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.
With the great development in the field of the Internet, the talk about the new media and its implications began, And its interactive services have made the future of media material sometimes participating in it and manufacturing it at other times,
the public is seeking information and choosing the appropriate ones, as well as exchanging messages with the sender after what the role of the receiver is just receiving information only.
This study aims to demonstrate the effects of using digital media in various forms and types to construct the value system of Iraqi society through the identification of the following aims:
Identify the most popular digital media for the Iraqi public in their daily lives on the Internet.
Identify
The research problem lies in identifying the challenges facing spreading the culture of peace in Iraq, and the most important factors of its instability from the point of view of leaders and intellectual elites.The research derives its importance from the fact that the peace imposed by justice leads to a stable Iraq and a prosperous future.
The study aims to identify the most prominent challenges and obstacles created by wars and faced the process of spreading the culture of peace and instability in Iraq, and to shed light on the reasons leading to the employment of the capabilities of community leaders in spreading the culture of peace.The objective of the current research is to identify the challenges of spreading the culture o
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The modern business environment has witnesses tremendous developments as a result of the globalization of markets and economic openness and technological as well as the acquisition of the issue of corporate governance of great importance regarding it as one of the global innovations trends of control provisions on the management of companies as result of these developments ,increasing on competition between economic unit ,thus a decrease in market share because they do not take into account the response to the requirements of customers ,which kept her to search a modern management accounting methods to help them keep up with the changes and the availability of information for the various adminis
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The study was conducted to assess the attitude and awareness of a sample of people regarding the indiscriminate slaughter and its effects on health and the environment compared with slaughtering in a slaughterhouse. The sample consisted of 120 persons from six equal professional groups contacted with the butchery labour (livestock keeper, truck driver, butcher, veterinarian, shopkeeper and consumer). The age ranged 22-76 years old, mean 52±10 years, lived ≥ 5 years in the Baghdad city. The results showed that there is a preference for slaughtering inside the slaughterhouse due to the presence of veterinary examination, slaughtering and preparing meat in a healthy, easy-to-clean places, unlike the indiscriminate sla
... Show MoreThe rapid developmemt of information technology and its use in all fields has a bositive influence on all fields , and financial markets have a share of this development through the use of an electronic trading system to settle transactions and enhance transparency and disclosure in all activities of these markets and stimulate their performance .
It is worth nothing that these revolutions remove the necessity for nonstop connection with persons through the internet or phone networks , novel knowledge decreases the charges of structure original transaction system and reducing the fences of new participants entry .
The development in transportations expertise allows for quicker or
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The mechanism of managing religious difference
God is the Lord of the worlds, forget them and their jinn, Arabs and non-Muslims, He is the Lord of Muslims and Lord of non-Muslims, as He created them male and female despite their differences in tongues and colors, so He created them according to their diversity and distinction in beliefs and religions.
To prevent flare-ups due to differences, the Lord of the worlds set limits that he has forbidden to cross, and draw clear maps as mechanisms for managing religious differences and lifting psychological barriers between the different, so that they can coexist in peace and freedom, each adhering to his faith, and practicing the rituals of his religion.
... Show MoreThe power of advertising is immense. Producers of commercial goods and services routinely pour vast sums into promoting their wares through the advertising media, knowing that a successful campaign can win them vital market share , and that failure to advertise effectively can have devastating results . The function of advertising is promotional ; to draw our attention. In order to achieve this function it must reach its target audience , then capture that audience with a message that is both attractive and memorable.
From a linguistic point of view, the language of advertising must be informative, instructive , distinctive and persuasive . It must employ&nb
... Show MoreThe current research aims to identify the Vocational Self of the educational counselors as well as to identify the significant difference in the professional self according to the gender variable (male-female). The researcher adopted the scale of al-hasani (2015), which consisted of (34) items. It was applied to a sample of (300) school counselors (male-female) who were randomly selected from the six directorates in the Baghdad governorate for the academic year 2020/2021. The results showed that the research sample of educational counselors has a vocational self-concept. There are no statistically significant differences in the vocational self-concept between males and females among the educational counselors.
All modern critical approaches attempt to cover the meanings and overtones of the text, claiming that they are better than others in the analysis and attainment of the intended meanings of the text. The structural approach claims to be able to do so more than any other modern critical approach, as it claimed that it is possible to separate what is read from the reader, on the presumed belief that it is possible to read the text with a zero-memory. However, the studies in criticism of criticism state that each of these approaches is successful in dealing with the text in one or more aspects while failing in one or more aspects. Consequently, the criticism whether the approach possesses the text, or that the text rejects this possession, r
... Show MoreThe issue of dignity is one of the topics that do not pass as long as the earths and the heavens remain; Because the earth is not devoid of the righteous, the believers, the saints, and the pious, and these do not cease from them aid, dignity, insight, or good vision, and from here the authorship in this section was continuous; Because the people’s need for it is confirmed as time progresses, and in that, Ibn Taymiyyah says in the sum of his fatwas, “And from what it should be known is that dignities may be according to the man’s need, so if the weak needs them Faith or the needy, he is given from it what strengthens his faith and fulfills his needs, and he who is more complete is the guardianship of God than him. He is independent
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