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.
Background: The Covid-19 pandemic changed the world; its most important achievement for education was changing the approach from traditional to virtual education. The present study aimed to investigate the role of virtual education networks on mental health of students including personality, beliefs, scientific, and cultural dimensions, in selected countries.Methods: This was an exploratory and applied study. According to the phenomenology strategy, theoretical saturation occurred after 24 semi-structured and targeted qualitative interviews with teachers from Iran, Iraq, Syria and Lebanon, in 2023. Quantitative data was collected through a researcher-made online questionnaire with 423 participants. Teachers with at least a Bachelor’s degr
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The study investigates the possibility of utilizing public interactive sculptures to enhance physical activity in Saudi Arabia. The paper uses a descriptive-analytical methodology to identify the characteristics of interactive sculptures promoting physical activity in public areas as follows: The size and space of the work area are appropriate to the type of physical activity that is achieved, and the importance of the work site in the city and its relation to the surrounding space, identifying participants at the same time and their relationship to ensure safe interaction, as well as the relationship between the esthetic and intellectual concept of working in the community. The study concludes that three technical proposals were present
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As the child is growing up, he goes through different phases which will be accompanied by physical and psychological changes. These changes set the basis for processes of designing and making children's clothes which in turn give its required benefits and meet the physiological, psychological and community needs. That will help provide the child with healthy physical and psychological growth.
The aim of this research is to recognize the decoration of clothes by colors and drawings and its role in clothes' richness and children's education. The research limits are objective, The limits are for female (3-5) years old. The research was done in teaching kindergarten in the college of education for women in 2016. The researchers found many
Concert place high school in the community Keep pace with societal change and what is going through Iraqi society from the wars and occupation and the sectarian and ethnic conflict and authoritarian policies and Dictator ship .
This is the circumstance of the most important historical stages that require .
Precision sons is Keep up with the progress and development and the advancement of the educational march .
The school is a social institution that organizes the members of society all walks of life and their habitats working on crafting members of the extraordinary alve of progress At the multiplicity of functions and tasks school pequires members qualified scientific and practical Becomes complementary members seek progress a
Economic units can benefit from the cleaner production strategy, which aims to reduce the environmental impact of economic activities while improving efficiency and profitability. Accordingly, the aim of the research was to clarify the knowledge foundations of cleaner production costs and to indicate their role in reducing the costs of poor quality (the costs of failure). A set of conclusions has been reached, the most important of which is that cleaner production has achieved a reduction in the costs of external failure, represented by the costs of guarantee, by an amount of 12,339,000 dinars. Contributes to reducing the costs of failure, and based on the conclusions, a set of recommendations were presented, the most important of w
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(3)
The research aims to demonstrate the impact of internal audit in Iraqi economic units on enhancing social performance reports, through the statistical models used, as a survey list (for the independent variant) of the search, which contains five axes of each axis, contains a set of The questions were prepared on the basis of the standards issued by the Institute of Internal Auditors (IIA) and were distributed to a sample of internal auditors, as for (for the approved variable) the researcher obtained numerical data represented by the financial statements of the research sample and used statistical models such as model (Kolmakrov-Smirnov) is a good match (goodness of fit) which assumes that the data is distributed naturally as wel
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The research aims to test the impact of servant leadership in management information systems, as well as to identify the level of servant leadership practice and management information systems in the Directorate of Communications and Information Systems in the Iraqi Ministry of Interior, in terms of the importance of the research variables to the directorate and the sample community, as the research adopted the exploratory analytical descriptive approach In his achievement, through a survey of the opinions of an intended quota sample of (266) individuals, By adopting the questionnaire as a main tool for data collection that includes (44) items divided into the two research variables, As well as conducting open interviews to identify the pro
... Show MoreBackground: This study is to evaluate the necessity of prescribing prophylactic antibiotics for nasal packing in spontaneous epistaxis. There are few published papers of infective complications in such patients.
Methods: This prospective study analysed 149 consecutive patients admitted to AL-Kindy teaching hospital with spontaneous, epistaxis, who underwent nasal packing over 2 years period . in the first year, 78 patients received prophylactic antibiotics , In the second year 71 patients were not given prophylatic antibiotics. Exclusion criteria included antibiotics prescribed for unrelated pathology and post-operative epistaxis. Signs and symptoms of acute otitis m
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This study aims to explain the role of green target costing technique in improving the relationship with suppliers in a sample of industrial companies listed on the Iraq Stock Exchange. The descriptive analytical approach was used, where a questionnaire was designed that included a set of questions that were directed to a sample of 84 individuals including production managers, finance managers, quality managers, and purchasing managers in these companies. The study uses some statistical analyzes such as correlation analysis and regression analysis to analyze the questionnaires. The study finds a positive impact of the green target costing technique on improving the relationship with suppliers. The results indicate that the relation
... Show MoreThis study examines the role of strategic planning in reducing youth migration in Iraq by promoting sustainable development. It highlights how comprehensive strategies can address economic, political, and environmental drivers of migration, offering practical alternatives for a stable future for Iraqi youth.
A descriptive–analytical qualitative approach was used, combining a literature review with a structured workshop of 100 political science students. Data from focused group discu