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.
In contemporary cities, the expansion of the use of vehicles has led to the deterioration of the urban environment. To counter this, many concepts and strategies emerged that attempted to regulate mobility in cities and limit its effects. The concept of a "complete street" is one of the modern trends concerned with diversifying means of transportation and reducing the disadvantages of mechanical transportation methods This paper discusses the role that complete streets can play in developing the urban environment in the Alyarmok District of Baghdad, which suffers from traffic congestion and its associated problems.In this study, 104 people were surveyed in the Alyarmok region, and the linear regression method was used to analyze their op
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Care research examining the relationship between the variables of search presidents (employee training and organizational commitment) to determine the effect of the training of employees in organizations in achieving organizational commitment of employees towards their organizations and by the fact that training is one of the most important activities adopted by the administration and by which can benefit realized for workers and for the organization .ttjsd problem Search lack of training considered as a factor of the important factors in the development of staff skills and development work in many Iraqi companies, including vegetable oils company (where to look), which in turn raises the relevance and commitment
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Dairy wastewater generally contains fats, lactose, whey proteins, and nutrients. Casein precipitation causes the effluent to decompose into a dark, strong-smelling sludge. Fluid waste contains soluble organic matter, suspended solids, and gaseous organic matter, which cause undesirable taste and smell, grant tone and turbidity, and advance eutrophication, which plays an essential role in increasing biological oxygen demand (BOD) in water. It also contains detergents and disinfecting agents from the rinses and washing processes, which increase the need for chemical oxygen (COD). One of the characteristics of dairy effluents is their relatively high temperature, high organic contents, and wide pH range, so the discharge of wastewater into
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The current study aimed at identifying the impact of each of the full and part time summer enrichment programs on the performance of gifted students. Moreover, it aimed to study the difference between the full and part time programs on the performance of gifted students. The study sample consisted of (115) students from the full time programs and (137) students from the part time programs, they have been randomly selected from the gifted students participating in the full and part time summer enrichment programs. The researcher used the scale of student performance. The results indicated that there were statistically significant differences between the averages of the pre and post applications of the
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Federico Garcia Lorca is considered in european and american literary circles as revolutionary symbol of contemporary literature writer through close association with the concerns of his country and the world, and also through the violent propensity to freedom, emancipation and innovation. This personal multi-talent has a significant impact in the spanish literary movement, in particularly, and in world, in general. If Lorca has andalusia blood, is no stranger to contemporary arab man to read to him, and contemplates his experience analyst and literary critic. This research is serious study of this character. There is no doubt the reader will put in front of many facts about personali
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يهدف البحث إلى وضع إطار معرفي ومفاهيمي شامل لموضوع البحث, واغناء القارئ والمستفيد بالمعلومات الوافية عنه وتقليص الفجوات المعرفية للمهتمين به وقياس مدى ما هو متوفر وغير متوفر من المتطلبات الأساسية والضرورية لإنشاء صناديق التحوط في البيئة العراقية, وتمثلت صناديق التحوط بالمتغير الرئيس للبحث اما المتغيرات الفرعية فشملت (المتطلبات المالية, المتطلبات البشرية, البيئة التشريعية, الب
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The present work describes the adsorption of Ba2+ and Mg2+ions from aqueous solutions by activated alumina in single and binary system using batch adsorption. The effect of different parameters such as amount of alumina, concentration of metal ions, pH of solution, contact time and agitation speed on the adsorption process was studied. The optimum adsorbent dosage was found to be 0.5 g and 1.5 g for removal of Ba2+ and Mg2+, respectively. The optimum pH, contact time and agitation speed, were found to be pH 6, 2h and 300 rpm, respectively, for removal of both metal ions. The equilibrium data were analyzed by Langmuir and Freundlich isotherm models and the data fitted well to both isotherm modes as indicated by higher correlation of deter
... Show MoreThis study was conducted to determine the effects of concentration of hydrochloric acids, temperature, and time on the hydrolysis of soya proteins (defatted soya flour) by determining the value of total protein nitrogen concentration, and amino nitrogen concentration of protein, peptides, and amino acids, and then calculated the hydrolysis rate of proteins.
The variables of the conditions of hydrolysis process was achieved in this study with the following range value of tests parameter:
- Concentration of HCl solution ranged between 1-7 N,
- Hydrolysis temperature ranged between 35-95 °C, and
- The time of hydroly
This research includes depositionof thin film of semiconductor, CdSe by vaccum evaporation on conductor polymers substrate to the poly aniline where, the polymer deposition on the glass substrats by polymerization oxidation tests polymeric films and studied the structural and optical properties through it,s IR and UV-Vis , XRD addition to thin film CdSe, on of the glass substrate and on the substrate of polymer poly-aniline and when XRD tests was observed to improve the properties of synthetic tests as well as the semiconductor Hall effect proved to improve the electrical properties significantly
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Bruggeman's symmetric effective-medium model of vanadium oxide is introduced, in which the transmittance was studied because of its importance in the subject of smart windows, it was studied from ( 5 nm-1000 nm) for each of the regions of the electromagnetic spectrum, the ultraviolet and visible region, and the near and medium sub-regions of the infrared and the results showed that the importance of studying the transmittance of vanadium oxide as a good candidate For this kind of industries. Our results showed that the small sizes of the material guarantee an almost constant and high transmittance to the visible region; this is due to the agreement of the direction of the dipoles in the material with the direction of the internal el
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