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.
Objective(s): The present study aims at identifying the Iraqi Colleges of Nursing Deans' leadership
behaviors effectiveness and faculty members' motivation towards work in these colleges.
Methodology: Descriptive design has been used for the sample survey manner, which is the
appropriate approach to the study of social phenomena in the field where provides data on the reality of
these phenomena and relations between the causes and consequences and an analysis of it and perhaps
the factors affecting it and how it appears. The study relies on a questionnaire to collect data from the
participants which is composed of (86) items distributed on three axes: First, the demographic
characteristics which are composed of (8) i
The sustainable competitive advantage for organizations is one of the requirements for value creation, which centered on the possession of scarce resources that achieve maximum flows to invest in intellectual capital, if what has been interest in them, measured and employed the way properly and style, so I figured the need for new technologies to enable organizations to measure the intellectual and physical assets and to assess its performance accordingly, so it sheds search light on the measurement of the added value of existing knowledge using the standard value-added factor is the intellectual (value added intellectual coefficient) (VAIC) and to develop a set of assumptions about the extent of the difference between the sample
... Show More
Scientific research on the environment of the Iraqi marshes, its beauty and its characteristics is considered one of the most important functions of Iraqi universities and scientific institutions, because of its great historical impact related to the identity of Iraq and the Iraqis and the basis of science and science, through which the first letter and the first human civilizations were established and in the same importance technical research is among the most important functions of departments Institutes and colleges of the arts, research centers and museums inside and outside Iraq. Also, research centers specialized in the natural environment of Iraq, including the marshes. Therefore, it is hoped that this research will develop the a
... Show More
The research's aim is to place two teaching methods ( total and analytical method) and to know which one of them is better than the other in teaching the counter-attack with Epee. The researchers have used the experimental method for being considered suitable to solve the problem of the research. The sample of the research includes third –stage female students of college of physical education and sport sciences / Baghdad University in the subject of fencing, their number amounted 60 female students. It has been used SPSS for processing the results. They have concluded that the two groups of the research and the two methods (( total and analytical) have learnt the counter- attack of the two over mentioned groups. they have recommended to c
... Show MoreThe adopted method in the teaching of history is conservation and indoctrination in all grades, and this will lead to a lack of students interact with teachers in the course of the lesson, and poor use of teachers to questions that raise students' thinking during the lesson, which leads to a lack of interest in the topic of the lesson and wasting opportunities contribution making it the teacher at the center of the educational process, and to provide arrogating the researcher to contribute to teaching style with the belief that the use of this method of teaching could lead to overcome the difficulties and problems faced by the teaching material.
And there are educational complexes integrated approac
... Show MoreThe purpose of this research is to design a list of the scientific and moral values that should be found in the content of the computer textbook for the second intermediate grade, as well as to analyze the content of the above- mentioned book by answering the following question:
What is the percentage of availability of scientific and moral values in the content of the computer textbook for Second Intermediate grade issued by the Iraqi Ministry of Education / the general directorate of the curriculum, for the academic year (2017-2018)?
In order to achieve the research objectives, the descriptive method (content analysis method) was adopted. The research community has been iden
... Show More
The effectiveness and quality of legislation depend on the extent to which it relates to political , economic ,social ,geographical , health and moral realities , so the unrealistic legislation and its failure to address all the problems facing society make these legislation out of reality , this requires this legislation be able to regulate all aspects related to public health in society in exceptional circumstances such as cases of wars ,diseases and pandemics as outbreaks of corona virus in the word ,this study focuses on the effects of legislative omission on the effectiveness of the administration when performing its tasked in health administrative control in exceptional circumstances in light of spread of corona virus pandemic in Iraq
... Show MoreTeaching through the system of personal learning, known as (Clare's plan) is amongst the most prominent plans which depend on self-education, as it received worldwide recognition. The plan lets the learner achieve learning by depending on himself after being familiar with the educational goals given to him, then he starts to solve the exercises and the drills accompanying the unit. After that, he checks his achievement by answering the self-evaluation tests. This method offers more opportunities for personal interaction than do the traditional systems, and individual leaning is a methodical expression aims at taking care of the learner and making him the locus of the processes of teaching and learning.
Aims of the study
... Show More