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 support qualitative information regards as an additional step in the process of decision-making where the method following by companies to provide information help in the creation of value because it is very important to deliver information to investors about their stratigies and what happen truly inside the companies i.e. every case relating with the expectations of stockhotslder and the prices of markets depending on those expectation ,and if the matter isn’t that there will be lack of confidence thate couldn’t be backed again. The decisions of the investors effected by security ,economic ,political, psychological, emotional ,and financial factors .
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A study of taxonomic quality of algae attaching Three concert bridges built on the Tigris River within city of Baghdad including Al-Jadriyah Bridge in Al-Jadriyah area and the Bab Al-Mu'adam Bridge in Al-Shalajiya area, while the third site included Al-Muthanna Bridge in north of Baghdad city, for the period from Autumn 2021 and Winter 2022. The study identified 114 species of 32 Genus in which the predominance of Bacillariophceae (74 species, 14 Genus) Followed by Cyanophyceae (30species, 12 Genus) and 10 species (6 Genus) of Chlorophyceae. The study showed an increase in species of Bacillariophceae, Cyanophyceae which has the ability to secretion gelatinous substances that enable it to stick to solid stand, the number of the larges
... Show MoreEnglish has for long been one of the most widely used media of communication globally, especially in the Malaysian universities. It has been termed as a Lingua Franca because it is shared with other languages which are considered first languages by different speakers. For this reason, English as a Lingua Franca (ELF) has attracted a number of researchers to investigate its variety via other languages in various communities. The objective of this paper is therefore to establish the strategies which are employing by the international students at the National University of Malaysia/ UniversitiKebangsaan Malaysia (UKM) as an example of one of the Malaysian universities; when they e
... Show MoreSeasonal variations of the species composition and abundance of Cladocera were studied in two stations at the end of the Tigris River and one station at the confluence of the Tigris with Euphrates area, at the beginning of the Shatt Al-Arab River in Al-Qurnah North of Basrah Province, from October 2015 to August 2016. Samples of zooplankton were collected by plankton net 100-µm. mesh size. The population density of Cladocera ranged between 1 Ind /m³ during summer and 211 Ind./m³ during winter at station 1 (Al-Jewaber Bridge). A total of 16 species of Cladocera belonging to 12 genera were recorded in the study. The average density of Cladocera ranged from 23.2 ind./m3 at Station 2 (Hamayon Bridge) to 53.7 Ind./m3
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Soft clays are generally characterized by low shear strength, low permeability and high compressibility. An effective method to accelerate consolidation of such soils is to use vertical drains along with vacuum preloading to encourage radial flow of water. In this research numerical modeling of prefabricated vertical drains with vacuum pressure was done to investigate the effect of using vertical drains together with vacuum pressure on the degree of saturation of fully and saturated-unsaturated soft soils. Laboratory experiments were conducted by using a specially-designed large consolidometer cell where a central drain was installed and vacuum pressure was applied. All tests were conducted
... Show MoreObjective: To identify of the effect of the different concentrations of the special liquid (for mixing the investment, Gilvest)
and mixed with water/powder ratio on setting time of phosphate–bonded investment.
Method and materials: The present study is (60) specimens made from phosphate bonded investment divided into (4)
groups (control and experimental groups), (15) specimens for each group. The Gillmore needle device is used to setting
time of phosphate bonded investment mixed with different concentration of Gilvest and water.
Results: Showed that there is a high significant difference (P<0.01) between each groups in the ANOVA test and a
significant difference (P<0.05) between the group (A) and control group i
Abstract
Agricultural investment is one of the main requirements in most economies of the world for its importance in the development of the agricultural sector through the agricultural and technological infrastructure and agricultural research, as well as its impact on most economic, social and service activities, especially if managed and employed scientifically, which generates income and productive capacities and services and new commodities, Unemployed as agricultural investments in Iraq fell significantly after 2003 due to economic, political, social
Since the beginning of the second decade of the twenty-first century, Saudi Arabia tried to pursue an open foreign policy towards many countries in the Horn of Africa, especially with Ethiopia and Somalia, due to the geostrategic qualities that these two countries possess.Despite the development of Saudi foreign policy towards Ethiopia and Somalia, it was soon affected by the tension after the events that the Gulf states went through, that is, the Qatari crisis with Saudi Arabia,especially after most of the countries of the Horn of Africa adhered to a policy of neutrality towards the Gulf-Gulf crisis.
Thus it is expected that despite the geographical proximity and the historical, economic and political relations between Saudi Ara
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