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 difference The doctrines of the four jurists were built in Achieving the purposes of Tesper in Islam
Abstract
The basic orientation of the research is an attempting to apply the cost determining method according in the contract sector projects for Al- Iraq ceneral company, that this subject has a big value according to its modernity and its influence on the future and the eaning of the company.
The research aims to find out the effect of the method for determining cost based on the activity in determining the cost of the construction sector projects.The research was conducted in Iraq General Company for the implementation of irrigation projects. Bani search on three assumptions, the first is (that the application of the method for determining the cost on the basis of
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This research is aiming to analyze the impacts of the current budget in Iraq by using the Government Finance Statistics Manual (GFSM) , the research is based on hypothesis: (There is an impact on the using of the Government Finance Statistics Manual (GFSM) In public budget in Iraq) .This hypothesis was demonstrated by using the questionnaire, a number of conclusions were reached, the most important being the lack of terminology adopted in the government accounting system and the Iraqi financial and accounting manual as a result of their adoption of the monetary basis for the lack of accounting terminology that meets t
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This study aims to prepare educational sessions for the strategy (team-pair-solo) in practical volleyball lessons for female students and identifying its effect on learning the accuracy of the spiking skill in volleyball. An experimental design with experimental and control groups was employed on a purposive sample of (30) female students who were to constitute (42.254%) from their community represented by the sophomores at the College of Physical Education and Sports Sciences for Girls / University of Baghdad who are in good standing in the morning study for the academic year (2022-2023), whose total number is (71) students. According to the determinants of the experimental design, participants were divided into two equal groups, a
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This research aims to demonstrate the nature and concept of the Corona pandemic, its implications for the global economy, and the management and performance of companies in particular. Additionally, the research intends to measure the impact of the Corona pandemic on companies' financial performance. Listed on the Iraqi Stock Exchange, which has finished compiling its year-end financial statements for 2019-2020. The investigation arrived at several findings, the most significant of which was that most businesses were not prepared for such a crisis technologically or to develop human resources to deal with this pandemic. In addition, most companies experienced a decrease in their financial performance as a direct result of the Corona pandemi
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The aim of the research is to prepare practical volleyball lessons by using the four pillars strategy for middle school students, and to identify the effect of the four pillars strategy in performing the transmission and volleyball skills in the second intermediate students, to assume that the two researchers assume that there are no statistically significant differences between the results of my skill performance tests Sending and preparing tribal and remote volleyball for the experimental and controlled groups, and there are no statistically significant differences between the results of the performance of the transmission and preparation skills of the volleyball between the two experimental and control groups, and the research co
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The study of images in the cognitive field receives considerable attention by researchers, whether in the field of media and public relations or in other humanities. Due to the great importance in shaping trends of public opinion, especially trends that individuals and the behaviors of people, institutions or ideas are determined by forming images that they hold in their minds towards these persons or institutions. Modern enterprises have realized, whether they are governmental ministries and official departments or non-governmental organizations as civil society organizations, the importance of studying the dominant image in the minds of the masses and make decisions and draw plans to configure this image as these institutions wishes.&n
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The theater benefited from the concept of (hypertext) to create different virtual worlds. The four chapters of the research included the first (methodological framework), the second (theoretical framework) came in two sections (hypertext, its concepts and applications) and (hypertextual space in theatrical performance), and the investigations resulted in indicators, including:
1- Hypertext is interacting interactively, but it is organized by correlation as a basic feature that defines it with different manifestations.
2- The hypertext combines the word with other formative elements that reduce a set of tagged information (word, image, light, shadow, color, number).
In the third chapter (research procedures) (Lord play) was
Drama is one of the means of transmitting human experiences, as it presents within it the life ideas and visions of the spectator, who is subject to their influence on him, robbed of the will in front of its charm and various display arts, which invade him with its dimensions and affect his references, and this art form is based on stories revolving around personalities involved in events that have grown As a result of the struggle of two conflicting opponents, or two opposing forces or emotions generated as a result of a voluntary conflict, as this dramatic conflict represents the most important elements of those events, as it is embodied in an inevitable scene that emerges from other scenes, and this scene is sometimes subject to the
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Thanks and gratefulness be to Allah , the most merciful , and prayers be on his messenger and our prophet mohammed and his descendants.The voices have great influence on the diversity of methods of complaints and implication in the Qur'anic expression through
their inspiration , forms and notes. They also have influence on performing semantic and psychological condition of the emitter . that is because of the connection between the complaints and human behavior and emotions , since it is considered as the outlet by which the human expresses his repressed desired and instincts . he resorted to it " when he is helpless physically and mentally i.e. he cannot reach his goals or satisfy his needs." Complaints come from deprivation , social