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 tourism industry, with its two sides (recreational and religious), is one of the important investment fields in Iraq, it is represented Iraq as the second economic source after the oil sector. So a need for serious efforts to develop the tourism sector and maintain its sustainability. This paper will be one of the important contributions in this field; the paper aims to explore the extent of the impact of the sustainable strategy on the level of overall performance in the Iraqi tourism sector. The field of research was some Iraqi tourist institutions at Iraqi tourism, Which covers the field of study on the one side, and can be studied on the other side, for the developing study methodology and organizing its main parts, the research pap
... Show MoreComplexity is the inherent characteristic of contemporary organizations. It is characterized by the intertwining and expansion of its relations, by the severe disorder and rapid change in its environment, which makes it suffer from a state of uncertainty in determining the direction of its future or the assessment of the rules governing its paths. All organizations tend to evolve with increasing sophistication, And to take measures that contribute to the simplification of the system as it moves towards complexity, allowing the administration to easily control its movement and directions, and the problem of complexity in the university is based on the entanglement and overlap in the goals and processes betwe
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The diversity of ideas and freedom of expression among the authors, who are looking for what's new serve the goals of musical expression and aesthetic, which calls for the use of traditional instruments with the formation of the great instrumental music and well-known orchestra, is a major challenge from several quarters, the failure of some of those musical instruments or limited potential or method performed by costly sometimes prevents the use of a permanent in this great configuration, had to be the emergence of some of the problems faced by the author and musician on the one hand and the receiver on the other hand, which must be looking for the perfect, some of these musical instrument are used systematically follows the work of the
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Experiments were conducted to study the behavior of the solid particles (proppant) inside the hydraulic fracture during the formation stimulation, and study the effect of the proppant concentration on the hydraulic fracturing process, which lead to bridge and screen-out conditions inside the fractures across the fracture width that restricts fracturing fluid to flow into the hydraulic fracture. The research also studies the effect of the ratio between the fracture size and the average particles diameter “proppant", on fracture bridging. In this study two ratios were considered β= 2 and 3 ,where β=Dt / Dp where: Dt= hydraulic fracture size (width) and Dp=Average particles diameter.
This work pr
... Show Morethe first part of the research involves investigate the aspect of the radiation superposed on the one bright soliton pulse propagated on ideal single mode
The industrial production sector has an important role in the national economy of the advanced countries as well as the developing ones to get higher levels for their economy . We in Iraq , just like most of the develpoing countries , our economy still suffers of great shortage in this active sector in spite of the repeated statements about the desire of activating the contribution of this sector in the national economy . The industrial sector in Iraq suffers in general of many problems , especially the public industrial sector (manufacturing) . These problems have been existed because of the unnatural conditions that Iraq has passed during the previous decades especially in the political and security sides . which reflecte
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Abu Firas al- Hamdani is one of the most prominent abbasid poets Who characterized their poetry with high artistic quality especially in his Romyate which blended the quality of feelings of grief, sorrow, longing and nostalgia that makes sensitive self conflict that stems with time from one hand and with place on the other hand. Because we are dealing with a poet lived west spatial coercive which it has been hurt him within a time conflict swinging between despair and some times patience and hope other times between the present and his painful reality also between the past and the beautiful times.
This researcher is to stand on this Romyat by monitoring effectiveness of the poetic text based on conflict between the presenc