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 aim of this investigation is to study and analysis the role of governance in the evaluation of the and social performance of the economic units to be addressed through the concept of corporate governance and then to the social performance and its relationship to corporate governance.
The most important obtained results from this research is that the corporate governance of extreme importance, and derive their importance from being an essential tool to contribute to the transparency and fair disclosure of the financial results of economic units in the fight against financial and administrative corruption in economic units, thus providing protection and confidence of all parties, and the evaluating soci
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Abstract:
Bajila regarded as descending from Anmar Ibn Nizar. Al-Masudi accepts
Bajila and Khath”am as being of Nizar, and asserts that it was only out of the
enmity that they were said to be from the Yemen.
Al-Ya”qubi tries to harmonize this by assuming that Anmar married a
women of the Yemen and that his sons Bajila and Khath”am are thus
connected to the people of this region only through their mothers line.
Bajila embraced Islam in the period of the prophet. Omar 1 forced this
tribe to go to Iraq instead of Al-_Sham, and gave them the quarter of Al- Saw
ad. Then they prohibited from that quarter by given money as reward that
made them against omar1.
This tribe assisted the forth rightly guided ca
In this work, a comparative analysis for the behavior and pattern of the variations of the IF2 and T Ionospheric indices was conducted for the minimum and maximum years of solar cycles 23 and 24. Also, the correlative relationship between the two ionospheric indices was examined for the seasonal periods spanning from August 1996 to November 2008 for solar cycle 23 and from December 2008 to November 2019 for solar cycle 24. Statistical calculations were performed to compare predicted values with observed values for the selected indices during the tested timeframes. The study's findings revealed that the behavior of the examined indices exhibited almost similar variations throughout the studied timeframe. The seasonal variations were
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ABSTRACT
The multi-drug resistant efflux pump is a glycoprotein pump whose function is to push foreign substances. The efflux pump is found in humans, animals. It also has wide-ranging properties in bacteria and fungi. They are found in all species of bacteria, and efflux pump genes can be found in bacterial chromosomes or mobile genetic elements, such as plasmids. The most sensitive function that leads to a global problem is its resistance to antibiotics in bacterial cells, which increases the ability to bacteria from becoming strong virulence factors that most or all antibiotics cannot kill. It also has othe
... Show MoreObjective: The aim of the present study is to assess the practices of nurses towards standard precautions at Azady
Teaching Hospital in the City of Kirkuk.
Methodology: A descriptive study, which uses the assessment approach and it was conducted on nurses from January
18th, 2009 to September 30th, 2009, using non-probability sampling a purposive sample of (37) subject (male and
female nurses) who worked at surgical wards in Azady Teaching Hospital in Kirkuk city was selected. Two study
instruments were utilized for proper data collection [questionnaire and observational checklist]; a questionnaire was
developed for the purpose of the study. It was comprised of two parts which included the nurses' demographic
characte
The present study was set to demonstrate the prevalence of toxoplasmosis infection and its effects on patients with systemic lupus erythematosus (SLE) through determining their serum levels of anti-dsDNA and IL-18 antibodies. For this purpose, the sera from 132 SLE and/or toxoplasmosis patients and 30 healthy women, were collected. The study sample was divided into four groups of SLE, toxoplasmosis, SLE coinfected with toxoplasmosis, and healthy control. Anti-Toxoplasma IgG antibodies were examined for all the samples using ELISA kit. The results showed a high mean level of anti-Toxoplasma IgG among SLE patients coinfected with toxoplasmosis (104.8792±12.31585pg/ml) in comparison to that in toxoplasmosis patients (91.1705±12.577
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Background: Reliable detection the etiological agent of amoebic dysentery and extra-intestinal amoebiasis have Public health importance specially in asymptomatic human and animals, Since the acquisition of pet dogs in the recent period has become widespread in our city. Aim: To give correct perception of infection rate in asymptomatic individuals (human and domestic dogs) for the first aspect and about detection and diagnosis of the pathogenic species of Entamoeba histolytica from another morphologically similar and commensal one using the molecular technique in stool samples of asymptomatic individuals the second aspect. Methods: During the study period from the beginning of September 2020 to the end of February 2021, a total of 95 stool s
... Show MoreBackground: Although underdeveloped in Iraq, telehealth was one tool used to continue health service provision during the COVID-19 pandemic. Aim: To assess women’s experiences and satisfaction with gynaecological and obstetric telehealth services in Iraq during the COVID-19 pandemic. Methods: Free telehealth services were provided by 4 obstetrician-gynaecologists associated with private clinics in 2020–2021. All patients who accessed the services between June 2020 and February 2021 were invited to complete a postconsultation survey on their experience and satisfaction with services. Results were analysed using descriptive statistics and logistic regression conducted using SPSS version 25. Results: A total of 151 (30.2%) women re
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