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.
After this systematic presentation of the phenomenon of rotation of formulas, ie the construction of the verb and the verb, and the narrated narratives therein differed among the readers, it became clear to us how the difference was clear between reading and the other, and how readers have varied in their readings of the verb, As we have noted through our modest research that the phenomenon of building the verb for the actor and the effect have included the act of both past and present tense, and not limited to a specific time, and this difference in reading was not limited to a particular environment, but beyond To more than one environment This is evidenced by the readings of various readers from the environment of Kufa, Basra, Mecca,
... Show MoreThis research sheds light on the contributions of a group of scientific Kurdish scholars in the seventh and eighth Hijri centuries, who devoted themselves to serving science with the bad political and economic conditions at the time, and the research pointed to the flowering of science and how students travel in order to provide them with science, obtain a scientific certificate, then take up The research efforts of the scholars in the two Hijri century mentioned in the science of the Qur’an, whether in the field of recitations, intonation or interpretation, and the research ends with a conclusion in which I mentioned the most important conclusions reached in this research.
The heritage of the human peoples remains a beacon of data, after renewed awareness of them, open to their propositions, which are born from the womb of intertwined elements of customs, knowledge, arts, and literature ... Misleading the reception process, it may be something intriguing to identify with caution with the text sample selected by the current search procedures prepared according to the adoption of a descriptive therapist in a three-dimensional approach, as well as a comprehensive textual reference for that specific communication dimension within Anthology Andalusian - Moroccan poetry in the book of pleasure in the perception of the five senses Tahdib ibn Manzoor (d. 711 e) from the origin of Tivashi (d. 651 e) Tagged: Separat
... Show MoreAfter completing the research, with the help and success of God Almighty , I will summarize what has been mentioned in a concise and understandable form, without boring prolongation or abbreviation .
The subject, in general, was clarified, clarified and corrected, as I mentioned, for an incorrect concept, about paying zakat on trade goods.
It has known trade offers parts and combination of language and idiomatic .
The rule of zakat on trade goods, and evidence from the Qur'an, Sunnah and consensus .
As well as the conditions of its zakat according to the jurists and their differences in it .
It
... Show MoreThe research aims to show the impact that the information of the supporting bodies can have and its dimensions represented by (information credibility, efficiency and effectiveness of information, cooperation with the tax administration, obligating the taxpayer, accuracy and completeness of information and the appropriate time) in tax inventory, as well as clarifying the moral differences in The response of the surveyed sample according to the personal variables represented by (gender, educational attainment, scientific specialization, job title, years of service), and the descriptive analytical approach was adopted and in light of it, the questionnaire was designed as a main tool in collecting data from the sample of (80)
... Show MoreThe goal of this research to identify the effect of the probing questions in the collection of material literature with students of the Kurdish language department, to achieve the aim of the research, the researcher has chosen a sample from the students of third stage of the Kurdish language Department, Faculty of Education / Ibn Rushd as a field for the application of experiment.The number of sample reached (71) students divided into two groups represented two divisions of the experimental groups under study to the style of questions sounding by (35) students, and represented the other division of the control group, which studied in the way normal and by (36) students, as rewarded r
... Show MoreAbstract
This study aims to evaluated the user satisfaction of retrieval services
concerning to universities thesis and dissertations in university dissertation
unit of Baghdad Library for achieving the following objectives:
1- Evaluating the performance of this unit (thesis unit of Baghdad University
Library) regarding to users opinion.
2- Recognizing the reasons in this unit behind the case of non satisfaction of
its users and trying to find the suitable solutions.
To achieve those two objectives, the questionnaire tool was performed
and determined the user's satisfaction level by using a sample survey. 1118
graduated students were subjected to this experiment. The following main
results were appeared:<
The financial markets are one of the sectors whose data is characterized by continuous movement in most of the times and it is constantly changing, so it is difficult to predict its trends , and this leads to the need of methods , means and techniques for making decisions, and that pushes investors and analysts in the financial markets to use various and different methods in order to reach at predicting the movement of the direction of the financial markets. In order to reach the goal of making decisions in different investments, where the algorithm of the support vector machine and the CART regression tree algorithm are used to classify the stock data in order to determine
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(1)
Abstract
The perpetuity of the Quranic discourse required being suitable for all ages.
Accordingly, the method of the Glorious Quran a pre request for the conscious
investigation and realization in order to detect the core of the texts, as the Quranic
discourse is considered a general address for the humanity as a whole. For this
reason, the progress of the concerned studies neceiated that it should cope with the
current development in the age requirements and its cultural changes within ages.
The texts of the Glorious Quran lightened the human reason as being the
Creator’s miracle for it is characterized by certain merits that makes it different from
poetry and prose. It is a unique texture in its rheto
... Show MoreThe purpose of this research is to highlight the relationship between the administrative investigation and the improvement of institutional performance, and the research sought to achieve a set of cognitive and applied goals. the administrative investigation is the modern trend of managing the offices of the general hginspectors and the main source to build the necessary standards to manage and invest its resources efficiently and effectively required to achieve the goals it seeks. The institutional performance is the cornerstone for the implementation of all tasks and duties carried out by institutions operating within the borders of a particular country, The significant change
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