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 city of Ghana is one of the important commercial cities in the country of Sudan, as it was a major source of commercial exchanges, and a commercial mediator across the countries of the Maghreb and the metropolises of the countries of Sudan. Many, and most of them take the desert road, Which traders had to endure the hardships of these roads from the insecurity, high winds and dust that sometimes destroyed the trade convoys, in order to obtain gold, which is one of the most important minerals that Ghana traded with various countries, in addition to the different goods that the merchants carried In particular, salt and its trade with Ghana, and also taxes, which were an important financial resource imposed by some gov
... Show MoreThe Concept of the Constitution and the most Important of Human Rights
Many studies have been made and still concerning the field of translation. Since the mid-90's a considerable amount of researches has tackled the problem of gender and its effect on the process and the product of translation. Simon (1996, p 508) points out that when comparing women and men as translators and writers through history, women seem to be the weaker side. This paves the way to feminist movements which produce prominent studies concerning gender as a concept and translator's gender as practice on the quality and the accuracy of the translation.
Flotow (in Meschia, 2012, p 1-4) outlines several issues that can be
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This study includes the direct influence of (single & multi) dose of Cold Atmospheric Plasma (CAP) on the no. of platelets for mice for different exposure time (15, 30, 60, and 120) sec. the influence of CAP on mice was measured after 1, 2, 3, 7, and 14 day from exposure.
The results obtained in this study indicate that the effect of low doses of CAP on platelets was stimulatory effect in the first few hours from exposure (1day) but the high dose was inhibitory, It was found that after two weeks of exposure that the number of platelets became normal comparable to the control one, and this indicates that plasma effect was removed after this period.
The importance of internal audit in the growing demand for services in the public and private economic units, and in the rapid growth of its systems professional, has also been recognition of the importance of internal audit quality and the quality of information provided in a long time, as well as the importance of achieving the greatest possible quality in his work to reduce accounting risks of financial reports misleading or fraudulent, which is one of the important features of the audit.
The internal audit quality are linked with the ability of auditors to detect errors in the financial statements, and their willingness to express an opinion technical neutral and non-aligned based on the results of th
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The study of this topic is not to underestimate the previous studies but to the great importance of the Sunnis of the report. The reasoning of the Hadiths of the report is a kind of invisibility in that the significance is not a phenomenon such as the emergence of reasoning in the words of words and deeds. With the introduction of all types of Sunnah and protest, there is no difference between them, and that the Sunnis argument like other Sunnah. What we will see in the research.
The research is aimed at dynamics the dynamics of the artistic form within the theater and the dynamics of this movement in the development of the form and the multiplicity of meaning. This research came to address a problem of great importance in the creation of the image and the form of theatrical presentation. The evolution and transformation within the display system requires a dynamic structure that enables the form of growth and growth. The aim of the research was to identify the dynamics of form in the Iraqi theater. The researcher then identified two terms: form and motor.
In the theoretical framework, it was divided into two sections: the first (the dynamics of the artistic form) and the second (the dynamics of the act of dir
The linguistic researcher reads a systematic crisis, idiomatic problems within the linguistic term coming to the Arab culture. Where most of them return back to problems of receiving these sciences which are represented by phenomena like the multiplicity linguistic term, disturbance translated idiomatic concept and its duality.
Aims of the research :
1-Initializing new textbooks to form linguistic project and Arabic linguistic theory.
2-Determination adjusted knowledge, concepts of Arabian heritage linguistics subject
3-Observation the causes of disturbance crisis of linguistic term and its relation to
... Show MoreTheatrical performances began with the Greeks when the theatrical scenes and skeletal figures were encoded, where the large wall of the Alskina, which contains three doors, the middle of them with a high height, and the two sides took the natural size, where the middle door indicated a symbolism of the god or demigods, as we find the condensation of the symbol in the architecture of the theater, and the symbol was taken In the theatrical scene, the development semantically and aesthetically, and interpreting and interpreting the current day, where the laser light formed the symbolism of the contemporary virtual scene, and in order to identify the aesthetics of the symbol in the theatrical scene, the current research was evaluated into fo
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