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.
This research aims to demonstrate the impact of the going concern assumption in different accounting applications to provide a realistic look and more accurate result of activity and financial situation, as well as determining the responsibility of the Company's administration in compliance with the going concern assumption during the preparation for their financial statements, and to clarify the concept of integration between internal audit and external audit about going concern assumption, besides its importance and usefulness on the work of both of the internal auditor and the external auditor, as well as on the company under auditing process.This research purports preparing an internal audit program, including a set of auditing actio
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The aim of the research is to explain the role of quality costs their importance and their classification, and to clarify the most important tools that help to reduce costs.
In order to achieve the objective of the research and test hypotheses adopted the descriptive approach, as well as the adoption of the analytical approach in the study of applied data has been relied upon in providing data on the financial and production reports of the research sample company, the data were used to study and analyze financial and productivity reports . A number of conclusions have been reached the most important being the following
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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
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The current research aims to identify the nature of the relationship between training human resources in administrative innovation elements In the General Directorate for the education of the third Rusafa one of the formations of the Iraqi Ministry of Education in Baghdad, In order to achieve the objectives of the research, the researcher provided a comprehensive theoretical framework and the preparation and development of a questionnaire as a tool for collecting data based on the prepared measurements and benefit from previous studies, which contains (28) For the purpose of obtaining realistic results for the variables of the research, the researcher used the random sample in the selection of the research sample A total of (63)
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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
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(2)
The Industrial Banks in most countries in the world plays an essential and vital role in developing the industrial sector due to its effective importance in the economic and social development. The research aims to study the ability of the Industrial Bank of Iraq to the growth and development of the mixed industrial sector companies through loans granted to them. In addition, the research seeks to study credit policies pursued by the Industrial Bank of Iraq to finance the mixed industrial sector companies. The data of the research has been collected from the financial statements of the Industrial Banks of Iraq for the period 2007-2011, and by means of questionnaire distributed to a sample of the mixed industrial sector companies in
... Show MoreBackground: 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
The research aims to monitor the methods of Counter psychological warfare in the Iraqi press during the operations to liberate Mosul from the control of the terrorist organization ISIS.The research used the survey method, and “Tareek Al Shaab” Newspaper as a research sample, chosen according to the systematic random sample.
The research reached the following results:
1- The Communicator’s relied on the contents of the counter-psychological warfare and its methods in the battle of “Qadimun Ya Naynawa” used in the newspaper. The methods used were labels assigning such as : inevitable victory, prodding and morale, consensus, breaking of opposition morale, stereotyping, demonization of the opponent
The genus Hafnia, a member of the family Enterobacteriaceae, consists of Gram negative bacteria that are occasionally implicated in both intestinal and extraintestinal infections in human. This genus contains only a single species (Hafnia alvei). Methods The above bacterium was identified from 250 bacterial strains which were isolated from 220 urine samples of patients with urinary tract infection. Results One H. alvei strain was isolated from an elderly patient, and identified by conventional biochemical tests and API20E system at the first time in Iraq. Antimicrobial susceptibility test showed that this strain is sensitive to Cefotaxime, Ciprofluxacine, Chloramphenicol, Doxycycline and Trimethoprim-sulfamethaxzole, while it is resistant t
... Show MoreMyoma is a common benign uterine tumor; therefore
it is common in pregnancy. One in ten women will
have complications related to myoma in pregnancy.
Few treatment options are available during pregnancy,
conservative treatment with analgesia, reassurance and
supportive therapy is almost always adequate but in
carefully selected patients, myomectomy has been
performed successfully without jeopardizing
pregnancy outcome. The usual indications for surgery
during pregnancy include torsion of pedunculated
uterine myoma and obstructed labor, surgical
intervention during pregnancy is occasionally
necessary in uncommon cases of intractable pain.
19 years old lady presented with intractable lower
abdominal