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.
Increased epidemic when Akbari in his book Explanation in the expression of the Koran
An Expression for the transition charge density is investigated
where the deformation in nuclear collective modes is taken into
consideration besides the shell model transition density. The
inelastic longitudinal C2 and C4 form factors are calculated using
this transition charge density for the Ne Mg 20 24 , , Si 28 and S 32
nuclei. In this work, the core polarization transition density is
evaluated by adopting the shape of Tassie model togther with the
derived form of the ground state two-body charge density
distributions (2BCDD's). It is noticed that the core polarization
effects which represent the collective modes are essential in
obtaining a remarkable agreement between the calculated inelastic
longi
This study aims to know the extent of the impact of Strategic Leadership as an independent variable in Strategic Learning as a dependent variable to help the senior leadership in Anbar University to take the right decisions to develop Strategic Learning programs in light of the circumstances of the Covid-19 and the sudden decisions adopted by the university to switch to E-learning and to blend. The survey was conducted by distributing a questionnaire that was adopted as a primary tool in data collection from the study sample represented by the university's senior leaders, An intentional random sample of (105) was selected from our community of (127), the data were analyzed by (SPSS) Depe
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To get access into the orbital floor 3 paths are commonly used which are transconjunctival, subciliary and subtarsal approaches. Each one of these approaches has its advantages and disadvantages. The study assessed the outcomes of the transconjunctival retroseptal approach, which reflects our experience in this type of surgery. Along 8 years, 26 patients received in the emergency room diagnosed with pure isolated orbital floor fractures, all of them admitted to the maxillofacial surgery department and approached by transconjunctival incision without lateral canthotomy. Three types of complications occurred: laceration of the lower eyelid, injury to the lacrimal system and entropion. All of these complications were managed accordingly with n
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Purpose: The research aims to diagnose the current availability of knowledge workers characteristics and the role of these characteristics in knowledge acquision in the city of Sulaimaniya Directorate of Electricity, and to identify the differences between personal and occupational characteristics of a sample of research and its impact on the availability of such properties.Design/methodology/approach :to achieve the objectives of the research questionnaire was developed especially for it and then distributed to a sample of engineers and technicians working in the Directorate of Electricity city of Sulaimaniya, where the sample of the research (52) respondents.
Findings: the most important conclusions reached
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This study aims at identifying the role played by Public Relations in the field of security awareness of the dangers of terrorism. The research is directed to the employees at the Directorate General of Public Relations and Media at the Ministry of Interior. And that on the basis that those who play an important role in the security awareness are the security institutions, primarily the Ministry of Interior, since this Directorate is responsible for all subjects related to the public security using public relations science. It aims at identifying the functions, methods and communication tools used by the Directorate to raise awareness about the dangers of terrorism. In order to achieve the research objectives, the researcher uses the sur
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Time affects all elements of the intellectual scene or the theatrical scene. It came along with the theatrical doctrines according to the conditions of those doctrines and their conceptual ideas or the method of their mechanisms in the application. While it is classically or realistically integrated, we see it in the expressionist doctrine inconsistent and its inconsistency makes it responsive for the deconstruction strategy. Hence the researcher entitled his study (deconstruction the theatrical time in the expressionist doctrine) so that deconstruction would be a field for his study. The study starts with an introduction presenting the research problem, importance and objective. The theoretical framework consisted of three s
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The Islamic orthodox caliphs had a great importance in the history of Arabs in
particular, and of Muslims in general.
Some attributed poetry to them. This issue to see whether such an attribution is correct
or not.
This research tried to deal objectively with this poetry .it discussed the topic,
exploring the scholars’ opinions about poetry attributed to the Islamic orthodox
Caliphs, stating their dispute : some of them agreed while others rejected the
attribution.
The research adopted the opinon that had rejected for reasons stated in the
research, of them: the weakness of poetry and its dealing with unimportant things, for
example, the caliph Omar composed verses about a new garment worn by him.
Is it
The research aim is to identify the concept of fair value and its measurement approaches, shed light on the concept of fraud and its forms, motives, as well as how to identify fraud under the fair value method.
I have been using the program package SSPS statistical in the calculation of the research variables, and the research sample was a group of university professors and auditors working in the federal board of Supreme Audit.
The researcher has reached some conclusions, the most important; the lack of conclusive evidence about management's intent in adopting the use of fair value raises several doubts about the credibility of the statements prepared in under the fa
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God created man with a social nature, that is, man cannot live alone, but there must be a society associated with him. And when God addressed Adam, the first of His creation, he addressed him with the speech of the Muthanna to him and his wife. “This tree, then you will be among the wrongdoers” (Al-Baqara: 35), and thus was the divine discourse for the first human experience on earth. It accommodates a social relationship, which is (the family), husband and wife. And since a person needs to meet, as Ibn Khaldun said: (The human meeting is necessary, and the wise men express this by saying (the human being is of course civil)) (). And as it is known that with the meeting, relations arise from love and hate, cooperation and struggle, a
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