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 discus throwing event is one of the complex events in athletics, and it is characterized by a performance method that depends on the principle of mechanical moments and requires high explosive capabilities of the thrower in addition to some physical specifications,which depends effectively and effectively on the biomechanical aspects in generating large moments during rotation. The importance of the research is highlighted by the interest in athletics, especially the effectiveness of the discus throw and the continuation of its development process, the importance of kinetic analysis in revealing the most important weaknesses and strengths of shooters, and the importance of explosive power And the moments generated in the rotation of the
... Show MoreThis study intends to examine the content of photo coverage related to the Gulf Cup (Gulf 25) as presented by Iraqi photojournalists on Instagram between 02/01/2023 and 27/01/2023. Utilizing content analysis, the two researchers employed the survey method to evaluate 674 digital photos posted by seven photojournalists specializing in this sporting event, which concluded with the Iraqi team's victory in the city of Basra.
Key findings from the study include:
1. The Category "Photos from the Gulf Cup matches" predominated, accounting for 291 instances or 42.794% of the total.
2. Photojournalists exhibited a keen interest in capturing images of attending fans and documenting celebrations surrounding th
Background: Normal occlusal features of primary dentition are crucial for normal development of the permanent dentition. Breastfeeding is an important factor for both general and dental health of children. Aim: The aim of the present study is to assess the impact of the breastfeeding duration on the prevalence of normal occlusal features of the primary dentition among preschool children in Baghdad. Materials and Methods: The sample was 630 Iraqi children (270- boys, 360 girls), aged 3-5 years selected from four kindergartens in Baghdad city. The study was carried out through questionnaire and clinical examination. Normal occlusal features were examined as the presence or absence of interincisive spaces (IS) and primate spaces (PS), termi
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Brainstorming is considered as one of the manners that develop learners' mental abilities. Besides, it can help learners get a lot of ideas and thoughts. And by following applied steps to answer the problem concerned, the researcher carried out this practical study aimed at:Developing the ideas of design of third year students/Institute of Fine Arts/Evening Studies- Baghdad/First Rusafa by employing Brainstorming mechanism to develop the ideas of design of institute students in designing the technical advertisement and to achieve the authenticity of the goal of the research, Department of Plastic Arts/Institute of Fine Arts/Evening Studies/Baghdad-First Rusafa was chosen as a case study for the research. It embraced (20) students who rep
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The research studies the main variables for the concept of sharing in knowledge in one of the most important control agencies in Iraq, which is (The Federal Board of Supreme Audit). Also, the quality of the controlling businesses by the Board in light of the major challenges that facing the fight against signs of cheating and administrative and financial corruption for offices submitted to controlled and auditing, with the increasing and intensification of these appearances. In order to enable the Board to cope with this situation, has to be thinking hard about how to achieve excellence, progress and development to face these situations, through the application of sharing in knowledge for the financial controller, and then achiev
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TRIPS agreement was The first to apply protection by patents. However, this type of protection, which grants exclusive and monopoly rights to patent owners, came at the expense of developing countries which are considered rich in biodiversity and also at the expense of traditional and poor knowledge of modern technologies. The release of new plant varieties has led to the emergence of biopiracy and looting of the rights of developing countries without a license
Many researchers ' views about class selectors popular theatre in the world, whom he found in political deals popular presentations while others in comedy shows or dealing with social problems, or simply build a direct pattern of relationship between actors and audience were popular, and certainly the Iraqi popular theatre has its own parameters, structural differences result of Iraqi society at all levels, so the researcher found the search problem is to answer the question that (what are category classes Or within the category of Iraqi popular theatrical-in the play of - the string and the bird which un – example ) , then select the aim has his research of detecting those parameters, and search scientific significance as to scholars
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This study attempts to provide an approach analysis for the news, depending on the bases and principles which conceptuality semiotic researchers of this field first of them «A. J. Gremas» for the theory of «narrative discourse analysis», to more clarify we tried to apply it on a published press- news, to concludes the most important steps and methods that are necessary to follows gain more understanding of the press- news.
The ritual is a Sunnah between the two prostrations, not as some of the worshipers do, where he made it in the last tashahhud when the tasleematin, and it may be in the last tashahhud.
The assumption is Sunnah and most of the scholars say that in the middle tashahhud session as we have shown through research.
The Turks are Sunnah as well, and it is at the end of the prayer, whether it is double, triple or quadruple, whether it is naval or NAFTA, whether it is urban or travel, which is the view of most scholars from the three imams and others.
If we say weighting, say the audience of the three imams (Malik, Shafi'i, and Ahmad) is the most correct, and it is also the son of values, and if we say the choice is as Ibn Rushd said: by
MII Al-Itabi, WH Abdulameer, OSS Al-Mashhadani, Review of International Geographical Education Online, 2021 - Cited by 1