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 research addresses the most important elements of the ancient Iraqi heritage represented by architecture and plastic arts being the direct means that preserved the heritage due to the ease of preserving them and the speed of circulating them and diversity of their topics. Through the features of these elements, the research problem has been defined in the form of questions including: what are the most important elements of the ancient Iraqi heritage? What are the plastic arts? What are the most important topics adopted? What is the concept of palm in the ancient Iraqi heritage? What is the evidence for that?
Has it been employed in the Iraqi contemporary art? What is the evidence for that? How to employ it in the arts and t
the research was exposed to a study the importance of the role of the supportive entities in providing the useful information to the tax administration and their ability to extend the level of the tax base of taxpayers, through the improvement of the tax payers determination and their tax settle for the purpose of increasing the tax revenue, and shed light on the legal evidence through which these entities become officially assigned to perform a supplementary task to the General Committee for Taxes GCT, to help it to perform its task efficiently, and to study the reasons of the weak cooperation of the supportive entities and their reluctance to provide useful information which leads to limiting the tax base.
The research data hav
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The research aims to know the extent of the impact of the risks of foreign exchange centers represented in the risks of commitment, exchange rate changes and liquidity risks in audit procedures, and accordingly the research will provide an applied framework of knowledge that shows the relationship between the variables addressed, and the importance of the research lies in the light of its presentation of intellectual, cognitive and applied contributions On the risks of foreign exchange centers and audit procedures, the research community is represented in the banking sector. The sample included nine private commercial banks listed in the Iraqi Stock Exchange. The research relied on a time series consisting of four years that extended fro
... Show MoreHomosexuality is one of the important topics that have emerged in recent times in the Islamic and Arab world, as the topic was in the past one of the taboos and majorities and one of the topics that arouse disgust and is talked about secretly and practiced secretly as well.But today, with international and organizational support for this anomaly and its misrepresentation under the name of gender once again and gender again. It began to spread in all countries of the world, including Islamic and Arab countries, and with the presence of associations and influential people in the legislative and judicial authorities of countries that protect and defend homosexuals. Writing on this subject has become a necessity and a duty; to warn against the
... Show MoreHighlighting the role of the movement and its dramatic dimensions, as an artistic product, whether at the level of cinema or television in general, and the stages of its influence within the structure of the cinematographic scene in particular, had an effective role in the continuation of the structure of the event according to its dramatic and aesthetic process, and from this the research problem crystallized in the following question: What is How the kinetic diversity of the camera in the structure of the cinematographic scene is achieved to achieve the maximum possible benefit by extrapolating all opinions in line with the objectives of the research, the research presented and two topics and the introduction were divided, which
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Examination of the blood and the alimentary canal of moorhens in two sites around
Baghdad area in the middle of Iraq showed that 38% of the examined birds were infected with
one or more of the following parasites, Haemoproteus baghdadensis, H. gallinulae
(Protozoa), Cyclocoelum mutbile (Trematoda), Diorchis inflata, Ligula intestinalis (Cestoda),
Amidostomum fulicae and Porrcaecum sp. (Nematoda) .The stomach analysis revealed that
the bird is omnivorous in feeding including wid range of invertebrate animals with some plant
origin food items.
Concentrated research topic in the study of variables key to the work of offices of inspectors Amyin ، a (re- design function، and performance Organisational ) and took this message to know the nature of the relationship and the impact of the dimensions of the re- design function as a variable interpretative through its dimensions، is ( the diversity of skill، selecting the task ، the importance of task، autonomy، feedback )، and performance Organisational variable responsive through two dimensions are ( effectiveness ، efficiency )، and in order to test the research hypotheses were absorbed variables in the form of a questionnaire and were questionnaire primary means of gatheri
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In this research, damping properties for composite materials were evaluated using logarithmic decrement method to study the effect of reinforcements on the damping ratio of the epoxy matrix. Three stages of composites were prepared in this research. The first stage included preparing binary blends of epoxy (EP) and different weight percentages of polysulfide rubber (PSR) (0%, 2.5%, 5%, 7.5% and 10%). It was found that the weight percentage 5% of polysulfide was the best percentage, which gives the best mechanical properties for the blend matrix. The advantage of this blend matrix is that; it mediates between the brittle properties of epoxy and the flexible properties of a blend matrix with the highest percentage of PSR. The second stage
... Show MoreEnvironment 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
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
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