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 legal nature of the Build-Operate-Transfer-Ownership Contract (B.O.T) The Build, Operate, and Transfer of Ownership Contract (BOT) has emerged as the most successful and safest method for involving the private sector in public sector services. The major infrastructure projects that are built through the BOT contract are no longer financed by the state and its budget, but the private sector has played a major role in financing These projects, especially developing countries that need to establish infrastructure or modernize their existing infrastructure, especially in the areas of transport, communications, services, electricity, water ..... and other public utilities.
Reservoir study has been developed in order to get a full interesting of the Nahr Umr formation in Ratawi oil field. Oil in place has been calculated for Nahr Umr which was 2981.37 MM BBL. Several runs have been performed to get matching between measured and calculated of oil production data and well test pressure. In order to get the optimum performance of Nahr Umr many strategies have been proposed in this study where vertical and horizontal wells were involved in addition to different production rates. The reservoir was first assumed to be developed with vertical wells only using production rate of (80000–125000) STB/day. The reservoir is also proposed to produce using horizontal wells besides vertical wells with pr
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Praise be to God, Lord of the worlds, and prayers and peace be upon our master Muhammad and upon his family and companions.
And after:
Muslim scholars have fought in the extent of regard to these interests, each according to his opinion and according to his evaluation, and his consideration of this interest, but it remains important that the legislation in them needs more precaution and caution against the predominance of passions, because the passions often decorate spoilers so they see an interest, so practical application must To realize the spirit of Islamic Sharia in its entirety of its rulings, and the preponderance between the interests and evils that prevail in our societies, which c
... Show MoreThe subject of fear is one of the most important tasks that one should seek to find out the reasons behind it, and push it up with all its sound mental concepts.
The main reason for the lack of security and fear and disturbance in the world is to commit the legitimate violations that God warned us in his Holy Book as well as in the Sunnah of His Prophet (peace be upon him).
The talk about the causes of fear in the Koran is not limited to the word (fear) Fakk but came in different and varied methods such as (horror) and (awe) and (shares) and (narrow).
Abstract
The research is presented according to an objective study on the ideological problems, especially the distortions that the divine scriptures have been subjected to under a false pretext that does not pertain to religion, namely that the heavenly books of the Torah and the Bible have been damaged or lost as a result of apostasy and persecution, and the writing of these books has been entrusted by people who have been bestowed Holiness, they have the testimony of the Church, so they distorted and omitted it in a manner suitable for securing their good and worldly gains, and the Holy Qur’an mentioned this explicitly, and they continued later, especially the Jews, in distorting the verses of the Holy Qur’an. This researc
... Show MoreThe achievement of world peace is a humanitarian demand that humanity has sought since its existence. Despite the international and regional efforts to achieve this demand, it is still reaching its desired ambitions if conflicts, contradictions, and internal and external wars continue to justify us clearly in terms of ethnic, religious and sectarian conflict. The revolution of informatics and the impact of globalization opened a new era of communication and openness and the negative and positive impact of others, which re-published and distributed values, ideas and new cultures Some of them carries extremist ideas urging violence and destruction and other abolition, it became necessary to follow policies and reward The culture of peace,
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The United States has stood by Iraq and supported militarily and morally, but the relationship did not quickly be strained again before August 1990, when the oldest former political system in Iraq after Iraqi troops entered the territory of Kuwait, the United States stood beside Kuwait because the two parties link military ties opted States United to support the Kuwaiti side relying on the resolutions passed by the UN security Council, the United States and found in this issue right opportunity to execute the mechanics of meddling in Iraqi affairs and the various means of political, economic, military, and methods for dealing with Iraq, especially after finding the impediment standing in front of the implementation of its goals The strat
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Abstract
The current research aims to know the reality of the research's coefficients, to know correlation and effectiveness between the organizational Agility and high performance . The current research has been applied on the official banks , including a sample of senior administration members (120) ; besides , the research has used questionnaire that being considered as the main tool for gathering information and data . It includes 59 questions in addition to the personal interviews program as to support the questionnaire and to fulfill a great deal of reality. It has been anal
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