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 launch of the EU’s Eastern Partnership in 2009 intended to signal a new, elevated level of EU engagement with its Eastern neighborhood. Yet there remain several long-simmering and potentially destabilizing conflicts in the region, with which EU engagement thus far has been sporadic at best. The Union’s use of its Common Security and Defense Policy (CSDP) in the region and to help solve these disputes has been particularly ad hoc and inconsistent, wracked by inter-institutional incoherence and undermined by Member States’ inability to agree on a broad strategic vision for engagement with the area.
The three CSDP missions deployed to the region thus far have all suffered from this incoherence to various extents. In particu
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study aims to examine education and the challenges of globalization in light of Corona pandemic. The examination involves surveying a randomly selected sample from the University of Baghdad’s professors, particularly from the colleges of Education for Women, Arts, and Sciences. The purpose of this examination is to learn about the dimensions of globalization, its effects on the educational process, and the importance of distance education during the spread of Corona virus quarantine. To achieve this, the researcher followed a descriptive and analytical approach by applying a questionnaire to a sample of 70 teachers who were randomly selected electronically. Results have shown that 78.6% emphasized the contribution of globalization duri
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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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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
Objective (s): To determine factors associated with the pregnancy complications (Maternal age, education,
obstetrical history, gravidity, birth space interval, and smoking).
Methodology: A cross-sectional study conducted at Al- washash & Bab-almoadham primary health care
centers. The sample was (non probability convenient sample) which included (550) pregnant women. The
study started from 1st April 2014 to 1
st of April 2015. The data was collected by direct interview using
special questionnaire to obtain socio-demographic information.
Results: the result shows that mean age of the subjects was 26.5± 4.39 years, 57.8% were housewives, the
sample included 103 premature uterine contractions, 98 pregnancy induce
BackgroundThe diagnosis and important aspects in treating acute abdomen during pregnancy tend to be delayed due to the peculiar physiological features of pregnancy and the restrictions imposed on imaging diagnostic techniques such as x-ray and CT.Aim of the studyTo identify the most common causes of acute abdomen during pregnancy and identifying the approaches for early diagnosis and to take a correct decision for surgery and assigning the complications that may occur during and/or after surgery for the mother and the fetus.Patients and Methods This is a prospective study that involves data obtained from 91 pregnant patients admitted in the surgical wards in Baghdad teaching hospital during the period from January 2008 to December 2009 .
... Show MoreThe research aims at a statement Internal Debt options during shocks and the impact of this borrowing in the volume of the foreign reserve, using induction and deduction with available data analysis. During the period (2004-2013) did not require the use of borrowing across (financial institutions, discounted transfers, bonds); it was only sufficient by transfer with commercial banks that can finance of temporary budget deficits: rose and decline of volume of foreign reserve according to the changes of oil prices and the volume of purchases and sales of the Central Bank of Iraq. Central Bank of Iraq (CBI) has significantly contributed to Internal Debt through bond and discounted transfers in the secondary market; thus, funding the
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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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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
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