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 work was undertaken to obtain the crude extract of PPO and laccase enzyme from the leaves of Malva parviflora. All leaves were washed with tap water, then the extraction was performed to acquire the crude extract’s enzymes. One gram of Malva parviflora leaves was homogenized in various volumes of distilled water (1:10, 1:5, and 1:2 w: v). The results showed that polyphenol oxidase and laccase with a ratio of 1:10 (w:v) gave the highest specific activity of 112.3 with 0.394 U/mg proteins. In addition, Malva parviflora leaves were homogenized with several types of buffers with two concentration (0.2 and 0.1 M) for PPO and laccase extraction. These buffers were potassium
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The phenomenon of negative behavior has studied as a social and psychological phenomenon that effect on the performance and life of workers inside and outside the organization. The adoption of this phenomenon is studied in terms of the role of the internal environment of the organization in addressing this behavior, being the variables belong to the field of organizational behavior to see the results of those variables on the Iraqi organizations, since the specificities of it differ from the rest of the Arab and foreign environments. Therefore, this study focused on testing the relationship of the internal environment of the organization and its role in addressing the negative behavior of the workers.
thi
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The added value of internal audit greatly contributes to adding value to the institution, but most departments of economic units in Iraq neglected the role of internal audit and the added value that can be achieved by those institutions, since the term added value of internal audit is a relatively vague term from the premise that what cannot be measured is difficult Determine it, and perhaps descriptive standards for it is the extent of compliance with international auditing standards (IIA).
The research aims to study the procedures and results of auditing to verify that they have given an added value to the audit with a positive impact, develop its aspects and research, identify deficiencies for the audi
... Show MoreBased economic units to technology to add innovations that lead to contribute to customer satisfaction, under intense competition and rapid development in customer taste, the economic units tend to apply the concepts that contribute to customer satisfaction led by the introduction of artificial intelligence techniques. In the production prominent role in the contributing and responding to the rapid changes in customer tastes, and consequent impact this in achieving customer satisfaction. Search gained importance of relying on artificial intelligence techniques to achieve customer satisfaction through speed of response to changes in the tastes of customers and thus be able to increase its market share، and sales growth، and to achieve a
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Founding a System to secure deposits and protecting the depositors is considered one of the important and exchanged subjects out there in the banking system/field in Iraq at the current time, and the reason behind the exchange and spread of this subject is due to the financial crisis of which the banking sector is suffering from and the stumbling of many banks, those factors have had led to the insecurity of the depositors and their mistrust towards banks, thus, it is necessary to create a system to secure deposits in which depositors would be compensated for the losses caused by the banks' failures. in addition, it could be a countermeasure system which maintains the banking stability, protects the rights of depositors and gains
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AbstractOBJECTIVES: To evaluate the long-term remission efficacy and safety of isotretinoin in the treatment of Behcet's disease (BD). PATIENTS and METHODS: This single-blind, controlled therapeutic study was conducted in the Department of Dermatology and Venereology at Baghdad Teaching Hospital from February 2011 to January 2012. Thirty patients with BD were included in this work. Each patient received isotretinoin 20 mg orally once daily for 3 months. They were assessed at week 2 and then monthly depending on the Clinical Manifestation Index (CMI) and to record any side effects. At week 12, isotretinoin was stopped and patients were given placebo therapy in a form of glucose capsules for another 3 months. RESULTS: Thirty patients were tre
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The aim of the research is to identify the role of ethical leadership in achieving comprehensive quality standards in public education schools in the Al-Ardha governorate. To achieve this goal, the descriptive approach was used, the researcher developed a questionnaire consisting of (35) items, divided into two sections: the first one is related to ethical leadership includes (17) items, and the second section relates to total quality management includes (18) items. The research sample consisted of (405) teachers from the stages of public education. The results showed that the level of ethical leadership practice (ethical personal characteristics, ethical administrative features, teamwork, and human rela
... Show MoreIslamic banks are a financial institution that is interested in attracting financial savings from financial entities and directing them towards those with financial deficits, both for consumption purposes or for investment purposes. It provides banking services provided by commercial banks and other services But based on the principles and principles of Islamic law, and because of its recent emergence in Iraq, its ability to attract savings is not like non-Islamic commercial banks, which puts them in the option of using their capital to achieve its objective of banking. The research started from the premise that "Islamic banks in Iraq during the period (2008-2012) rely on their capital to perform their activities more than they rely on d
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The goal of present study was to investigate the benefits of broccoli (as antiandrogenic plant) in protection and treatment for reproductive hormonal and metabolic disturbance, which combined with polycystic ovarian syndrome (PCOS). The PCOS model was introduced by injecting subcutaneously prepubertal female rats at 21 days old with Letrozole for 39 days, and divided into 6 groups (8 rats each ) as follows:
Group 1: Female rats were injected with 0.1 ml of normal saline. Group 2: Female rats were injected with 0.1 ml of 400 µg Letrozole Group 3: Female rats were injected with 0.1 ml of 400 µg L with orally gavaged of broccoli juice. Group 4: Female rats were injected with 0.1 ml of normal saline and at the end of the last
Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with a wide range of clinical symptoms. Some studies have indicated the association between RANKL, Sclerostin, PD-1, and vitamin D concentrations and the pathogenesis of SLE. The current study aimed to evaluate the role of RANKL, Sclerostin, PD-1 and vitamin D in the pathogenesis of SLE. The study included 180 females diagnosed SLE patients and healthy control (60 females as early diagnosed patients without treatment, 60 females as patients under treatment with (prednisolone, and hydroxychloroquine), and 60 females healthy as a control group, with ages ranging from 20 to 45 years. The serum concentration levels of RANKL, Sclerostin, PD-1 and vitamin D were assessed by E
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