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.
Abstract: The international community now places significant emphasis on achieving zero carbon emissions, requiring both new researchers and experienced policymakers to prioritise this goal. This article examines the effects of carbon taxes, carbon cap and trade, renewable energy (RE) production and consumption, and economic growth (EG) on carbon emission reduction in the United States, Japan, Canada, and Australia. The study collected secondary data from the World Development Indicators (WDI) secondary source spanning the years 1991 to 2022. The study examines the relationship between variables using the cross-sectionally augmented autoregressive distributed lag (CS-ARDL) approach. The findings indicate that carbon taxes, carbon cap and tr
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Throughput accounting is concerned with a throughput measurement process to determine the efficiency of the company, to know the problems and obstacles it suffers from, to determine their causes and ways to address them.The research problem is represented by the following question: does the application of a throughput accounting lead to maximizing the company's profits? The aim of the research is to demonstrate the importance of throughput accounting, which is one of the tools of management accounting in providing an efficient information system that provides the company’s management with the information it needs to improve its production processes, increase a throughput, and thus maxi
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Search procedures on the treatment research has tended include what cam followers Astaratejaat available to the business organizations to achieve competitive advantage and continued benefits of the form in which the organization can maintain its success in the race competitive and increase production efficiency.
The objectives of the study , the study came with the number of goals and the most important one the knowledge of the relationship and the influence between the variables of the study and review of the latest literature frameworks intellectual and philosophical to the variables of the study and come up with recommendations that could help the organization improve its performance .
... Show MoreOccupies total quality management applications play a key role in the development of institutions of higher education performance and achieve its strategic objectives through the commitment of senior management and their employees to continuous improvement of the quality of performance in the various areas of work, and can be integrated knowledge management processes, which means identifying information of value and how to take advantage. The data were collected using the style of the questionnaire for the purpose of analyzing their results on a sample composed of 83 member of the administrative leadership in colleges as representing the decision-making centers in those colleges .
 
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The article examines metaphors as one of the fundamental means used by D. Rubina when writing the novel “Parsley Syndrome” to form images of dolls as equal heroes of the work. The author of the article continues research related to the work of Dina Ilinichna Rubina, a representative of modern Russian prose.
Objectives: The current work aimed to reveal the impact of gentamicin on the fibronectin binding proteins (fnbp) gene expression and its relation to biofilm and agr type in Staphylococcus aureus. Materials and Methods: A total of 25 S. aureus isolates were enrolled in this study previously isolated from different specimens. Identification confirmation and methicillin resistance were achieved by amplification of 16SrRNA and mecA. Multiplex polymerase chain reaction (PCR) based assay was employed to evaluate the agr typing. The gene expression of fnbA and fnbB genes was tested by real-time PCR technique. Minimum inhibitory concentration was estimated by micro broth dilution methodology. Microtiter plate method was performed to determine the a
... Show MoreGovernment-sponsored projects in Iraq significantly improve the economic situation and provide services but face high rates of troubling blocks. This work aims to identify indicative factors of the Troubled Project using periodic health check reports based on a literature review and interviews with Iraqi experts. As a result, a questionnaire was prepared that included four sections. The first is personal information; the second section is information about knowing the level of institutions’ implementation of project management through prepared documents. The third section is about indicative factors for the project's trouble, including 25 workers; the fourth section is about the questions in the periodic reports to che
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Consistent with developments emerging environmental and canaccept by Iraq of the opportunities and challenges ahead in many fields,including economic areas, it requires the face of those developments andadaptation by adopting a lot of related concepts, including the concept ofcorporate governance and commitment to its principles, standards andmechanisms, especially those related to the formation of audit committeesand identify the tasks and duties entrusted to its members and terms oftheir independence as well as the rehabilitation of both scientific andpractical manner that is consistent with the interests of shareholders andother stakeholders in the companies, including banks, research sample, theresearch aims to shed light on the conc
... Show MoreThis research focuses on detecting the financial corruption cases in Iraq in light of adoption the strategic audit, the paper deals with the problem of the proliferation corruption cases particularly financial in Iraq and dramatically in the presence of audit and control devices as well as inspection and integrity devices, which indicates the existence of deficiencies and weaknesses in those devices in the implementation of audit and control functions in order to detect the corruption cases in the economic units in Iraq.
Stems objective of this research through the provision of approach of strategic audit concepts and indicate the extent importance of adopting of strategic audit as a means to detect the f
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