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.
To investigate the research objectives, the researchers put the following hypothesis:
There was no statistically significant difference at the level of (0.05) between the average score of the students of the experimental group who studied the language of rhetoric according to model of learning method, and the average score of the students of the control group who studied the same article in the traditional way acquiring rhetorical concept. The researchers relied on the experimental design with the partial setting of the post-test, which depends on the experimental group that is taught using the model of the learning method, and the control group taught using the traditional method.
... Show MoreFailure in asphalt mixture and distress in pavement are major issues to roads infrastructure. Selecting an appropriate chemical composition of asphalt cement is a key component in avoiding these issues. This work aimed to investigate the effect of the chemical composition of different polar fractions on the rheological and physical properties of asphalt cement. Four types of asphalt cement with penetration grades of 20/30, 40/50, 60/70 and 85/100 were divided into four fractions. Complex shear modules, rutting resistance and rotational viscosity of the asphalt cement were determined by using a Dynamic Shear Rheometer and a Rotation Viscometer, respectively. The results show that an increase in the asphaltene content and Gastel index resulte
... Show MoreEducation is a process of learning and education at the same time. As the conditions of modern life necessitate every person to keep learning, education has become a necessity to meet life needs. The society today is concerned with the educational process and aims to live up the expectations. Since education is an integral part of education and its means, it has become as a mean to achieve its purposes. The educational environment was a traditional environment limited to specific inputs, possibilities and stimulus of both teacher and student. Due to the latest advancement, the educational environment has been expanded to become a rich, with strong connections. It has expanded to encompass the entire global environment. The current
... Show MoreSource of energy and protein Field crops considered an important needed for human
beings Due of this fact increases should appear in the quantities of their production in order to
meet the needs of continuous increasing in the population of the glope year after year ;
otherwise, an increase in the gap between the amount of production and consumption will
occur .
This study aims to reveal the geographical distribution of the potato crop in the district
of Abu – Ghraib. For this purpose, a study conducted about the cultivated areas, production
and crop yields per Dunam for period of 7 years lasted from 2005-2011.
The study shows that potato is one of the most important field crops that are grown in
the Abu –
The study addressed the water ecosystems of the marshes of Maysan Governorate as one of the important areas in Iraq in terms of the environmental, economic and tourism aspects. This area was exposed to great environmental changes due to natural and human factors which greatly affected the water ecosystem and made the area susceptible to many problems that affected the biological life of living organisms. The marshes of Maysan Governorate was affected by vital factors and non-vital factors. The marshes of Maysan Governorate was characterized by the UN Organization as one of the most important centers of biodiversity in the world because of the abundance of different and rare living organisms such as birds, fish, and reptiles as well as the e
... Show MoreAbstract
This research shows the history of political conflicts in Zimbabwe, the
merits of the political struggle for power in this country since the British
colonial period, especially after the British administration announced that
Zimbabwe is a local colony of the British Crown in 1923, as the settlement
process against the wide white deprive local people to own and lease land
and low income, as well as the 1961 Constitution, which granted access to
the white powers in accordance with the authority of the top menu for the
existing lower allocated to blacks.
These events and factors led to a national rejection in Zimbabwe,
which crystallized in the form of parties and political organizations through the
This study examined the problem of identifying the vocabulary of the methodology of teaching Arabic language in the faculties of Media. The researcher noticed the existence of an overlap between the syllabuses of the general specialization of the Arabic language and its Media sections in the universities with the special professional vocabulary that suits the study of the media student. Thus ,this study is regarded as a real attempt to present a methodological model of media language that concerns with fillfuling students ‘linguistic and knowledgeable needs relying on measuring their benefits from the methodological Arabic curriculum . Key words:problem, teaching’ methodology of Arabic language, media language.
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Where the accounting system in Iraq is still using many of these accounting practices according to the legal requirements to measure assets and liabilities away from the measurement that results in information representing the economic essence and represent honestly the financial situation and financial performance and future cash flows, and the needs of users of financial reports to useful accounting information adopted The International Accounting Standards Board (IASB) represents the true representation of accounting information in accordance with the concept of economic substance, which is the basis for the preparation and development of international accounting standards, and because accounting is part of the
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This study deals with the absence of state control over the whole of the Syrian geography in creating an environment conducive to the emergence of a new force represented by armed groups and organizations that point to fundamental changes in the conflict and to transform competition for control over the land into a struggle for influence. Which in itself represents the prospects of change in the Syrian scene, and that understanding their interests requires shedding light on the extent of the continuation of this competition and the conflict on land and expansion at the expense of the other, and thus contribute to complicate the Syrian scene, especially after attempts to bite Of land and annexation to each party's areas of influence, espe
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Absract
The letters of the Al-Safa Brothers contain many tales, in which each story is a literary text that is independent from the other texts, but it constitutes a unified entity in its entirety, because these stories contain recurring structural elements that go into building each one of them. The stories - the subject of the analysis - were not keen on something that was keen on adhering to the Sufi vision and its apparent effect on the tales of the messages, starting with the announcement of the narration to the narrator and his attempt to persuade the recipient of the truth of what is being told and its realism, and made him believe it. The stories correspond to the formal construction of the ideal style defined by th
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