost no Palestinian house is vacant without one or more prisoners، and even women،
children and the elderly are not spared from these arrests.
The problem of the study was to identify the role of public relations in the Ministry
of Detainees and Ex-Prisoners Affairs in educating the Palestinian public about the
issue of prisoners، the nature of this role and the means used to bring support and
solidarity with this important and sensitive issue through the applied study on the
employee
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A new scheme of plasma-mediated thermal coupling has been implemented which yields the temporal distributions of the thermal flux which reaches the metal surface, from which the spatial and temporal temperature profiles can be calculated. The model has shown that the temperature of evaporating surface is determined by the balance between the absorbed power and the rate of energy loss due to evaporation. When the laser power intensity range is 107 to108 W/cm2 the temperature of vapor could increase beyond the critical temperature of plasma ignition, i.e. plasma will be ignited above the metal surface. The plasma density has been analyzed at different values of vapor temperature and pressure using Boltzmann’s code for calculation of elec
... Show MoreThe aim of this research is to calculate mass transfer coefficient, kd, during cathodic protection of low carbon steel in neutral seawater (3.5% W/V NaCl in distilled water with pH = 7). Two types of cathodic protection were used:
First: Sacrificial anode cathodic protection (SACP) were a pipeline of steel carrying seawater using zinc as a sacrificial anode and with variable temperatures ranged (0 – 45oC) and volumetric flow rate ranged (5 – 900 lit/hr). It was found that the kd increases with increasing temperature and volumetric flow rate of seawater, where kd ranged (0.24×10-6 – 41.6×10-6 m/s).
Second: Impressed current cathodic pr
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The research aims to diagnose the shortcomings and weaknesses in applying the dimensions of the quality of work life and the extent of their impact on employees’ attitudes and behaviors, and thus their relationship to enhancing their core competencies. The scientific value of the research stems from highlighting the importance of the dimensions of the quality of professional life in improving the productive efficiency of workers in the public sector and raising the level of organizational performance. Because the quality of working life plays an important role in enhancing the core competencies of employees in the public sector, it can also be an incentive or a disincentive for any employee by adapting to the economic and social condit
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Money laundering is consider a crime in legal perspective and aphenomenon of negative effects in economic and Social perspective for thevarious countries of the world by the diversity of their economies to make thebadly damaged in the banking service and its reputation in some cases may leadto bankruptcy of banks, and the fact that banks is one of the most importantcircles that revolve the illicit funds, Due to its branched the banking operations,speed and overlap and increase it's complicated with the progress of bankingoperations and the use of electronic services modern here's challenges atvarious levels between the application of the legislation to combat moneylaundering and between actual fact it must find ways and means of legislat
... Show Moreيهدف البحث إلى تشخيص أوجه القصور ونقاط الضعف في تطبيق أبعاد جودة الحياة الوظيفية ومدى تأثيرها على اتجاهات وسلوكيات الموظفين، وبالتالي علاقتها بتعزيز مقدراتهم الجوهرية. وتنبع القيمة العلمية للبحث من إبراز أهمية أبعاد جودة حياة العمل في تحسين الكفاءة الإنتاجية للعاملين في القطاع العام ورفع مستوى الأداء التنظيمي. ولأن جودة الحياة العملية تلعب دوراً مهماً في تعزيز المقدرات الأساسية للموظفين في القطاع الع
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The research aims to diagnose the shortcomings and weaknesses in applying the dimensions of the quality of work life and the extent of their impact on employees’ attitudes and behaviors, and thus their relationship to enhancing their core competencies. The scientific value of the research stems from highlighting the importance of the dimensions of the quality of professional life in improving the productive efficiency of workers in the public sector and raising the level of organizational performance. Because the quality of working life plays an important role in enhancing the core competencies of employees in the public sector, it can also be an incentive or a disincentive for any employee by adapting to the economic and social condition
... Show MoreWas conducted neutralize content Albulamedi for local isolates using Alacardan dye orange selection experience showed loss of local isolates resistant life antibiotic ampicillin, chloramphenicol