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 Intelligence of the Child in Relation to some Variables
The semantic analysis is characterized by its ability to describe the communicative pattern and its high efficiency in questioning its semantic manifestations and its deliberative purposes, which helped to understand the symbolic, contextual and cultural manifestations of the structure of the pattern, whether verbal or nonverbal. In order to highlight the role of the semiautomatic approach and its application to a sample of slogans collected from "media, social networking sites, in-kind views, media institutions, etc." to study the components and analyze the contents and highlight the signs. His boat logo is not just uttered as a linguistic transmission of a message, but as a political Tghieria actually . For example, the slogan "People Wan
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The study discusses ''The Security Intellectual Proposals of the Paris and the Welsh Schools'', which are considered one of the most important contemporary European monetary schools that emerged in the nineties of the twentieth century, and how did it approach the concept of security, criticizing the traditional trend that prevailed during the Cold War period regarding limiting the concept of security to the state or to the military aspect (National Security), and an attempt to expand the concept to economic, social and environmental dimensions, as well as political and military dimensions. The most important proposals that the Wales School provided are “Security as an emancipation policy”, “ individual security”, and “The ro
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The American vision of the Non-governmental Organizations in Iraq the topic area of that’s paper dealing with Civil Society as concept and practice, its already consider as Western concept and associated with liberalism and political development, they are many definitions of its but most significantly is all organizations, agencies, trade unions and non-governmental institutions, that’s agencies were established after 2003 and received funds from United States and UN development agencies. The non- governments organizations played a significant role as support and develop many cultural, healthy, educational, and social projects, also that’s organizations try to reduction the effects of terrorists actions especially after ISI
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The text has many connotations in the Arabic language, such as vowel points, designation, completion, etc., and the original meaning of the text is to show. The Western text has its owen independent semantic unit .The biblical texts are a mixture of what was reported by the Prophet Moses (peace be upon him) and what the authors described in terms of texts over many centuries.The meaning of the text is guidance and payment, and it is a natural connotation. The religious text for Muslims is divided into peremptory texts that are national proof. The evidence for the meaning of the text is proven by language, and it is not required that the researcher be a jurist. The approach is a factual questionnaire by the researcher according to a speci
... Show MoreThe present research aims at recognizing the difficulties and problems which hamper teachers and educators alike when using the internet for educational purposes.It discusses the benefits of the internet as a source of information or publication and as a communicative tool.Arandom sample of (30) teachers working at schools in Baghdad / Second Risafa,was selected.Three of the sample members use the internet for student project plans via internet centers, whereas 16 of them use it for chatting, emailing and research purposes.The rest of the sample have limited knowledge of the internet. The researcher used the interviewing method to gather data from
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The use of symbols is considered an important part of visual expression since ancient civilizations till the present time, and detecting the significance of these symbols is a communication means between the artwork and the recipient. The current study aims to detect the clarification of the concept of symbolic connotations, and to detect their importance in the works of the artist Eugene Delacroix, through description and technical analysis, and trying to monitor the technical aspects of these connotations and using them in forming the artwork; This shows the importance of the study in trying to benefit the scholars in the field of visual arts and the analysis of artworks in particular.
The study used the descriptive analytical appr
Theatrical techniques took upon themselves the responsibility of building and organizing the theatrical form for the various forms of performances, and it was the important tool that the show makers could rely on in carrying out the various works at the audio-visual level, and lighting is one of the most important elements of the visual formation of the image in the show, as it is related to the visual process and what it can achieve in operations The contrast that constitutes the aesthetic and intellectual values of the theatrical show, especially since the process of adjusting the element of time and the timings for receiving or delivering, moving, and the movement of the actor is what can determine the rhythm of the scene, which in it
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The current report dealt with the effect of pesticides on the ecosystem through their impact on soil, water, and microorganisms and their impact on human health. As well as this study dealt with the biodegradation process of pesticides and the organisms involved in this process, even some previous studies proved that Bacillus spp. And Pseudomonas sp. Bacteria is the most efficient in the biodegradation of pesticides, at the same time, other previous studies dealt with the environmental factors that affect the biodegradation process of pesticides. It proved that each of the incubation periods, pH, and temperature have different effects on biodegradation. Most of the studies indicated that the best incubation period for biodegradation is 7-8
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Nineteenth century Gothic literature was deeply concerned with the threats against masculinity. Perhaps one of the most important changes that happened at that time was the emergence of the New Woman model which posed a great threat against masculinity and the male role in the Victorian society. Bram Stoker’s Dracula (1897) portrays female characters who embody this transition in female roles from the domestic wife to the New Woman. This paper focuses on the female characters Mina Murray and Lucy Westenra, their roles in their society, and the different fates they face at the end of the novel, with special focus on Mina’s transformation to the model of the New Woman.