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 agricultural sector suffers from many risks and natural disasters, such as droughts and heavy rains that cause floods, as well as hail and agricultural pests, etc., that threaten agricultural activity and reduce it, which leads to the failure of farmers and peasants for fear of being subjected to continuous losses. Nevertheless, we notice almost complete reluctance to move towards agricultural insurance, due to the dependence of farmers on the government, which adopts the principle of compensation instead of agricultural insurance when natural disasters happen despite the difficulties and financial hardship as well as the suspicion of corruption that haunt the compensation process and this represents the most important problem for resea
... Show MoreThe aim of this research is to show the importance of the effective use
of the internet in academic libraries; to improve the services and to increase
the competence of librarians.
The research has given some recommendations to improve the quality
of services and the need for cooperative network among academic libraries.
Medina was according to its importance and religious status the basis for the emergence and emergence of historical schools, it is the emigration of the Prophet and the presence of the companions , and it was natural to shine the beginnings of historical codification, whether in the process of collecting and codification of the verses of the Koran or the Hadith, and once the pillars settled Islam in the Islamic areas until the Muslims began to go to the city to provide a broader knowledge of the Islamic religion and everything related to the biography of the Prophet and the significance and actions, and in return took the jurists and preservation and readers of the companions and followers to undertake the task of teaching in work
... Show MoreThis paper is a part of a cytological studies of the genus Bromus L. in Iraq . Cl number for 103 specimens ropro^eming l^species determined . The course of meiosis including an analysis of chromosome configuradon for 27 collections belonging to 8 species were investigated . Meiosis was regular in most species . Tetraploid for B.scoparius L. (new cytotype ) and hexaploid ?'or " Kunth. were re^rted for the first time, cytological findings were supported the view of maintaining the closely related species B.danthoniae Trin. and B.lanceolatus Roth, as distinct species .
Hepatitis is one of the diseases that has become more developed in recent years in terms of the high number of infections. Hepatitis causes inflammation that destroys liver cells, and it occurs as a result of viruses, bacteria, blood transfusions, and others. There are five types of hepatitis viruses, which are (A, B, C, D, E) according to their severity. The disease varies by type. Accurate and early diagnosis is the best way to prevent disease, as it allows infected people to take preventive steps so that they do not transmit the difference to other people, and diagnosis using artificial intelligence gives an accurate and rapid diagnostic result. Where the analytical method of the data relied on the radial basis network to diagnose the
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Were studied changes in the concentration of copper, iron and zinc in blood serum of one hundred patients with chronic kidney and treated dialysis blood were also measured the level of calcium kidney and phosphate Calciotropic in serum of these patients took samples of blood from these patients before and after treatment dialysis vessels as well as the statement of changes in those standards Alkimaahiatih Results were compared with twenty-five healthy people (control group)
The sacred totem is one of the social phenomena that occupied the ideas of researchers, and took up a wide area of their research, and it is one of those phenomena that emerged from one of the translations of the Tabu; Who took a psychological and anthropological analysis Because it is one of the social practices, and the main focus of it is the human group and its source is religion. Therefore, this research came with demands, the first of which is to give a semantic concept of the Tommy sanctuary, and then the analytical aspect by standing on the sacred things in the Qur’anic text that God Almighty sanctified, and the third requirement is to examine what people have sanctified, as an analysis of the verses that have
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Abstract This study seeks to deal academically with how the EU treats clandestine immigration, through adopting a purley security approach, based on the European understanding of security threats posed to the security of communities and States in EU at all levels. So they agreed upon criminalizing this threat within the bloc while using repressive tools and steps to limit illegal immigrants flow to European territories. Accordingly, the EU gave the phenomen a security character. So it takes it from low politics level , that of employment and economic field to that of high politics, as a new security problem lying within a new security language embraced by ruling European elites, in other words EU touched on this issue as a speech act emp
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Abstract
This study aims at clarifying the current performance appraisal system in government units and the extent to which they contribute to the development of the performance of these units by evaluating and measuring the performance of these units on an ongoing basis to subject their services to an assessment and measurement process in order to improve the efficiency of these units to reach their objectives efficiently and effectively. (Iraqi hospitals) by trying to determine the possibility of the government accounting system in the process of evaluating performance, through the comparison of financial performance for successive years and different hospitals using the financial and non-financial model of the evaluati
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