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 current research aims to determine the impact of the cognitive reconstruction program on the development of psychological hardness among middle school students through the experimental verification of three hypotheses. The research sample consisted of (16) out of (450) students selected from Ibn Rushud preparatory school- Al-Rusafa 2. These participants have been randomly distributed into two equal groups. The researcher has used the method of cognitive reconstruction with the experimental group, whereas with the controlling group, he used nothing. The researcher has further used the scale of psychological hardness of Kobassa with the participants; the scale has been built in a way that suits the sample of the study, which consisted
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The present study discusses one of the most relevant and required topics in the recent period during globalization, the modern Russian system of terms for the oil and gas industry as a whole acquired a complete form in the second half of the twentieth century. The period of the late XX - early XXI centuries. marked by cardinal transformations in all areas of the political, economic, social and cultural life of Russia. These changes could not but affect industrial production. Transition to a new vector of development of the Russian economy based on the development of commercial trade, on the change and improvement of the development of industrial enterprises in the context of the implementation of national projects and the introduction
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Lately great interests have emerged to find educational alternatives to teach and improve motor skills according to modern educational methods that take into account individual differences and speed in learning for the learner through individual learning that the learner adopts by teaching himself by passing through various educational situations to acquire skills and information in the way he is The learner is the focus of the educational process and among these alternatives the interactive video, the researchers noted through the educational training units at the Model Squash School of the Central Union, and that most of the methods and methods used in learning basic skills take a lot of time in the educational program and do not involve
... Show MoreThe occurrence of two species of the genus Myxobolus Bütschli, 1882 (Myxozoa: Myxosporea) for the first time in Iraq from freshwater fishes.
MA Mahde, HAA Kadhim, HN Tarish…, Pakistan Heart Journal, 2023 - Cited by 4
Research topic: (The Epistemological Foundations for Comparison of Religions by al-Amiri)
The research sought to study the topic with: a descriptive methodology by investigating the components of al-Amiri's approach to the interfaith comparison. And analytical, by showing the applied perception of an objective model in the comparison of religions to answer two questions: What are the cognitive foundations of al-Amiri? And what is his approach to establishing an objective comparison between religions?
The research started by introducing Abu al-Hassan al-Amiri, and then presented four topics: An introduction to al-Amiri's efforts in the interfaith comparison, his knowledge foundations, an applied model
... Show MoreThis research seeks the effects of dubbed Turkish TV series on Iraqi audiences. The chosen sample is about 600 Iraqi students at Baghdad and al-Anbar Universities. This study consists of four sections: section one deals with the theoretical framework of the study. Section two studies the dubbed Turkish TV series. The third section explores the role of mass media in forming tendencies, and the last section seeks the field study by analyzing the tendencies if Iraqi viewers of these series.
The goal of this study is to know the role these series played in affecting the behavior and attitudes of Iraqi people and how it can change their morals.
The research ends with the number of results like the negative effect of these series on the
Abstract
The research aims to identify the level of effectiveness of the teaching practices of science and mathematics teachers in light of the national framework for future skills in Omani schools. To achieve the objectives of the study, the researchers used the descriptive approach, as he designed a note card consisting of (30) phrases distributed on three axes: basic skills, practical skills, and technical skills. After verifying the validity and reliability of the tools, they were applied to a sample of (116) teachers. The results of the research revealed that the level of effectiveness of the teaching practices of mathematics teachers has recorded a medium degree with a mean (3.05). The results a
... Show MoreTen blue swimming crabs Portunus segnis (Forskål, 1775) were collected from the north west of the Arabian Gulf off the Iraqi marine waters from October to November 2017 at 29ᵒ 37′ N to 48ᵒ 47′ E.
The barnacle Octolasmis angulata (Aurivillius, 1894) was found on the gills of the present species of crab, the mean incidence of infestation was 30%, while the mean Intensity of infestation was 12.3. The barnacle have a long and slim shaped calcareous plate with the presence of carina and the absence of tergum, in addition to the elongated shape of carina and scutum. The current study represents the first record of the barnacle O. angulata in the Ar
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