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.
Incivility in nursing education can negatively affect the academic achievement. As there is no tool in Arabic to assess incivility among nursing students, there is a need for a valid and reliable tool.
This study aimed to investigate the psychometric properties of the Arabic version of the Incivility in Nursing Education- Revised (INE-R) survey.
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Electrochemical Machining is a term given to one of nontraditional machining that uses a chemical reaction associated with electric current to remove the material. The process is depending on the principle of anodic dissolution theory for evaluating material removal during electrochemical process. In this study, the electrochemical machining was used to remove 1 mm from the length of the a workpiece (stainless steel 316 H) by immersing it in to electrolyte (10, 20 and 30 g) of NaCl and Na2SO4 to every (1 litter of filtered water). The tool used was made from copper. Gap size between the workpiece and electrode is (0.5) mm. This study focuses on the effect of the changing the type and concentration of electroly
... Show MoreThis current research aims to identify the effectiveness of a training program in developing moral intelligence and mutual social confidence among middle school students. The researcher made a number of hypotheses for this purpose to achieve the goal of the research.
The researcher relied on the (Al Zawaida 2011) scale prepared according to Coles (1997), including (60) items, and the mutual social trust scale for (Nazmi 2001) based on Roter's theory including (38) items.  
... Show MoreIn this work a hybrid composite materials were prepared containing matrix of polymer (polyethylene PE) reinforced by different reinforcing materials (Alumina powder + Carbon black powder CB + Silica powder). The hybrid composite materials prepared are: • H1 = PE + Al2O3 + CB • H2 = PE + CB + SiO2 • H3 = PE + Al2O3 + CB + SiO2 All samples related to electrical tests were prepared by injection molding process. Mechanical tests include compression with different temperatures and different chemical solutions at different immersion times The mechanical experimentations results were in favour of the samples (H3) with an obvious weakness of the samples (H1) and a decrease of these properties with a rise in temperature and the increasing
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Objectives: To choose the best mode of delivery
for term, frank or complete, breech presentation
through studying the perinatal outcome of each mode of
delivery decided when managing a group of pregnant
ladies presented with breech delivery in our centre.
Methods: One hundred and fifty pregnant ladies
presented at term with singleton, frank or complete,
breech presentation for delivery in our centre during the
period from May 2004 toAugust 2005.
Mode of delivery, parity, gestational age, maternal age,
maternal medical illness, and birth weight where the
variables that have been tested in each delivery
included in the study to verify their relationship to
perinatal outcome.
Results: No significant
The role of internal control is based on the effectiveness of the budget through an analysis of the reality of the budget in the research sample as it was studied in the preparation and preparation stages and the implementation stage. The sample showed that the sample did not comply with what is stated in the Ministry of Finance publication of instructions and ceilings. In the process of preparing and resulting from the occurrence of deviations in large proportions both in the discussion of the Ministry of Finance or when implementation as a low rate of implementation and the absence of allocations for some items, although there is a need for them as well as the transfer of large proportions of transfers both up or down and the purpose o
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This article investigates the decline of language loyalty in the age of audiovisual nearness. It is a socio-linguistic review of previous literature related to language disloyalty. It reviews the current theoretical efforts on the impact of audiovisual nearness created by social media and language loyalty. The descriptive design is used. The argument behind this review is that the audiovisual nearness provided by social media negatively affects language loyalty. This article concludes that the current theoretical efforts have paid much attention to the relationship between the audiovisual nearness and language loyalty. Such efforts have highlighted the fact that the social media platforms have provided unprecedented nearness that provoke in
... Show MorePurpose: The research aims to study the measurement of the performance of accounting units level of the research sample by using the Federal quality Model European (EFQM) Design/methodology/approach: the (EFQM) which included seven dimensions "Leadership, Strategic Planning, External Focus, Information and Analysis, Faculty / Staff and Workplace Focus, Process Effectiveness & Outcomes and Achievements" And its effect on the Control Environment, which includes three dimensions: "Integrity, management philosophy and commitment to powers" . the sample is supervisory units of colleges affiliated with the University of Baghdad in Iraq, and a sample was chosen that included fifty-one individuals in the accounting departments.
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In The Name Of God the Most Gracious, the Most Merciful [Should he not know he that created? And he is the one that understands the finest mysteries (and) is well-acquainted] surah Al-Mulk verse No. (14), this Qur’anic verse is one of the pieces of evidence that indicates the suitability of Sharia for the human life, since God Almighty created the creation and he is the best-known concerning the needs of his creation to survive and for life to continue.
One of the key ways for the continuity of human life is Sharia's possession of the feature of suitability for every time and place, and for the whole world, and it is comprehensive to all the details of life and its integrated systems, a systems that comp
... Show MoreThe study aims to measure the impact of reporting on value creation on the earnings quality of the economic unit by presenting and discussing the conceptual aspects of the value creation process through multi-capital and the importance of reporting it in Iraqi private banks in addition to presenting and analyzing the concept of profit quality and its measurement models. Therefore, the checklist prepared for this purpose was used based on previous studies related to the subject in order to determine the level of reporting of the research sample banks by analyzing the content of the annual reports of those banks as well as adopting the Tobin's Q scale to measure the value of the economic unit and then using some statistical models to
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