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.
يسعى المجتمع من خلال الوحدات الإقتصادية إلى الوصول إلى تحقيق أفضل الإنجازات التي لا تتمثل بالسلع والخدمات حسب وإنما بما يتحقق من مردود لكافة الاطراف المعنية بالوحدات الإقتصادية على ان لايتم ذلك على حساب قيم المجتمع وأخلاقياته وآدابه العامة. وعليه تصبح الوحدات الإقتصادية مسرحاً لصراعات قوى متعددة كل منها له قيمه الأخلاقية سواء كان فرداً أومجموعة افراد أو وحدة إقتصادية أو أي جهة أُخرى، وبحكم مسؤولياته
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The present study aims at knowing the reasons of the student of secondary school abstention from participation in the theatrical activity, and to know the reasons that resulted in this abstention. In addition to that, the study aims at knowing the differences according to variables (gender, scholastic stage, and major of study). The sample of the study was chosen from the secondary schools in Baghdad in the random manner from Al-Karakh and Al-Rusafa districts of (147) students. The questionnaire was used to collected data.
The result showed that all the items are intense, the item of (Students do not know how to use their leisure time) obtained the hi
... Show MoreMatrix acidizing is a good stimulation process in which acid is introduced into the reservoir near the wellbore area via the wellbore or coil tubing. In the oil industry, formation damage is a prevalent problem. Bypassing wellbore damage by producing wormholes in carbonate reservoirs is the main purpose of acidizing the matrix of the formation. When doing lab tests, scientists are looking for a wormhole-inducing injection rate that can be used in the field. Meantime the ongoing works on the Ahdeb oil field's Mishrif reservoir, several reports have documented the difficulties encountered during stimulation operations, including high injection pressures that make it difficult to inject acid into the reservoir formation; and only a few
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This Paper aims to know the modern approaches of determining the Qiblah and its ruling in Islamic Faqah, as well as to find out the required in the identity of the Qiblah or the eye, and the care of the advanced Jurists in this matter, and to present some of their sayings on the issue. we have followed the Descriptive analytical method of the aspects of the jurists ’difference in what is required when facing the qiblah either the eye or aspect, the approach of several demands branched out from each topic, which were answered in the theoretical framework of the research, and the research concluded with the most important results: The need to receive the eye of the qiblah for the worshiper who is close to it and it is no
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The study of topography most important studies and depth of any literary or artistic text and occupy the thinking of many who work in art at generally. There is hardly any film scenario from description in general of the indispensable elements of the composition and place one. So the place starts form since the scriptwriter begins to view the result of the description begins to feature the emergence of there are simple operations in the scenario soon to receive growth as a final achievement in the film. The description of the place begins to take on an allegorical character as a language version in the script, soon translated into another language, the language of the picture. Which in turn complement the creative ring of cinematic art a
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This study is concerned with revealing the semiotics of thresholds, and its role in building textual coherence at the form and semantic level in Sunset Garden Diwan of the Saudi poet Ghazi Al-Qasaibi. This research aims to spotlight on the semiotic theme of the title threshold and its relation to other thresholds. As the death phenomenon and absence dominated the poetic achievement space through intertwined semiotic relationships that lead to each other through the parallel text semiotics.This study is based on the semiotic method which concerns with searching for the interpretive connotations and revealing the profound symbols in the threshold structure and its role in the whole formation of the Diwan. Among the most prominent conclusio
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Objective: preparing educational units for the magnet poles strategy in learning the spiking skill in volleyball, and identifying the effect of the magnet poles strategy in learning the spiking skill in volleyball for female students.Research methodology: The experimental design with two equal experimental and control groups with tight control was also adopted in the pre- and post-tests. The boundaries of this research community are represented by fourth-grade middle school students at Basra Girls' Middle School (2024-2025), whose total number is (90) students, distributed by nature into 4 sections. Sections (A-B) were determined by lottery, so that Section (A) represents the experimental group and Section (B) represents the control
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Paul Auster's City of Glass is here singled out as representative of the writer's The New
York Trilogy. All throughout his novelistic career, Auster has been working on a pseudothesis
that adheres to a certain aesthetic of disappearance. The study engages this Austerian
aesthetic apropos of certain theoretical stretches such as the Emersonian "Not Me", the
Thoreauvian "interval" or "nowhere", the Deleuzian "nomadic trajectory", the Derridian
"grammè" or "specter", and the Baudrillardian "disappearance". The city of the novel's titling
is here seen as the trope of all that which has already disappeared, and hence it is seen as the
space (mise en scène) where the perfect crime of the murder of the real is to be thoro
Study Purpose. highlighting the origins of the sport's philosophy. Studying the development of the sport of kendo across different historical periods and its adaptation to societal and cultural changes. Identifying the establishment of the most prominent organizations and federations that contributed to its development, and exploring the sport's basic tools and rules and its most prominent championships. Materials and Methods. The historical approach was adopted in studying the historical process of the development of kendo, as it is appropriate to the nature of the problem. The information has been simplified and presented in a sequential manner that presents the development of the sport of kendo, starting from the origins of its p
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The study aims at finding out:
1. The students' attitude towards the mixed learning at the university.
2. The statistically significant differences in attitude towards the mixed learning at the university according to the specialization variable.
3. The statistically significant differences in attitude towards the mixed learning at the university according to the gender variable.
The researcher has constructed a scale for measuring the students' attitude towards the mixed learning at the university.
After assuring its validity and reliability, the scale has been given to a sample of (100) students. The sample is selected randomly from (4) colleges of the university of Baghdad, (2) for scientific specialization and (2)for h