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.
Developing countries have depended since long time on the developed countries to increase the levels of development and improving rates of growth direction to the best way where taking this dependence many shapes influenced by the evolution form of international relations and this dependence shows how the great deficiencies in sources of local financing, which called developing countries to increase their reliance on external funding sources, represented in the form of grants, subsidies, loans and foreign investment, pursuing States in that the application of economic reform policies in pursuit of faster economic growth and restructure its economy and achieve economic stability. In the early eighties of the last
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This researchable paper aims to focus of the role & mechanism of market makers in Iraqi stock market through analyzing its role in other Arabian as well as global stock ones, especially in current period through activate the use of bonds, shares, and trying to create a continued price balance. Then decreasing the opportunity having gaps between highest and lowest level without reasonable causes. In addition trying to deactivate the common decision without supported information. Moreover, this paper aims to explain the rules of increasing liquidity and having balance to lead the market into positive direction. Thus, for achieving the above-mentioned requirements, such conditions should be underlined by market makers as well as t
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Abstract
The various countries seek to encourage their local investments through the various policies they follow. The most important of these is the monetary policy, which is a means and procedures taken by the monetary authority to control the supply of money and maintain its stability of its financial impact on economic activity.
The effect of monetary policy is to stimulate domestic investment through money supply that is inversely related to the interest rate and a direct relationship with domestic investment. When money supply increases, interest rates fall and local investment growth rates rise, but when the rise in money supply is high, Inflationary measure
This research investigates the engagement of the Iraqi audience with ethnographic programs and their impact on knowledge enhancement and intellectual perspectives. A questionnaire consisting of closed-ended questions was designed and administered to a purposive sample of 400 participants who exclusively follow ethnographic programs and documentary channels. The data were transcribed and subjected to statistical analysis using the SPSS software to ensure reliability and test hypotheses. The findings revealed that Al Jazeera Documentary Channel had the highest viewership percentage among respondents for ethnographic programs, while DW (Deutsche Welle) had the lowest viewership percentage. This suggests that Al Jazee
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In the years recently city planning projects have been confirmed sustainable high concentration on planning streets and pedestrian paths being the most prominent component of the urban structure in the city and these me and diverse departments link the city’s sectors and serve as a space for economic, service, and social activities. On the other hand, pedestrian traffic is an essential component of the various means of transportation within the city. Suffer cities in the Middle East and Arab cities in particular are neglecting pedestrian paths in the vital urban environment. Vehicle control mechanisms on roads, and changing the uses of pedestrian paths as result of encroaching on the sidewalks designated for pedestrians. Which leads to a
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This study aims to identify the most important legislatures and legal frameworks pertaining to advertisement for children. It focuses on the western approach, which is characterized by the variety of its perspectives in presenting issues and in identifying problems. However, if studies show that there is a certain awareness about the advertisement impact on children, it is obvious that most of legislatures reject the laws restricting the broadcast advertising spots intended for children under 12 years of age, with the exception of the Swedish and the Canadian province of Quebec experiences, which opted for total ban on advertising spots broadcast messages targeting children. |
The arise of Islam as a multidimensional changing phenomenon with its own revolutionary and comprehensive character was inherent with a lot of alterations in social aspects , and this is explicit particularly in the scope of urban life and town planning . Essentially, Islamic style of life has its own urban identity. The urbanization process in Islam has been developed across two integrated sides, the first one concerned on ideational and theoretical aspects , while the other associated with practice .Many urban centers emerged during the Islamic era since the erection of Basrah , the first Islamic town in the middle of the 7th. centaury. Some contemporary urban concepts , both environmental and social could be noticed in Islamic
... Show MoreObjective: To investigate and prove that aspirin
protects, or at least attenuates amikacin ototoxicity in
humans.
Method: This study was conducted in 60 patients that
completed all
requirements .The patients were divided into two
groups:
• Control group: receive placebo treatment.
• Drug–treated group: They receive aspirin
coated tablets (1.5gm/ day), 500mg 8 hourly.
Both groups had similar aspects regarding the gender,
age and weight. The duration of therapy was 7 days
and dosage of amikacin was 1gm/day (500mg 12
hourly).
Results: Comparison of Audiometry test in
Ear/Nose/Throat (E.N.T.) Department (Pure Tone
Audiometry) at 1000 Hertz (Hz), 2000 Hz, 4000 Hz,
and 8000 Hz showed sig
The problem of the paper focused on the role of the learning organization in the crisis management strategy, and the extent of the actual interest in both the learning organization and the crisis management and aimed at diagnosing and analyzing that and surrounding questions. The Statistical Package for the Social Sciences (SPSS) program was used to calculate the results and the correlation coefficient between the two main variables. The methodology was descriptive and analytical. The case study was followed by a questionnaire that was distributed to a sample of 31 teachers. The paper adopted a seven-dimensional model of systemic thinking that encourages questioning, empowerment, provision of advanced technologies, and strategic lea
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This study focuses on how tax administrations in Iraq use Artificial Intelligence (AI) techniques to monitor tax evasion for individuals and companies to achieve Tax Compliance (TC). AI was measured through four dimensions: Advanced Data Analytics Techniques (ADAT), Explainable AI (EAI), Machine learning (ML), and Robotic Process Automation (RPA). At the same time, TC was measured through registration, accounting, and tax payment stages. We relied on the questionnaire form to measure the variables. A sample of employees in the General Tax Authority in Iraq was selected, and a questionnaire was distributed to 132 people. The results indicated that the dimensions of AI affect achieving TC at all stages. This study provides evidence of using A
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