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.
Abstract
Tourism is one of the essential economic fields of many countries, both developed and developing. The social plays a greater role in the continuous awareness of a tourist culture based on the need to attract tourists continuously. the tourism heritage and state-owned tourism are the main factors in attracting more tourists. The interest in this strategic sector makes the country the first and most active framework in the development of appropriate mechanisms for investment in this sector, all within the framework of sustainable development of society through the rational use of resources obtained by various bodies in the implementation of seve
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The role of Iraqi newspapers in instilling political culture among the public after 2003, a field study on the audience of the city of Baghdad, University of Baghdad, College of Information, Department of Journalism, 2019,
The problem of research is to investigate the role of Iraqi newspapers in instilling the political culture of individuals after 2003, and monitor this role Through the contents and messages provided by the Iraqi newspapers to the public. the research is classified within descriptive research, it adopts the survey methodology and used the questionnaire tool. In fact, the questionnaire was distributed to a sample of 400 individuals that was selected according to the method of multi-stage cluster sample of those who re
The organization of sporting activities at the local and international levels requires a lot of money, which has increased interest in marketing in the sports field, as it is one of the modern topics that represent the basic knowledge needed by the sports marketer and which represents one of the basic concepts to enhance the benefits and returns of sports clubs. The research problem was the weak awareness of the members of the administrative body of Iraqi sports clubs of the role of sports marketing in the dimensions of competitive superiority and not exploiting them in the optimal way that enables clubs to achieve competitive superiority. The research aims to know the role of sports marketing in competitive superi
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The aim of the present study is to provide the adequate knowledge about the role of time management in facilitate the work requirements for employees of the administrative department at the Ministry of Higher Education and Scientific Research. The research depend on studying four important dimensions which are (time planning, time organization, time direction and time observation). In addition to study other five dimensions which are (new procedures, clear procedures, short procedures, the available information and the simplicity of the methods
used).Questionnaire sheets consist of (38 questions) distributed to (170) employees and (146) sheets only were considered in the study. SPSS program was used
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This study presents a mathematical model describing the interaction of gut bacteria in the participation of probiotics and antibiotics, assuming that some good bacteria become harmful through mutations due to antibiotic exposure. The qualitative analysis exposes twelve equilibrium points, such as a good-bacteria equilibrium, a bad-bacteria equilibrium, and a coexisting endemic equilibrium in which both bacteria exist while being exposed to antibiotics. The theory of the Sotomayor theorem is applied to study the local bifurcation around all possible equilibrium points. It’s noticed that the transcritical and saddle-node bifurcation could occur near some of the system’s equilibrium points, while pitchfork bifurcation cannot be accrued at
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بعد ثورة تموز عام 1958في العراق, لم يكن يسمح للقطاع الخاص بأن تكون له استثمارات كبيرة في القطاعات الاقتصادية. وذلك بسبب الإيديولوجيات التي كانت تؤطر الفكر السياسي. حيث كان النهج الاشتراكي هو الغالب في إدارة الأنشطة الاقتصادية. إذ قامت الدولة بتأميم معظم الاستثمارات الخاصة الكبيرة ،لاس
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The paper investigates the impact of role-playing as a classroom technique on Iraqi EFL students’ speaking skill on Iraqi EFL students at the college level. The students are 40 college language students in University of Baghdad, College of Education Ibn-Rushd randomly chosen. Then, they were divided into two groups, experimental and control groups. Thirty questions were applied to both groups as a pre-test of speaking and the students asked to answer them orally. The experimental group was taught speaking skill of the targeted role-play technique while the control group was taught in traditional method. After 20 lessons of the teaching, the post-test of speaking was conducted in which the students in both groups were asked to answ
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Gender has considered and become a new trend in women's studies, as it reflects the behaviors, roles and attitudes imposed by society on its members in accordance with their biological nature,with focusing on gender rather than on concentration on women, which is closely linked to the vision that concentrates on women's problems which are not primarily according to their biological differences But rather to a greater extent to social, cultural, historical and religious barriers and Obstacles.
Therefore, the qualitative division due to the concept of "gender" is not a rigid biological division, but is relied on the broad general context through which the social division of work is done. Thus, content in the pages of Facebook with high-
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Background: Diabetes mellitus is a common health problem of the world. Iron may be a part of the cause of the disease and its Complications
Objectives: This study was designed to determine the relationship between the levels of iron indices and diabetes mellitus type 2. Type 2
Type of the study: Cross –sectional study.
Methods: diabetes mellitus is clinical condition characterized by hyperglycemia due to the absolute or relative deficiency of insulin. It is also followed by pathological abnormalities like impaired insulin secretion, peripheral insulin resistance, and excessive hepatic glucose production. Although type 2 diabetes mellitus i
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خلاصة (استطاعت اليابان بعد الحرب العالمية الثانية ان تنهض من جديد، وان تحقق تجربة تحديث سياسي جعلها تشهد تبدلات جذرية من الفقر الى الغنى ومن سيطرة الحكم العسكري الى الدولة المنزوعة السلاح ومن التخلف الى التكنولوجيا الاكثر تطورا في العالم, ومن الانغلاق والعزلة وذهنية سكان الجزر الى الانفتاح على ثقافات عصر العولمة ووسائل اعلامها. فكيف يمكن الاستفادة من هذه التجربة الحديثة سياسيا بل وحتى اقت
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