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 environmental cost management focus on continuous improvement of processes and the various activities of the organization in order to improve the environmental performance by producing an environmentally friendly products lead to a competitive advantage for the organization and supports the activities of their sustainability.
The study was carried out in Bagel cement factory, one of the pioneer projects in Yemen in manufacturing field, The study found the need to develop a separate section for environmental management in order to put plans and environmental policies and the introduction of a special division in the Department of costs cares about Management practices cost and measure environmental costs, also give solu
... Show MorePatients with decompensated cirrhosis have typically prescribed a combination of therapeutic and prophylactic medications. Polypharmacy increases the probability of medication errors and drug related problems. Clinical pharmacists are highly effective at identifying, resolving, and preventing clinically important drug-related problems in their patients' care. The objectives of the study were the identification and classification of drug-related problems, as well as the discussion of these problems with health care providers (physicians, pharmacists, and nurses) and patients. Reduce their incidence as effectively as possible and educate all research participants on the significance of following their prescribed drug regimen
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Abstract: In recent times, global attention has increasingly focused on the critical issue of environmental sustainability, owing to escalating environmental degradation exacerbated by the utilization of green spaces and technological innovation. This phenomenon necessitates thorough examination, prompting the present study to scrutinize the impact of various factors, namely green spaces, technological innovation, environmental taxes, renewable energy consumption (REC), inflation, and economic growth (EG), on environmental sustainability within the context of Iraq. Secondary data extracted from the World Development Indicators (WDI) spanning the period from 1991 to 2022 served as the foundation for this investigation. Methodologically, the
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Neuro-ophthalmology, bridging neurology and ophthalmology, highlights the nervous system’s crucial role in vision, encompassing afferent and efferent pathways. The evolution of this field has emphasized the importance of neuroanatomy for precise surgical interventions, presenting educational challenges in blending complex anatomical knowledge with surgical skills. This review examines the interplay between neuroanatomy and surgical practices in neuro-ophthalmology, aiming to identify educational gaps and suggest improvements.
A literature search across databases such as PubMed, Scopus, and W
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The aggregation capacity of human reb blood cells lies between that of the non- aggregated arythrocyte and the remarkably full sedimentation. As the ability to aggregate is atributed to many factors such as the availability of macromolecules and plasma lipids, the role of plasm lipid profile on RBC aggregation and sedimentation changes in normal and diabetic patients is studied.Also serum lipid profile measurement (Total cholesterol, Triglyceride, HDL, LDL, VLDL) in normal and diabetic subjects were made. The principle of measurement includes detecting the transmitted laser light through a suspension of 10% diluted red blood cells in plasma. In all diabetics, the raulux formation and sedimentation rate is enhanced.
The principal objective of this study is to demonstrate how green quality management and product life cycle costing may help an organization gain a competitive advantage. Green quality management's influence on increasing product quality and meeting environmental criteria, as well as tracking the activities of product life cycle before, during, and after production, is demonstrated. Orienting these activities toward the production of eco-friendly products that fulfill the needs of customers, hence increasing organization's market share. We found from our study that proposed framework can help organizations improve their competitiveness. Green quality management contributes to environmental protection and the provision of high-qualit
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There is limited data and evidence about the effects of COVID-19 on Maternal health, especially when new information is emerging daily, through pregnancy, child birth and post natal period, women are vulnerable to have the infection, this article, aimed to show the suitable measures that should be applied for women at reproductive age who are suspected /confirmed with COVID -19 infection,
During pregnancy it is advisable to continue the antenatal care schedule, although reducing face to face visit is recommended (unless the pregnant condition required that ),and prioritize ANC at health facilities for high-risk pregnancy and during second half of pregnancy with adequate infection prevention control measures.
Regardi
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The importance of kick tolerance in well operations has recently increased due to its implications in well design, in drilling and well control. To study a simple method for the application of kick tolerance concept in an effective way on the basis of field data, this research purpose is to improve knowledge about Kick Tolerance and represents a technical basis for the discussion on revision of standard procedure. The objective of this work is to review and to present a methodology of determination the kick tolerance parameters using the circulation kicks tolerance concepts. The proposed method allows to know, to evaluate and to analyze the kick tolerance problem in order to make the drilling execution safer and more economical by reducin
... Show MoreThe importance of kick tolerance in well operations has recently increased due to its implications in well design, in drilling and well control. To study a simple method for the application of kick tolerance concept in an effective way on the basis of field data, this research purpose is to improve knowledge about Kick Tolerance and represents a technical basis for the discussion on revision of standard procedure.
The objective of this work is to review and to present a methodology of determination the kick tolerance parameters using the circulation kicks tolerance concepts.
The proposed method allows to know, to evaluate and to analyze the kick tolerance problem in order to make the drilling exe
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