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.
In this work we fabrication holographic optical element diffraction grating thickness 40?m and mirror90?m by using dichromated gelatin,to perform that we have to use the Nd-yaG laser doubling frequency of wavelenght (532)nm and its powers of (80)mWatt.we have studyed the thickness and concentration dichromat effect in mirror reflaction ,effect of angle of reconstruction beam in band width and diffraction efficiency ,study effect gelatin hardener of the diffraction efficiency.
Abstract
What the research come to:
1- The presentation of the image of the proud person in this
mortal life appeared in several styles such as (conversation)
arousing the insert once and convincing in other time,
(confirmation) in all its types، (argument) scolding with the
gradual progress of time of the discourse .Interview and
parallelism are two of these styles with the presences of the
repetition style especially in the topics that has a reference to
the theme of (pride) being implied not directly stated. The
Koran discourse varied in its reference to the theme of pride
according to the context which is mentioned directly
(eighteen times) which formed one third of the number of
Praise be to God, who has seen uniting the wonders of manufactures, and pronounced Pthamidh oddity Alambdoat, and swam his creation in different languages, Glory is not equal to one in the earth and the heavens, praise Him, and I bear witness that there is no god but Allah alone with no partner certificate towering branches, and I bear witness that Muhammad is His slave and Messenger sent swage Arab government balance, and clearest statement, and the highest residence and Ohllagha words, and Oovaha Zmama, he pointed the way and advised the creation, and the month of Islam, breaking idols, and showed provisions, uncle Balanaam, God separated blessings and peace upon our Prophet Muhammad and the God of the good and virtuous and his compani
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summary of the research
The heart is the pine-shaped flesh on the left side of the chest. The moral gentleness in this flesh is called the home of perception, reason and understanding, as well as the place of desires and passions, so it turns between one desire and another between good and evil. As for its parts, it consists of four main parts called chambers, two rooms on the right As for the two chambers below, it is called the ventricle, the heart works regularly and accurately to pump blood and distribute it to all parts of the body and vital organs. And the Holy Quran divided the types of heart into two main types of healthy hearts, which are types (healthy, hidden, living....)
And the second type is sick hea
... Show MoreIt included the introduction to the research and its importance, as the knee joint is one of the important joints in the human body that are susceptible to injury, and among these injuries is the roughness of the knee that occurs as a result of weakness and imbalance in the work of the quadriceps muscle, so its treatment is through rehabilitation exercises to treat weakness and gain flexibility and strength.Hence the importance of the research by developing rehabilitation exercises with different resistances in the water medium and restoring flexibility and muscular strength for patients with knee roughness for ages from 30-40 years, and the experimental method was used to solve the research problem, and the research sample included (6) of
... Show MoreThe research problem has crystallized and in light of these capabilities, the level of performance depends on the application of modern training methods based on actual experimentation, and those methods aim to develop the components of achievement in this competition, including the quantities of exerting the distinctive strength with speed for the arms and feet, which reflects on good skillful performance because the skill of shooting by jumping forward and high forms A major role in achieving goals during the competition that qualifies the team to win, and through the follow-up of the researcher in the field and academic field, I noticed that there is a weakness in some physical abilities, which affects performance and skill level
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(1)
The aim of this research is to show the level of banking leadership trends in the importance of organizational confidence and its reflection in the dimensions of the strategic position the research was applied in a bank (Al- Mansour Investment, Business Bay), and the Questionnaire Was adopted as a tool to collect data and information from the number of the sample (15) who are in allocation (Department Manager, Department Manager Department Manager, Division Officer, Unit Officer) and he used the statistical program (spss) to calculate (standard deviation, arithmetic mean, percentages, regression, analysis,F-test coefficient of determination R2, Coefficieent, square Kay and the research reached a number of conclusions, the mos
... Show MoreThe article examines the definition of the verb in the form of the imperative mood (imperative) _ general information about the verb in Russian .
A verb in Russian is one of the parts of speech that unify all parts of speech, expressing the meaning of action, movement, process in grammatical forms of time, type, mood, face and voice. The imperative mood is a grammatical feature of the verb expressed through several forms of the verb that urges someone to do things. In other words, imperative mood or (imperative) : - one of the single meaning of the form . The form of the imperative expresses a supplicatio
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The purpose of this research is to identify the youth issues in Talk Shows in the Iraqi satellite channels via monitoring a sample of episodes of the Talk Shows episodes which are concerned and analyzed the youth issues in the Iraqi satellite channels, namely, «Hala Shabab Program» at Al-Iraqia satellite Channel and «Shabab wa Banat Program» at Al-Sumaria satellite Channel by recording and re-watching them again. This research is classified as one of descriptive researches. The survey method was adopted in this study.
For this purpose, the researcher prepared an analysis form. The researcher de
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