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 excellent specifications of electrodes coated with lead dioxide material make it of great importance in the industry. So it was suggested this study, which includes electrodeposition of lead dioxide on graphite substrate, knowing that the electrodeposition of lead dioxide on graphite studied earlier in different ways.
In this work the deposition process for lead dioxide conducted using electrolytic solution containing lead nitrate concentration 0.72 M with the addition of some other material to the solution, such as copper nitrate, nickel nitrate, sodium fluoride and cetyl trimethyl ammonium bromide, but only in very small concentrations. As for the operating conditions, the effect of change potential and temperature as well
... Show MoreThe research aims to know the extent of the impact of the risks of foreign exchange centers represented in the risks of commitment, exchange rate changes and liquidity risks in audit procedures, and accordingly the research will provide an applied framework of knowledge that shows the relationship between the variables addressed, and the importance of the research lies in the light of its presentation of intellectual, cognitive and applied contributions On the risks of foreign exchange centers and audit procedures, the research community is represented in the banking sector. The sample included nine private commercial banks listed in the Iraqi Stock Exchange. The research relied on a time series consisting of four years that extended fro
... Show MoreThe present research deals with studying the formal variations for the Quranic calligraphy at the beginning of Islam , as being regarded from the original Arabic calligraphies which were developed later till they became as they are now, where the calligraphers in pushing for simulating these original calligraphies and knowing the methods of their writing by the calligraphers at that time.That helped in enriching and developing the aesthetic and designing valuesFor these calligraphies, as being calligraphic achievements represent transmission resulted from the objective, aesthetic and indicative vision in producing the verses according to a certain form. This has a clear impact in tendency to the technical, aesthetic and expressing develo
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Values are penetrating or interfering in the lives of individuals and groups and are connected to them in the sense of life itself, because they are closely linked to the motives of behavior, hopes and goals, and can be said that values are everything. The concept of values is one of the concepts that have received the attention of researchers from different disciplines. This has resulted in a kind of confusion and variation in use from one specialization to the other, and uses multiple uses within one specialization. Therefore, there is no uniform definition of values because they relate to individuals. Individuals differ in many things, such as perception,
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The present study aims at knowing the reasons of the student of secondary school abstention from participation in the theatrical activity, and to know the reasons that resulted in this abstention. In addition to that, the study aims at knowing the differences according to variables (gender, scholastic stage, and major of study). The sample of the study was chosen from the secondary schools in Baghdad in the random manner from Al-Karakh and Al-Rusafa districts of (147) students. The questionnaire was used to collected data.
The result showed that all the items are intense, the item of (Students do not know how to use their leisure time) obtained the hi
... Show MoreThe research aims to study the extent of the influence of the dimensions of sensory marketing on the perceptual mental image of customers, knowing the type of relationships that link the dimensions of sensory marketing with each other, no one from the researcher mentioned (as far as the researcher knows) the link between sensory marketing and mental image, from this point of view the main goal is determined, the effect of sensory marketing on the mental image taken from customers, as the research was conducted on a number of first-class restaurants represented (Chef City, Chili House, Mado, Fried Chicken Saj Alreef) and the research community was represented by the customers of the aforementioned restaurants, a
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Matrix acidizing is a good stimulation process in which acid is introduced into the reservoir near the wellbore area via the wellbore or coil tubing. In the oil industry, formation damage is a prevalent problem. Bypassing wellbore damage by producing wormholes in carbonate reservoirs is the main purpose of acidizing the matrix of the formation. When doing lab tests, scientists are looking for a wormhole-inducing injection rate that can be used in the field. Meantime the ongoing works on the Ahdeb oil field's Mishrif reservoir, several reports have documented the difficulties encountered during stimulation operations, including high injection pressures that make it difficult to inject acid into the reservoir formation; and only a few
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The centers of cities and historical quarter are exposed to a severe threat to the values of the physical and legal urban environment as a result of the value deterioration and the emergence, emergence and spread of new values on the intellectual and urban context, which generates the loss of the urban environment for its spatio-temporal continuity, flexibility, adaptation and continuity, and thus urban obsolescence, Hence the problem of the research in “the lack of comprehensiveness of studies on the phenomenon of urban obsolescence and its impact on the decline in the values of the quality of the built environment in historic
... Show MoreTransportation Sector classified as one of the services sectors which is without the production activities cannot be complete its rule. Is act asmoving actions which operate at production and non production goals for the organization and individuals insides the country and with others, that is why this sector act as one of the main which is occupied an important status on the way the economic activities and on the level of the economic institutions the transportation work on transforming all the commodities and products from productions locations to consumption location then its effect the productivity process and create the location utility and on the level of economic it considered as one of the economic supportive structure an
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In this research, damping properties for composite materials were evaluated using logarithmic decrement method to study the effect of reinforcements on the damping ratio of the epoxy matrix. Three stages of composites were prepared in this research. The first stage included preparing binary blends of epoxy (EP) and different weight percentages of polysulfide rubber (PSR) (0%, 2.5%, 5%, 7.5% and 10%). It was found that the weight percentage 5% of polysulfide was the best percentage, which gives the best mechanical properties for the blend matrix. The advantage of this blend matrix is that; it mediates between the brittle properties of epoxy and the flexible properties of a blend matrix with the highest percentage of PSR. The second stage
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