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 Political loyalties of the individual considered as the most important democracies through direct psychological identification in a particular party. The political parties regarded as the important elements and the foundations of the democratic system. They have effective interaction between the voters and the government institutions. The aim of the current research is to identify the quality of Islamic, the Civilian parties, and the most preferred for students. also, the research attempt to identify the level of identification party that the university students have, and the difference of identification party according to the gender (male, female), the difference of of social class (upper, middle, poor). The sample
... Show MoreThis study presented more than twenty books that dealt with the subject of (Weights of the Tawshih art), whether their study was independent and dedicated the art of Tawshih as a part of book. Therefore, the review of the sources and references on the art of the Tawshih is not specific for place or time, it was a broad and comprehensive review of all the places where the muwashahat appeared in the east and west, Andalusia was one of the most important areas covered by the study arbic Maghreb and Iraq. The art of tawshih took different forms according to the countries in which they appeared. Muwashahat is a new art that appeared in Andalusia, its main goal was to renew the Khalilian weights and to find the poetic rhythm that fits with the so
... Show MoreThe current research aims to identify the possible self of university students and the differences in the level of possible self of students in terms of gender, specialization (scientific-humanitarian), and the interaction between them. In order to achieve the objectives of the current research, the two researchers have prepared a scale of the possible self, based on the theory (Markus and Nurius, 1986). The research tool was applied to a sample of (400) male and female students who were selected through a random stratified method from Al-Mustansiriya University students/morning studies for the academic year (2019-2020). The researcher reached the following results: the research sample has a high level of possible self; there is a differ
... Show MoreThe research aims at:
- Identifying the problems facing kindergarten teachers.
- Identifying the nature of the problems facing kindergarten teachers.
To achieve the aim of the research, the researcher prepared a questionnaire to identify the problems that face the teachers of kindergartens. The questionnaire was subjected to the consultation of a group of specialized expertise in the educational and psychological sciences to certify the propriety of the items of the questionnaire and it gained a rate of (80%), and the stability of the scale gained (0.91) and it stands for a correlation parameter with a statistical significance and it was calculated by using Person’s R Corre
... Show MoreAl- belenoby , Andalusian obscure poet .I choose to study poetic rhythm in this poetic and the appropriateness of with what rhythm touring in his self to give beautiful meaning raise to receiver to put the hands of continental placements creativity in poetry .I divided my research into ideas are presented in a sequential manner , I started researching with poetic rhyme than rhyme they represent the form of the poem, they represent the external form of the poem and their music that farm the general concept then the rhetorical styles that represent the internal form of the poem and it music that the listener works and enjoying it part by part all this led to the put the hands of the receiver placement creativity in Belenoby Poet.&nbs
... Show MoreDBN Rashid, Journal of Education College Wasit University 1(1):412-423, 2007
The importance of research stems from the prominent role of leaders in the political, administrative, economic and societal spheres in general, which requires highlighting this angle. Research Hypothesis Modern policies work with mechanisms that limit the clear role of governors and transform the ruler into an executive man. It can be assumed that the type of public policy of the state is the only criterion that transfers the ruler from a ruler to an executive.
Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world’s rivers, representing the environmental influence of 471.4 million people across
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(954)
Public spending represents the government’s financial leverage and has a significant impact on real and monetary economic variables, and one of these effects is the effect of public spending on the exchange rate as an important monetary variable for monetary policy, As we know that public spending in Iraq is financed from oil revenues sold in US dollars, and the Ministry of Finance converts the US dollar into Iraqi dinars to finance the government's need to spend within the requirements and obligations of the state's general budget, And converting the US dollar into Iraqi dinars has an impact on the parallel exchange market, even if there is a contractual exchange rate between the Ministry of Finance and the Central Bank of Iraq to
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Abstract:
Thanks for people's God who brought the great book, prays and peace for
his prophet "Mohammad" the master of missioners to all people.
Allah created human being in it's best way and give him a soul thus ,
he will be a human with faith that has movement and life and the centre of his
soul is the sense which differentiate human from other animals. This
sensation generated from different senses that made the soul.
God had given him a protected heart, talkative tounge and clear seeing
to understand with consideration, so he will prevent himself of falling in wrong
by thinking and situation that he will pass by.
The significance and probability of sensation had talken our attention in
Qur'an . Hence