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 (floors and transparent role in the design studios satellite channels) and presented as a study-oriented, and the research aims to identify the role of flooring transparent spaces studios satellite channels and side performative and aesthetic, and formulas design to highlight the role floors transparent spaces studios satellite channels. And highlight the importance of research, particularly in its contribution to the clarification of the concept of the relationship between transparency and performing aesthetic treatments for floors by clarifying its role in the designs of the internal spaces of the studios, as well as his contribution to the founding of the theory of looking at the base of such concepts. To achieve the object
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This world is moving towards knowledge economy which basically depends on knowledge and information. So, the economic units need to develop its financial reporting system which helps to provide useful information in timeliness for investors in accordance with the requirements of the knowledge economy and meets the needs of those investors. This research aims to revealing the reflects of knowledge economy on the approaches of financial reporting and suggesting a financial reporting model in the environment of knowledge economy, depending on combining the value approach with the events approach using database and communication technology and providing useful accounting information for all users regardless of
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In the years recently city planning projects have been confirmed sustainable high concentration on planning streets and pedestrian paths being the most prominent component of the urban structure in the city and these me and diverse departments link the city’s sectors and serve as a space for economic, service, and social activities. On the other hand, pedestrian traffic is an essential component of the various means of transportation within the city. Suffer cities in the Middle East and Arab cities in particular are neglecting pedestrian paths in the vital urban environment. Vehicle control mechanisms on roads, and changing the uses of pedestrian paths as result of encroaching on the sidewalks designated for pedestrians. Which leads to a
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It is not long time since globalization has started along with knowledge economy and, communication media and technical information control on the world. As a result serious events appeared like failure in businesses, financial corruption and shortage of administration and control.
In spite of the great efforts held by international organizations and foundations to find organizational frames that adopt independence, que
... Show More« The emergence of satellite channels has led to fundamental changes in the supposed role of television, making it a center of culture and an important tributary to social upbringing and influencing the attitudes and values of individuals and in making public opinion regarding various issues, some television programs target ordinary people at home by virtue of the nature of their subjects, where there is a large audience of viewers, who consume and absorb what is offered to them from the cultural production of those satellite channels that play with the aspirations of groups of society to find metaphysical or magic solutions to their social problems or psychological delusions. The media, through its various messages, contributes to brin
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Rheumatoid arthritis (RA) is a chronic inflammatory polyarithritic disease
associated with remission and exacerbation with different immunological
features.Rheumatoid factor(RF) screening test was used quantitatively and qualitatively
using an enzyme immunoassay (EIA), RF-isotypes (RF-IgG, RF-IgM, RF-IgA) ,
Interleukin-18 (IL-18) and Interleukin – 18 binding protein (IL-18BP) were detected
quantitatively usingenzyme linked immunosorbent assay(ELISA). Results indicated a
51% positivity in RF among RA patients and a prevalence of the RF-isotype (RF-IgM)
with the highest level at (41.6±16.3 U/ml) (p < 0.05) among other RF-isotypes at a
percentage of 85.5% , results also indicatedan elevated serum level of IL-18
Banking institutions are considered one of development foundations,and they also performe active role in supporting national economey and itsinstitutions. Banks became diversed in their activities that specialized Banksbecame one of the constituents of developing work in any activity, especiallyin investiment sector .In view of the importance of insurance sector and thenecessity of developing its divices and its working instituments, studyinginsurance Banking reality became a necessity, because insurance Companies inIraq are suffering of weakness in the level of insurance service, in addition tothe existence of a problem in the relationship between Banks network andinsurance industry.So this research aims to define insurance reality; the
... Show MoreThis research investigates the engagement of the Iraqi audience with ethnographic programs and their impact on knowledge enhancement and intellectual perspectives. A questionnaire consisting of closed-ended questions was designed and administered to a purposive sample of 400 participants who exclusively follow ethnographic programs and documentary channels. The data were transcribed and subjected to statistical analysis using the SPSS software to ensure reliability and test hypotheses. The findings revealed that Al Jazeera Documentary Channel had the highest viewership percentage among respondents for ethnographic programs, while DW (Deutsche Welle) had the lowest viewership percentage. This suggests that Al Jazee
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This aims tackles the importance of the organizational energy of the hotel organizations that search the success in the business field to penetrate in the whole tourist markets, and to draw the policies and firm rules which must be framed with the administrative strategies that contributed in creativity and achievement the targets besides provide a future vision due to its position among the competitive henceforth achieving the activity. This is what the chapters tackle in the theoretical side. Also many general questions have been arisen to determinate the importance of the research and many other special questions that express the problem of the study. To limit the levels of study alter
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This researchable paper aims to focus of the role & mechanism of market makers in Iraqi stock market through analyzing its role in other Arabian as well as global stock ones, especially in current period through activate the use of bonds, shares, and trying to create a continued price balance. Then decreasing the opportunity having gaps between highest and lowest level without reasonable causes. In addition trying to deactivate the common decision without supported information. Moreover, this paper aims to explain the rules of increasing liquidity and having balance to lead the market into positive direction. Thus, for achieving the above-mentioned requirements, such conditions should be underlined by market makers as well as t
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