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 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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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.
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.
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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
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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Brucella melitensis isolates were obtained from human infections , and milk which obtained from aborted sheep at Mosul city vicinity . One isolate from each source was used in carrying out this study. Brucella liquid culture was added to sheep milk at 2.5 % for treatments . To first treatment 2 % of yoghurt starter ( Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarius subsp. thermophilus ( 1: 1 ) ) . Second treatment was carried out without addition of yoghurt starter but the pH was lowered using lactic acid in pattern similar to first treatment . Third treatment was similar to the first treatment but contained buffer to alleviate the reduction in pH , which reduced to 6.1 in comparison to 4.9 of the first treatment .
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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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This research is a modest contribution to Put the finishing touches on therole of managerial leaders represented by static companies belonging to theministry of transport and communication/ [iraq] . the research has adopted thedescriptive. Analytical methodology and field study technique, using thequestionnaire as a tool for data collection [58] forms Nar, been distributed tothe research sample. The sample has been deliberately selected {generalmanager, as assistant general manager and heads of department}. Thequestionnaires and the main hypotheses of represented by the existence ofsignificant correlation and impact between successful managerial leadershipand crisis management using the software {SPSS}, were analyzed. Resultswere identic
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Characteristic of money laundering phenomenon is a compound and complex nature like the style of regular crimes . These operations are planned and excuted with those who have high quality experiences to hide the evidences of their deeds so They ask the help of financials ,economicals and legists to plan for money laundering. Banks are important and suitable places for illegal circulation of money because of the different types of accounts , rapidity and overlap which emphasis of its main duty to dislocate illegal money which comes from illegal sources without adding legal characteristic to it . Here we should explain the important role of banks in striving the phenomenon –Bank should try to show and analyze inward proced
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