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.
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
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 MoreThe 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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The understanding exchange rate policy is fundamental in order to identify the mechanism by which works out macroeconomic, And the vital for macroeconomic analysis and empirical work to differentiate between the de facto regimes and de jure regimes, Where the proved surveys and studies issued by the international monetary fund that there is divergence between the de facto regime (Regime of exchange applied by the country actually) and between the de jure regime (Regime de jure through the documents and formal writings of officials of the central bank), And launched studies on the de facto regime (Being a the basis of evaluating monetary policy) Stabilized (peg-like)arrangements or
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Research includes evaluation of projects implemented and which entered into trial operation period in accordance with the evaluation criteria and of (cost, quality and time) to determine the size deviations gap for the sample of projects during the years of assessment (2011-2012-2013-2014) of each of the three evaluation criteria, and then followed by a calculation the size of the overall gap to the problem based on the research problem to determine deviations from the specific implementation of each project by answering several questions to answer turns out the reasons for these deviations occur.
The importance of research Focus on the evaluation of received projects from contractors executing the projec
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SummaryBackground: Rotavirus infection is the most commoncause of watery viral diarrhea in children younger than 5 years of age; it is a major cause of childhood morbidity and mortality.Objective:The aim of the study is todetermine the clinical picture, age distribution of patients with rotavirus infection and their maternal educational background.Patients &methods: A total of 202 patients suffering from diarrhea were included in this study, over 6 months period( from 1stof March 2011to 30th of August 2011),in Children Welfare Teaching hospital. History and physical examinationwere carried out, anthropometrics measures were done and plotted on Centers for Disease Control& World Health Organization charts to determine the nut
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Result of studying (61) urine samples collected from students department of Biology in the College of Education-Tikrit University and the people who hold signs and symptoms of urinary tract infections with those who do not have any signs or symptoms through a questionnaire has been with the collection of samples, and the total cases were infected (39 ) cases, a rate (63.9%) distributed (28) cases a female (68.2%) and male (11) cases event rate (55%), while the distribution of positive cases among age groups have emerged group (20-22 years) is the highest rate (56%) females. The results of urine cultures accompany the presence of different types of bacteria sick and E.coli bacteria is the highest ratios positive also it is the most comm
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The unresolved COVID‐19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID‐19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow‐up, and outcome prediction.
This narrative review summarized the hematological changes including the blood indices, coagulative indicator
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Background: The patient's vital signs must stay stable pre a pulmonary function test since the approach demands the patient to breathe slowly and deeply and exhale quickly. However, events that cause variations in normal vital signs may impact the patient. Many strategies can be utilized to stabilize vital signs, including music treatment. The purpose of this study is to compare the effectiveness of music therapy on the vital signs of client's pre a pulmonary function test. Methods: An experimental design study with an application (pre-test, post-test), to determine the effectiveness of music therapy for clients pre pulmonary function test for 106 clients in Al-Diwaniyah, Al-Shamiya, and Al- Hamza public hospitals In Iraq. Parti
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