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.
Cumhuriyet Üniversitesi Fen-Edebiyat Fakültesi Sosyal Bilimler Dergisi | Volume: 48 Issue: 2
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
Random laser gain media is synthesized with different types of dye at the same concentration (1×10-3 M) as an active material and silicon dioxide NPs (silica SiO2) as scatter centers through the Sol-Gel technique. The prepared samples are tested with UV–Vis spectroscopy, Fluorescence Spectroscopy, Field Emission Scanning Electron Microscopy (FESEM), and Energy Dispersive X-ray Diffraction (EDX). The end result demonstrates that doped dyes with silica nanoparticles at a concentration of 0.0016 mol/ml have lower absorbance and higher fluorescence spectra than pure dyes. FESEM scans revealed that the morphology of nanocrystalline silica is clusters of nano-sized spherical particles in the range (25-67) nm. It is con
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The rent is one of the sources of investment that generates returns for the owner of the housing unit, and it is also one of the importance expenditure for the tenant.
The importance of this research comes in addressing the deficiency in the field of analyzing the factors affecting the rental value of residential units, which affects many segments of the population of Baghdad.
The aim of this research is analyze and evaluate related variables on the rent value of residential units in neighbourhood 409 in city of BAGHDAD, which is a hypothesis that: There are a set of variables affecting the rental value, including those related to the internal environment of the dwelling, such as: income level, plot area, building area, n
... Show MoreThe article presents the results of studies of the species composition of phytopathogens of winter soft wheat grain affected by ear fusarium. For the first time, studies were conducted using a complex of electron microscopic, molecular genetics, and mycological methods. The species F. graminearum dominated in all samples (frequency of occurrence 42.8%). The species F. avenaceum (23.3%), F. sporotrichioides and F. equiseti (8.8% each) were noted with high frequency. Next in descending order of frequency of occurrence: F. oxysporum, F. boothii, F. poae, F. proliferatum, F. accumatum, F. incarnatum, F. vorosii, F. tricinctum, F. cerealis, F. sambuticum. For the first time, 7 species were found for the plain zone of the Pre-Caucasus: F.
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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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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 MoreThe utilization of artificial intelligence techniques has garnered significant interest in recent research due to their pivotal role in enhancing the quality of educational offerings. This study investigated the impact of employing artificial intelligence techniques on improving the quality of educational services, as perceived by students enrolled in the College of Pharmacy at the University of Baghdad. The study sample comprised 379 male and female students. A descriptive-analytical approach was used, with a questionnaire as the primary tool for data collection. The findings indicated that the application of artificial intelligence methods was highly effective, and the educational services provided to students were of exceptional
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Aim of the Study: The paper aims at identifying the extent of the role of strategic leadership represented by its four dimensions (administrative, transformational, political, moral) in fulfilling the requirements of university governance (Context, message and Goal, Management orientation, Independence, Issue, Sharing)
Methodology: A survey is applied to (107) members of the teaching staff at the college of Administration and Economics/ University of Mosul. To achieve the goals of the study, the researcher makes use of a number of tools such as: questionnaire, statistical tools and methods (repetitions, perce
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