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.
Praise be to God, Lord of the worlds, and the outcome is for the righteous, and prayers and peace be upon the author of the clear communication, to whom was revealed the saying of the Lord of the worlds (And We have sent down to you the message that you may make clear to the people what has been sent down to them, and that they may reflect.)
His family, companions and followers, as for what follows:
Among the Qur’anic studies related to Islamic matters, ancient and modern, (the clear and similar in the Holy Qur’an), and due to the importance of the topic, we found the attention of scholars to it.
With many studies and research on it, and their efforts in overcoming its major obstacles, you will not find a scho
... Show MoreThe learner has face difficult in learning if not accompanied by strong motivation and directed towards the goals that set for himself,as the type of goals set by the learner for himself is behind the difference in achievement of the tasks and levels of learning, and these goals are directed and determine his behavior Academic in the way of his study and his direction towards the lecture and colleagues.
Current research aims:
- Build tools for thegoal orientations
- Measuring the goal orientations for the university studentsaccording to variables (type/class/specialization).
In order to achieve the objectives of the research, a tool was constructed for the (the Goal orientation), and the psych
... Show MoreThe decoration structure in calligraphy painting is one of the variables that characterized the structure of the calligraphic composition due to the artistic, aesthetic and expressive properties of the letters of the Arabic calligraphy, which are represented by flexibility, compliance and the ability to form. Therefore, the researcher defined his problem by asking the following question: What is the decorative structure in the calligraphic painting? The study aimed to reveal the structure of the ornamentation in the calligraphy painting, while the researcher dealt with in the second chapter three sections, the first (the ornamental concept and meaning) and the second topic (the structural characteristics of the Arabic letter in the calli
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Egypt and Ethiopia have connected in a strong relation as there are historical facts that
deepen these relations, one of these is Egypt's cooperation in establishing the first economic
and financial banking system in Ethiopia.
Beside the religious relation between The Egyptian and Ethiopian churches the Nile River is
considered one of the effective connections
That strong then the relations as it leads to some tension between the two countries because
Ethiopia believes that Egypt seeks to control the river tries to build its project over the Blue
Nile means a threat to the Ethiopian national security.
The tension continues even after the revolution of 25th of January 2011because the Nahda
dam which is a clear t
Background: presence of lingual vascular foramina and canals in the interforaminal regionmay increase the risk ofsurgical complications during implant placement or any surgical procedure in this area.Aim of this study is the radiological evaluation of the anatomic characteristic of the lingual foramina and their vascular canals in the anterior of the mandible using cone beam computed tomography. Materials and Methods: Prospective study including 72 Iraqi subjects (31 male and 41 female) ranging from 20 to 59 years, all subjects attended AL- Sharaa dental clinic in AL-Najaf AL-Ashraf city, scanned with CBCT from September 2016 to February 2017. Using 3dimentional and sagittal cross section to detect lingual foramina and their vascular canals
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AO Dr. Ali Jihad, Journal of Physical Education, 2021
This study aims to identify the impact of using the infrastructure of the Information Technology (IT) on the performance of human resources in the public universities. This process is done by doing research in the size, quality, and efficiency of the performance, also speed of achievement and simplification of procedures. Diyala University was chosen for the diagnosis through the opinions and attitudes of its employees. Consequently, suggestions that contribute to improve the performance of the employees and thus its overall performance are obtained. Another objective of this study is identifying the human resources which are currently used in academic institutions and educational services systems because the significant role of th
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The issue of auditing contracts according to the related services is one of the important topics It has also become necessary to develop traditional procedures and auditing according to international standards to improve the profession of accounting and auditing. From this standpoint, the research aims to indicate the reflection of the contracting audit in accordance with the related services on the auditor's report. in line with the new directions regarding the need to adopt international standards in the Iraqi environment as the research problem focused on the non-comprehensiveness of the audit programs that deal with auditing contracts according to assurance commitments to contribute obtaining Governing evidence, The research
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