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 current research aims to find out the effect of strategic sensitivity in enhancing organizational immunity at the leadership levels in the Iraqi Ministry of Education, as the strategic sensitivity variable includes two dimensions (strategic foresight and strategic Insight), and the organizational immunity variable addresses three dimensions (organizational learning, organizational memory and organizational DNA). The main purpose of this research was related to the extent to which the Ministry’s immunity was achieved through the role played by strategic sensitivity. A sample of (349) individuals was selected . The questionnaire was relied upon to collect data, and the number of questionnaires suitable for analysis was (330). Re
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This study aimed at highlighting the role of small and medium enterprises in bringing about economic development in Jordan. The study examined the impact of the number, size of investment and the number of jobs provided by these enterprises on the rate of growth in gross domestic product (GDP) as an indicator for economic development. To achieve its objectives, the study adopted descriptive and quantitative analysis. A linear multi regression model was developed with a growth rate of GDP as dependent variable and the number of institutions, size of investment, and the number of job opportunities as independent variables. The study concluded that each increase by one small or medium enterprise lead to an increase in the rate of gr
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This study examines the role played by the Iraqi media in promoting the values of citizenship and the dimensions of the various sectors of Iraqi society, an important segment namely university youth section.
The study intended to identify “the role of the Iraqi media organizations in promoting The sense of citizenship among young Iraqi university”, through: -
1. Identifying the most important Iraqi media, which works to promote the dimensions of citizenship and values.
2. To identify the extent of the contribution of the Iraqi media in promoting citizenship in dimensions (patriotic belonging, legal, political, economic, social, cultural).
The study provided a set of hypotheses, namely:-
The most important contemporary issues which related to the survey of the influence of communication development technology to land use sustainability. The research aims to explain the changes that happened in the quality & land use activities performance by understanding the transformations due to modern technology and its impact on current uses and its impact on changing functional relationships between those uses to create new combinations or hybrid uses.Research will follow the analytical descriptive approach in presenting the problem of research. Research has several conclusions & recommendations, one of conclusions is the change of the place concept and its relation to changing the concept of land use and its sustai
... Show MoreBackground: Low-level laser therapy (LLLT) has been extensively applied to improve wound healing due to some biostimulatory properties presented by laser arrays apparently able to accelerate the repair of soft tissue injuries. However, the role of proinflammatory interlukines not been studied yet. IL_1 ? represent one of the most important poroinflammatory interlukines that involved in wound healing. The goal of this study was to investigate the effect of 790-805nm diode laser on the expression of IL_1 ? during wound healing in mice. Materials and Methods: Standard-sized wounds (1.5cm) were carried out in the face of 96 white albino mice. Half of them underwent LLLT treatment (360 J/cm 2) at 790-805 nm delivered immediately after wound pro
... Show MoreThe main objective of this research is to identify the role of job satisfaction in influencing strategic agility through knowledge sharing. The researcher used the descriptive as well as the analytical approach in the completion of this research by collecting data by means of the questionnaire as the main tool on a sample of the General Company for Food Industries' employees, whose number reached (76) individuals. Moreover, some statistical methods were employed to process the data; including the arithmetic mean, Standard deviation, simple linear correlation coefficient (Pearson), simple linear regression, and the median variable test. It was represented that there is a significant and essential impact of job satisfaction in influen
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The current study aims to demonstrate the role of strategic renewal in enhancing organizational immunity through strategic renewal mechanisms represented by (Reanimating, Rejuvenation, Venturing, and restructuring). The main idea of this study relates to the extent to which organizations’ immunity is achieved through strategic Renewal mechanisms, by measuring these dimensions with Organizational immunity represented by organizational learning, organizational memory, and organizational DNA. The study population was the headquarters of the Iraqi Ministry of Education, and the sample included (330) individuals from the upper, middle, and lower leadership levels. Several statistical methods were used to deal with the results of the questionna
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