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.
This research investigates the subject of the impact of wars (as a manifestation of crisis) on architecture, and the extent of continuing wars physical and moral results of wars, even after the end of the cause of the crisis. The impact of different rebuilding which exposed to the effects of the war seems different in crisis regions.
The problem of research is about the uncertainty of the impact of the way chooses for reconstructing the buildings after wars in the continuity of the crisis of war. The goals of this research are to clarify the influence of methods of reconstruction of buildings in a city chosen which is Beirut, on the continuation of the war crisis with the argument of demolishing and rebuilding newly or keeping tr
... Show MoreThis paper was conducted to identifying the body growth averages for the infants of the age (3-6) months and their relation with brest (natural ) or artificial feeding The results showed that the higher percentage was for the infants with the natural feeding in comparison with those of the artificial or mixed feeding. Also there was a clear increase in the average of the body growth for those with the natural feeding and such results were closer to the standard criterion. While the averages of body growth for those with the artificial or mixed feeding were low. In addition, it was clear that the averages of body growth of the i
... Show More
Is the efficiency of physical and your endurance is of great importance for some activities and field, as it whenever the situation has improved student career was able to perform physical exertion more with energy saving efforts, so the identification of physical aptitude and endurance private students, was based on that there are positively correlated the carrying of training and pregnancy fact on the shoulders of the student. In other words, physical aptitude and endurance in your control level that can be shown by the student during the performance of training and competitions. Therefore, lies the importance of research to test physical aptitude and endurance your help to reveal the career of the body in the light of their relationship
... Show MoreAbstract
The research aims to demonstrate the commitment of the Federal Financial Supervisory Bureau to meet the requirements of the International Organization of Supreme Audit Institutions (INTOSAI) 3000, the general and private supervision of performance as the highest supervisory authority in Iraq, which is the only authorized to carry out the process of monitoring the performance of government work and activities. To analyze and present the results of the survey questionnaire prepared for the compliance of the Bureau with the requirements of the general and specific criteria related to the performance control process. The researcher reached a number of conclusions, the most important of which is the commitment of the
... Show More
The research aims to know the extent of the impact of the risks of foreign exchange centers represented in commitment risks, liquidity risks, and exchange rate risks on the continuity of the economic unit. The research in the light of its presentation of the intellectual, cognitive and applied contributions about the risks of foreign currency centers and the continuity of the economic unit, and represented the research community in the banking sector, and the sample included nine private commercial banks listed in the Iraq Stock Exchange, and they relied on the research on a time series consisting of four years that extended from one year 2017 to 2020. The research problem was the impact of the risks associated with foreign currency cent
... Show More
(2)
(1)
This study includes the direct influence of (single & multi) dose of Cold Atmospheric Plasma (CAP) on the no. of platelets for mice for different exposure time (15, 30, 60, and 120) sec. the influence of CAP on mice was measured after 1, 2, 3, 7, and 14 day from exposure.
The results obtained in this study indicate that the effect of low doses of CAP on platelets was stimulatory effect in the first few hours from exposure (1day) but the high dose was inhibitory, It was found that after two weeks of exposure that the number of platelets became normal comparable to the control one, and this indicates that plasma effect was removed after this period.
Water drainage pattern in the rivers and changed the nature of the renewed feeding areas
in the basin in terms of topographic and geological conditions and climate in addition to the
human role in organizing the process flow within these basins. This study addressed the
development of the Tigris River Hydrological in the city of Baghdad and found that the
annual rate of water drainage in the Tigris River was driven down very significantly,
especially in the past twenty years, and since 1996 up to 2014 record flow rates of less than
the overall rate of discharge of water, a (950 m3 / s ), in addition to the quarterly decrease the
discharge rates, especially since the beginning of the year 2000 and took converge all fo
The Concept of the Constitution and the most Important of Human Rights
The importance of internal audit in the growing demand for services in the public and private economic units, and in the rapid growth of its systems professional, has also been recognition of the importance of internal audit quality and the quality of information provided in a long time, as well as the importance of achieving the greatest possible quality in his work to reduce accounting risks of financial reports misleading or fraudulent, which is one of the important features of the audit.
The internal audit quality are linked with the ability of auditors to detect errors in the financial statements, and their willingness to express an opinion technical neutral and non-aligned based on the results of th
... Show More
(2)