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.
В статье рассматриваются понятие наглядности и ее классификация, эффективное применение принципа наглядности, возможность и преимущество использования наглядности и современные инструменты ее реализации в ираке.
Вследствие глобальных изменений во всем мире изменилась и роль иностранного языка в системе образования. Современный человек, шагающий в ногу со временем, не мыслит себя без зна
... Show MorePrograms and performance budget represents a sophisticated method of public budget numbers, which includes all allocations to be determined for each job or activity within a government entity, which is analyzed according to their needs and costs, and this method can be applied using one of the cost accounting techniques, which is the technique of analyzing the value chain that reduces costs by avoiding activities that do not add value and enhance activities that add value to the economic entity, the current research aims to develop the budget system in government entity by using the budget of programs and performance as a tool for planning and monitoring events and activities, thereby reducing the waste of public money by reducing unnecessa
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Metalloendo peptidase is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones, including atrial natriuretic factor, giucagon, enkephalin, substance p, neurotensin, oxytocin, and bradykinin. It is also a major enzyme for the degradation of beta-amyloid. This study aimed to measure enzyme activity and compare it with other biochemical changes in sera patients with diabetic nephropathy. The study included 35 pathological samples of people with diabetic nephropathy, 24 samples from males and 11 samples from females, as well as the same number of healthy people as a comparison group of 15 males, 20 females, with the ages of both groups of patients with diabetic nephropat
... Show MoreAbstract The current study is a theoretical study that aims to underline the role of picture books as a serious genre of children's literature in raising children's understanding of English literature and life concepts; especially for non-English speakers. Unfortunately, most Iraqi people have developed a social phobia of learning English since childhood. This phobia is resulted from the heavy traditional reading and writing assignments as well as hard exams. Therefore, this study suggests incorporating more interesting literary material like picture books that would bring pleasure and help in raising children's love and cognition of English Language. More significantly, it calls to replace the old curriculum with a more vital one
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Abstract The current study is a theoretical study that aims to underline the role of picture books as a serious genre of children's literature in raising children's understanding of English literature and life concepts; especially for non-English speakers. Unfortunately, most Iraqi people have developed a social phobia of learning English since childhood. This phobia is resulted from the heavy traditional reading and writing assignments as well as hard exams. Therefore, this study suggests incorporating more interesting literary material like picture books that would bring pleasure and help in raising children's love and cognition of English Language. More significantly, it calls to replace the old curriculum with a more vital
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The aims of study is to detect the inhibitory effect of Saccharomyces boulardii and Lactobacillus acidophilus on Escherichia coli that has been isolated from recurrent urinary tract infection in women. The sensitivity of E.coli isolates to antibiotics had been studied and the most resistant E.coli isolate to antibiotics had been studied .The cup assay was used on nutrient agar and Muller-Hinton agar to detect the inhibitory activity for each S.boulardii yeast grown on YEGP media and L.acidophilus grown on MRS media in which the result showed a high inhibition activity for each of them .Also in this study the adhesion property of E.coli had been evaluated in the presence of S.boulardii at concentration of 1×109 and L.acidophilus at conc
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The objective of the research is to identify the efficiency of risk management in various names at Baghdad International Airport in the face of various risks (financial - technical - human - natural ..) facing the sample of the search of the General Establishment of Civil Aviation and the Iraqi Airways Company where the researcher identified the hypothesis that summarizes There is a significant significant correlation between risk management, risk management and risk review and assessment. The researcher used the means of research from observation and interviews with the relevant officials in this field, as well as used the questionnaire and distributed a sample of 170 employees in the field of risk management (SMS Department) in Iraqi A
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Purpose/ to build clear perceptions about the level of the effects of organizational failures on the competitiveness of dairy factories and the role of dynamic knowledge capabilities in minimizing these impacts
Mythology/ Design approach Use deduction approach, the research was conducted in four dairy factories in Baghdad (Abu Ghraib, Agriculture, Halal and Ayon Al-Rafidain). It was applied to a sample of (155) individuals representing a sample of the research community from factory owners, managers, Engineers, technicians and experienced workers in the dairy industry. The questionnaire was used as a main tool for collecting data, information and statistical tools in the extraction, testing and analysis o
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