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.
The research deals with the important and modern two subject (career path and the type of training program), and tries to find identify the extent of the impact of the requirements of a career path in determining the type of training program in the Ministry of Oil.
In order to achieve the aim of the research was the formulation of the following hypothesis: the impact of the requirements of the career path a meaningful moral influence in determining the type of training program.
The survey was adopted in the search, and sample consisted of (75) people were a factor in the Oil Ministry of People's managers and officials and staff, and used the questionnaire as an es
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Increasing material prices coupled with the emission of hazardous gases through the production and construction of Hot Mix Asphalt (HMA) has driven a strong movement toward the adoption of sustainable construction technology. Warm Mix Asphalt (WMA) is considered relatively a new technology, which enables the production and compaction of asphalt concrete mixtures at temperatures 15-40 °C lower than that of traditional hot mix asphalt. The Resilient modulus (Mr) which can be defined as the ratio of axial pulsating stress to the corresponding recoverable strain, is used to evaluate the relative quality of materials as well as to generate input for pavement design or pavement evaluation and analysis. Based on the aforementioned preface, it is
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The city suffers from the weakness of the civil defense to provide services where there are clusters of residential Guy covered services for that requires the study of the geographic distribution of the civil defense centers in Baghdad care great because they take care of Protect the population and their own property and protect state institutions. Through a review of the problems faced it is expected that this study will help decision-makers to take appropriate steps to develop this service core
ZSM-5 zeolite was synthesis under hydrothermal conditions at 175oC. The synthesis parameters have been investigated to find optimum synthesis method. Firstly, the crystallization time has been investigated to find the optimum crystallization time. Also, the ageing time was studied. The morphology, structure, and composition of the synthesized ZSM-5 zeolite were characterized using scanning electron microscopy (SEM), pH meter, viscometer, and X-ray powder diffraction (XRD). The bulk Si/Al ratio of ZSM-5 zeolite was in the range of 9.5—11.7. The synthesized ZSM-5 zeolite with appropriate ageing time could adjust crystal size and degree of the crystallinity. The crystal size of ZSM-5 zeolite obtained at an agei
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The aim of this paper is to determine the role of job engagement in the Iraqi Residency Affairs Directorate and its impact on employees, as the job engagement variable based on the Rich’s model included dimensions of cognitive engagement, emotional engagement and physical engagement. This variable has been studied in the Directorate of Residence Affairs which are one of the specialized directorates in the Iraqi Ministry of Interior. This study relied on a questionnaire as a main tool for measuring and collecting data based on the random sampling method . The sample size included 206 individuals among 400 individuals. However, the respondents were 190 whereas the final
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Chlorine doped SnS have been prepared utilizing chemical spray pyrolysis. The effects of chlorine concentration on the optical constants were studied. It was seen that the transmittance decreased with doping, while reflectance, refractive index, extinction coefficient, real and imaginary parts of dielectric constant were increased as the doping percentage increased. The results show also that the skin depth decrease as the chlorine percentage increased which could be assure that it is transmittance related.
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The form imposes its importance in the structure of the artwork through its indication of the type of relationship between the artist and his external world in all its aspects, as well as its manifestation of artistic and aesthetic values, and the multiplicity of experimental means of expression that include the artist's feelings and imagination. The form is also a recording of the events in their temporal and spatial circumstances, and in that it is of value in directing his artistic discourse with the aim of influencing the recipient with its connotations and emotional states. Horses in the drawings of Amer Al-Obaidi, and the research came within two frameworks: The first framework is the methodological framework that represents us t
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The problem of solid waste from domestic, industrial, commercial and medical sources is one of the most important problems facing the local administration in all Iraqi cities. The danger of this problem increases with the rapid increase in the population, changing lifestyles, consumption patterns, limited land suitable for landfill, and high costs of collection and disposal. This research aims to solve these problems by determining the locations of current landfills located in the outskirts of Baghdad Governorate. The ArcGIS program was used, where the sites of the landfills were determined on the map and through the available data about the areas. it was concluded that the existing landfill sites do not meet environmental conditions and
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The numerical response of Chrysoperla mutata MacLachlan was achieved by exposing the larvae of the predators to various densities of dubas nymphs Ommatissus lybicus DeBerg. Survival rate of predators’ larvae and adults emergence increased with increasing consumption . Repriductive response of predator was highly correlated with the amount of food consumed (+0.996).