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.
This paper deals with a dilapidated urban part with a proposal to renew it and return it to the life cycle of the city, as in the neighborhood of Al-Mdawar, adjacent to the port of Beirut. It discusses the challenges and the need for renewal, the causes of urban deterioration, the urban development approach and the history of the regulations applied to Beirut, In the studied area. It also proposes solutions to improve its lifestyle based on urban planning tools and design to achieve people's aspirations, preserve identity and rearrange its integration with the Beirut central district area.
Logic is one of the sciences that have receded and regressed in the field of Islamic sciences. This regression is the result of several factors, the most important of which are:
1- The Aristotelian logic, concerned with the seemingly essential shape and the underlying truth in the text, which has been translated into Arabic, is no longer able to keep pace with scientific revelations and epistemological spaces of our time.
2- The existence of logic in the curricula of Islamic studies was not subject to a study linking logic and Islamic sciences. Therefore, we find that the student studies logic as if it were a strange subject that has nothing to do with the subjects of Islamic studies and even Islamic philosophy.
3- Logic is
Alopecia (Baldness) is very usual trouble in current time. It is accompanied by an intensive weakening of the scalp's hair and follows a specific pattern. Hereditary predisposition plays a very important role in alopecia despite not completely understood. Alopecia can be typed to various categories according to etiology, may be due to hereditary factors, autoimmune disease, and drugs or chemicals. There are many options of strategies of treatment according to the type and causes of alopecia. Chemical or synthetic medications apply for the management of hair loss are accompanied by a wide range of undesirable effects. Naturally occurring drugs also play important role in alopecia management with minimal side effects.
The subject of the Internet of Things is very important, especially at present, which is why it has attracted the attention of researchers and scientists due to its importance in human life. Through it, a person can do several things easily, accurately, and in an organized manner. The research addressed important topics, the most important of which are the concept of the Internet of Things, the history of its emergence and development, the reasons for its interest and importance, and its most prominent advantages and characteristics. The research sheds light on the structure of the Internet of Things, its structural components, and its most important components. The research dealt with the most important search engines in the Intern
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The study of triples seeks to deal with the comprehensive nature of the Qur’an texts, and the choice fell on the trilogy of great torment, pain, and humiliation in the Noble Qur’an - an objective study, the title of this research, in which I tried to shed light on these terms, and the nuances between them, and in particular torment The eschatological terminology varied, which can be summed up in three terms, namely the great, the painful, and the offensive. The types of torment, the pain is the painful one that is described by the severity of pain and its horror, as for the humiliating punishment, it is that which humiliates the one who has fallen on it, and the diversity of torment is due to the diversity of sins.
Abstract
The image of the soldier, as a hero who sacrifices everything to defend his
country and values, is no longer depicted in modern drama. With two World Wars
and many regional wars and civil wars, the soldier becomes a victim, not a hero.
Authors present the character of the soldier as a man who suffers a lot as he is
victimized by his own government and its politics that forces him to be in such a
position. Dramatists express their views about race, oppression and war through
their characters, such as the character of the soldier, as in the two selected plays for
this research: The Hostage by Brendan Behan and A Soldier's Play by Charles
Fuller.
The Hostage depicts, through its events, the Irish oppre
The current research aims to identify the level of impact of strategic improvisation as an independent variable on organizational health. The dependent variable in the Department of Health of Dhi Qar to reach appropriate mechanisms in order to reach appropriate mechanisms and recommendations proposed to contribute to the achievement of organizational health in the Department of Health of Dhi Qar (the research department) and based on the importance of the subject of research in government institutions and the important and service role of the Department of Health of Dhi Qar in the Iraqi society. The descriptive analytical approach was adopted in the completion of the research based on the opinions of the leaders in the surveyed depa
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This research aims to identify the impact of Daniel's model on the development of critical thinking. In order to achieve this objective, the following hypotheses are formulated: 1. There is no statistically significant difference at the significance level (0.05) between the average differences in the posttest scores of the experimental group taught according to Daniel's model and the control group taught according to the traditional method in the measure of critical thinking. 2. There is no statistically significant difference at the significance level (0.05) between the average differences in the preand post-tests scores of the experimental group taught according to Daniel's model in the measure of critical thinking. The current research i
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