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.
Studied Seen fungi water in nine stations or selected sites along the Tigris River began from the city of Mosul in the north to Qurna in episodes were measured some chemical agents and Alvezaúah water ranged pH values ??(11p) between 7.0 to 8.3 either temperatures ranged between 10to 28 m study showed isolated 22 species of 14 genera of fungi
The research aims to identify the relationship between employing future skills during teaching from the viewpoint of students of Islamic studies at the Northern Border University, as well as their attitudes towards future professions. The researcher employed the correlational descriptive approach. The tools were a questionnaire for employing future skills, and a scale for the attitude towards the future profession. The two research tools were applied to a random sample of (242) male and female students from the department of Islamic Studies, College of Education and Arts. The findings showed that the total level of employing future skills and their three axes during teaching was average. It was also found that the attitude towards future
... Show MoreThe herein research was carried out in order to identified the presence of bacteria in cervix and uterine lumen in Iraqi cattle during the different estrus phase with focusing on Protus and E coli. Estrus phases were determined by the structures which found on ovary (follicular growth for pro-estrus, mature growing follicle for estrus, hemorrhagic corpus luteam for meta-estrus and active corpus luteam for di-eatrus). Forty cervical swabs (ten for each estrus phase) and forty uterine swabs (ten for each estrus phase) were taken from macroscopically healthy reproductive animals after slaughtering and cultivated on nutrient agar and blood agar, the bacterial isolation were identified with biochemical teats. The present study found that
... Show More
It has become clear to see the role of the small and medium enterprises in the economy, and for the continuity of these projects it is necessary to supply finance from the banks, How ever the latter suffers risk of lending.
&n
... Show More
The provision of electric power is necessary for the advancement of the country's economy. It is the main engine of the economy and its various activities. It is an indicator of social welfare and it is considered as the basic pillars for achieving sustainable development (economic, social, environmental and institutional) by raising the levels of performance and meeting local needs. The problem of research was the absence of a program to audit the performance of the electricity sector contributes to ensure the application of sustainable development. The research was based on the hypothesis that the preparation of a proposed program to audit the performance of the electricity sector contributes to the achievement of The researchers sough
... Show More
This research aims to present a proposed model for disclosure and documentation when performing the audit according to the joint audit method by using the questions and principles of the collective intelligence system, which leads to improving and enhancing the efficiency of the joint audit, and thus enhancing the confidence of the parties concerned in the outputs of the audit process. As the research problem can be formulated through the following question: “Does the proposed model for disclosure of the role of the collective intelligence system contribute to improving joint auditing?”
The proposed model is designed for the disclosure of joint auditing and the role
... Show More
This research deals with the financial reporting for the non-current assets impairment from the viewpoint of international accounting standards, especially IAS 36 "Impairment of assets”. The research problem focused on the non-compliance with the requirements of IAS 36 which would negatively affect the accounting information quality, and its characteristics, especially the relevance of accounting information, that confirms the necessity of having such information for the three sub-characteristics in order to be useful for the decisions of users represented
The study problem is about the role of Shaqra University in building the mental image of the Kingdom’s 2030 vision among its female students. The study aims to examine the university’s role in providing information about the Kingdom’s 2030 vision, its role in shaping the vision’s image, the university’s role in the behavioral aspect of the vision, along with studying the extent of differences in answers of the sample individuals towards the study themes attributed to the personal variables. The researcher adopted the descriptive survey method. A sample of (1399) female students was used to achieve the study objectives. The results showed that university’s role in building the mental image of the Kingdom’s 2030 vision, among
... Show MoreObjective: To identify the role and importance of the clinical pharmacist in the Emergency Department on prevent
or reduced the medication error.
Methodology: We collected the medical file of 3400 patients, 1400 patient's file in (A) hospital, and 1000 patient's
file in each of (B and C) hospital, who admitted to the ED, at primary weekdays between 8 am to 2 pm, and
recorded all the intervention made by clinical pharmacist through an active search in clinical charts, with analysis
of the daily medical prescription. The potential severity of harm of the medication error judged by two reviewers,
a permanent emergency physician, and clinical pharmacist based on the National Coordinating Council (NCC) of
Medication Error
Due to the developments taking place in the field of communications, informatics systems and knowledge management in the current century, and the obligations and burdens imposed on the business organization to keep pace with these developments, the traditional methods of administrative decision-making are no longer feasible, as recent trends have emerged in management that focus on the need to rely on quantitative methods such as operations research.. The latter is one of the results of World War II, which appeared for the first time in Britain to manage war operations. The first method used in this field is the linear programming method. The use of operations research has developed greatly in the past years, and the methods of analysis in
... Show More