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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Construction is the opening of the important pillars of the construction of the film as a whole for this, we find that the first of any narrative of my film begin at the borders of this construction is the window that we look through the contents tale and puzzle narrative is of significance that degrade traveler when reservoirs expression later in reasoning and find justifications ills that came by those initiation, this initiation may be the window that lead us to the core, understanding the story through signals received to the recipient to sail because of the paths of pickling what is which is encoded, but this initiation may serve as keys that understanding the be puppies and signals that beset and surrounded to what He holds inevita
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Background: The influence of glucose metabolism is seen in many infectious diseases, making diabetic patients more vulnerable to sepsis and other serious sequelae of bacterial invasion such as UTI and vaginitis.Patients and method: sixty two patients (women) were suffering from GUTIs consulting Al-Elwya hospital from November- 2009 to March -2010. Two samples were taken from those patients (urine samples and vaginal swabs); these samples were cultured on Blood, Chocolate, and MacConkey's agar for isolation of bacteria.Results: The study group consists of sixty two women suffering from (GUTI), their ages range from 18-55 years. Thirty eight of them were diabetic women and twenty four of them were non- diabetic women. Twenty t
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Background: Helicobacter pylorus is one of the most harmful human pathogens & carcinogen. Of the world's population, more than 50% has H. pylori in their upper gastrointestinal tracts. It has been linked to a variety of extra gastric disorders. In correlation to hepatobiliary diseases; recently, the bacterium has been implicated as a risk factor for various diseases ranging from chronic cholecystitis and primary biliary sclerosing cholangitis to gall bladder cancer and primary hepatic carcinomas. However, the association between Helicobacter pylori (H. pylori) and gallbladder diseases is still vague and is controversial.
Aim of study: To elucidate the association of H pylori and gallbladder diseases (calculu
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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
A total of 37 Staphylococcus epidermidis isolates, isolated from corneal scraping of patients with bacterial keratitis and 20 isolates from healthy eyes (as control) (all isolates, isolated from, Ibn Al- Haietham eye hospital / Baghdad), were tested for slime production, 52.63% of all isolates were positive-slime production (23 isolates from patients and 7 isolates from controls). It was found that positive-slime producing S. epidermidis were exhibited a high resistance to antibiotics as compared to negative-slime producing isolates.
I have studied the relationship between blood groups in humans and disease Cutaneous injury for the first time in Iraq study showed the presence of a significant statistical relationship between them leather Bmsoy in hospitals in Baghdad and its suburbs