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.
This research deals with the topic of "the status of women" in the literature of Sufism. The researcher cites a bundle of mystical yarns, and examples of verses and poems from this high literature that look at women with reverence and appreciation. The researcher tried to find an appropriate explanation and away from the arbitrariness of the symbols used by the poets of Islamic Sufism In their poems.
The research is considered a comparative study of the Arabic and Kurdish dialects, by selecting six famous poets from the literature of literature, three of them from Arabic literature, and the other three from Kurdish literature, so the research is di
... Show MoreFive heavy metals, namely Cd, Cu, Fe, Mn, and Pb in the surface water and through the water column were studied at 10 selected stations in the Razzazah lake and Karbala drainage canal for the period between November 1990 to October 1991*. pH and total hardness were also measured. Lead was found to be the highest in concentration as overall average values, followed by an manganese, iron, copper then cadmium at the surface as well as along the water column. All the studied metals were below or close to the maximum allowed limits of Iraqi standards for inland water. The spatial and seasonal variations were discussed.
This research deals with the topic (the position of women) in the literature literature, and the researcher cites a bouquet of woolen yarn, examples of verses and poems from this fine literature that looks at the woman with respect and appreciation. In their poems.
The research is a comparative search for Arab and Kurdish literature, by selecting six famous poets in the literature, three of them are from Arabic literature, and the other three are from Kurdish literature, and thus the research is divided into two subjects and six demands.
Finally, the researcher tried to set a brick that would be an entry point to find an indicative explanation and a suitable explanation that would break those symbols and signs that caused the exp
In the present work, asphaltenes and resins separated from emulsion samples collected from two Iraqi oil wells, Nafut Kana (Nk) and Basrah were used to study the emulsion stability. The effect of oil resins to asphaltene (R/A) ratio, pH of the aqueous phase, addition of paraffinic solvent (n-heptane), aromatic solvent (toluene), and blend of both (heptol) in various proportions on the stability of emulsions had been investigated. The conditions of experiments were specified as an agitation speed of 1000 rpm for 30 minutes, heating at 50 °C, and water content of 30%. The results showed that as the R/A ratio increases, the emulsion will be unstable and the amount of water separated from emulsion increases. It was noticed that the em
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In this paper, investigates the biosynthesis of gold nanoparticles (AuNPs) by biochemical method using Myrtus communis leaves extract as reducing agent and Chloroauric acid (HAuCl4) as precursors. X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and FTIR were used in addition to UV-visible spectroscopy (UV) in order to characterize the AuNPs. The biosynthesized AuNPs exhibited inhibitory effects on alpha amylase and alkaline phosphatase in sera of patient with type 2 Diabetes Miletus and the sera of healthy control subjects; the inhibition percentage with alpha amylase was 72 % and 45 % for patient and control group respectively. Oral consent obtained from the most of patients and healthy subjects before them being under
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A program in Visual Basic language was designed to predict the type of radio storm that emitted from Jupiter at specific Local Time (LT) from two different Iraqi locations (Baghdad and Basra), such storms result from the Central Meridian Longitude (CML) of system ??? for Jupiter and phase of Io’s satellite (?Io). Some of these storms are related to position of Io (Io- A,B,C,D) and others are unrelated (non-Io-A,B,C,D) to its position. The input parameters for this program were user specified by determining the observer’s location (longitude), year, month and day. The output program results in form of tables provides the observer with information about the date and the LT of beginning and end of each type of emitted storm. Two Io-storm r
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This article discusses some linguistic problems that arise when translating the Holy Quran from Arabic to Russian. We analyze lexical, syntactic and semantic problems and support them with Examples of verses from the Qur'an, since the Qur'an is the word of Allah. It contains prayers and instructions full of both literal representations and figurative comparisons. The identification of linguistic and rhetorical features challenges translators of the Holy Qur'an, especially when translating such literary devices as metaphor, assonance, epithet, irony, repetition, polysemy, metonymy, comparisons, synonymy and homonymy. The article analyzes: metaphor, metonymy, ellipsis, polysemy.
The purpose of the current research is to identify the most important problems that primary school students suffer from inside and outside the classroom from the point of view of their teachers. A sample of (100) male and female teachers was chosen from the Rusafa\ second Directorate for the academic year (2018-2019). The research tool was prepared after reviewing literature related to the issue of problems and difficulties facing students or students in the school stage and even at university. The researcher reached several results that were discussed in the fourth chapter, with a set of conclusions based on the results of the research, and come up with several recommendations and suggestions.
A field experiment was carried out to find out the effect of some herbicides(Pallas, Crash, U46) on the companion weed to three cultivars of the oat crop (Shefa, Hamel, and Pimula) and the yield and its components of these cultivars. The results showed the superiority of the two treatments of spraying weed herbicides (T1 and T2 ) by giving the best results, as they recorded the lowest number of weed plants after 30 days of spraying reached 1.44 and 1.67 plant/m2 . Besides, the lowest weed dry weight was 0.11 and 0.00 g/m2, and the highest inhibition percentage in dry weight was 98.44% and 100.0% of the two treatments, respectively. The treatment T2 was also superior by giving the highest control percentage of 93.28% compared to the compari
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