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.
Portland cement is considered the most involved product in environmental pollution. It is responsible for about 10% of global CO2 emissions [1]. Limestone dust is a by-product of limestone plants and it is produced in thousands of tons annually as waste material. To fulfill sustainability requirements, concrete production is recommended to reduce Portland cement usage with the use of alternative or waste materials. The production of sustainable high strength concrete by using nanomaterials is one of the aims of this study. Limestone dust in 12, 16, and 20% by weight of cement replaced cement in this study. The study was divided into two parts: the first was devoted to the investigation of the best percentage of replacement of waste
... Show More
(10)
The present studies are focused on the modification of the properties of epoxy resin with different additives namely aluminum, copper by preparing of composites systems with percentage (20%, 40% and 50%) of the above additives. The experimental results show that the D.C of conductivity on wt% filler content at ( 293-413 ) K electrical conductivity of all above composites increased with temperature for composites with filler contact and find the excellent electrical conductivity of copper and lie between (2.6*10-10 - 2.1*10-10)?.cm . The activation energy of the electrical conductivity is determined and found to decrease with increasing the filler concentration.
Improving the quality of health services in the health sector is an important and necessary matter that must be taken care of and improved, and this study seeks to demonstrate the role of quality costs in improving the quality of health services and achieving a high level of quality to satisfy the beneficiaries and to provide health services of good quality, and the research concluded that the main point of service provision Good health is the costs of prevention and evaluation (costs of quality conformity) and attention to it, and that technical competition contributes greatly to the development of the level of quality, as well as the use of health and medical staff with competent expertise, and that the costs of internal failure and th
... Show MoreThe main objective and primary concern to every investor not only to achieve a greater return on his or her investments, but also to create the largest possible value of these investments the, researchers and those interested in the field of investment and financial analysis try to develop standards for performance valuation is guided through the  
... Show MoreThe Marshlands cover an area of about 24% of the land area of Iraq, which gives it special importance to the country with its resources, resources and human capabilities, and because the conditions of this region are different from other areas environmentally and living necessitates subject to certain design principles achieve sustainable environmental integration to maintain them from For future generations, the idea of research is crystallized by the interest of environmental organizations and urban designers in planning and establishing special laws to exploit the region environmentally, economically and tourism, especially after the current focus of the country's economic revival. T tourism and begin the development
... Show MoreThe current research aims to identify the level of digital skills of kindergarten teachers, identify the level of professional competence of kindergarten teachers, as well as to identify the relationship between digital skills and the professional competence of kindergarten teachers. The current research was determined by kindergarten teachers in the second Baghdad / Karkh Education Directorate for the academic year (2021-2022). The research sample consisted of (100) teachers chosen in a simple random way. To achieve the objectives of the research, the researcher developed a digital skills scale of (20) items and a scale of professional competence consisting of (22) items. The results revealed that kindergarten teachers have a high level
... Show MoreThis study has been conducted to investigate the influence of preservatives(sodium propionate and potassium sorbate) at different levels to extend the storage life of laboratory processed biscuit.The results have shown that When%0.10 sodium propionate was added bacteria and fungi was not found for three months while found in the fourth month of storage.However bacteria and mold didnot grow until the sixth month of storage as %0.20 and %0.30 concentration was used. On the other side as %0.03 potassium sorbate was used,the growth of bacteria was cheched for 3 months and 4 months for molds..When %0.06 potassium sorbate was used no growth of bacterial or mold was found until the sixth month of storage . Three types of bacteria have been appeare
... Show More
Abstract:
The research aims to achieve defining the concept of environmental quality and associated costs. Studying the impact of environmental quality costs on the performance of economic units. Measuring the relationship between environmental quality and environmental performance of the units. Where the research problem is represented in the weak awareness of some economic units of the importance of environmental quality costs and their impact on evaluating environmental performance, and this leads to neglecting environmental considerations and not improving environmental performance effectively, which negatively affects the en
... Show MoreA developed model has been put for the hypothesis of capturing moons in explaining the origin of Jupiter moons, and study the change of the orbital properties of these satellites as well as the distance from the planet. Jupiter moons were divided into two types according to their physical and orbital properties, they are the moons , which are formed from the same material as the planet, so it was named the original moons ,while the moons that have been captured from the surrounding space was renamed exotic moons . And the moons of exotic origin asteroid belt and the Kuiper belt in the region which is behind Neptune, the origin of each clique of moons is an asteroid fragmented after colliding previously with another body and
... Show More