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.
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The importance of this research has been to rationalize the cost of producing maize seeds through the followers of modern techniques and methods in agricultural activities such as genetic engineering for increasing production efficiency of maize seeds as well as the importance of calculating seed cost rationalization through the ABC system and thus rationalizing government spending. The research is based on one hypothesis in two ways that the use of genetic engineering on maize seeds works to: one - increase production efficiency of seeds and savings in agricultural inputs. 2. Rationalize the costs of examining and planting maize seeds. In order to calculate the costs will be based on the cost system based on activities ABC. The research
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Media plays an important role in shaping the mental image of their audiences for individuals, groups and organizations, States and peoples. It is the window through which overlooks the masses on events and issues, and in the light of their exposure to these means are their opinions and impressions.
Despite the importance of direct experiences in shaping opinions, drawing pictures and impressions, it is inevitable to rely on these means as individuals can not engage in direct experiences with thousands of events, issues and topics that concern their community and other societies.
There is no doubt that media is of great importance at the present time, because of its significant impact in the management of the course of pol
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The identity of the cultural identity of the party (the ego and the other) during a series of questions subject to the transformations of history and the process of culture, the search of identity and its characteristics within the novel discourse calls to address the cultural impact communication discourse aims to reveal the functional and intellectual benefits that contributed to the formation of cultural identity, and stand at the most important manifestations And the secretions that mimic a world remains part of it present in the imagination of the producer of the text is moving in accordance with the holistic perception of the world embedded between the lines of the trial.The question of identity as an intellectual dimension in orde
... Show MoreThe research discusses the issue of attribution to the verb, because the Arab scholars are unanimous in preventing attribution of the verb, because it is always informed of it, and does not inform about it, but this consensus violates the linguistic use. The research discusses this matter.
t. The current study was conducted on the umbilical cord blood of newborns in the Banks Hospital in Baghdad, Diyala, and Khalis in Diyala, where the study included 90 samples of blood, and samples were collected for the period from the 1st of October;2020 to The first of February;2021 AD, where the study included measuring levels of interleukin-6;Adiponectin,glucose and bilirubin in the blood, comparison study between the study variables with the child's weight (greater than 3 kg),(less or equal 3 kg),the mother's age (greater than 25 years, less or equal to 25 years),the sex of the child (male, female).The results of our study showed that there were no significant differences between the variables of the current study between the two sex
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Abstract
This research aims to determine the role of the quality of higher education in achieving organizational excellence at the universities of Baghdad and Al-Nahren, was based on research on the main hypothesis is:First:- There is correlation and between the quality of higher education dimensions (continuous improvement, measurement and analysis, the culture of the organization, optimal use of resources , customer satisfaction) and organizational excellence dimensions (strategic planning, focusing on the market and the customer, information and analysis, the effectiveness of operations, processes and resources), Second:- Second, there is the impact of relationship sig
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Summary of the jurisprudence research
Praise be to God, Lord of the Worlds, and prayers and peace be upon the Master of the Messengers, our master Muhammad, and upon his pure family, and his ignorant and ignorant companions, and those who followed them in goodness until the Day of Judgment.
Then:
The many jurisprudential aspects that the Shafi’i imams said are of great importance, because these aspects are nothing but the opinions of venerable jurists who have reached a high degree of knowledge until they have become among the owners of faces. And among them are the Shafi’i jurists, the jurists may differ among themselves, either because there is no text about their imam in a
... Show Moreتحتل أدوات السياسة المالية (الإنفاقية والإيرادية) مكانة مهمة بين أدوات السياسات الاقتصادية الأخرى لما تتمتع به من تأثيرات اقتصادية واجتماعية على مجمل النشاط الاقتصادي .
وفي بحثنا هذا سنركز على الآثار الاجتماعية لأدوات السياسة المالية (الإنفاق العام والإيراد العام) لما للتنمية الاجتماعية من أهمية متزايدة في عالمنا اليوم خاصة فيما يتعلق بمقوماتها غير المادية المتمثلة في خدما
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