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 Mediating Role of Cobit 2019 in Managing the Relationship Between Qualitative Characteristics of Accounting Information and Information Asymmetry
After the success of the reforms Keynesian save the capitalist system from collapse and to apply the concepts of state intervention in economic activity in order to revive aggregate demand to achieve the purposes of macro-economic policies which draw their scope of economic (John Keynes) theory of effective demand, which created the new role of the state away from the classical concepts. Valley transmission role of the State of (State Guardian) to the process of state overlapping that increased and social functions have become responsible for raising the standard of living of classes with limited incomes, in particular, and the rest of the classes in general, through the expansion of the delivery of public servic
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The objective of this study is to explain the role of credit policies in agricultural development of Iraq during the period 1979-1989 which were represented by the policy of co-operative agricultural bank the organization that responsible to finance agricultural sector for various reasons. It has been shown that there was no clear credit policy existed during the period concerned due to the differences between loans from year. The loan growth rate was low in general comparing with objectives of the agricultural development plans, a low production rates comparing with loans paid, the growth rate of average number of trees in each donum and the growth rate of livestock number was also low.In conclusion there should be a clear plan for cred
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This study tries to examine a model involving human resources management practices, employees’ outcomes, governmental support, and organizational performance of small businesses in Malaysia. It was hypothesized that HRM practices will be positively related to the organizational performance (financial and operational), and that employees’ outcomes would serve as a mediator in the relationship between HRM practices and performance. Also it was hypothesized that the governmental support will be positively related to organizational performance. The statistical results on data gathered from a sample of 265 small manufacturing businesses will demonstrate the nature of relationships among the study variables. Theoretical and practical
... Show MoreSocial networking sites represent one of the modern communication technologies that have contributed to the expression of public opinion trends towards various events and crises of which security crisis is most important being characterized by its ability to influence the community life of the public. In order to recognize its role in shaping opinions of the educated class of the public that is characterized by a high level of knowledge, culture and having experience in dealing with the media. Its advantage is that they have an active audience by expressing their views on the situations, events, and news published on them as well as expressing their attitudes and sympathy with the events. So a number of questions are included in the ques
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The optical energy gap(Eopt) and the width of the tails of localized states in the band gap (?E) for Se:2%Sb thin films prepared by thermal co-evaporation method as a function of annealing temperature are studied in the photon energy range ( 1 to 5.4)eV.Se2%Sb film was found to be indirect transition with energy gap of (1.973,2.077, 2.096, 2.17) eV at annealing temperature (295,370,445,520)K respectively. The Eopt and ?E of Se:2%Sb films as a function of annealing temperature showed an increase in Eopt and a decrease in ?E with increasing the annealing temperature. This behavior may be related to structural defects and dangling bonds.
Abstract The results of isolation, morphological and microscopic diagnosis, Chromic Agar, Vitik technology and Bact Alert showed that the diagnosis of fungi isolated from blood samples of end-stage renal patients who did not undergo dialysis and those who underwent dialysis was 60 samples for each type. The total number of fungal isolates isolated from people who did not undergo dialysis was 26 pathogenic fungal isolates, with a percentage frequency of 43.33%. In this study, 4 genera of pathogenic fungi were identified: Candida spp, Rhodotorula spp, Cryptococcus spp. and Aspergillus spp. The number of Candida isolates reached 13 isolates, with a frequency of 50%. The results also showed that the diagnosed species from the genus Rhodotorula
... Show MoreThis study aimed to assess orthodontic postgraduate students’ use of social media during the COVID-19 lockdown. Ninety-four postgraduate students (67 master’s students and 27 doctoral students) were enrolled in the study and asked to fill in an online questionnaire by answering questions regarding their use of social media during the COVID-19 lockdown. The frequency distributions and percentages were calculated using SPSS software. The results showed that 99% of the students used social media. The most frequently used type of social media was Facebook, 94%, followed by YouTube, 78%, and Instagram, 65%, while Twitter and Linkedin were used less, and no one used Blogger. About 63% of the students used elements of social media to l
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The study seeks to clarify the role of International Auditing Standard No. (320) of the relative importance in determining responsibility for planning and implementing the process of auditing financial statements and expressing neutral technical opinion through the analytical procedures of the auditor, whose responsibility is to obtain appropriate and reliable audit evidence that helps the auditor to form a general conclusion about whether The financial statements were consistent with the auditor's understanding of the entity. The relative importance contributes to defining the important accounts that help to set priorities for the auditor to set the necessary analytical procedures for these accounts. One of the most important co
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