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.
11-22 Description An apology may be defined as “the act of declaring one’s regret, remorse or sorrow for having insulted, failed, injured, harmed or wronged another (Internet Encyclopedia of Philosophy IEP). A definition quite interested in the function suggests that “an apology is a speech act addressed to B’s face–needs and intended to remedy an offence for which A. takes responsibility.”(Holmes, 1990: 159). Apologies are also" speech acts" that are hard to identify, define or categorize, a difficulty that arises directly out of the functions they perform (Lakoff, 2001: 201) and the forms they take. In function, they range from selfabasement for wrongdoing to the formal display of appropriate feeling. In form, they range from
... Show MoreThe results of this study showed that the tongue of the adult Iraqi domestic cat is divided into three regions of apex, body and root. The dorsal surface of all regions possesses five types of lingual papillae, two mechanical which are filiform and cylindrical papillae, while the other three types are taste papillae which are foliate, fungiform and circumvallate papillae, while these papillae are absent on its ventral surface. The histological examination of all tongue areas revealed that it consisted of three tunica, the tunica mucosa and the tunica submucosa (the lamina propria) and the tunica muscularis. The tunica mucosa consisted of the epithelial lining, which is a stratified squamous epithelial tissue covering the lingual papillae, a
... Show MoreThe current research aims to verify the impact of digital leadership as an independent variable, in the effectiveness of crisis management as a response variable through centralizing strategic vigilance in the faculties of the University of Baghdad and its departments, and to investigate the level of interest of its leaders and subordinates in research variables, as well as coming up with recommendations that contribute to strengthening the practices of the three variables. In the university under study, and based on the researcher’s interest to diagnose the influence relationship between the variables, because of their importance in the university’s headquarters and its members on the one hand, and its refl
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The influence of fear on the dynamics of harvested prey-predator model with intra-specific competition is suggested and studied, where the fear effect from the predation causes decreases of growth rate of prey. We suppose that the predator attacks the prey under the Holling type IV functional response. he existence of the solution is investigated and the bounded-ness of the solution is studied too. In addition, the dynamical behavior of the system is established locally and globally. Furthermore, the persistence conditions are investigated. Finally, numerical analysis of the system is carried out.
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This study examines the species composition, biodiversity, zoogeography, and ecology of freshwater gastropods of 12 springs in Andijan region of Uzbekistan. The study used generally accepted malacological, faunistic, ecological, analytical, and statistical methods. As a result of research in the springs, 14 species of freshwater gastropods belonging to 2 subclasses, 5 families, and 10 genera were recorded. 7 of them are endemic to Central Asia. When indicators of biodiversity of mollusks were analyzed according to the Shannon index, it was found that the highest value was recorded in the springs besides the hills. According to the biotope of distribution and bioecological features, they were divided into cryophilic, phytophilic, pelophil
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Objective: This research was carried out in rats in a special place of the laboratory of histopathological diseases in the period 6/9/2018 until 23/11/2018, this study to detect effect of the addition of the alcohol extract of ginger in the reduction of fat in liver tissue of rats. Method: Eight groups and replicates for each group. The groups were homogenous in weights and were placed in 13 cages. Each group consisted of 10 rat and at 5 fares each. In the first treatment, rat were fed on regular feeding without adding and feeding rats in the second treatment sessions add to it the alcoholic extract of ginger in Turkey 150 mg/kg. The third group is the same as the normal food after adding the alcohol extract of ginger at a concentration of
... Show MoreThe techniques of contemporary Iraqi painting and their reflection on the productions of students of art education is an important subject in the field of painting at the theoretical and practical levels in academic study, whether theoretical or practical. Al-Iraqi is one of the arts with historical roots and a distinguished position among other artistic genres. Painting has received a sufficient level of development through the use of various contemporary techniques to advance it for the better.
The methodological framework included the problem of research and the need for it, and then the importance of research came in shedding light on the techniques of contemporary Iraqi painting, and the impact of these techniques on the producti
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This present work adopts the analytic and descriptive methodology to recognize and analyze the major challenges faced by the Iraqi government. The study focuses on the press and national partiers’ cabipility of changing and unifying the opinions of the public in a way that serves the Iraqi interest, taking into account the fact that the press is the fourth authority after the three major authorities, (Executive, Legislation and Judicial). The researcher has concluded that the Iraqi press and parties initiated a national front with the Iraqi people against the government’s signature of the treaty of (1930). The national front illustrated that signing the treaty strengthens the authority of the British occupation u
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Brainstorming is one of the fundamental and necessary concepts for practising the auditing profession, as auditing standards encouraged the implementation of brainstorming sessions to reach reasonable assurance about the validity of the evidence and information obtained by the auditor to detect fraud, as the implementation of brainstorming sessions and the practice of professional suspicion during the audit process lead To increase the quality of auditing and thus raise the financial community's confidence in the auditing profession again after it was exposed to several crises that led to the financial community losing confidence in the auditing profession.
The research aims to explain the effect of brain
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