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.
he current research aims to analyze the relationship and the level of influence of labor relations in reducing the cases of job withdrawal in private colleges in Baghdad. (265) individuals from department heads, university professors, and teaching staff in (7) private colleges located in the capital, Baghdad, and based on the Stephen Thompson equation for small samples, the sample size was determined by (157) teachers, and the questionnaire was adopted as a main tool for collecting data and information After ensuring the validity and reliability of its contents, and to test the relationship of influence, correlation and interaction between the research variables, two main hypotheses were formulated from which (5) sub-hypotheses eman
... Show More
The quality of the financial reports depends on set of accounting standards ,most of wich have been studied for the purpose of ascertaining the relationship between the standard used and the quality of the financial reports that contribute significantly to improving the financial performance of the institution, Research aims to detect the relationship between forensic accounting and the quality of financial reports, The research included a key hypothesis that forensic accountability could be applied to improve the quality of financial reporting, A sample of gentlemen (external auditors, tax assessors, judges, university professors, shareholders) (45
... Show More
(3)
Background: Plants used in folk medicine for
the treatment of peptic ulcer diseases is a very
promising approach to overcome the limitations of
classical medicines.
Aim: To explore the efficacy of medicinal
plants, namely turmeric, garlic and marshmallow,
in eradication of H. pylori.
Methods: This prospective study was carried out
on 225 of well-known dyspeptic patients who were
divided into four groups; a control group (received
classical medical therapy) and three other groups
that received one of the three medicinal plants,
plus the same therapy used in the control group.
The follow up was done by using a questionnaire
form, endoscopic examination, and determination
of serum levels of anti
Toxoplasmosis is an infection caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy.One hundered and twenty two aborted women were selected for this study. Serum samples were collected form Al-Kadhmia and Kamal Al-Samari Hospitals,and laboratories around Baghdad, and tested for specific IgG and IgM anti-toxoplasma antibodies to confirm toxoplasmosis in those women by using ELISA test.The result recorded that 51(41.8%) women had antibodies against Toxoplasma gondii, 25(59.5%) women were positive for IgG, and 17(40.5%) women were positive forIgM, while 9(17.6%)women were positive for both.
This study aims to show the level of organizational fairness at Hawija Technical Institute ,from the point view of the faculty ,and the degree of their performance, and the nature of the relationship between organizational fairness and their performance.
The researchers accomplish and develop a questionnaire on Likert a three - dimensional scale to de applied on a samp
... Show More
(1)
The research aims to show the effect of some short-term debt instruments (central treasury transfers, cash credit granted to the government by commercial banks) on the production of the wheat crop in Iraq, through its effect on money supply during the period (1990-2018), As the study includes two models according to the statistical program (Eviews9), the first model included measuring the effect of short-term debt instruments on money supply, and the second measuring the extent of the money supply's impact on Wheat crop production, as the results of the standard analysis showed that the short-term debt instruments used in the model were Significant effect on wheat crop production indirectly through its effect on money supply, As
... Show More
(1)
The role of the climate in the development of the performance of the administrative bodies of sports clubs
The compliance is considered
This study aimed to deduce the net atrioventricular compliance which is affected the trans mitral blood flow.
This study focuses on study group of 25 patients (15 males
(1)
(1)
This study is concerned with the comparison of the results of some tests of passing and dribbling of the basketball of tow different years between teams of chosen young players in Baghdad. Calculative methods were used namely (Arithmetic mean, Value digression and T.test for incompatible specimens). After careful calculative treatments, it has been that there were abstract or no abstract differences in the find results of chestpass, highdribble and cross-over dribble. The clubs were: (Al-Khark, Air defence, Police and Al-Adamiyah) each one separate from the other for the year (2000-2001). After all that many findings were reached such as the lack of objective valuation (periodical tests) between one sport season and the other. In the light
... Show MoreBackground: Laparoscopic cholecystectomy (LC) has become the standard treatment for symptomatic cholelithiasis. Bile duct injury and accidental gallbladder perforation with spillage of bile and stone are common complications of LC. This study was carried out to assess the early complications of gallbladder perforation during LC, and identify the risk factor of that perforation.
Objectives: to evaluate the early complications which may occur after the perforation of the gallbladder during laparoscopic cholecystectomy and to determine the risk factors which are associated with the perforation of the gall bladder.
Subjects and methods: A prospective comparative study o
... Show More
(1)