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.
Objective: To evaluate the therapeutic activity of probiotics mixture of Lactobacillus plantarum and Lactobacillus acidophilus towards Cryptosporidium infection in experimentally infected mice. Oocysts of Cryptosporidium were separated from the stool of humans to infect mice. Methods: Forty male albino mice were split equally into four groups, every group contained 10 mice, the group I (early treated group), were treated from the 1st day from infection to the 11th post-infection, group II (late treated group), were treated from the 4th day from infection to the 15th post-infection, and group (III) (untreated group), were mice considered as a positive control group. Results: It was showed that daily application of a mixture of L. plantarum w
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Drought is a major abiotic stress, severely affecting the physiological processes and growth of plants. The present investigation aimed to evaluate the impacts of drought stress with three periods for irrigation: every 3 days(control), every 6 days, and every 12 days and foliar spray with different concentrations of ascorbic acid (0, 75, 150, 225) mg.L-1 on the wheat plant. Pots experiment was conducted as a completely randomized design with three replications in the green house, Department of Biology, College of Education for Pure Science (Ibn Al- Haitham), University of Baghdad, during the growing season, 2018 – 2019. The results indicated that drought stress decreased plant growth and hastened the senescence of flag l
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Purpose: Determining and identifying the relationships of smart strategic education systems and their potential effects on sustainable success in managing clouding electronic business networks according to green, economic and environmental logic based on vigilance and awareness of the strategic mind.
Design: Designing a hypothetical model that reveals the role and investigating audit and cloud electronic governance according to a philosophy that highlights smart strategic learning processes, identifying its assumptions in cloud spaces, choosing its tools, what it costs to devise expert minds, and strategic intelligence.
Methodology:
The correct and sincere process of socialization is working on appropriate social climate in
which this process is the provision, and the climate is achieved in the presence of a positive
environment free of negatives and contradictions, but when there is a socialization processes
inadequate and contradictory was not based on the principles of punishment and reward nor a
balance between methods soft and intensity of treatment and interaction with small and
adolescent does not require intensive social care formulas do not create the conditions
essential items required by the successful and effective socialization, the young and the young
people who are going through in such Altanisah and educational operations will be
Refuse derived fuel (RDF) is considered one of the most important types of low cost thermal energy which can be tapped in the industry, especially the cement industry in particular being the need of high thermal energy during the production processes, and in this paper we have implemented the use of a derivative of the fuel RDF as a substitute for gasoline , to reduce production costs and thereby achieve production efficiency, and the methodology used in this research statistical analysis as well as the use of the cost of kaizen target for the purpose of reducing costs and achieve production efficiency, and this has reduced the cost total cement production by which led to reduce total costs of cement production by 8.4% and an incre
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تتبلور فكرة البحث حول التوصل لنوع العلاقة التي تربط التعليم الالكتروني خلال جائحة كورونا برفع المهارات التكنولوجية للأساتذة والطلاب، وتبرز أهمية البحث في ان نجاح الوصول لهذه العلاقة يمكن الإفادة منها في تغيير منهجية تطوير المهارات التكنولوجية مستقبلا وذلك باعتماد الجوانب التطبيقية الفعلية بدلا من الدورات وورش العمل والتي قد لا تضاهي الطريقة العملية في رفع مستوى المهارات المختلفة سواء التدريسية او التكنو
... Show MoreJalal Jaafar Al-Awqati is a military figure who played a significant role in developing the Iraqi Air Force after the July 14, 1958 revolution. His personality crystallized during his studies. He was a thoughtful person, a good communicator, a man of few words, and held firm principled positions. He was known for his unique way of thinking. He was not violent in his daily dealings. He believed in democracy as a political doctrine and saw it as the best means and sure guarantee for solving the country's problems.
The current research aims through its chapters to verify the relationship and impact of strategic leadership as an independent variable in the marketing performance as a respondent variable, in a leap cement plant, and try to come up with a set of recommendations that contribute to enhancing the practice and adoption of the two variables in the organization under discussion. And based on the importance of the research topic to the community, and to the researched organization and its members, the analytical and analytical approach was adopted in the completion of this research, and the research community included a leap cement plant in Anbar Governorate, while the research sample was represented by (department heads, and people o
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The current research aims to highlight the role of social networking sites in the dissemination of scientific knowledge and the importance of their use by researchers, and the researcher relied on the descriptive approach and the survey method. Among the data collection tools are the questionnaire and paper and electronic sources. Among the most important results that the research came out with: The number of the subscribers’ sites was (14) sites, and the most used social sites for receiving and Disseminating Scientific knowledge are: Facebook, Telegram, WhatsApp, Viber, Messenger and YouTube. All respondents receive tacit knowledge (Exchange of Messages and News) through social networking sites, and few of them do not receive explicit kn
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The aim of this research is to highlight the importance of reducing the cost of a flight ticket by using information technology and the Internet, in the process of purchasing tickets for electronic flights, and to shift from the traditional method of purchasing and payment operations to the electronic method, to reduce the financial and non-financial risks associated with the traditional purchase process, as well as saving the cost Time, effort and money for the customer, and the researcher used the deductive approach in linking the variables (Internet of Things technology and reducing the costs of air tickets) wi
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