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.
Global Navigation Satellite System (GNSS) is considered to be one of the most crucial tools for different applications, i.e. transportation, geographic information systems, mobile satellite communications, and others. Without a doubt, the GNSS has been widely employed for different scientific applications, such as land surveying, mapping, and precise monitoring for huge structures, etc. Thus, an intense competitive has appeared between companies which produce geodetic GNSS hardware devices to meet all the requirements of GNSS communities. This study aims to assess the performance of different GNSS receivers to provide reliable positions. In this study, three different receivers, which are produced by different manufactur
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The achievement of world peace is a humanitarian demand that humanity has sought since its existence. Despite the international and regional efforts to achieve this demand, it is still reaching its desired ambitions if conflicts, contradictions, and internal and external wars continue to justify us clearly in terms of ethnic, religious and sectarian conflict. The revolution of informatics and the impact of globalization opened a new era of communication and openness and the negative and positive impact of others, which re-published and distributed values, ideas and new cultures Some of them carries extremist ideas urging violence and destruction and other abolition, it became necessary to follow policies and reward The culture of peace,
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The concept of self is considered one of the important dimensions in the human personality, because feeling of self is an important characteristic in this phase from the psychological point of view.
The first source which forms the concept of self is the physical image, where the built and appearance of the body is considered among the vital matters which determine the person's image of himself/herself.
The current research aims to:
1) Identify the level of physical self concept at the kindergarten children.
2) Identify the level of psychological self concept at the kindergarten children.
3) Iden
... Show MoreOver last decade, rapid growth in economic and population accompanied with depletion of the energy resources lead to serious impacts on environment and humanity. This development coupled with active constructions, which in some examples ignore the impact on the environment and human activities. Therefore, principle of sustainability has required in order to reducing this negative impact on the environment and the humanity.In developing countries, it seems that there is a huge gap between the current construction practices and sustainable principle, which need more attention to clarify and define the problems in order to find suitable solutions before it comes more difficult and expensive. The study aims to choose one of the develo
Global Navigation Satellite System (GNSS) is considered to be one of the most crucial tools for different applications, i.e. transportation, geographic information systems, mobile satellite communications, and others. Without a doubt, the GNSS has been widely employed for different scientific applications, such as land surveying, mapping, and precise monitoring for huge structures, etc. Thus, an intense competitive has appeared between companies which produce geodetic GNSS hardware devices to meet all the requirements of GNSS communities. This study aims to assess the performance of different GNSS receivers to provide reliable positions. In this study, three different receivers, which are produced by different manufacturers, were fi
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من أجل فهم دور سلطنة عُمان في المفاوضات الإقليمية والوساطة وحل النزاعات يجب تقدير سياستها الخارجية، والتي سيتم تقييمها من أجل فهم كيفية نشأتها وتشكلها وأثر ذلك على مواقفها السياسية طوال سنوات حكم السلطان الراحل قابوس بن سعيد. وتقع عُمان في منطقة مضطربة، وقد طُلب منها في عدة مناسبات أن تعمل كمفاوض أو وسيط في الصراعات الإقليمية. سيبحث هذا البحث في كيفية قيام السلطنة بالوساطة الدولية، خاصة في الصراع الأمريكي
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This research deals with the perceived and the imagined in the texts of Yusef Al-Sayegh, considering language as the most important source in literature and theatrical criticism, and given the importance of the subject, the researcher monitored many philosophical and psychological opinions and theories related to (the perceived and the imagined), and they were discussed and their compatibility with the Iraqi theatrical t As for the second chapter, where (the theoretical framework), it included two topics, and the first topic was about the concept of the perceived and the imagined, and the second topic was about Youssef Al-Sayegh and the structure of the theatrical text.
In the third chapter, where (research procedures), the research
The issue of the other in the graphic design and specifically the advertising constitutes a cognitive study of the structure of the intellectual expansion in the cognitive and intellectual creative systems because of the implicit and declared embodiment it provides within the mechanisms of reading in the advertising design that appeared according to the other and through the embodiment of the textualism, the difference and the binary opposites is nothing but a reaction to the design thought and what constitutes of the manifestations of the other in advertising design. Based on the above, we review this study (Manifestations of the Other in Graphic Design) to clarify the topic through four chapters. The first chapter included the research
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Requires economic work finding built institutional paint strategies and policies are formulated general economic and clarity in its stated objectives and the involvement of all economic institutions, political and stakeholders to discuss all the issues of economic, financial, monetary and analyzed for the purpose of renewal energies and determine the duties and responsibilities, leaving full freedom to the private sector in the formation of institutions to carry out his duties economic, and that the institutional structures to create the right climate for the implementation of its economic policies, which would facilitate the task of the private sector, and this h
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Recently, Knowledge Management Systems (KMS) consider one of the major fields of study in educational institutions, caused by the necessity to identify their knowledge value and success. Hence, based on the updated DeLone and McLean’s Information Systems Success Model (DMISSM), this study set out to assess the success of the Perceived Usefulness of Knowledge Management Systems (PUKMS) in Iraqi universities. To achieve this objective, the quantitative method is selected as the research design. In total, 421 university administration staff members from 13 Iraqi private universities were conducted. This study highlights a number of significant results depending on structural equation modeling which confirms that system, information, and s
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