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.
Background: In the Thermafil as a root canal obturation, system little is known about the effect that varying rates of insertion have on the adaptability of thermoplasticized GP and the amount of apical extrusion. Materials and methods: thirty simulated root canals were obturated with thermafil obturators and Apexit Plus sealer at three different insertion rates. The obturated canals were sectioned at three different levels, the sealer average film thickness for each section was calculated and the amount of apical extrusion for each canal was conducted. Results: the higher adaptability was seen with the faster insertion rate while the slower insertion rate showed fewer tendencies to cause apical extrusion. Conclusions: the intermediate i
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The current research aims to find out (the effectiveness of teaching TRIZ theory in the expressive performance and the development of creative thinking among preparatory school students)
To achieve this, the researcher adopted on an experimental design is located in women with partial seizure experimental designs field in order to achieve the goals of the research, has sample consisted of two divisions seminars Mentzmtin in junior high school Diyala for Boys, and divided the sample of (60) called on the two groups, the first pilot of ( 30) student, and the other officer and number (30), student, and studied researchers experimental group theory TRIZ, while he studied the officer in the traditional manner, the researcher conducted a pa
The research aims to know (the effect of the pdeode strategy) in acquiring historical concepts among the fourth-grade literary female students in the history module. To achieve the goal of this research, the following null hypothesis was formulated. There is no statistically significant difference at the level of (0.05) between the average scores of the experimental group students, who study history according to the PDEODE strategy, and the average scores of the control group students who study the same module in the traditional way of the historical concepts acquisition test.The researcher chose the experimental method for the current research and adopted the experimental design of partial control with a post-test, which depends on the
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Abstract
The current research aims to identify the effect of using a model of generative learning in the achievement of first-middle students of chemical concepts in science. The researcher adopted the null hypothesis, which is there is no statistically significant difference at the level (0.05) between the mean scores of the experimental group who study using the generative learning model and the average scores of the control group who study using the traditional method in the chemical concepts achievement test. The research consisted of (200) students of the first intermediate at Al-Farqadin Intermediate School for Boys affiliated with the Directorate of General Education in Baghdad Governorate / Al-Karkh 3 wit
... Show MoreThis research discusses one of the largest and most important issues of a doctrinal and philosophical dimension at the same time, which is the issue of man’s freedom to choose his actions, and thus his responsibility for those actions, by looking at the nature of these acts, their being and the origin of their creation. He showed that they were created in man by force, and that he was their original creator, and that they were among the creatures of the God Almighty God like others, but they are attributed to man through acquisition. So to the first saying went Jahmiyya or Jabariyya, and to the second saying went to fatalism in the past, and the existentialists shared with them in the modern era, and to the third saying went to the Sun
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Objective: In order to evaluate the effect of different typed of Separating Medium on the roughness of the fitted
tissue surface of acrylic denture base.
Methodology: Chosen three types of separating medium (Group A Tin foil), (Group B Detery Isolant),(Group C
Cold Mould Seal),used 30 samples of hot cure acrylic resin ,10 samples for each group, after complete curing of
these samples , Profilometer device was used to measure the surface roughness of each sample in all groups.
Results: Using One Way ANOVA Test and LSD test, the results were highly significant in differences among all
groups. Although (Group A) showing lest roughness, (Group B) showing a satisfactory result of roughness, While
(Group C) Showing the hig
this research concern with material function subject by using it in Baghdad education in formational places , because it considered as one of the most important spaces which needs a material presentation for the interior consistings that shares with prepairing the right mode for thos who use these spaces, regarding to that this research includes four chapters: Chapter one: concern with the research problem represented by the following question: can we use the material to place the hole spaces of information place ? So the aim of the research seems very obvious in functioning the material these places, and to take a close view on the importance of the research the theory , implementation and objective limits also concerning the terminolog
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