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.
First: People’s need for advocacy:
Calling for a legal necessity for all people, regardless of their races, colours, tongues, and culture, to explain the truth, spread fear, bring benefits, ward off evil, regulate a person’s relationship with his Lord, and his relationship with creatures, so that he knows his money and what he owes.
All of creation is in dire need of the call to God’s religion with insight due to their inability to reach out to goodness, righteousness, guidance, and success on their own. Man is limited in thinking in this universe, limited in his resolve, unable to know what will improve his affairs in the two worlds. His need for religion is one of the necessities of his life, and one of the comple
... Show MoreThere are many reasons made Basra a good defense, first of all was the
establishment of the famous Arab tribes, like Bakir bn. Wail and Tamim. Besides there were
A lot the armed forces. In addition to that the strategic place of Basra. All these reasons
played a good part when the war broke out.
The Arabic tribes played a good part in the war to engaged Persians, and prevent
them from sending any helps to their armies against the Kufain who were fighting Persians in
the North of Iraq. While the Basrain army aiming to Conquer the south of Iraq.
Basra become the first strategic place for the Islamic movement of the conquers.
Latter on Kufa and Bahrain were the second and third.
The Muslims guranted the pupils of
Abstract
Social media has thrived recently and public organizations at Thi-Qar governorate across different levels are experimenting with launching government social media (GSM) to facilitating two-way interactions between the government and its citizens. Both scholars and practitioners are focusing on understanding the key success factors related to the create of GSM. This study aimed to identify the key success factors by exploring the formation mechanism of individuals’ continuous usage intention. Through the theoretical perspective of the uses and gratifications theory. We identify the gratification factors that stimulate users’ continuance intention toward GSM. Furthermore, we draw upon the stimulus–organism–
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abstract
the research discussed a stage of strategic management. The strategic of the evaluation of the proposed strategy through feedback is to ensure that it is implemented with the least possible variation. The research aims at evaluation a proposed strategy for the Ministry of Planning for the years 2018-2022 in line with the orientations of the state, taking into account the surrounding environmental conditions. It relies on scientific bases and steps to formulate the strategy The extent of the strategy suitability was tested through a set of statistical means and its objectivity was verified through a survey of a number of specialized experts who were selected in accordance with the principle
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(2)
This study is one of the descriptive studies, where the researcher used the survey method, which seeks to provide an accurate and appropriate description of the main and sub-categories of the content of the research for television documentaries on the Iraqi satellite channel, relying on the research questions and objectives to analyze the content of the documentaries according to the approach referred to above. The objectives of the research were summarized to identify the function of the documentary programs in Al-Iraqiya channel to detect the crimes of the former regime, to know the frameworks highlighted by the documentary programs in Al-Iraqiya channel to reveal the crimes of the former regime, to identify the extent of the circ
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Abstract:
Interest in the topic of prediction has increased in recent years and appeared modern methods such as Artificial Neural Networks models, if these methods are able to learn and adapt self with any model, and does not require assumptions on the nature of the time series. On the other hand, the methods currently used to predict the classic method such as Box-Jenkins may be difficult to diagnose chain and modeling because they assume strict conditions.
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Improvisation is that spontaneous automatic achievement which is formed by a new cognition that is not based on something prior to it or a previous cognition. It is instantaneous. Whereas in art, improvisation also inters in all types of applied and performance arts as a foundation for launching and initiating it in music, painting, cinema, television and theater. In order to study the improvisation of the actor, the researcher put forward a theoretical study that included two sections. The first section is (the improvisation concept) and the second section is (improvisation in the show). The researcher, in the research procedures, took an intentional sample that was represented by the theatrical show (Rehearsal in Hell Play) and after t
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The aim of the research is to find out the effect of the SPAWN strategy on the life skills of second-intermediate-grade students. This study stage represented the research community within the intermediate and secondary governmental daytime schools affiliated with the Directorate of Education of Diwaniyah. The experiment was applied in Al-Razai Intermediate School on a sample of second-grade intermediate students, including 66 students distributed into two groups: (32) students within the experimental group and (34) students within the control group. The two groups were equivalent with a number of variables (chronological age, intelligence test, previous information test, life skills scale). The results indicated that the two groups were
... Show MoreIt is very necessary for the political theater to be within the space of every theatrical performance, so that the theater carries the diverse and enlightened values and cultures of this world. political theatre. In the first chapter, the researcher dealt with (the methodological framework), which includes the research problem identified by the researcher with the following question (the functional diversity of the directorial vision in the political theater)
Importance, purpose, limits and seal by defining terminology.
In the second chapter, the researcher dealt with the theoretical framework on two topics, the first (transformations of directorial vision in theatrical performance) and the second topic (aesthetic experiences i