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.
In light of the increasing importance of interim financial statements they provided these lists of information that enables users of accounting information to make wise investment decisions and predict the company's activities in light of changes the updated rather than wait until the end of the year and accessing information provided by the annual financial statements. In light of this research has come to the most important set of conclusions the adoption of interim financial information has been audited by the external auditor to the availability of basic qualitative characteristics in the accounting information contained in the (appropriate and timely manner, reliability and comparability) and this in turn leads to the impact on reli
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Documentary Credit passes through many practical phases starting from Opening credit and matching documents and payment of the amount of credit……etc. It is worthy to mention that there are several aspects that are varied and differed from Bank to another one which can offer Competitive Advantage for the bank …This will be shown in this research.
For the purpose of achieving the objective of this research within the theoretical aspect, the researcher had seen and briefed several books and researches which are mainly related to the subject of the research.
As for the practical aspect, has included Questionnaire which included many questions that are fit and suitable to the hypotheses.
Research sample has
... Show MoreThe conservatorship is a legal action to protect troubled banks from credit risk and bankruptcy risk that banks cannot hedge them .The Central Bank role has to protect the financial system from these risks by controlling and supervising. This research studied these risks and explained the role of The Central Bank. This research presented and analyzed the legal framework for supervision and the imposition of conservatorship bank to address the effects that have been achieved as a result of poor management and weak internal controls. Baraka Bank for Investment and Finance was a research sample to measure the financial ratios for the troubled bank, and analysis the results that led to put the conservatorship. The research depends on the hyp
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This study examined the effect of elements of internal marketing activities on customer satisfaction through an exploratory study of banking services in the city of Baghdad, if the research problem crystallized by asking a group of questions, the most important (is there a correlation and impact between the dimensions of internal marketing and customer satisfaction, this study aims to determine The effect of internal communication, training and internal market research on customer satisfaction, represented by the quality of service, loyalty and market share, and embodied the objective of this study to identify the level of availability of internal marketing activities and programs in the research banks, data were collected using
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Gastritis can be defined as histological inflammation of the gastric mucosa. It can be classified according to the time course of the disease as acute or chronic, histological findings, anatomic location, and pathological mechanisms. The objective of this study was to evaluation of serum levels of the proinflammatory cytokines IL-8, IL-17 and IL-22 in Helicobacter pylori infection and their association with the degree of gastritis histopathology in a sample of Iraqi patients. The case-control prospective study consists of 60 patients who attended the Gastrointestinal Tract Center at Al-Kindy Teaching Hospital during the period from December 2019 to April 2020. In addition, the control group included 60 apparently healthy individuals. Bio
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This research aims at answering many questions raised by the research problem concerning the view of the organizations under consideration for the concept of smart leadership and its most important dimensions, as well as the view of crisis management and its concept and most important methods through research objectives that define and clarify the smart leadership with its dimensions and methods of crisis management.
For the purpose of reaching the results of the research and testing the assumptions about the relationship between smart leadership and methods of crisis management, the researcher adopted a questionnaire, designed especially to be a criterion for the research, as the main tool for data coll
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The ionospheric characteristics exhibit significant variations with the solar cycle, geomagnetic conditions, seasons, latitudes and even local time. Representation of this research focused on global distribution of electron (Te) and ion temperatures (Ti) during great and severe geomagnetic storms (GMS), their daily and seasonally variation for years (2001-2013), variations of electron and ion temperature during GMS with plasma velocity and geographic latitudes. Finally comparison between observed and predicted Te and Ti get from IRI model during the two kinds of storm selected. Data from satellite Defense Meteorological Satellite Program (DMSP) 850 km altitude are taken for Te, Ti and plasma velocity for different latitudes during great
... Show MoreObjectives of the study: To assess nurses knowledge regarding oxytocin administration during labor and
delivery in maternity hospitals, and to find out the relationship between nurses knowledge and studied
variables (age, level of education, work times (shift) experience year, training course in nursing field).
Methodology: Descriptive analytic study was conducted on non-probability sample (convenient) of (70) nurses
to assess nurse’s knowledge related to oxytocin administration. The study is conducted at Al- kut Hospital for
Gynecology Obstetrics and Pediatrics and Al- Zahraa Teaching Hospital during periods 5th February to 24th
April 2013, A questionnaire was used as a tool of data collection to fulfill with objecti
Objective: To assess the impact of anxiety and stress during pregnancy upon neonatal outcome Methodology: A descriptive purposive study was used to assess the impact of anxiety and stress during pregnancy upon neonatal outcome. The study was conducted from (22nd \ September \ 2020 to 15th \ February \ 2021). A non-probability sample (purposive sample) was selected from 100 women. Data were collected through an interview with the mother in the counseling clinic, during the third trimester of pregnancy, as well as after childbirth in the labour wards to assess the outcome of pregnancy. Data were analyzed through descriptive statistics (frequency and percentages). Results: The most important thing observed in this study was the n
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