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.
The search aims to find out the most important requirements for the success of marshes investment and maximize the expected returns of investment was marked by a problem find aquestion for availability requirements necessary for the success of marshes investment has a research community owners decision in the province Maysan the most important conclusions to the search is that the investment great importance in support of the economy and raising the cultural and social level, there is no investment successful but only with configure the investment environment appropriate economic, social, cultural, political, and security ways. the most important recommendations are working on the provision of the investment environment appropria
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Granulation Technique for Gamma Alumina Catalyst Support was employed in inclined disk granulator (IDG), rotary drum granulator (RD) and extrusion – spheronization equipments .Product with wide size range can be produced with only few parameters like rpm of equipment, ratio of binder and angle of inclination. The investigation was conducted for determination the optimum operating conditions in the three above different granulation equipments.
Results reveal that the optimum operating conditions to get maximum granulation occurred at ( speed: 31rpm , Inclination:420 , binder ratio:225,300% ) for the IDG,( speed: 68rpm , Inclination: 12.50 , binder ratio: 300% ) for the RD and ( speed:1200rpm , time of rotation: 1-2min )for the Caleva
Research aims to know the impact beyond the defined in the collection. The research community is the second school students at Baghdad University and a research sample (63) students, the number of experimental group (27) students and a control group (30) students. The researcher was rewarded in variable lifetime for students and educational attainment and educational level of the parents and the educational level of mothers. The researcher has developed a test took the number of paragraphs (20). A test was true after it has been submitted to the Group of arbitrators. The test was consistent with test method used and the reliability coefficient (0, 88). Either the statistical methods used by the researcher are: Pearson correla
... Show MoreIn this paper an estimator of reliability function for the pareto dist. Of the first kind has been derived and then a simulation approach by Monte-Calro method was made to compare the Bayers estimator of reliability function and the maximum likelihood estimator for this function. It has been found that the Bayes. estimator was better than maximum likelihood estimator for all sample sizes using Integral mean square error(IMSE).
Prepared zeolite type A was used for theremoval of cesium ions from aqueous solution. The experimental data were analyzed by Langmuir, Freundlich isotherms. Various parameters, such as contact time, zeolite weight, pH, and initial concentration, were studied. The results indicated that the highest removal efficiency was95.53% at (2h time, 0.04 g weight, and pH=6.8). The results also showed that the Freundlic model fits well with the experimental results and is better than the Langmuir model.
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The Urban Residential has developed and changed in different periods of time with successive and gradual shifts, as it cast a shadow over the characterization of modern urbanism in Iraq. The semi-total absence of the governing legislation of urbanization as well as the weakness of the State's role of supervisory in addition to neglecting urban heritage contributed in offering a strange environment in relation to its traditional identity. That was increased by the pressure of the using urban environment as a result of the increasing of population as well as the growth of people’s needs. The research aims to provide an objective view for a mechanism of the application of urban legislation to monitor the implementation o
... Show MoreThe article characterizes metaphors and comparisons as a means of rethinking the phenomena of the surrounding world; two directions are named within which metaphors and comparisons are studied: 1) the linguo-classification direction combines several classifications of metaphors and comparisons, which are basically focused on comparing two denotations through the meanings of word forms that are part of the trope; 2) the theoretical and conceptual direction is associated with the concept of conceptual displacement and is the basis of the theoretical and methodological study of metaphor and comparison, i.e. the modern theory of metaphor is being formed; The main attention is focused on the comparative concept of Aristotle, which postul
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Drilling fluid properties and formulation play a fundamental role in drilling operations. The Classical water-based muds prepared from only the Syrian clay and water without any additives((Organic and industrial polymers) are generally poor in performance. Moreover, The high quantity of Syrian clay (120 gr / l) used in preparing drilling fluids. It leads to a decrease in the drilling speed and thus an increase in the time required to complete the drilling of the well. As a result, the total cost of drilling the well increased, as a result of an increase in the concentration of the solid part in the drilling fluid. In this context, our study focuses on the investigation of the improvement in drilling mud Prepa
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Media writing is accuracy writing. Clarity and concision are its predominant features. It is a writing that goes straight to the essence because it has no time to waste. Furthermore, it must be as accurate as scientific writing. It is destined for the average reader and has to be understood by everyone. However, it can be as elegant as literary writing. The variety in its forms of expression does not prevent media writing from having its own amplitude.
In short, this study is a practical approach that aims at studying different kinds of writing styles and identifying the specificity of media writing using some patterns and examples
Background: Tobacco smoking and tuberculosis (TB) are two major public health problems; Associations between smoking and tuberculosis including death from tuberculosis have been reported , A reduction in smoking could be expected to have a significant impact on TB incidence and prevalence .
Objectives: to assess the effect of smoking on tuberculosis.
Methods: This study was conducted from June 2011 to June 2012 in 200 patients, adult ( aged 17 years and more), newly diagnosed patients of pulmonary tuberculosis, at the chest and Respiratory Disease Specialized Center in Baghdad. Demographic data, presenting symptoms, data on smoking, and recurrence of disease were compared. Information on smoking status, tobacco smoking was collecte