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.
Through this descriptive study of the image of the Islamic Republic of Iran in the independent Iraqi press, the researcher relies on surveys, content analysis, and observation tools. The research community selected was the Iraqi independent press, represented by the Al-Zaman, Al-Dustour, and Al-Mada newspapers. The researcher adopts the comprehensive inventory method for newspaper issues produced between October 2019 and January 2020.
The results of this study show that Iran's interference in Iraq's internal affairs was one of the most prominent components of the picture that independent Iraqi newspapers seek to paint about the Islamic Republic of Iran.
Land Transport regards a main element in the In Fra – structure of the national economy where distance and time shortness, open new opportunities of work, develop the different regions and rise the standard of living….
It is necessary to emphasize that the circumastances surrounding Iraq such as wars, economic sanctions, blockade occupation effected negatively upon economic Indicators of land Transportion including Value of output Value added contraction of Investment allocation and Investment expend tuer and the period of implementation and fulfillment of the projects of Land Transport to be ready to offer their service in underdeveloped country Like Iraq aiming to satisfy Fast and acomprehensi
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The research aims at measuring the impact of visual media on the development of the tourism services sector, which is a field study for the public. It aims at determining the impact of visual media on tourism sector development, clarifying the concept of visual media and its functions and studying the role of media in the development of tourism culture among the public. For a sample of the employees of the University of Baghdad, consisting of (120) male and female. A questionnaire was prepared for this purpose consisting of (21) questions distributed to the sample. The data were analyzed and the hypotheses were tested using the statistical program spss to unload the results and calculate the frequencies, percentages and correlati
... Show MoreThe current research aims to examine the effect of the rapid learning method in developing creative thinking among second-grade female students in the subject of history. Thus, the researcher has adopted an experimental design of two groups to suit the nature of the research. The sample of the study consists of (36) randomly selected students from Al-Shafaq Secondary School for Women, which are divided randomly into two groups. The first group represents the experimental; it includes (31) students who studied the subject of history using the quick learning method. The second group, on the other hand, is the control group, which consists of (32) students, who studied the same subject using the traditional way. Before starting with the exp
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The monogenean Gyrodactylus taimeni Ergens, 1971 was recorded in this study for the first time in Iraq from gills of the common carp Cyprinus carpio Linnaeus, 1758. The description and measurements of this parasite as well as illustration were given. In addition, a list of species of Gyrodactylus so far recorded from C. carpio in Iraq is also included together with a list of all other hosts recorded for each gyrodactylid species.
To avoid the negative effects due to inflexibility of the domestic production inresponse to the increase in government consumption expenditure leads to more imports to meet the increase in domestic demand resulting from the increase in government consumption expenditure. Since the Iraqi economy economy yield unilateral depends on oil revenues to finance spending, and the fact government consumer spending is a progressive high flexibility the increase in overall revenues, while being a regressive flexibility is very low in the event of reduced public revenues, and therefore lead to a deficit in the current account position. And that caused the deficit for imbalance are the disruption of the
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With the increase in competition between insurance companies in addition to the increasing numbers in the number of insurance companies, whose number decreased to (32) private companies until the end of the year (2020). The blue ocean at the level and its effects on increasing the market share. Therefore, the two researchers tested the hypothesis and the research concluded that there is a relationship A .Also the researcher put some recommendations the most prominent is that the invention is considered one of the successful strategies an d the company has to encourage the employees according to inventive thoughts
Every researcher must say that the world in continually progress toward the best and that
the Arab and Islamic civilization had produced much of systems and virtuous educational
practices which raised from Islamic heritage. This nation was not isolated from external
world, but it was made a clear active for promote the banner of other nations which entered
under her influence to promote Islamic banner and Muslims. Consequently also Muslims are
affected and influenced, this resulted a clear impact in the civilization and educational
ideology especially in the contemporary teaching methods.
چکیده
کشورعراق مرزهای زمینی ایران دارد که علاوه بر این ، مشترکات وروابط متعدد اقتصادی ،سیاسی، فرهنگی ودينى ميان هر دو ملت می باشند . عراق بعلت موقعیت جغرافیایی ونزدیکی به ایران سهم بیشتری برای ورود واژه های فارسی به لهجه ی خود داشت ، علاوه بر این رویدادهای سیاسی متقابل قدیم و جدید میان دو کشور سبب ورود بسیاری از لغات فارسی به لهجه ی عراقی شد که کاربرد این لغات هم اکنون در لهجه ی عراقی آشکار است ، ای
... Show MoreOne of the most common procedures in oral surgery is the removal of impacted mandibular third molars, often followed by pain, swelling, alveolitis, and trismus. Purpose. To compare the outcomes of the intrasocket application of 1% hyaluronic acid oral gel (HA) and advanced platelet-rich fibrin (A-PRF) on the expected postoperative complications, pain, swelling, and trismus follow the surgical extraction of the impacted mandibular third molar. Material and Methods. A randomized controlled trial was conducted at the Oral and Maxillofacial Surgery Unit, Dental Teaching Hospital. Healthy patients who required surgical removal of the impacted mandibular third molar were divided randomly into three groups. The extraction site of the group
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