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 topic is considered to be of a high degree of importance to every Muslim, and its importance is due to the fact that monotheism is:
Prove that God Almighty is the God who created everything and everything opposite to monotheism is polytheism, and it is taking other than God Almighty as a deity.
Therefore, we have to know the concept of God. If he is known, then he knows the concept of monotheism and the concept of polytheism
In this paper , concrete micro-piles were used to improve the bearing capacity of the soil which is supporting the shallow foundation by using groups of (4; 6 and 9)bored short micro-piles which have, (D=0.125m and D=0.1m), and length to diameter ratio (L/D) equal to (6; 10 and 12) respectively. To calculate the bearing capacity of the micro-piles,(Tomlinson) and (Lamda) methods were used; also the soil properties were taken from Al-Muthana airport,(Al-Qyssi,2001) [1]. The results show that; increasing the number of piles and/ or the diameters and lengths; and the interaction between the bearing capacity of the shallow foundation with the bearing capacity of the pile group which leads to increasing the strength against the external loads
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Form recurrence of financial crises phenomenon disturbing and attention , and returns the reasons so that its negative effects were sharp and dangerous , because of the nature and cause of Ncaha , threatened political and economic stability of the countries in which they occur these crises , in addition to Machmlh these crises spread of contagion across multiple channels to include other countries many developed and developing , and the reason for this to the openness of the economic and financial witnessed by the countries affected by crises and other countries concerned, the financial crisis is a case of financial turmoil appears in one of the sections of the financial system one and extends to
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The current research tackles the self-efficacy and its relation to the cognitive assessment for the daily disturbances for the University of Baghdad students. Two criteria have been adopted to achieve the objectives of the research. The sample of this study consists of 200 male and female students who were chosen randomly. The data were analyzed statistically, revealing that the university students owned their own self-efficacy as well as a cognitive assessment for the daily disturbances and they recognized them as self-threatening. The results also indicated the existence of a prediction activity in the field of the cognitive assessment to the daily disturbances selection. In light of the acquired results, the study recommends the neces
... Show MoreIn this paper all possible regressions procedure as well as stepwise regression procedure were applied to select the best regression equation that explain the effect of human capital represented by different levels of human cadres on the productivity of the processing industries sector in Iraq by employing the data of a time series consisting of 21 years period. The statistical program SPSS was used to perform the required calculations.
In this work, the impact of different geomagnetic storm events on the plasma-sphere layer (ionosphere layer) over the northern and southern hemisphere regions was investigated during solar cycle 23. To grasp the influence of geomagnetic storms on the behavior and variation of the critical frequency parameter of the F2 ionospheric layer (foF2), five geomagnetic storms (classified as great, severe, and strong), with Disturbance storm time (Dst) values <-100 nT were chosen. Four stations located in different mid-latitude regions in northern and southern hemispheres were designated, the northern stations are: Millstone Hill (42.6° N, 288.50° W) and Rome (41.90° N, 12.50° E) and the southern stations are: Port Stanley (-51.60° S,
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Abstract
The research dealt with a studying the impact of oil price fluctuations on one of the rules of financial discipline, which is the rule of budget deficit in the Iraqi economy for the period (2003-2020) as it is one of the quarterly economies that rely mainly on volatile oil revenues that fluctuate with oil prices in global markets, and therefore the general budget suffers. from The state of instability and then the government resorts to borrowing for a long time . this deficit in the general budget and increase the debt burden in the public debt.The research aim to measure and study the impact of oil price flu
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The current research aims to demonstrate the relationship of correlation and influence between the independent variable strategic control through its dimensions represented by (organizational structure, human resources management, commitment to specialization, defining powers and responsibilities, values and integrity) and the dependent variable the performance of the insurance company, and the degree of arrangement of these dimensions according to their importance, as well as Detection of significant differences in the sample's response to the questionnaire paragraphs in the researched company, and the research problem
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