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 semantic analysis is characterized by its ability to describe the communicative pattern and its high efficiency in questioning its semantic manifestations and its deliberative purposes, which helped to understand the symbolic, contextual and cultural manifestations of the structure of the pattern, whether verbal or nonverbal. In order to highlight the role of the semiautomatic approach and its application to a sample of slogans collected from "media, social networking sites, in-kind views, media institutions, etc." to study the components and analyze the contents and highlight the signs. His boat logo is not just uttered as a linguistic transmission of a message, but as a political Tghieria actually . For example, the slogan "People Wan
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The American vision of the Non-governmental Organizations in Iraq the topic area of that’s paper dealing with Civil Society as concept and practice, its already consider as Western concept and associated with liberalism and political development, they are many definitions of its but most significantly is all organizations, agencies, trade unions and non-governmental institutions, that’s agencies were established after 2003 and received funds from United States and UN development agencies. The non- governments organizations played a significant role as support and develop many cultural, healthy, educational, and social projects, also that’s organizations try to reduction the effects of terrorists actions especially after ISI
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Different additives are used in drilling fluids when the demanded properties cannot be gotten with clays. Drilling muds needs several additives and materials to give good characteristics. There are local alternatives more suitable for enhancing the rheology and filtration of drilling fluids. An experimental work had been conducted to assess the suitability of using potato starch to enhance rheological properties and filtration in drilling mud. This study investigated the potato starch as a viscosifier and fluid losses agent in drilling fluid. Results from this study proved that rheological properties of potato starch mud increased when pH of drilling fluid is increased. Potato starch could be used to enhance gel strength at low pH
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The search for wealth and money is a matter of ethics in the Islamic economy
God Almighty said: "We have honored the sons of Adam (and ridiculed the universe and what he said) mocked you
He said, "He who created you from the earth."
And he commanded you, and he said to him, "He who made you."
Land, and the amount of Rezko and
He said: "You love the money with great love."
And then guide him by exaggerating the ethics of Islam and its legislation in Tamkak and not exceeding it.
In order to darken the doors of inflation with wealth Vakar
And the hereafter and achieve satisfaction and fairness in all actions
To ensure that society has a right not to harm others and to abuse the interests of the economy
Is
Many researchers ' views about class selectors popular theatre in the world, whom he found in political deals popular presentations while others in comedy shows or dealing with social problems, or simply build a direct pattern of relationship between actors and audience were popular, and certainly the Iraqi popular theatre has its own parameters, structural differences result of Iraqi society at all levels, so the researcher found the search problem is to answer the question that (what are category classes Or within the category of Iraqi popular theatrical-in the play of - the string and the bird which un – example ) , then select the aim has his research of detecting those parameters, and search scientific significance as to scholars
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Abstract
The role of the independent variable and human resources capabilities was the role of the adopted variable. The aim of the research is to identify the level of participation in the knowledge of the organization through human resources and the rigorous scientific investigation to develop new mechanisms of action that help To manage the organization in the implementation of its mission and achieve its main objectives that have been found for it is to encourage the work of scientific research and maintain the preservation of its continuity to increase the competencies of knowledge, technical and skill to form a future workforce qualified to work In the sectors of society.
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Out of the search for the truth, the reader of the Holy Qur’an should know the fate of the sorcerers whom Pharaoh threatened when they announced it as pure monotheism in front of seeing the stick as it turned into a clear serpent, when they said: We believe in the Lord of the worlds, the Lord of Moses and Aaron, and the clear promise came to cut and crucify the trunks of palm trees, and they said what they said if Being supplicants to God (May God cause us to die as Muslims), did Pharaoh actually carry out what he promised them?? So we studied that subject from this angle. Because what looms on the horizon of the Holy Qur’an is that there is no one who seeks refuge with God Almighty in times of adversity except that God Almighty has
... Show MoreTheatrical techniques took upon themselves the responsibility of building and organizing the theatrical form for the various forms of performances, and it was the important tool that the show makers could rely on in carrying out the various works at the audio-visual level, and lighting is one of the most important elements of the visual formation of the image in the show, as it is related to the visual process and what it can achieve in operations The contrast that constitutes the aesthetic and intellectual values of the theatrical show, especially since the process of adjusting the element of time and the timings for receiving or delivering, moving, and the movement of the actor is what can determine the rhythm of the scene, which in it
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Sports and legend rooted deep in human history, and although they meet in the oldest epics as was the hero Gilgamesh legend and a hero of the heroes of wrestling has been named the oldest regular sports tournament in history in his name, a Algeljamchih Games which will be held events in Mesopotamia in August of each year and will continue nine days and take place in competitions in more than a sports game ..
In our time re-production of sports legends to serve the objectives of the huge investment both sports on the commercialization level or at other levels of marketing, including political marketing.
In this context, a move sports media for the production of myths we studied Semiaiaa in an effort to learn how the production proce
The text has many connotations in the Arabic language, such as vowel points, designation, completion, etc., and the original meaning of the text is to show. The Western text has its owen independent semantic unit .The biblical texts are a mixture of what was reported by the Prophet Moses (peace be upon him) and what the authors described in terms of texts over many centuries.The meaning of the text is guidance and payment, and it is a natural connotation. The religious text for Muslims is divided into peremptory texts that are national proof. The evidence for the meaning of the text is proven by language, and it is not required that the researcher be a jurist. The approach is a factual questionnaire by the researcher according to a speci
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