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 influx of Arab Qahtani and Nizari tribes continued to the countries of Baluchistan and the Levant in pre-Islamic times until the Levant became open to the Arab-Islamic tide during the first century AH. The Islamic Orient until the early Islamic Arab Army reached the western borders of China. What we will see in the folds of the search.
The problem with research in the question of whether art forms in the religious icon Byzantine, heiress docility and tradition craftsman arts civilizations of the above? ... And if you are well, you helped a quotation on the entry of strange ideas rampant within religious traditions, and are prompted to do Movement rejected prohibition, and the outbreak of the icons war? ... Or is it, in fact - and as researcher finds - the result of a need communication between the religious and the recipient organization in the establishment of a deliberative speech, be visible, along with reading it and audible? .. And lies the importance of this study is being added technical knowledge of the library that will enrich researchers and scholars in this
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The folkloric games widely considered as expressional forms of nations culture and their environment which can be an important element in Iraqi child theatre shows. For its moral and habits relation to the needs of children which present an effective mean to preserve the true identity of the society character and moral. The research concluded many topics considering the importance of folkloric games in the Iraqi child theatre, the first chapter studied the problem , the necessity , the aim of the research to clarify the importance of folkloric games in Iraqi child theatre, the second chapter is the theoretical part of the research that studied the concept of folkloric games and its implementation in Iraqi child theatre . the third chapte
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The definition of "prostitute" and prostitution is a difficult one and a
question over which the legislators of many lands and nations differed. A
notable feature of prostitution is its epidemic increase at times of war,
revolution and armed commotion, on account of economic, social and
psychological factors generated by such conditions of mortal conflicts. Wars
invariably deprive young wives and lovers of their men folk, resulting in
financial , sexual and emotional frustrations . At no time is the natural
balance between the sexes more seriously disturbed than during wars, when
thousands of men are thrown into one sector of the country and hundreds of
towns and villages are left to women and children only. Lo
The concept of Justice in the Ancient western political thought The title of research is the concept of Justice in the ancient western political heritage. It includes the definition of the idea of Justice as well as its evolution and relation to the Law the study discussed two main period . the first one was regarding the concept of Justice in the Greek political thought ( sophists ,Socrates , plato , Aristotle ,Epicureans , and stoics ) . While the second ocused on the concept of justice in Roman political thought Via their great thinkers as polypus and Cicero .
The sound effects in TV dramas achievements have become very important not only in terms of function and implementation, but at a greater and wider level in terms of artistic and aesthetic values, which are produced and employed in the most important world artistic achievements of drama, using the latest and most prominent technologies and equipment and according to the expressive and dramatic values expressed by these modern digital sound effects. Therefore, the researcher chose the aesthetic effect of digital sound effects in television drama to identify the aesthetic aspects provided by digital sound effects by employing them and their accompaniment for the image.
The researcher, therefor, divided this study into the methodolo
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Communication and media technologies have seen several changes in the last two decades. These changes put the basis for the emergence of communicative and media practices on several levels including political, economic, technological and artistic. And these, in turn, led to the emergence of new media trends and phenomena in various areas of media worthily to be studied and researched for example online advertisings. Online advert
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Nathaniel Hawthorne is famous for his psychological and moral themes. He is also famous for using symbolism in presenting his poignant themes of sin and its consequences. This research paper studies the use of symbols in Hawthorne's The House of Seven gables as an example of his general use of symbolism in his novels. The general pattern of Hawthorne's symbolism is that he presents one major symbol that embodies the main idea, and supports it with a number of minor symbols that develop and elucidate it. In The House of the Seven Gables, the major symbol is the house itself, which stands for corruption, evil, and the injustice of the past. This symbol is supported by such secondary symbols as the heart, the fountain, the
... Show MoreThe importance of this research in studying the actor life existence on the stage through the performance art;where as all the literary theatrical dimensions didn't ignore the importance of the actor's performance.
So, it is shed a light on the nature of the scenery in the actor's performance and what its representations in the temporary directions ……..
The research set off from the imitation as a human instinct to the performance of the actor in post-modernity theater; so the researcher found that there is a question must be answered which is :Is the actor live a regression state in his theatrical performance ,or that the performance of the actor connect with collective conscience of human being which is repeated in certain
God sent the Prophet Muhammad as a teacher and promising harbinger {that is sent to the illiterate messenger reciting to them His signs and purifies them and teaches them the Book and Wisdom} [Friday: 2]; the wisdom of Baos Prophet him peace be and am back to teach people, - Education and therefore his life was very rich educational tactics And has passed the Prophet in different circumstances and conditions that can be experienced by a teacher or educator in any time, anywhere; there is no case of going through the educator or teacher only finds the same or similar or likened to, or close to it in the life of the Prophet peace be upon him Prophet has lived God's peace be upon his strengths and weaknesses, victory and defeat, he lived or
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