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 modern stylistic lesson has become more committed to the scientific limits in which it believed, and more confident in itself, and it is no longer just a scientific procedure that helps other curricula and sciences that preceded it.
Based on this, our modest research ((a stylistic vision of the objection in the Quranic discourse)) arose to explore an artistic rhetorical phenomenon that was included in the Holy Quran text. ; Because analysis is a situation that allows us to see a lot and absorb the stranger more clearly.
And since the horizontal arrangement of the linguistic elements in which stylistically undistinguished elements meet with distinct ones, the other trend has emerged that believes that the stylistic dis
... Show MoreThe search for wealth and money is a matter of ethics in the Islamic economy
God Almighty said: "We have honored the sons of Adam (and ridiculed the universe and what he said) mocked you
He said, "He who created you from the earth."
And he commanded you, and he said to him, "He who made you."
Land, and the amount of Rezko and
He said: "You love the money with great love."
And then guide him by exaggerating the ethics of Islam and its legislation in Tamkak and not exceeding it.
In order to darken the doors of inflation with wealth Vakar
And the hereafter and achieve satisfaction and fairness in all actions
To ensure that society has a right not to harm others and to abuse the interests of the economy
Is
The killing of Imam Hussein (AS) and his family and his companions is a big tragedy that has sustained Islam and Muslims has remained generations Islamic considers the death of Hussein (AS) of the major calamities and pays homage to the memory of grief and mourning . The taking Shiite poets their active role in the perpetuation of this painful anniversary taken by the Shiites that way to stimulate and stir up emotions against the killers of Ahl al-Bayt ( peace be upon them ) has not missed poets of Andalusia and Shiites from this Wave Shiite overwhelming Vahioa anniversary and Ozvoha best recruit barely era of eras Andalusian literature but was Hussein certificate ( AS) on the tenth of Muharram day Consolation year held the celebrations
... Show MoreBefore introducing an accurate description of the publication of news about the Iraqi-British war in the press of the Great Iraqi revolution, it is necessary to note the importance of this research as it examines a remarkable phenomenon that lies at the heart of public attention at this particular time, where we live the repercussions of a new war similar, with some of its facts and activities, to the events of the Great Iraqi Revolution that broke out in many Iraqi cities. Therefore, the results of this research can be a starting point for new research characterization of the phenomenon of news coverage of war in the Iraqi press.
The importance of research in the press of the Great Iraqi Revolution, according to the well-known r
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Interval lies at rest in the speech; so as to improve to speak out, which is how Evaln Koran by other speech, called separators; for the secession of Alkalaman then, as the last verse separation between it and its aftermath in the Al-Jinn had a comma significant impact on the statement of the case of gin, as portrayed interval Gin and like the distraught after hearing of the Koran
This Sura carried various types of repetition represent wordy repeat itself and repeat some of the votes as well as the repeated sound of a thousand who remained in Sura breaks Bhaa also repeat the voice of the shredder breaks
Linguistic sounds of Koranic breaks played a significant role in a statement carried by the linguistic meaning of these interludes
Sports and legend rooted deep in human history, and although they meet in the oldest epics as was the hero Gilgamesh legend and a hero of the heroes of wrestling has been named the oldest regular sports tournament in history in his name, a Algeljamchih Games which will be held events in Mesopotamia in August of each year and will continue nine days and take place in competitions in more than a sports game ..
In our time re-production of sports legends to serve the objectives of the huge investment both sports on the commercialization level or at other levels of marketing, including political marketing.
In this context, a move sports media for the production of myths we studied Semiaiaa in an effort to learn how the production proce
The archaeological and religious sites play a prominent role in the rest of the other tourist activities as cultural and spiritual needs that can not be dispensed with. Archaeological sites represent cultural origins of the nation. Religious sites represent the state of man's orientation to God in places of worship . The focus was on the city of Babylon because it is an ancient city and tourist because of its characteristics and elements. The importance of the city of Babylon is illustrated by highlighting its archeological and religious status through its geographical distribution. This gives the subject special importance for the purpose of knowing the city's important sites. And come out with a number of results and a set of recommend
... Show MoreChristianity rejected abortion, since its inception, it took a luck against abortion, although there is no mention of it in the Bible, as there is no explicit text for abortion in the Old or New Testament and that the early Christians considered abortion a sin in all stages, and beliefs included abortion as an act of murder. What is forbidden in the Ten Commandments is “Thou shalt not kill”, and it is understood that killing here is either plundering one’s personal life (suicide) or stealing another person’s life (killing), or stealing the life of a person who has not yet been born (aborting fetuses). Based on the above, it was necessary for individuals to search for (Abortion in the Christian Religion / Descriptive Study) The resea
... Show MoreOut of the search for the truth, the reader of the Holy Qur’an should know the fate of the sorcerers whom Pharaoh threatened when they announced it as pure monotheism in front of seeing the stick as it turned into a clear serpent, when they said: We believe in the Lord of the worlds, the Lord of Moses and Aaron, and the clear promise came to cut and crucify the trunks of palm trees, and they said what they said if Being supplicants to God (May God cause us to die as Muslims), did Pharaoh actually carry out what he promised them?? So we studied that subject from this angle. Because what looms on the horizon of the Holy Qur’an is that there is no one who seeks refuge with God Almighty in times of adversity except that God Almighty has
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