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.
اعداد : أسرار عبد الزهراء علي - علاء الدين - ب. جواد حسن عودة عبد الله - جامعة بغداد جامعة بغداد كلية البصرة للعلوم والتكنولوجيا - كلية الإدارة والاقتصاد. كلية الإدارة والاقتصاد المركز الديمقراطي العربي – مجلة القانون الدستوري والعلوم الإدارية : العدد التاسع شباط – فبراير 2021 المجلد 3 ،
In Iraq, there is a limited research work exploring the clinical pharmacists' role from the point of view of other healthcare professionals. To investigate physicians' assessment of clinical pharmacy services at Baghdad hospitals, and compare junior physicians with senior physicians' point of view. The study was conducted in twelve governmental hospitals in Baghdad, Iraq. Data was collected from a sample of two hundred physicians, and through a validated, self-administered questionnaire, which comprised twenty statements in addition to a non-personal information form that precedes the questionnaire The study findings reveal a somewhat positive point of view towards clinical pharmacists' performance in Baghdad h
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According to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c
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Toxoplasmosis is the term for infection and disease in man and animal caused by a parasite called Toxoplasma gondii. The more susceptible to infect with toxoplasmosis is the Diabetic patients, due to low level of immunity response. The aim of current study is to investigate the immune status of diabetes mellitus type 2. One hundred and seventy five samples of both diabetes mellitus type 2patients and controls which had been tested by ELISA technique to detect anti-Toxoplasma Abs (IgG and IgM). The positive toxoplasmosis samples were tested to detect the level of TNF alpha and MIG. Results for all samples clarified that seronegative for IgM antibodies while 53 (53%) diabetic patients were seropositive for IgG antibodies and for toxoplasmosis
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ABSTRACT:
The study aimed to identify the impact of the role of voluntary accounting disclosure in enhancing confidence in the informational content of financial reports. Correlation - Spearman to measure the degree of correlation, as well as the method of simple linear regression analysis, and the study reached several results, including: The level of enhancing the information content in the annual financial reports of the Palestinian banks listed on the Palestine Exchange under study reached the overall average (total) (94.1%), and also Voluntary Accounting Disclosure in Enhancing Confidence in the Informational Content of the List of Change in Ownership Equity of Listed
... Show MoreThis study aims at identifying the correlation between digital transformation and knowledge building in educational institutions, as well as finding the influence relationship between digital transformation and knowledge building in educational institutions and knowing the dimensions of digital transformation that have the most impact in improving the level of knowledge building, and by adopting the methodological descriptive analysis method in the Ministry of Education. Education and educational institutions in Baghdad. This research deals with digital transformation as an independent variable according to two dimensions (digital adaptability and digital readiness). Knowledge building was adopted as an approved variable using the s
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This research aims to examine the correlation and the impact of Cultural Intelligence with their dimensions (Strategy, Knowledge, Motivation, Behavior) on Drawing Local politics and their dimensions (Empowerment, Flexibility, Organizational Justice, Local Funding) In Dhi Qar Provincial Council To determine the extent of the presence of significant statistical differences between research variables Due to the recent experiment which requires clarification of the role of the pivotal and important carried out by the provincial council in the exercise of his work in light of the diversity of cultures and the peculiarities of the local community, which may impede the provision of equal services to all those parties
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It has aimed by this research at presenting new interpretations to diversification phenomenon and its possible effects on firm value. These interpretations are culminated by the disclosure of the distinct role of resource-based view in the study of relationship between diversification strategy and firm value. The study has conducted on a sample consisted of the largest American companies listed in Fortune 500 along with seven years period
(2005-2011). This first local attempt, which has based on panel dat--a analysis for interpreting an expected variance of firm value due to diversification strategy, may helps with a clear vision to solve the contradiction and confusion surrounded the true linkages between t