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.
The study aimes to analyze the discourse of Arab tweeters regarding the normalization of Arab-Israeli relations on the social media site (Twitter).
Study Methodology: The study relay on the survey method, using the comprehensive survey method, and this research is one of the descriptive types that aim to describe the phenomenon in a qualitative way, and discuss it through the method of in-depth analysis, in addition to using the tools of (discourse analysis).
Study sample: A sample of (8686) tweets for (7425) tweeters, which was posted on Twitter during the period from 15/9 to 30/9/2020, on the issue of normalizing Arab-Israeli relations.
Study tools: The data study was collected using the data mining tool from social networks (
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Nowadays, the field of radionuclide treatment is enjoying an exciting stage and preparing for further growth and progress in the future. For instance, in Asia, the large spread of liver and thyroid diseases has resulted in several new developments/clinical trials using molecular radiotherapy (i.e. targeted radionuclide therapy). Iodine-124 has unique physical properties including long half-life that adding an advantage for pharmacokinetics and radiopharmaceutical analysis. One of its applications in nuclear medicine is in Positron Emission Tomography (PET).
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The Islamic religion is a religion of tolerance and is pleased with worship and other legislation and the idea of peace is an authentic and profound idea related to the call for coexistence with all religions. The Prophet (PBUH) was keen to organize his relations with non-Muslims on the basis of cohabitation, On the basis of love and intolerance, God Almighty says: "If your Lord wants to make people one nation and they are still backward." Surah Hud: 118 Islam has taken care of the people and made them tolerant brothers who sympathize with their different beliefs. Which means that everyone has the right to live, believe and believe what he sees right and have the freedom to perform the acts of worship and beliefs he deems correct. The di
... Show MorePraise be to God, Lord of the worlds, and peace and blessings be upon our master Muhammad and his family and companions as follows:
For God Almighty has swapped for every age a group of religious scholars who give news to the narrators, so that they can lie against the Sunnah of the Mustafa, who is among those who memorized Ibn Al-Mulqin, as he followed the ruler in his book Al-Badr Al-Munir in the Hadith of Al-Sharh Al-Kabeer, and our research included two topics, which we explained in the first topic: The sequels in which the teacher's son Al-Malqin disagreed, and we discussed in the second topic: the followings in which Ibn Al-Malqin agreed to rule.
This research included important results, th
We need to know the basic facts concerning planning top and bottom limits including any critical levels or the threshold over which the cost would be much higher for land development. Therefore this paper concerned with Baghdad Municipality decision No.2/1004 dated 7/12/2004. The reason behind this decision is the hope to face up at least in the severe housing crisis in the city of Baghdad. This paper attempts to know the attitude of the local community in the general through a field study of people living near such dwelling where third floors are added of. This might indicate any positive or negative effects whether on short or long-term including its effect on the theoretical side including the population growth of Baghdad, the
... Show MoreThe research aims to shed light on the amount of proceeds annual tax for each of the way the contract total and percentage of completion method - see which is better - as well as the current problems arising from the application method of the contract in full in settling accounts tax - to identify problems - related to postpone settling accounts tax in accordance with the way the contract fully and determine the advantages and disadvantages of each of the methods through practical application , and then use the results as inputs to help in the decision to confirm the continuation of the GCT using a full decade in settling accounts tax for long-term construction contracts or forgo them.
Were the result of research the existence of
... Show MoreAutoría: Jehan Faris Yousif. Localización: Opción: Revista de Ciencias Humanas y Sociales. Nº. 89, 2019. Artículo de Revista en Dialnet.
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Several studies have indicated an unprecedented increase in the number of Arab youth who watch music videos. It is also a custom in Arab countries to broadcast songs at their happy parties such as weddings, engagements and birthdays. We see that guests and party owners interact by dancing and singing with the songs, while the viewership rates of Arab music videos have reached millions on YouTube. The researcher decided to study the image of women through the lyrics of these songs, due to their importance in shaping the image of women in the minds of young people and shaping the (self-image) of young women. Twenty songs were selected from the most watched songs on YouTube for the year 2024, and it was found that the negative qualities of t
... Show MoreTo achieve excellence in the quality of performance in school sports administration, which has suffered a lot of problems and constraints on the administrative system, supervision and education level as well as the regulatory environment and available resources available and contribute to the provision of some processors and overcome difficulties to participate in the formation of the individual good of itself and society through sports activities. Hence the importance came this study to create a reference to the quality of the performance criteria school sports from the perspective of supervisors (specialists and technicians) in the districts of breeding Baghdad, to be of help to all those involved in school sports and maintaining an excep
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The purpose of this research is to demonstrate the effectiveness of a program to address the problem of mixing similar letters in the Arabic language for students in the second grade of primary and to achieve the goal of the research. The researcher followed the experimental method to suit the nature of this research and found that there are statistically significant differences between the tribal and remote tests, The effectiveness of the proposed educational program. At the end of the research, the researcher recommends several recommendations, the most important of which are: 1 - Training students to correct pronunciation of the outlets, especially in the first three stages of primary education (primary) and the use of direct training
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