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 main source of water supply in Iraq is the surface water, especially Tigris and Euphrates Rivers and their tributaries. In the recent years there was a great drop in the water levels of Tigris River within Baghdad City which had affected the operation of twelve water supply projects located on the banks of Tigris River in Baghdad City, due to significant climate changes, and the expansion of hydraulic construction (dams) and implementation of new irrigation projects in Turkey, these factors have greatly reduced the water flowrates of river by about 46%. In the present study the flow characteristics of Tigris River within Baghdad City was studied, the reach involved was about 49km in which it represents the urban zone
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To study the striking perturbations of ionospheric Total Electron Content (TEC) before, during, and after the earthquake (M≥5) for earlier prediction to avoid calamities, ionospheric TEC data are taken by using red shift technique from two-frequencies GPS signals.. Tohoku earthquake on 11th March 2011 is chosen as case of our study (A magnitude M9.0 earthquake reported by the US Geological Survey gives its origin time at 05:46:23 UTC; the epicenter was located at 38.322oN, 142.369oE of the east coast of Honshu). The study was made 15 days before and 15 days after earthquake occurred over Japan at four different geographic positions, Kokubunji (35.7oN, 139.5oE), Wakkanai (45.2oN, 141.8oE), Yamagawa (31.2oN, 130.6oE) and Okinawa (26.7oN,
... Show MoreThis work aims to provide a statistical analysis of metal removal during the Magnetic Abrasive Finishing process (MAF) and find out the mathematical model which describes the relationship between the process parameters and metal removal, also estimate the impact of the parameters on metal removal. In this study, the single point incremental forming was used to form the truncated cone made of low carbon steel (1008-AISI) based on the Z-level tool path. Then the finishing was accomplished using a magnetic abrasive process based on the Box-Behnken design of the experiment using Minitab 17 software was used to finish the surface of the formed truncated cone. The influences of different parameters (feed rate, machining step s
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In this study the (geoelectric – hydrogeologic) parameters which are obtained by the
quantitative interpretation of (80) Schlumberger Vertical Electrical Sounding (VES)
points distributed in six linear profiles within the study area are used in addition to
(6) pumping test locations for the groundwater reservoir located to the south of Jabal
Sinjar (Sinjar anticline). The studied area covers about 7920Km2. The (VES) field
readings were interpreted manually by using the auxiliary point method-partial
resistivity curve matching,then the interpreted results enhanced by using computer
software specialized for the 1D- (VES) resistivity curves interpretation. The (VES)
results analyzed by using modern techniques in or
Abstract
Tourism is one of the essential economic fields of many countries, both developed and developing. The social plays a greater role in the continuous awareness of a tourist culture based on the need to attract tourists continuously. the tourism heritage and state-owned tourism are the main factors in attracting more tourists. The interest in this strategic sector makes the country the first and most active framework in the development of appropriate mechanisms for investment in this sector, all within the framework of sustainable development of society through the rational use of resources obtained by various bodies in the implementation of seve
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Contemporary developments in various sciences and the impact of technological changes require an integrated vision of the activities and work of the organization in Iraq in light of the high costs of products and their low quality compared to imported products of high quality and low cost, and the need to use modern cost techniques based on a clear and specific philosophy that contributes to increasing the efficiency and effectiveness of management In the business environment and how it can contribute to reducing product costs and being environmentally friendly at the same time, it is no secret that the main goal of most organizations is to maximize profitability and reduce costs to the minimum, but this matter is not achieved autom
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