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.
Due to the Geographical links, language is one of the multiple affects among Arabs and Turks. As the different studies demonstrate, Turkish contains many words derived from other languages, yet Arabic remains the language that has great affects on Turkish. Unlike Turkish language, Arabic is a derivative language that requires no suffixes. Thus, Arabic verbs are tuned into Turkish verbs by adding auxiliary verbs. The present study traces some of the Turkish compound words of Arabic roots with an explanation that shows the Auxiliary added to form the Turkish verb as found in the stories of Otman Chevek Sawy’s Like A voice in the Dark. The conclusion sums up the findings of the study illustrated by numbers.
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The importance of this research is to clarify the nature and the relationship between the indicators of financial policy and banking stability in Iraq, as well as to find a composite index reflects the state of banking stability in Iraq in order to provide an appropriate means to help policymakers in making appropriate decisions before the occurrence of financial crises.
Hence, the problem of research is that the fiscal policy has implications for the macro economy and does not rule out its impact on banking stability. Moreover, the central bank does not possess a single indicator that reflects the stability of the banking system, rather than the scattered indicators that depend o
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تعد الرماية واحدة من الألعاب التي يقاس مستوى الانجاز فيها بالأرقام إذ ارتفعت الأرقام المسجلة بالنسبة لسلاح المسدس الهوائي حتى وصلت عند بعض الأبطال العالميين إلى الانجاز النهائي ، وقد لجأ المدربون إلى مختلف الطرق التدريبية, وان ضعف الثبات والتركيز هما اللذان يقودان إلى هبوط مستوى الانجاز في الرماية ، ولتحقيق التركيز والثبات المطلوبين أثناء الرمي يجب التدريب على مطاولة حمل السلاح التي تعد من أصعب تدريبات الر
... Show MoreThe developed financial system is essential for increasing economic growth and poverty reduction in the world. The financial development helps in poverty reduction indirectly via intermediate channel which is the economic growth. The financial development enhancing economic development through mobilization of savings and channel them to the most efficient uses with higher economic and social returns. In addition, the economic growth reduces the poverty through two channels. The first is direct by increasing the introduction factors held by poor and improve the situations into the sectors and areas where the poor live. The second is indirect through redistribution the realized incomes from the economic growth as well as the realiz
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The aim of the research is to assess the practice of tax administration to diminish the strategic direction of (proactive, analytical, defensive, response) and the nature of its relationship to organizational excellence represented by (leadership, strategic planning, focus on taxpayers, information and analysis and knowledge management, focus on operations, focus on forces. The questionnaire was adopted as a main tool in collecting data and information from the sample members of the General Authority for Taxes (110) who are in the site (m. Second Division Manager, Ms The statistical program (SPSS) was used to calculate (mean, standard deviation, difference coefficient, correlation coefficient, t-test). The research reached a number
... Show MoreThe research aims to identify the importance of using the style of the cost on the basis of activity -oriented in time TDABC and its role in determining the cost of products more equitably and thus its impact on the policy of allocation of resources through the reverse of the changes that occur on an ongoing basis in the specification of the products and thus the change in the nature and type of operations . The research was conducted at the General Company for Textile Industries Wasit / knitting socks factory was based on research into the hypothesis main of that ( possible to calculate the cost of activities that cause the production through the time it takes to run these activities can then be re- distributed product cost
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Abstract
The research aimed to test the relationship between the size of investment allocations in the agricultural sector in Iraq and their determinants using the Ordinary Least Squares (OLS) method compared to the Error Correction Model (ECM) approach. The time series data for the period from 1990 to 2021 was utilized. The analysis showed that the estimates obtained using the ECM were more accurate and significant than those obtained using the OLS method. Johansen's test indicated the presence of a long-term equilibrium relationship between the size of investment allocations and their determinants. The results of th
... Show MoreThe research gets its importance through the importance of the annual regulations in the taxation accounting and its efficiency to fulfill accounting justice under the effect of the financial changes and the truth of the activity of the taxable businesses .This through the problem of the research which is found in many objections about taxation accounting according to the annual regulations issued by the General Commission of Taxes , Their aim is to get the real benefits and to decrease the difference in opinions during the estimation to fulfill justice in distributing the burden of taxation .
The research expose many conclusions and recommendations namely , the taxation justice fulfillment is not only in justic
... Show MoreThe tourism industry has undergone exponential transformation, reshaped by online travel agencies (OTAs), shifting consumer preferences, and technological advancements. Established OTAs like TripAdvisor and Travelocity face pressures to adapt their strategies to capitalize on these disruptive landscape changes. This research involves a comparative analysis examining the key challenges confronting TripAdvisor and Travelocity, with a focus on opportunities to leverage artificial intelligence (AI) in enhancing personalization and the traveler experience. The study utilizes publicly available data on the companies and academic literature on AI innovation diffusion. Findings reveal that while TripAdvisor has actively developed AI-based trip plan
... Show MoreThe aim of the research is to measure the change in the impact of the factors of the Corona pandemic on psychological sensitivity and COVID-19 phobia in a sample of Bisha University students and to detect the differences in the phobia (phobia) Covid-19 among the sample members in the measurement before the ban and after the ban was opened, in addition to the differences in psychological sensitivity of The sample has between sizes before and after the spread of the Corona pandemic, as well as the differences in them according to the gender variable (male, female). The researcher relied on the comparative approach. The scale of psychological sensitivity and COVID-19 phobia was applied to a sample of (62) male and female respondents.
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