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 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 modern stylistic lesson has become more committed to the scientific limits in which it believed, and more confident in itself, and it is no longer just a scientific procedure that helps other curricula and sciences that preceded it.
Based on this, our modest research ((a stylistic vision of the objection in the Quranic discourse)) arose to explore an artistic rhetorical phenomenon that was included in the Holy Quran text. ; Because analysis is a situation that allows us to see a lot and absorb the stranger more clearly.
And since the horizontal arrangement of the linguistic elements in which stylistically undistinguished elements meet with distinct ones, the other trend has emerged that believes that the stylistic dis
... Show MoreStubbornness is of the nature of the mean, we do not see it in the character of a person whose heart God filled with faith, wisdom and knowledge. And stubbornness does not fall into it except hearts that are arrogant, envious and objectionable, hearts that do not admit mistakes, and are not satisfied with the truth. Rather, you see humiliation,humiliation and shortcomings in returning to Him. He loves corruption * Except in humiliation, humiliation and shortcomings, the stubborn fall, even if they are proud when it is said to him, "Beware of God", pride takes him for sin, so his count is Hell, and his misery.
traces of stubbornness :key wor
... Show MoreChristianity rejected abortion, since its inception, it took a luck against abortion, although there is no mention of it in the Bible, as there is no explicit text for abortion in the Old or New Testament and that the early Christians considered abortion a sin in all stages, and beliefs included abortion as an act of murder. What is forbidden in the Ten Commandments is “Thou shalt not kill”, and it is understood that killing here is either plundering one’s personal life (suicide) or stealing another person’s life (killing), or stealing the life of a person who has not yet been born (aborting fetuses). Based on the above, it was necessary for individuals to search for (Abortion in the Christian Religion / Descriptive Study) The resea
... Show MoreThe history of the arts is closely connected with the history of humankind, since it is impossible to separate our scientific and artistic advances’. Therefore, the current research focuses on the close bond between art and other disciplines. The connection of the arts to the sciences is unequivocal and undisputed; the contributions of artists to the various scientific domains are clear. If one scrutinises the ability of artists to participate in building societies, one will find that the arts have penetrated deeply into a range of products and inventions, starting with the pencil and ending with the missile. The artist’s contributions play a part in the minutest of details across all fields of industry: production, craftsmanship, me
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This research aims to identify the nature effect of some mechanisms governance in the Accounting Conservatism for a sample of the practices of companies (banks) in the Iraq Stock Exchange and identify any of this mechanics most effects in the accounting Conservatism. To achieve this objective the use of all of it (the size of the board of directors, management ownership, ownership concentration, the auditor's report) as independent variables was used model Basu revised to measure the Accounting Conservatism , which was considered a variable follower with taking into account the effect of the control variables represented by the (company size and leverage) of a sample of listed on the Iraq Stock Exchange companies for the pe
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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 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 hero traditionally has such admirable traits as courage, fortitude,
chivalry and patriotism. In the literary works, the hero is the leading
character and the pivot around which all the characters and the events
revolve. The characteristics of the hero usually reflect the cultural values
of his time. Because, in each age, Man's attitudes towards himself and the
world change, different images of the hero emerge.
In Greek Mythology, the hero is frequently favoured by the gods;
therefore, he is himself semi-divine. The Greek hero is of princely birth
and is endowed with good physique, exceptional strength, skill in
athletics and battle, energy and eloquence, like Odysseus who is the hero
of the Odyssey, long
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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