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 study aimed to get acquainted with kindergarten teachers in the development of
emotional intelligence in children, To achieve this a study too, which consisted of 40 items,
within four areas was condncted: (managing emotions, emotional knowledge, empathy, social
networking) The study tool was applied to the sample amounting (200) teachers of the
kindergarten teachers in the province of Jerash and after analyzing the results statistically
using arithmetic averages standard deviations and variance analysis quartet the following
results were reached :
- presence of statistically significant differences at the level of (α =0,05) is attributable to the
impact of the educational level in the areas of empathy and so
The importance of operational risks increases with the increase in technological development, the development of banking operations, the extent of banking compliance, and the attempt of many banks to achieve quality in banking services. And the extent of the position occupied by Iraqi banks for banking compliance and reducing operational risks. The Basel Committee (2) paid its attention to operational risks and the interest of international banks to follow policies that work to ensure banking compliance and cover operational risks, because of its role in reducing losses due to increased costs and achieving an increase in profits. Realizing and working to confront the best possible and traditional methods, that some risks Operational problem
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Background: The thyroid gland, a vital endocrine organ, the thyroid gland synthesizes and secretes hormones, such as triiodothyronine (T3), thyroxine (T4), and calcitonin. The pineal gland produces and releases melatonin, which is stimulated in the dark and suppressed in the presence of light. Objectives: This study aimed to assess how melatonin influences adult male rats’ thyroid performance.Methods: Eighteen adults male Wistar albino rats (Rattus norvegicus) (approximately 12-14 weeks old and weighing 220±10 g) were randomly divided into three groups, each containing six rats, and were treated for 30 days as follows: The control group (A) received distilled water (DW). The A1 group received 10 mg/kg body weight (B.W.) of melatonin oral
... Show MoreBackground: the conflict in opinions about the dental and skeletal changes induced by classII malocclusion activator therapy is still present. The aim of this study was to assess theskeletal and/or dental outcomes of treating moderate-severe skeletal class II division Imalocclusion by the activator.Materials and methods: the sample consisted of pre and post treatment records(cephalometric radiographs) of 11 iraqi adolescent patients (7 females 10-11 years old, and 4males 12-13 years old).Results: the results showed significant skeletal and dental changes that reflected significantimprovements in the cardinal features of class II (overjet, overbite, ANB angle, and loweranterior facial height).Conclusion: correlation of the overjet, overbite,
... Show MoreFaced economic units face the option of restoring the capital budget annually, and the information provided for the preparation of these budgets, including financial and non-financial aspects have an important impact in the numbers of these budgets, and these units differ in the ability of their own accounting systems to maintain this information. The aim of this research is to investigate the volume of accounting information that is relied on and the reasons for the differences between one unit and another in the various economic sectors in the Iraqi environment.
The most important results of the research is the weakness of the adoption of decision makers in the Iraqi environment and lack of sufficient attention in the decision-
... 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
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)
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 MoreA vital instrument to foster the long-term goal of high-quality education has developed in the form of digital technologies. The educational system has been found to be significantly impacted by these technologies. The recent COVID- Pandemic has strengthened the legitimacy of using digital tools in education. The entire educational system has undergone a paradigm shift as a result of these digital technologies. Along with sharing knowledge, it also serves as a mentor, an assessor, and a co-creator of information. Students' lives have been simpler as a result of educational technology advancements. Nowadays, students prepare presentations and projects utilizing a variety of software and tools rather than pen and paper. The weig
... Show MoreThe 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
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