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 primary aim of the study was to find out the values of some biomechanical variables for the long serve skill in badminton and to identify the effect of biomechanical feedback on the performance of long serve. The present study had a single group, pre-post experimental study design. The research community was determined by the intentional method of one group with a pre-and post-test. The players of the Assyrian badminton club constituted the research community. A total of 12 players were present in the research community. The badminton players falling within the age group of 15-17 years for the season 2020-2021 were recruited as the participants for the study. A total of five players were selected as the participant
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This research is a result of other studies made about the iraqi public and its relationship with different states institutions, until recently, such studies were almost non-existent. The main characteristic that distinguishes scientific research is that it involves a specific problem that needs to be studied and analysed from multiple aspects. What is meant by identifying the problem, is to limit the topic to what the researcher wants to deal with, rather than what the title suggests as topics which the researcher doesn’t want to deal with. The problem of this research is the absence of thoughtful and planned scientific programs to build a positive mental image of the institutions of the modern state in general and the House of Represe
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The researcher was interested in studying a crucial aspect of the systematic world music culture. He highlights the analysis of the harmonic construction in the musical compositions of the artist Khalil Ismail, where harmony is a significant Western musical science, a pillar of the structure of instrumental and vocal music.
It depends on the compositions of vertical sounds performed simultaneously, as tones coincide and are sometimes dissonant to give sound resonance that enriches musical work and attracts recipients. Hence, the researcher has many questions, including: Can the composition of the writings of the artist Khalil Ismail determine in an objective research framework? Is there a study on this subject in some detail? whic
The research aims to build a training program to develop the willpower in the kindergarten children. In order to achieve the objective of the research, the two researchers have developed a Training Program according to the following steps:
- Determining the general objective of the Training Program.
- Determining the behavioral objectives of the Training Program.
- Determining the content of the Training Program.
- Implementing the content of the Training Program sessions.
- Evaluating the Training Program.
The training program consisted of (15) sessions, each session included a set of parts (title, general objective, methods, time and place to implement the sessions, behavioral goals, tool
... Show MoreThe images and drawings reduce the intellectual, symbolic and cognitive dimensions inside them that make them an intermediary that imposes itself on the educational method, as they have become responsive to all the needs of the student in the modern era unlike the previous periods. The artistic direction of the illustrations in the scientific books meets the educational and pedagogical needs of the learner and their frame in an illustrative educational method that contributes in developing the student's abilities to benefit from the scientific curricula in the age of scientific and cognitive development.
Here, the researcher finds that the artistic direction of the illustrations lacks the achievement of scientific and technical p
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Background: The objectives of this study are to evaluate the effect of addition of Multi-Wall Carbon Nano Tubes (MWCNTs) of different concentrations (0.05 mg.mL-1,0.25 mg.mL-1,0.5 mg.mL-1and1 mg.mL-1) on dimethyl sulphoxide DMSO and distilled water (DW) on tooth enamel. It intends to evaluate enamel microhardness in (Kg. m-2) pre and post the application of Multi-Wall Carbon Nano Tubes (MWCNTs). Materials and Methods: Thirty specimens prepared for the present study to measure the hardness of the enamel. Results: The results showed that a significant increase in the enamel microhardness for groups 0.05 mg/mL (group B), 0.25 mg/mL (group C), 0.5 mg/mL (group D) and 1 mg/mL (group E) compared with control group (group A) in dimethyl sulphoxi
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Each school of Islamic jurisprudence has principles and rules upon which the diligent work in these schools is based. This is due to the view of sanctification of these rulings, as they are divine rulings. Therefore, the goal is to reach a ruling that represents the intent of the legislator as much as possible.
Hence, these schools of thought established rules for issuing fatwas with the intention of restricting the performance of a fatwa to the hands of those who are qualified for it and have met its conditions, so they gave priority to the most knowledgeable person over others to perform the fatwa. In the Hanafi school of thought, for example, the saying of Imam Abu Hanifa (may God have mercy on him) is given precedence over others,
In this research, we attempt to show the extent of harmony in an aspect of the text according to the stylistics for the Knowing of the stylistic value of the title threshold, and the pathways of titles that suggest and support the meaning when the recipient reads the literary text, in addition to the interpretations that reflect the purposes of the poet who contributed to the drawing of his poetic achievement. The research presented a brief about the poet and his most important works, because they are the text which will be studied according to the stylistics. The research also explained the concept of style and the stylistics in the preface , because of the stylistic is the method adopted by the research to study the title thresholds in
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