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.
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Deposits with the Industrial Bank, together with loans received from others, are non-financial financial resources, which are sources of supply to the Industrial Bank of funds that allow the Bank to expand the granting of loans. The increases in this resource indicates that the bank is practicing comprehensive banking, which is consistent with the nature of the transformation of the banking system towards multiple businesses. Therefore, the research comes to highlight the causality of the trend between total deposits and total loans. And if the causality is found, is it one-way or two-way? How long is the impact?
The aim of this investigation is to study and analysis the role of governance in the evaluation of the and social performance of the economic units to be addressed through the concept of corporate governance and then to the social performance and its relationship to corporate governance.
The most important obtained results from this research is that the corporate governance of extreme importance, and derive their importance from being an essential tool to contribute to the transparency and fair disclosure of the financial results of economic units in the fight against financial and administrative corruption in economic units, thus providing protection and confidence of all parties, and the evaluating soci
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In this research, the seasonal Optimal Reliable Frequency (ORF) variations between different transmitter/receiver stations have been determined. Mosul, Baghdad, and Basra have been chosen as tested transmitting stations that located in the northern, center, and southern of Iraqi zone. In this research, the minimum and maximum years (2009 and 2014) of solar cycle 24 have been chosen to examine the effect of solar activity on the determined seasonal ORF parameter. Mathematical model has been proposed which leads to generate the Optimal Reliable Frequency that can maintain the seasonal connection links for different path lengths and bearings. The suggested ORF parameter represented by a different orders polynomial equation. The polynom
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Urinary tract infection is a bacterial infection that often affects the bladder and thus the urinary system. E. coli is one of the leading uropathogenic bacteria that cause urinary tract infections. Uropathogenic E. coli is highly effective and successful in causing urinary tract infections through biofilm formation and urothelial cell invasion mechanisms. Other organisms that cause urinary tract infections include members of the Enterobacteriaceae family, streptococci and staphylococci species and perch. In addition, K.penumoniae is another important gram-negative bacterium that causes urinary tract infections. With the PCR technique, unseen bacterial species can be detected using standard clinical microbiology methods. In this study, the
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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
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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Bajila regarded as descending from Anmar Ibn Nizar. Al-Masudi accepts
Bajila and Khath”am as being of Nizar, and asserts that it was only out of the
enmity that they were said to be from the Yemen.
Al-Ya”qubi tries to harmonize this by assuming that Anmar married a
women of the Yemen and that his sons Bajila and Khath”am are thus
connected to the people of this region only through their mothers line.
Bajila embraced Islam in the period of the prophet. Omar 1 forced this
tribe to go to Iraq instead of Al-_Sham, and gave them the quarter of Al- Saw
ad. Then they prohibited from that quarter by given money as reward that
made them against omar1.
This tribe assisted the forth rightly guided ca
ABSTRACT
The multi-drug resistant efflux pump is a glycoprotein pump whose function is to push foreign substances. The efflux pump is found in humans, animals. It also has wide-ranging properties in bacteria and fungi. They are found in all species of bacteria, and efflux pump genes can be found in bacterial chromosomes or mobile genetic elements, such as plasmids. The most sensitive function that leads to a global problem is its resistance to antibiotics in bacterial cells, which increases the ability to bacteria from becoming strong virulence factors that most or all antibiotics cannot kill. It also has othe
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