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 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
... Show MoreRefuse 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 MoreThe 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
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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Iraqi industrial units face strong competition due to many problems including1- high production costs2- weak interest in studying the market3- lack of government support for their products4- dumping the market with imported products with specifications and a competitive price as well as adopting the traditional cost system in calculating costs that do not provide appropriate information for pricing decisions Which requires studying and analyzing these problems and dealing with them by adopting modern technologies so that they can compete, so the research aims to show the knowledge bases of technology Activity- Based Costing, with an indication of the role of technology Activity- Based Costing in rationalizing the tax In, and the
... Show MoreBackground: Cardiomyopathy (CM) is a cardiac muscle disorder that can lead to heart failure (HF). It has several phenotypes, including dilated, hypertrophic, and restricted. Pro-inflammatory cytokines play a crucial part in the development and advancement of CM. Objective: This study aimed to measure the concentration of certain cytokines [Interleukin- 1β (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF-α)] in the serum of Iraqi patients with CM. Materials and Methods: Sixty CM patients and 30 healthy individuals with age ranged from 40 to 70 years old were enrolled in this study through their presence at Iraqi Center for Heart Diseases, Ghazy Al-Hariri Hospital for Surgical Specialties in the Medical City in Baghdad. The st
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Bathyplectes curcurlionis (Thomson) is the sole parasitoid encountered in west Baghdad parasitising larvae of alfalfa weevil Hypera postica (GylIenhal). Percent of parasitisation did not exceed 8% in 1989 and 1990 and overall rate of parasitisation was 5%. Additional reduction in percent of parasitisation caused by presence of the fungal pathogen Erynia phytonomi. High survival percent of weevil's larvae under the study conditions explains why this insect is a key pest of alfalfa. Suggestions were made to inhance the role of B. curcurtionis in controlling the weevil.
Background: It's believed that HBD-3 is involved in the tissue remodeling process of articular cartilage. Also, HBD-3 has anti-inflammatory properties. Objectives: The purpose of this study is to assay human beta-defensine-3 (HBD-3) in serum from rheumatoid arthritis (RA) patients and investigate its correlation with proinflammatory cytokines. Methods: In this case-control study, fifty-eight RA patients were aged 20–65 years, and 29 age-matched healthy subjects (HS) had no inflammatory rheumatic diseases. The disease activity score-28 joint erythrocyte sedimentation rate (DAS28-ESR) was used to measure RA activity. CRP, ACPA, HBD-3, TNF-α, and IL-1β were assessed using the enzyme-linked immunosorbent assay technique (ELISA). Res
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