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 accession of countries to the World Trade Agreement and the openness of markets to each other without restrictions led to the emergence of the philosophy of "a world without borders and business units without countries", which required adapting the modern business environment to that philosophy, which is considered as objectives for the activities of the units that must be implemented in order to achieve competition. The objective of the units has changed from making profit to meeting the desires of customers, which is what imposed a new role for management accounting as a field of knowledge renewed in it visions of competitiveness between units. Because of the increasing needs for information in light of environmental change
... Show Moreيعد علم التدريب الرياضي الحديث عملية تربوية علمية مبنية على اسس صحيحة هدفها وصول اللاعبين الى التكامل في الاداء الفني وهذا يتم عن طريق التأثير المنظم والدقيق بواسطة استعمال التمارين البدنية التي تحدث تغيرات خاصة في عمل اعضاء واجهزة جسم الرياضي والتي بدورها تؤدي الى رفع كفاءة الاعضاء والاجهزة لتحقيق الانجازات الرياضية العالية ولقد استعملت الباحثتان اسلوب حديث من اساليب التدريب الرياضي من اجل تطوير تحم
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Purpose – The main purpose of this research is to highlight the main role of strategic leadership skills for top managements in accessing to effective management in accordance with the (VUCA Prime) methodology in (VUCA) environment as Miniature virtual environment, which refers to (Volatility), (Uncertainty), (Complexity), and (Ambiguity).
methodology – To achieve the research objective, this study selected the quantitative approach in research design, Questionnaire was used as the main instrument for data collection, the sample comprised the opinion poll (106) individual who functions as a head department. (Structural equation modelling by (Smart Pls3)
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The importance of culture moot ( visual ) in the community , serves as the conceptual basis for the technical and aesthetic awareness , as all the fields of art represents a kind of social consciousness can not be separated from the practice of performance and awareness of it. That the link between what you do image that expresses the cognitive aspects and performance , and what is reflected on the receiver by turning the event into a set of symbols and meanings that have a correlation relationship to society , education, and other fields. Therefore must provide " material conditions and psychological " that helps the learner to interact effectively and with the active elements of the learning environment in the classroom and gain
Provides the style of benchmarking the best possible use whenevaluating the performance and evaluation, as well as improved performance,due to its consistency with the principles of good evaluation of theperformance, an extension of the completion of several functions of the timeand cost less, thereby increasing the efficiency of the management of theinstitutions, especially institutions, the media, as it became public the future ofthe message sender to the same time Zaorosaúl new media is challenging thetraditional media of what distinguishes this new interactive media and mass ledto this transition . However, the media Aljdidhoosaúl traditional mediacontinue to coexist and reinforce each Menhmaalakhr, for his wealth offreedom of opin
... Show MoreFor the first time in Iraq, two species of monogenetic tretamtodes of the genus Dactylogyrus were recorded from gills of Alburnus caeruleus from Tigris river at Al-Zaafaraniya, south of Baghdad during June 1995. The first species, Dactylogyrus sphyrna is characterized by having the seventh pair of marginal hooklets almost twice as large as other marginal hooklets, powerful inner and outer processes of median hooks especially the inner one which is expanded terminally, one connecting bar and long spirally twisted copulatory organ. The second species, Daclytogyrus phoxini differs from the first one by having marginal hooklets of the same size, inner and outer processes of median hooks are not powerful, two connecting bars
... Show MoreThe research aims at showing the effectiveness of the existing deposit facilities in the liquidity of the Iraqi banking system for the period 2010/2017. The problem of research indicates that the Iraqi banking system enjoys high liquidity levels exceeding the standard rate set by the Central Bank of Iraq amounting to 30% For an appropriate level of liquidity remains a major challenge to the management of the bank because it is a trade-off between profitability and liquidity, and also indicates the existence of funds disabled and not available for credit and investment opportunities, and based on the research hypothesis:
The existence of a significant effect of the deposit facilities existing in the liquidity of the Iraqi banking
... Show MoreThere are many problems facing the economic entities as a result of its mass production &variation of its products , the matter which had increased the need & importance of cost accounting which is regarded a main tool for the managerial control.
The actual costing system is unable to meet the contemporary management needs ,so the Standard costing system appear to provide the management with required information to perform its functions by the best use& way.
This research aims to determine the standard cost for the direct material for oil extraction activity by applying it in the north oil company.