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.
المقدمة
تتعامل الجهات الضريبية في مختلف دول العالم بأساليب عديدة لجباية الضرائب من المكلفين بغض النظر عن فئات وأصناف هؤلاء المكلفين،وفي العراق تم اعتماد العديد من الأساليب لجباية الضرائب على امتداد المدد الزمنية المتعاقبة،وكان لأسلوب التقدير الذاتي وهو أحد تلك الأساليب مجالاً للتطبيق خلال مدة زمنية معينة،حيث جرى تطبيق هذا الأسلوب على وحدات اقتصادية معينة، وبالرغم من المساوئ التي قد ترافق تطبيق
... Show More
(10)
(6)
(4)
Purpose: The aim of this study was to gain insight into causes of time delays and cost overruns in a selection of thirty case projects in Iraq. Delay factors have been studied in many countries/contexts, but not much data exists from countries under the conditions characterizing Iraq during the last 10-15 years.Design/methodology/approach: A case study approach was adopted, with thirty construction projects selected from the Baghdad region, of different types and sizes. For the case of the study, the participants in the projects provided data about the projects through the data collection tool distributed through the questionnaire directed to them. Statistical data analysis was used to build statistical relationships between time and cost d
... Show More
Magnetosphere is a region of space surrounding Earth magnetic field, the formation of magnetosphere depends on many parameters such as; surface magnetic field of the planet, an ionized plasma stream (solar wind) and the ionization of the planetary upper atmosphere (ionosphere). The main objective of this research is to find the behavior of Earth's magnetosphere radius (Rmp) with respect to the effect of solar wind kinetic energy density (Usw), Earth surface magnetic field (Bo), and the electron density (Ne) of Earth's ionosphere for three years 2016, 2017 and 2018. Also the study provides the effect of solar activity for the same period during strong geomagnetic storms on the behavior of Rmp. F
... Show More
(1)
The aim of the study is to prepare a measure of the role of academic coaches in handball skill performance from the point of view of the researchers. The researchers used the descriptive approach in the research procedures as it is an appropriate approach in achieving the research objectives. The next question is: To what extent will the players benefit from the academic coach in developing their skill performance? This is the measure of the role of academic coaches. From 16 items, the research community included players (Al-Karkh Club - Al-Hashd Sports Club) and the number of players was (Al-Karkh 14 - Al-Hashd 14). The research sample was intentional and represented (the research community 100% The researchers concluded that measuring the
... Show MoreAbstract
The aim of the research is to develop specific skills of 21 century, one schedule, renewable: (sex, years of experience, academic degree) from the viewpoint of the research sample. The descriptive tool was used to collect information for research purposes. It was applied to a sample of (339) male and female teachers in Al-Ardhah governorate schools to teach Jazan. The application was carried out in the second semester of the year 1442 AH. The research concluded with a set of results, the most important of which are: the approval of the sample members to a large extent on the expressions of the role of school leaders in the practice of developing male and female teachers in acquiring these three skills fr
... Show MoreThis study dealt with the management strategy as an independent variable and the integrated industrial distribution as a variable. The study aimed at finding the integrated industrial distribution that fits with the management strategy in providing the needs of the firm on the one hand and reducing the cost of management that is reflected in increasing its profits.
The researcher selected the data from (130) decision makers in the corporation and used the questionnaire as a tool for collecting data and used a set of statistical tools and tools suitable for the nature of information and were processed using the data analysis system (SPSS version 24) Based on the analysis of the responses of the sample and the test of correlation and
The present study deals with the effect of teaching speaking Strategies (SS) on EFL Iraqi College students. The use of speaking strategies not only solves learners’ communication problems, but also enhances the learner’s interaction in target language, and improves their oral proficiency .The aim of the study is to find out the effect of teaching SS used by EFL College students .The learner of the first stage is population of the study at the Department of English, College of Education /Ibn-Rushd .The sample consists of (60) students distributed on experimental group(A) as well as control group(B) each group contains (30) students . In order to achieve the aim of the study, questionnaire has been constructed to be taught on the experime
... Show MoreAbstract
On 11/1/2008 amounts of snows fell on various sections of Iraq, one of
which is Baghdad. The analysis process of climatic maps proved that the
advance trough of Sudanese depression towards the city is the reason behind
the formation of this weather state supported by could trough in the (500) mb
pressure level. .
The research concluded that the phenomenon of global warming
witnessed by the world recently had a main role in the occurrence of this
phenomenon due to the raise in earth temperature as a result of evaporation
rate increase leading to an increase in water vapor and cloud formation with
high tops and low bases which form sows with high rates accumulating at high
and moderate latitudes le