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.
Dissolution of gypsum rock in water is significant, which may result in hydrocarbon reservoir formation and evaporate deposits. However, the complexity of the gypsum dissolution process is still of interest because of its uncleanness that requires more critical analysis. The objectives of this experimental study are emphasis on the dissolution characteristics of gypsum rock under room temperature and by various types of water; namely: deionized, tap, fresh, acidic, well, and normal rainwatre. In addition, the influences of dissolution on gypsum rock's mechanical and physical characteristics. Gypsum rock was obtained from Agjalar area, in the southwest of Sulaymaniyah city, Northern Iraq. Experimental results show that we
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The problem of research is the need to find out the obstacles and difficulties facing women in accessing leadership positions at the University of Baghdad from their point of view. The importance of research comes from the importance of women in the university and their vital role in the development of society. The research objectives summarized the most important obstacles facing women Access to the leadership positions in the university and the relative weight of these obstacles as well as trying to identify differences in their view of these obstacles according to the variables of specialization (scientific, human) and the scientific title (Professor, Assistant Professor, Teacher, Assistant Lecturer). They were (144) university female
... Show MoreThe study aimed to identify the degree of academic leaders practices at the University of Northern Border for creative leadership, which attribute to different variables (nature of work, employer, gender, years of experience in administrative work at the university). To achieve the goal of the study, the researcher used the descriptive approach survey. Therefore, the researcher used a questionnaire as a study tool, which consisted of (40) items that included dimensions (sensitivity to problems, initiative, originality, flexibility). The study sample consisted of (240) participants included (agents of colleges, and supporting deanships, and their employees) during the second semester of the academic year 1439/1440 AH. The results showed t
... Show MoreThe present study investigated the impact of fuel kind on the emitted emissions at the idling period. Three types of available fuels in Iraq were tested. The tests conducted on ordinary gasoline with an octane number of 82, premium gasoline with an octane number of 92, and M20 (consist of 20% methanol and 80% regular gasoline). The 2 liters Mercedes-Benz engine was used in the experiments.
The results showed that engine operation at idle speed emits high levels of CO, CO2, HC, NOx and noise. The produced emission levels depend highly on fuel type. The premium gasoline (ON=92) represents the lower emissions level except for noise at all idling speed. Adding methanol to ordinary gasoline (ON=82) showed high levels of emi
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The ceramic compound Mg1-xSixAl2O4 (x= 0, 0.1, 0.2, 0.3, 0.4) was prepared from nano powder of Al2O3 and MgO doped with Nano powder of SiO2 at different molar ratios. The specimens were prepared by standard chemical solid reaction technique and sintered at 1450 oC. Structure of the specimens was analyzed by using X-ray diffraction (XRD). The X-ray patterns of the specimens showed the formation of pure simple cubic spinel structure MgAl2O4 phase with space group of ̅ . The average grain size and surface topology were studied by atomic force microscopy. The results showed that the average grain size was about 73-90 nm. The DC electrical properties of the specimen were measured. The apparent density was found to increase and the porosity a
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Oil is considered the most important source for providing the funds for the national economic sectors. The revenues of oil constitute %95 of the GPD. Therefore, the development of the remaining sectors depend on oil..
The Iraqi Oil Marketing Organization (SOMO) depended on the a unified price for all the buyers, That may not reflect the real value of market and did not contribute in marketing the type of heavy oil. Then, to what extent had SOMO been able to market the light and heavy crude oil in a way that contains the expected increase in the crude oil production.
(1)
Poverty is defined as a low standard of living in the sense that a poor person can not afford a minimum standard of living. The phenomenon of poverty is one of the most serious problems that must be dealt with seriously. This phenomenon has persisted in Iraq for decades because of the harsh economic conditions and unstable security conditions due to the crises it has faced since 2013. This study requires much study and analysis. And rural areas as a special case. In this study, the researcher examined the poverty line as a criterion in estimating the poverty indicators, which include (poverty percentage H, poverty gap PG, poverty intensity PS), based on the continuous social and economic survey data for households in 2014. The ma
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Abstract
The study aimed to identify the expansion in granting credit to Iraqi banking institutions and its impact on the financial position of Iraqi banks in terms of revenues, profits, expenses and property rights in banks, as the expansion in granting bank credit will correspond to an increase or decrease in some items of the balance sheet and the financial position of banks, so the problem of the current study It will be determined through whether the expansion of granting bank credit will affect the financial position of Iraqi banks or not by studying the selected research community of the 10 Iraqi banks listed in the Iraq Stock Exchange, The research sample included the u
... Show MoreThe current study aims at identifying the impact of using learning acceleration model on the achievement of mathematics for third intermediategrade students. Forachieving this, the researchers chose the School (Al-Kholood Secondary School for Girls) affiliated to the General Directorate of Babylon Education / Hashemite Education Department for the academic year (2021/2021), The sample reached to (70) female students from the third intermediate grade, with (35) female students for each of the two research groups. The two researchers prepared an achievement test consisting of (25) objective items of multiple choice type, The psychometric properties of the test were confirmed, and after the completion of the experiment, the achievement test wa
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