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
The scope of the humanitarian tragedies in the Arab region has widened after the conflicts that erupted over the past years, exacerbation to include educational, cultural, and social dimensions, economic and moral aspects of the displaced families, especially after the emergence of terrorist organizations and sectarian conflicts which overthrew human and led to various political and demographic changes, forcing citizens to leave their homes, fleeing with their families from the danger of murder, terrorism, and violation to other safer areas inside or outside their countries. Women and children were the vast majority of the displaced who were subjected to great pressures, The host communities bore the pro
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This study was conducted to know the effect of some phenotype characteristics of corn plant on infection by (CSB), using 13 genotypes of corn plant, planting during autumn season 1997 and 1998. The result revealed that the mean of plant height (with male flowering) was (183-219) cm, the mean of leaf No./ plant in all genotypes was (16-18) leaf but the leaf area of plant was (4350-6249) cm2, there were significant differences of phenotype characteristics between genotypes ,the percentage of infection by (CSB) was (5.9-35.9),% the result showed that the phenotype characteristics had non effect on the infection percentage by (CSB) and the correlation coefficient was not significant.
The current paper was designed to find the possible synergic effect of EBV infection with the HPV-16 in Iraqi women suffering from cervical carcinoma. This retrospective study involved paraffinized blocks of two groups. The research included 30 carcinomatous cervical tissues and 15 samples from normal cervical biopsies. After sectioning using positively charged slides, immunohistochemistry (IHC) was performed to detect anti-Epstein Barr Virus LMP1 and Human papillomavirus type 16 primary antibodies. Sixty-three percentage (19 out of 30) of the studies group showed positive overexpression as shown in with a significant association of the expression with cervical cancer with a significant association (p = 0). The co-infection of the EBV and H
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(5)
The records of Primary Health Care Centres (Al-Risafa section of Baghdad) were inspected for communicable diseases during the period January-April 2006. There were 8622 recorded cases (the diagnosis was based on a clinical examination and laboratory findings), which were distributed as 4782 (55.5%), 1430 (16.6%), 1604 (18.6%) and 806 (9.3%) for Sadar city, Risafa, A'adhamyiah and Mada'in, respectively. The highest frequency was reported for chicken pox (42.7%), followed by mumps and typhoid fever (20 and 13.7%, respectively), while diphtheria and cholera were not recorded. These three most frequent diseases were further analyzed, and their distribution showed a significant difference (P ? 0.001). April was the month of the highest recorded
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The study deals with an analysis of the contents of the publications of the campaign (Together to defeat Corona), which was established by the United Nations Development Program in Iraq in the face of the Covid 19 virus.The research problem raises a main question:What are the implications of the campaign (Together to defeat Corona) of the United Nations Development Program (Iraq office) in addressing the Covid-19 virus in Iraq?From this main question, several sub-questions emerged, which were answered by this study in its chapters and investigations, including regarding the contents of advertisements, photos and videos for the publications of the (Together to Defeat Corona) campaign for the United Nations Iraq Office on their Facebook pageA
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The research focuses on the withdrawal of the United States from the nuclear agreement signed between the permanent members of the United Nations Security Council and the Islamic Republic of Iran concerning its nuclear program. This withdrawal has caused disruption in the official media discourse of the concerned countries. Therefore, the main question can be posed: Are there differences in the positions of countries related to the nuclear agreement, as well as those countries affected by it, before and after the official withdrawal of the United States on May 8, 2018?
The research aims to shed light on the trends in media discourse of the countries that signed the nuclear agreement and those affected by it b
(1)
Babesiosis is a tick-borne disease caused by Babesia microti. We present a case of false positive HIV in the setting of confirmed babesiosis infection. An understanding that patients with babesiosis can have a false positive HIV test result is important in management decisions.
(2)
The need for an intellectual understanding of the context from many aspects' dictates understanding the ways through which the graphic designer walks in simulating the intent of the design process and elevating it to levels of communicative perception that leads to communicating the idea to the recipient, and it is thus a need closely related to the context, if it is historical. Culturally or socially, and between the mechanisms of selecting and operating the elements and units of the graphic and design achievement. On this basis, the role of context in graphic design can be studied.
The research included four chapters, the first chapter of the research problem and the need for it, and the aim of the research was (discovering the
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ABSTRACT
The research aims to clarify the role of electronic marketing and what it can achieve in promoting the products of the national industry in Iraq. Marketing channel depends on modern communication and information technology that industrial and metal companies can use in promoting and selling their products along with traditional marketing outlets. To achieve the objectives of the research, a questionnaire was used, which consists of three axes, the first includes the personal data of the sample (gender, age, educational attainment, place of residence, marital status, income level), while the second axis includes various questions about the products of the national industry. Third axis includes que
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