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 materials of soil were affected by multi reasons; such as human activities, floods, tidal waves, ... etc. The change of the soil contents could be measured through different indexes; such as electric conductivities, salinity, concentration of the heavy elements, and concentration of essential elements ... etc. The land cover is affected by natural influences, like tidal energy, which plays a negative role in the salinization of land adjacent to the coasts, causing a problem for soils in all its details represented in changing of the dissolved elements in soil. One of the most important natural factors that cause soil salinity is human activity in all its forms, and one of the most important causes of salinity is the phenomenon o
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This study is concerned with revealing the semiotics of thresholds, and its role in building textual coherence at the form and semantic level in Sunset Garden Diwan of the Saudi poet Ghazi Al-Qasaibi. This research aims to spotlight on the semiotic theme of the title threshold and its relation to other thresholds. As the death phenomenon and absence dominated the poetic achievement space through intertwined semiotic relationships that lead to each other through the parallel text semiotics.This study is based on the semiotic method which concerns with searching for the interpretive connotations and revealing the profound symbols in the threshold structure and its role in the whole formation of the Diwan. Among the most prominent conclusio
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Knowing the Messengers, peace and blessings be upon them, and explaining their obligatory, impossible, and permissible qualities is a legal necessity. It is a rooting of the faith, a means of understanding the Sharia, and a preventer from falling into the scourge of denial and bad manners against them. Therefore, sound belief in their presence is a major reason for the validity of the faith in the aspect of divinity and unseen hearing. Studying the status of prophethood is an urgent necessity in a time in which knowledge is scarce and attachment to the Messenger, may God Almighty’s prayers and peace be upon him, his family, and his companions, is weak, and suspicions and ideas hostile to the faith abound until we begin to hear - unfort
... Show MoreThe study of topography most important studies and depth of any literary or artistic text and occupy the thinking of many who work in art at generally. There is hardly any film scenario from description in general of the indispensable elements of the composition and place one. So the place starts form since the scriptwriter begins to view the result of the description begins to feature the emergence of there are simple operations in the scenario soon to receive growth as a final achievement in the film. The description of the place begins to take on an allegorical character as a language version in the script, soon translated into another language, the language of the picture. Which in turn complement the creative ring of cinematic art a
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Environment suffered in recent years a large corrupting by human; and because of his ignorance of the dimensions of Caliphate in the ground and ignore what it means gearing. The gearing is that the son of Adam, which will benefit the board of Allah Almighty to him in the land of the causes of life, without exaggeration or negligence and without prejudice to the cosmic Balnoames enacted by the Almighty Creator, has urged verses of the Quran Muslim to preserve and protect the environment which is a religious duty, as it showed a great verses he is the author and the splendor and beauty of workmanship and manufacturer greatness of the Almighty, who created all things beautiful.
Koran played a major role in the consolidation of environmen
In this paper, the penetration of the stone column was investigated in order to get the minimum length of the stone column above which the increase in length has little advantage. The effect of using different materials in column are also studied. The material used is granular of different angle of internal friction (). The results of the investigation indicated that the effect of stone column remains constant when the ratio of the thickness of the soft clay layer to the stone column’s diameter is more than 15. The results also indicated that a pronounced effect is obtained when the angle of internal friction of the stone column material is increased.
This research studied the effect of magnetized water in concrete preparation and its effect on the presenting of cement in concrete mixtures also to find the ability of reducing the amount of cement in preparing one cubic meter, this is not exceed than 10% in one mixture , The experiments showed the preparation of standard cubes from the concrete which was used two kind of water magnetized water which was prepared by passing the tap water through the systems of different magnetic strength in terms of (6000,9000) Gauss and the ordinary water . The velocity of water through the magnetic field, which gives us the highest value for the compressive strength, was up to 1m/sec. to determine the best magnetic intensity, we examined The comp
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يسعى المجتمع من خلال الوحدات الإقتصادية إلى الوصول إلى تحقيق أفضل الإنجازات التي لا تتمثل بالسلع والخدمات حسب وإنما بما يتحقق من مردود لكافة الاطراف المعنية بالوحدات الإقتصادية على ان لايتم ذلك على حساب قيم المجتمع وأخلاقياته وآدابه العامة. وعليه تصبح الوحدات الإقتصادية مسرحاً لصراعات قوى متعددة كل منها له قيمه الأخلاقية سواء كان فرداً أومجموعة افراد أو وحدة إقتصادية أو أي جهة أُخرى، وبحكم مسؤولياته
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The aim of the research is to evaluate the response of the researched leaders towards practicing the concept of the lens, which is its dimensions with (stakeholders, resource mobilization, knowledge development, culture management) and the nature of its relationship to tax pioneer performance represented in its dimensions (strategic direction, leadership indicators, growth, renewal and modernization, efficiency, Effectiveness) The questionnaire was approved as a main tool in collecting data and information from the sample members in the General Authority of Taxes, which number (91) Who are on (M. General Manager, Division Director, Deputy Director, Senior Division Director, Deputy Director, Second Division, Division Officer, M. D
... Show MoreThe research aims to shed light on the nature of the tax gap in the income tax by the method of direct deduction and its reflection on the financial objective of the tax, and to determine the reasons for this gap in the deduction between the tax due in accordance with the laws and instructions in force and the tax actually paid. The tax gap is a real problem that cannot be ignored for what it represents loss of financial revenues due to the state.
The research problem is represented in the existence of a gap between the tax due according to direct deduction instructions and the tax actually paid according to the financial statements, and to achieve the objectives of the research and test the hypotheses, t
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