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 present work aimed to make a comparative investigation between three different ionospheric models: IRI-2020, ASAPS and VOACAP. The purpose of the comparative study is to investigate the compatibility of predicting the Maximum Usable Frequency parameter (MUF) over mid-latitude region during the severe geomagnetic storm on 17 March 2015. Three stations distributed in the mid-latitudes were selected for study; these are (Athens (23.50o E, 38.00o N), Jeju (124.53o E, 33.6o N) and Pt. Arguello (239.50o W, 34.80o N). The daily MUF outcomes were calculated using the tested models for the three adopted sites, for a span of five-day (the day of the event and two days preceding and following the event day). The calculated datasets were co
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Abstract Daily dressing changes cause distress and pain for victims of burn injuries. The study aimed to determine the effect of music in reducing the pain and anxiety of thermally burned children during routine dressing changes. This quantitative study employed a randomized controlled trial design. The participants comprised 80 children at the Specialized Burns Hospital, in Baghdad, Iraq who were divided into two groups. The intervention group were exposed to three generic musical pieces (children’s music, nature sounds, and classical music) for 10-15 minutes. The researchers used the Objective Pain Scale, State-Trait Anxiety Inventory, and physiological parameters to measure the children’s responses immediately before the dressing cha
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To identify the importance of the role of succession planning in developing human capital in organizations in light of the accelerating and dynamic events and changes in the work environment, and the research problem indicated the seriousness of employees retiring or leaving their positions for any reason and the extent of its impact on the organization in creating gaps in leadership and problems In managing the talent injection because there will be a shortage of talent, which in turn will affect the general performance of the business in the researched institute, so the importance of research appears in trying to present a set of solutions through which some of the problems facing the organization in quest
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This study deals with examining UCAS students’ attitudes in Gaza towards learning Arabic grammar online during the Corona pandemic. The researcher has adopted a descriptive approach and used a questionnaire as a tool for data collection. The results of the study have statistically shown significant differences at the level of "0.01" between the average scores of students in favor of the students of the humanities specializations. It has also been found that the students’ attitudes at the Department of Humanities and Media towards learning Arabic grammar online are positive. Additionally, the results revealed no statistical significant differences due to the variable of UCAS students’ scientific qualifications. The results stressed
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The rate of births delivered by cesarean section (CS) has gone up substantially all over the world. Post-cesarean surgical site infection (SSI) is a common cause of maternal morbidity and mortality that results in prolonged period of hospitalization with increased cost and direct health implications, especially in low socioeconomic population, resource- restricted settings, and war- related conditions with internal forced movement. This study was aimed to find incidence of post cesarean section surgical site infection withthe accompanying risk factors.Pregnant ladies admitted to department of obstetrics and gynecology at Medical City Hospital in Baghdad who had undergone CSs were followed up prospectively from first of January 2017 till end
... Show MoreMalaria is a curative disease, with therapeutics available for patients, such as drugs that can prevent future malaria infections in countries vulnerable to malaria. Though, there is no effective malaria vaccine until now, although it is an interesting research area in medicine. Local descriptors of blood smear image are exploited in this paper to solve parasitized malaria infection detection problem. Swarm intelligence is used to separate the red blood cells from the background of the blood slide image in adaptive manner. After that, the effective corner points are detected and localized using Harris corner detection method. Two types of local descriptors are generated from the local regions of the effective corners which are Gabor based f
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Seven isolates were identified as Pseduomonas aeruginosa from clinical samples. Antibiotic sensitivity test were done to determine their sensitivity to number of antibiotics, the results illustrated all that isolates were resistant to most used antibiotics. The ability of Pseduomonas isolates to produce haemolysin, protease and pyocyanin were detected in this study, all isolates had the ability to produce pyocyanin pigment, hemolysis and protease. The antimicrobial activity of the ethanolic extracts of Thuja orientalis and green tea against P.aeruginosa were investigated. The results showed that both these plant extracts have inhibitory effect against Pseduomonas isolates and it was shown that ethanolic extract of green tea was more efficie
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The research aimed to determine the role of the agricultural extension in educating farmers about the legislation on the protection of the rural environment from pollution with chemical pesticides working in the Department of Agricultural Extension and Training and the Department of Agricultural Extension in the directorates of agriculture of Najaf and Qadisiyah, and to determine the role of the agricultural extension in the axis of farmers' use of the correct methods to protect the rural environment from pollution with chemical pesticides and the axis of the reasons that lead farmers to pollute the rural environment with chemical pesticides, and to achieve the objectives of this research prepared A questionnaire in the light of rev
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This research concerns the fact of the school garden and how can we tackle this issue. The research starts with a question forwarded to those who are interested in the ministry of education matters; the question is that how is the extent of interest in the school garden project? And how it is activated in the Iraqi Educational Institution program? In addition, the analysis reveals the importance of the school garden since we, as teachers and students, suffer from seeing the view of the trashes, the wastes of school furniture, the stinking water and the weeds and how it is accumulated in the back yard of the school. To add fuel to the fire, the increase in number of the students; year after year. This increase leads to adding more classes
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