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.
One hundred Ninty two s mples were collected from (Cooling towers) between the period 1 /l/2004-13/12/2005. The Results Rev a)ecL that physical and chemic:a) analysefor watr samples including Tempera re,, pH and cWodde concentration ranges were f01:md
... Show MoreIn this Paper, There are attempts to compare the actual Observation Days in Decametric range (18-28 MHz), For Jupiter received by UFRO Earths’ station with the Prediction Observation Days that the Jupiter can be observed at Jupiter’s suitable location. The Jupiter’s Radio Observations actual data during year 2004, was taken from (Radio JOVE Data Archive website). The determination of the prediction days carried out by using the (Radio-Jupiter pro Jove Edition) software for Jupiter radio storms at UFRO station coordinates. Some Cases are considered according to Jupiter’s altitudes and Sun location at UFRO station Sky. The conclusion is, it could be found that there are (82) number of Predictions Observation Days, and It’s found
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The aim of this research is to calculate mass transfer coefficient, kd, during cathodic protection of low carbon steel in neutral seawater (3.5% W/V NaCl in distilled water with pH = 7). Two types of cathodic protection were used:
First: Sacrificial anode cathodic protection (SACP) were a pipeline of steel carrying seawater using zinc as a sacrificial anode and with variable temperatures ranged (0 – 45oC) and volumetric flow rate ranged (5 – 900 lit/hr). It was found that the kd increases with increasing temperature and volumetric flow rate of seawater, where kd ranged (0.24×10-6 – 41.6×10-6 m/s).
Second: Impressed current cathodic pr
... Show MoreA new scheme of plasma-mediated thermal coupling has been implemented which yields the temporal distributions of the thermal flux which reaches the metal surface, from which the spatial and temporal temperature profiles can be calculated. The model has shown that the temperature of evaporating surface is determined by the balance between the absorbed power and the rate of energy loss due to evaporation. When the laser power intensity range is 107 to108 W/cm2 the temperature of vapor could increase beyond the critical temperature of plasma ignition, i.e. plasma will be ignited above the metal surface. The plasma density has been analyzed at different values of vapor temperature and pressure using Boltzmann’s code for calculation of elec
... Show MoreIt is no secret to everyone that the Arab individual suffers from poor self-awareness and political awareness, which made the state and the importance of its existence and preserving its institutions not among his interests, which made researchers wonder about the possibility of strengthening it and the extent of its impact on the future of building the contemporary Arab state, so the study attempted Addressing the issue of community awareness and its impact on building the state through a clear intellectual vision that blended what is social and political to define the concept of community awareness and highlight its importance and role as a basic pillar in shaping and building modern Arab countries. In the Arab world and ways to enhanc
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The design fabrics of the most important episodes that are at the core process rhetorical communication, until they became these episodes ample room for research and investigation, and the issue of non-familiar formality is nothing but the result of those relationships Constructivism, which is the result of an effort builders coherent activate the shape and attributes of phenotypic, therefore it will cause him a lot of questions about his and founded the organization in order to activate the speech communication between the product(cloth)and the receiver .On this basis, the research problem identified on imposing the question follows:1. Does the non-familiar formal role in enriching communication discourse of women's fabric designs?2. Ar
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The banking sector is a cornerstone of the national economy because of its large role of economic development of a country, which requires the advancement of this vital sector and interest in all the accompanying changes to him in order to survive and grow and continue Accordingly dealt Find reversal (organizational culture, on the quality of banking service ) sought search to achieve a number of cognitive and practical goals by selecting (10), especially among the working banks in Iraq Iraqi banks and the period is the surveyed period (2005-2014) embodied the research problem in the dialectical relationship between the (organizational culture) and its impacts on banking service quality.
Through a set of
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The study aims to know the nature of the expected relationship between market share management strategies and the variation in the performance of the shares of a number of Iraqi industrial companies listed in the Iraqi Stock Exchange. For the period (2005-2018) in the light of both the monthly closing prices and sales volume during the research period, the (Panel Data) method was relied on through a stylistic test (fixed effects model and random effects model), and the results determined the need to adopt the fixed effects model method for sample data and test Assumptions, the results showed the positive impact of market share according to its strategies on the performance of stocks according to its studied indicators (Treynor index
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