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.
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The aim of studying the role of environmental taxation is to reduce or mitigate the problem of environmental pollution and obtain a clean environment. And the importance of research lies in the fact that environmental taxation is one of the basic tools to achieve environmental balance. As it is considered one of the sustainable economic tools that focuses on the concept of environmental taxes and fees. Therefore, the incentives stimulated institutions to invest in clean energy and use environmentally friendly machines. Through it, the rules of the competition are updated in favor of organizations that respect the environment so that they can obtain a green competitive advantage. And that the mai
... Show MoreThe financial fraud considers part of large concept to management and financial corruption, the financial fraud is appeared especially after corporate, that is Emerge agency theory, that is because recognize relationship between the management company and stakeholder, that is through group from constriction in order to block the management to fraud practice, that on the basis was choose another party in order fraud this practice and give opinion on financial statement, that consider basis decision making from stakeholder to basis the report auditor about creditability this is statement that reflect real activity for the company.The Auditor in order to lead work him Full professionalism to must using group from control Techniques, that is
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Digital commercial advertising depends on artistic formations to achieve attraction and arousal of attention, which is one of the most important communication factors that the designer seeks to achieve and is considered a key key to recognizing the beauty of the topic and its functional value. Reframe formal vocabulary.
The research included the introduction and includes the research problem and the need for it, which focused on the following question: What is the aesthetic role of artistic formation in the design of commercial advertising?
The aim of the research was: To reveal the aesthetic role of artistic formation in commercial advertising.
It also included the importance of research and research boundaries, as well as def
This study aimed to recognize and understand the concept of strategic management accounting (SMA) and how it's the effect on the competitive advantage for industrial companies in Jordan. The study's importance arises due to the lack of Arab studies that dealt with this topic, in addition to the important and vital role of strategic management accounting on companies that represent the artery of the decision-making process, and to identify the benefits associated with SMA technology. The necessary data were collected through the literature review and theoretical study of the references that relevant to the study subject, in addition to a questionnaire developed for this purpose, the study used (124) out of (250) questionnaires tha
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This study has taken into consideration two vital variables (leadership, leadership styles and intellectual capital). The research aim through the relations between the leadership styles and intellectual capital, to building conceptual frame for the variables of study and exploring the nature of correlation relations between these variables and their effects in enhancing intellectual capital.
The research was conducted at the Ministry of foreign in Iraq, and included a sample of leaders and subordinates amounted to (186), has been using the questionnaire as a key tool to collect data on the sample.
For the dealing with
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Neurogenic inflammation is pivotal in dental pulp repair, involving complex interactions between sensory nerves, immune cells, and dental pulp stem cells (DPSCs). This review aimed to identify the favorable pathways of neurogenic inflammation and neurogenic differentiation of DPSCs in the pulpal healing process. Also, to identify the techniques used to evaluate these inflammatory and differentiation processes. Both PubMed and Google Scholar databases were employed in the search strategy using keyword combinations based on MeSH terms. The search was performed for published articles in English from January 2014 to November 2024, including studies with histological and molecular findings. 29 articles only met the inclusion criteria. Neurogenic
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The study was conducted to detect the effect of addition of 0.03, 0.06 and0.10% potassium sorbate and 0.10, 0.15, 0.20 and 0.30% sodium propionate upon the sensory properties of laboratory made biscuit. The statistical analysis of the results revealed no significant differences (P<0.05) between the propionate treatment (A,B,C,D) and between the sorbate treatment (E,F,G) and the control (H) in most sensory properties of biscuit prior to storage. Upon six month storage of biscuit made with addition of different levels of sodium propionate 20-40C (room temperature) no significant differences (P<0.05) were shown on softness, flakiness and color in comparison with the control . No significant differences (P<0.05) were also
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Background : In order for a tooth to erupt, two obvious requirements are needed. First, there has to be alveolar bone resorption of the bone overlying the crown of the tooth such that an eruption pathway is formed. Second, resorption of bony crypt and apposition of new one, third, there has to be a biological process that will result in the tooth moving through this eruption pathway.The amniotic sac contains a considerable quantity of stem cells. These amniotic stem cells are multipotent and able to differentiate into various tissues, which may be useful for human application. Receptor activator of nuclear factor kappa B ligand (RANKL) is concentrated on bone biology, more specifically bone metabolism. RANKL plays a vital role in osteoclast
... Show MoreThe current research focuses on a major problem: the weak role of disclosing corporate information in the application of laws, regulations and instructions related to the application of corporate governance principles weakens the ability to protect the rights of shareholders and investors in companies listed on the Iraqi Stock Exchange and the study aims to study and analyze the role of disclosure and transparency in achieving the necessary protection to ensure the rights of shareholders. The study was applied to a sample of (42) analysis samples representing (84%) of the total questionnaires distributed to investors and shareholders in all listed companies in the Iraqi Stock Exchange. The results confirm the shareholder's right to obtai
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