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.
During his tenure in Iraq, al-Hadjjaj bin Yusif undertook administrative and economic reforms as well as linguistic reform.
The efforts exerted by Abu al-Aswad al-Dawali to control the reading of the Holy Quran were not sufficient, so the melody and error continued and became more pronounced, especially since the letters were written until then without any distinguishing features.
Al- Hadjjaj bin Yusuf realized the seriousness of the continuation of these errors and what he talked with the days of the causes of division and disagreement between the Muslim community ordered his book to put these suspicious characters marks was at the head of the book Nasr bin Asim and Yehi bin Muammar
The current environment is witnessing several developments as a result of the changes taking place in all areas of economic, social , political and legal that led to the transformation of the industrial economy , which depends based on quantitative production to a knowledge economy which relies based on information and knowledge , as the central pillar of this economy during the trading of these information and knowledge between all individuals in general and decision makers , in particular, through information and communication technology of computers and the Internet to achieve sustainable human development in the social dimension. &
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The study aims to examine the problem of forced displacement and its social and economic problems in light of the Syrian crisis. Such an aim helps to know the difficulties and challenges facing the children of displaced families in learning, and the reasons for their lack of enrolment. It also clarifies whether there are significant statistical differences at among the attitudes of the children of the displaced families towards education regarding the following variables: (the work of the head of the family, the economic level of the family, and the work of the children). The study has adopted the descriptive-analytical approach; a questionnaire was adopted as a tool to collect information. The study was applied to a sample o
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The article approaches the characteristics of Russian literature in the time of Khrushchev or the "thaw" period a very short period of Soviet history, characterized by the easing of the dictatorship of power and relaxation in various areas of people's lives. The interest in the research is focused on the importance of interpreting the family portrait in a short but distinct period in the development of Russian/Soviet literature. The research material is the story of Sholokhov's “The Fate of Man” 1956, the story of Panova “Serioga” 1955, and Abramov’s story “Fatherless” 1961. В статье рассматриваются особенности художественной литературы периода хруще
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The emergence of COVID-19 has resulted in an unprecedented escalation in different aspects of human activities, including medical education. Students and educators across academic institutions have confronted various challenges in following the guidelines of protection against the disease on one hand and accomplishing learning curricula on the other hand. In this short view, we presented our experience in implementing e-learning to the undergraduate nursing students during the present COVID-19 pandemic emphasizing the learning content, barriers, and feedback of students and educators. We hope that this view will trigger the preparedness of nursing faculties in Iraq to deal with this new modality of learning and improve it should t
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Allah created the human from clay and made the system of marriage between male
and female as a reason for life continuity and human staying. This system produced an
organization called (the society) which is defined as a group lived in limited time and place.
Islam put fundamental and conditions of the righteous society in the Holy Quran and
prophetic sunna. Islam also put the solutions for problems (if they got) , naturally, these
problems may happened because of the nature of the life.
The problem of the research is summarized by that the problems of the society
enlarged in our Islamic society more than time ago. In the same time , some solution are
imported from west and east and from scientist and ignorant wit
Abstract
Nowadays, the adoption of economic unity on the accuracy of financial reporting is very important. Economic units need accurate financial reporting to be more competitive and to improve the performance. Management can also achieve financial information in real time through the application of ERP systems. This system will facilitate management to access the most up-to-date information such as planning, monitoring and evaluating the business processes of the organization to be more effective.
On the practical side, the Enterprise Resource Planning (ERP) system was applied to the General Company for Vegetable Oils to demonstrate a course in enhancing the accuracy of financial reporting.
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Abstract
The goal of this research is to know the quality of working life and its impact on the level of the organizational sense of alienation among a sample of teaching Anbar University in the center of Baghdad. Find and seek to achieve a number of cognitive and practical goals.
Where the quality of work life constitutes one of the main sources to enable organizations of excellence in light of the volatile environment, as is one of alienation regulatory organizations avoid the phenomena that occur because of their negative effects on performance and thus achieve their goals. The most research problem in question the existence of the main deficiencies in the application of the concepts of organiz
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Objective: The aim of this study is to determine the role of spiral Computerized Tomography in the diagnosis and
detection the types of stroke.
Methodology: One hundred sixty two patients (162) (99 males and 63 females) their ages ranging from (13 – 80)
year, all of them are suffering from stroke. They were collected randomly from spiral Computerized Tomography
unit in Baquba Teaching hospital during the period from November / 2010 to December / 2011 .All the patients
were examined clinically and then done spiral Computerized Tomography examination.
Results : The results of this study showed that the stroke effected different age groups and both sex but males is
more affected than the females .The results of spiral