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.
The Islamic religion is a religion of tolerance and is pleased with worship and other legislation and the idea of peace is an authentic and profound idea related to the call for coexistence with all religions. The Prophet (PBUH) was keen to organize his relations with non-Muslims on the basis of cohabitation, On the basis of love and intolerance, God Almighty says: "If your Lord wants to make people one nation and they are still backward." Surah Hud: 118 Islam has taken care of the people and made them tolerant brothers who sympathize with their different beliefs. Which means that everyone has the right to live, believe and believe what he sees right and have the freedom to perform the acts of worship and beliefs he deems correct. The di
... Show MoreContext has occupied a distinguished place as far as the understanding of the texts and deducting the rules from them or analyzing them. The context was considered as one of the important presumptions as far arriving at the desired meanings is concerned. The word is worthless and the meaning is not known unless we know the context in which it came. The context in its two types the lingual and non-lingual types. It is the best for knowing the intended meaning of the Quranic verses to know the real meaning.
Specialized hardware implementations of Artificial Neural Networks (ANNs) can offer faster execution than general-purpose microprocessors by taking advantage of reusable modules, parallel processes and specialized computational components. Modern high-density Field Programmable Gate Arrays (FPGAs) offer the required flexibility and fast design-to-implementation time with the possibility of exploiting highly parallel computations like those required by ANNs in hardware. The bounded width of the data in FPGA ANNs will add an additional error to the result of the output. This paper derives the equations of the additional error value that generate from bounded width of the data and proposed a method to reduce the effect of the error to give
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This study was concerned with using ozone gas in drinking water treatment plant at Ibn-Sina Company. The main purpose of this research is to find the best contactor for ozone unit proposed. An investigation was conducted to study the absorption of ozone by water in two type of absorber. The effects of the process variables (such as height of water column, contact time, and pH) on the amount of ozone absorbed were investigated. Box-Wilson central composite rotatable design is used to design the experimental work for the mentioned variables. It was found that the optimum value of the variables studied was:
i) Height of water column (90 cm)
ii) Contact time (17-18 min)
iii) PH (7 - 7.5)
Lorraine Hansberry’s A Raisin in the Sun (1959) appeared at the beginning of renewed political activity on the part of the blacks; it is a pamphlet about the dream of recognition of black people and the confusion of purposes and means to reach such recognition. It embodies ideas that have been uncommon on the Broadway stage in any period. Situations such as a black family moving into an all-white neighborhood were not familiar before this time; they were just beginning to emerge. In depicting this so realistically, Hansberry depends more on her personal experience as an African American embittered by social prejudices and discrimination.
Psychology is one of the sciences that consciously overlap in terms of mutual influence with art forms in general and cinematic arts in particular. The psychological effect can be extrapolated into the visual image through the characters and their actions, especially the adoption of psychoanalytic ideas and proposals that came by (Freud), The cinema benefited from the concepts of psychology and participated in the process of creativity and the manufacture of events or the actions of characters, such as the concepts of consciousness and subconsciousness to express the psychological dimension of the film events, these data can be counted on the level of nightmares in the cinematic movies.
The methodological framework included the rese
The research tagged (the image of the soldier in contemporary Iraqi painting) dealt with the concept of the image as one of the basic concepts in the creative achievement, whether it is in the field of art, literature or beauty. Therefore, the concept of the image expanded to express the various aspects of human creativity, including the field of painting. To know the image of the soldier in contemporary Iraqi painting, the research included four chapters. The first chapter focused on the methodological framework of the research, while the second chapter included three sections. The first topic dealt with the philosophical and artistic concept of the image. The second topic was concerned with the representations of the soldier's image in
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The study aimes to analyze the discourse of Arab tweeters regarding the normalization of Arab-Israeli relations on the social media site (Twitter).
Study Methodology: The study relay on the survey method, using the comprehensive survey method, and this research is one of the descriptive types that aim to describe the phenomenon in a qualitative way, and discuss it through the method of in-depth analysis, in addition to using the tools of (discourse analysis).
Study sample: A sample of (8686) tweets for (7425) tweeters, which was posted on Twitter during the period from 15/9 to 30/9/2020, on the issue of normalizing Arab-Israeli relations.
Study tools: The data study was collected using the data mining tool from social networks (
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