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 main question raised in this paper is: Is it possible to translate the ‘genre’
of Quran? And if this ‘genre’ is Quran specific, a ‘genre’ of its own, i.e. a unique one,
how can the Quranic text be translated from Arabic into English or any other
language? This question has been raising a lot of controversy among translation
theorists, linguists, philosophers and scholars of Islam and specialists in the sciences
of Arabic language let alone Quran exegetes. Scholars of the Arabic language and
scholars of Islam have argued that because of the genre of Quran is the genre of (ijaz),
translatability can never be possible. Equivalence, thus, cannot be achieved especially
if we know that so far
A field experiment was carried out during winter season of 2019-2020 at Al-Mhanawyah Research Station - Agriculture Research Directorate - Babylon Governorate / Iraqi, to study the gene expression of Sgr gene responsible for controlling the duration of staying green in varieties of wheat under effect of plant growth regulator during the two growth stages (vegetative and reproductive) by using quantitative reverse transcription-PCR (RT-qPCR) technique and achieving the highest grain yield for a number of wheat varieties. Randomized complete block design (RCBD) arranged according to split plots used with three replicates. The experiment included twelve wheat varieties (Saberbic, Al-Rasheed, Iraq, Tamoz-3, Al-Adnaniya, Babel, IPA-99, Al-Latife
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News feeds are at the forefront of news forms that are close to the public's attention for their rapid news content in two directions:
- its speed in summarizing events in one or two sentences easy to be understood and realized.
- highlight the most important contents of screenings or news broadcast.
The researchers felt that the importance of these brief news compared to news broadcast, breaking news and news subtitle are still ambiguous, as well as their contents.
The researchers selected the city of Baghdad as a community to research and prepare a questionnaire form containing (11) questions.
The questionnaires were distributed to a non-relative stratified
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Bacteria form complex and highly elaborate surface adherent communities known as biofilms.Biofilm have been shown to be associated with several human diseases ,and to colonize a wide variety of medical devices . The current study focuses on contribution of extracted genomic DNA in biofilm formation by P. aeruginosa and K. pneumoniae isolates .The percentages of Pseudomonas aeruginosa recovery from drinking water in this study were 10%(20 positive P. aeruginosa samples ) and K. pneumonia., 7%(14 positive K. pneumonia samples).The results showed that all P.aeruginosa and K. pneumoniae isolates (100%) were slime producer but in different degrees by forming of black
... Show MoreThe current study aimed to assess the biological efficacy of the triple arbuscular mycorrhiza (AM) mixture of fungi Glomus etunicatum, G. leptotichum and Rhizophagus intraradices, and mix it with organic matter (O) and pathogenic fungi Fusarium oxysporum f.sp.lycopersici by using voyeurism in the plastic house in the growth of the tomato plant after four and eight weeks of cultivation. The results were shown after the treatment of the tomato plant in agriculture with the mixture of mycorrhiza and the pathogenic fungi and organic matter were treated with the mixture of mycorrhiza, organic matter and pathogenic fungi together. The effect of mycorrhiza and organic matter interference on the increase in the percentage of the lignin afte
... Show MoreThe article is devoted to the issue of word-formation motivation, which does not lose its relevance and plays a role not only in disclosing formal-semantic relations between words of one language and has not only theoretical, but also applied significance. The authors consider word-formation motivation consistently in its varieties in a comparative way on the materials of so different languages as Russian and Arabic and approach the mechanism of achieving semantic equivalence of translation. To the greatest extent, word-formation activity today, due to objective reasons, affects some special branch (technical, medical, etc.) vocabulary, which is increasing from year to year in national dictionaries. This extensive material, selected
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Abstract:
The research aims to monitor the image of the man in the group (The Cart and the Rain) by the storyteller (Badiaa Amin); With the aim of highlighting an aspect of feminist writing, especially with regard to the relationship of women to men, and determining the form adopted by the storyteller in drawing the features of men.
The research used the descriptive-analytical method in the space of its textual formation, which aims to stand on the text and deconstruct its narrative significance. To provide a comprehensive picture of it.
Three images of the man appeared in the group's stories, represented by (the authoritarian, the negative, and the positive), and the image of the authoritarian ma
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