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.
This research aims at answering many questions raised by the research problem concerning the view of the organizations under consideration for the concept of smart leadership and its most important dimensions, as well as the view of crisis management and its concept and most important methods through research objectives that define and clarify the smart leadership with its dimensions and methods of crisis management.
For the purpose of reaching the results of the research and testing the assumptions about the relationship between smart leadership and methods of crisis management, the researcher adopted a questionnaire, designed especially to be a criterion for the research, as the main tool for data coll
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The conservatorship is a legal action to protect troubled banks from credit risk and bankruptcy risk that banks cannot hedge them .The Central Bank role has to protect the financial system from these risks by controlling and supervising. This research studied these risks and explained the role of The Central Bank. This research presented and analyzed the legal framework for supervision and the imposition of conservatorship bank to address the effects that have been achieved as a result of poor management and weak internal controls. Baraka Bank for Investment and Finance was a research sample to measure the financial ratios for the troubled bank, and analysis the results that led to put the conservatorship. The research depends on the hyp
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The inhibition of mild steel corrosion in 1.0M HCl by 1-propanol and the synergistic effect of potassium iodide (KI) was investigated using weight loss and polarization techniques in the temperature range (30 ‒ 50) ̊ C. A matrix of Doelhert to three factors was used as the experimental design, adopting weight loss results as it permits the use of the response surface methodology which exploited in determination of the synergistic effect as inhibition on the mild steel. The results were confirmed using electrochemical polarization measurements. Experimental results showed that the inhibition efficiency (IE%) increases with increase in concentration of inhibitor and with increasing of temperature. The addition iodide ions t
... Show MoreApplying a well-performing heat exchanger is an efficient way to fortify the relatively low thermal response of phase-change materials (PCMs), which have broad application prospects in the fields of thermal management and energy storage. In this study, an improved PCM melting and solidification in corrugated (zigzag) plate heat exchanger are numerically examined compared with smooth (flat) plate heat exchanger in both horizontal and vertical positions. The effects of the channel width (0.5 W, W, and 2 W) and the airflow temperature (318 K, 323 K, and 328 K) are exclusively studied and reported. The results reveal the much better performance of the horizontal corrugated configuration compared with the smooth channel during both melti
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Drug consultation is an important part of pharmaceutical care. mobile phone call or text message can serve as an easy, effective, and implementable alternative to improving medication adherence and clinical outcomes by providing the information needed significantly for people with chronic illnesses like diabetes and hypertension particularly during pandemics like COVID-19 pandemic.
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This research aims to solve a problem in the field of accounting and financial knowledge in the world today, that is, the problem of creative accounting. Especially after the global financial crisis and the collapse of many large companies in the world, people find that they use creative accounting methods to distinguish them from reality, showing the results of their activities and their financial status. This research discusses the concept of creative accounting, the most important methods used in financial statements and its relationship with external auditing, and procedures to limit accounting creativity. This study uses descriptive analysis methods after confirming its theoretical aspects in practice. Using the statistical
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Objective. Infection with Coxsackie virus. This virus that damages pancreatic cells, has long been linked to the onset of insulin-dependent diabetic mellitus (IDDM). Pro-inflammatory cytokines can be produced as a result of this illness. Tumor necrosis factor-a is one of these pro-inflammatory cytokines. Materials and Methods. Blood sample were collected from 180 Iraqi participants. Ninety of them is type 1 diabetic patients and other 90 is healthy control .both groups were tested for the incidence of Coxsackie virus B IgG. So the patients groups is divided to two groups according to sero positivity of CVB-IgG .all 180 patients tested to measure of level of TNF-α. Results. The Results showed increasing in levels of TNF-α in CBV po
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Background: The skin functions as a barrier to the external environment, damage to this barrier following a burn disrupts the innate immune system and increases susceptibility to bacterial infection. Objective: This study was carried out to determine the bacterial isolates and study their antimicrobial susceptibility in burned wound infections at one burn's hospital in Baghdad.Type of study:Cross-sectional study.Methods: The bacteria were identified at species level by using Analytic Profile Index (API) system and The antimicrobial susceptibility test was performed according to Kirby-Bauer (disk diffusion) technique.Results: Over a period of one year (from October 2014 to October 2015). Out of 848 patients with different degrees of burns
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