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 general objective of the research is to better understand changes in land cover and their impact on climatic factors by measuring changes in land cover for the Baghdad city for the period 1999-2021 and evaluating changes in land cover and measuring changes in climatic factors (relative humidity and evaporation). This study from 1999 to 2021 and in two different seasons: the April of the growing season and August the dry season. When using the supervised classification method to determine the differences, the results showed remarkable changes, the study showed the spatial variations in LC from 1999 to 2021 as follows: increase in the vegetation and water bodies during April and decrease this in August while the soil and built up decreas
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Relations of the prophets Muhammad (May peace be upon him) with by
gantlines from the revelation to the trance of al-hdybya 6 A.H/610 A.C.
This research is concerned with Islamic historical events, particularly dunning
the time of the prophet Muhammad. It also explores relations of the apostle of god
with the rums and their allies the Arabs of Syria.
During the first years of revelation Muslim had achieved great victories
against the unbelievers. This accomplishm-ent had draw attention of some foreign
forces such as the Arabs of Syria, who became snapicions of this new and active
power. Their hostile attend was demonstrated by striking an economical siege against
Muslims. They attacked the nabtins merchants who
God Almighty has imposed on us obligations and set limits on us, and among these obligations is the prayer, which is considered a pillar of Islam. And recently on the statement of its importance, and through extensive explanations, they elaborated on the statement of its pillars, its obligations, its Sunnahs, its rituals, and its bodies, and it is known that the imam in prayer is an important part of the parts of prayer. Whoever assumes this responsibility must be aware of these conditions, the most important of which is jurisprudence in religion, and there has been a disagreement between the jurists, especially the owners of the four schools of thought, about who is qualified to lead the imamate, and this is within many and wide details
... Show MoreThis research deals with the topic (Fantasy Parody in the Design of the Advertisement) in view of the important role that fantasia plays in designing the most creative and attractive advertisements to the recipients. The research problem lies in accordance with the following question:
What is the Fantasy Parody in the Design of the Advertisement?
It means the imagination, the unfamiliar; and features that emerge for it that distinguish it from other concepts. Fantasy advertisement is creativity in innovative ways, either through collage, merging, or the use of various artistic expressions in terms of intellectual and cultural awareness. When uses in the parody of advertisement, it has helped to come up with an aesthetic experie
There is talk of the Prophet ﷺ proud of his relative, which is the uncle, and the importance of this subject, this search for doctrinal matters related to the two things between us: the interest of the Prophet ﷺ responsible, and also responsible forbidden marriage and marriage as it is forbidden to marry the uncle, and in the uncle language: mother's brother, aunt Her uncle may spend his uncle's nephew, the uncle may embrace his nephew, the uncle shall be the guardian of the little or the small, not to cut off the uncle if he steals from his nephew's money. "
The manufacturing industry in Iraq has faced, during the time stages, several obstacles that have had devastating effects on the Iraqi economy. These obstacles are represented by political events and wars that have led to the depletion of most human and material resources and the suspension of most vital industrial facilities from working, And the occurrence of this major deviation in the process of economic development, For the same reasons, the contributions of the manufacturing sector to the gross domestic product varied fluctuatingly, indicating instability in the growth rates of this sector, On the other hand, the supremacy of the belief that the dominance of oil resources as a main source for creating economic growth and achieving a h
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Because asceticism has a great impact on educating the human soul properly, according to what was mentioned in the Book and the Sunnah of the Prophet, and keeping it away from vices and what is devolving into it, and this world and its adornments keep the Muslim away from virtues and work with them in order to reach the Hereafter in which is the eternal bliss that God, peace be upon him, has prepared for the obedient. The two pious obedient ones. And because of the impact of this topic on the Islamic community and adorn it with good qualities. Likewise, I saw many Muslims who do not prefer the life of this world over the hereafter, and they began to fight over the world and enjoy its adornments, and they took pride in money, building, an
... Show MoreThe lexical connotation is one of the types of connotation that linguists have dealt with, and stipulated in their studies, meaning access to the real meanings of the words, that the lexicon can address after tracing the real meaning of the metaphorical meanings, if any, and this is known to the semantics additional significance, and the rhetorical meaning Figuratively.
The miraculous Qur'an in its systems often refers to the metaphorical uses of the words as well as the real use. The significance of the words in the Holy Qur'an came in a variety of contexts, making each word a special significance that belongs to it exclusively. This is the miracle of the Holy Qur'an. The coming of the slow walk, with its eight words (came, came, cam
the banks are one of the public services that must be available in the city to ensure easy financial dealings between citizens and state departments and between the state departments with each other and between the citizens themselves and to ensure easy access to it, so it is very important to choose the best location for the bank, which can serve the largest number of The population achieves easy access. Due to the difficulty of obtaining accurate information dealing with the exact coordinates and according to the country's specific projection, the researcher will resort to the default work using some of the files available in the arcview program
Transportation network could be considered as a function of the developmental level of the Iraq, that it is representing the sensitive nerve of the economic activity and the corner stone for the implementation of development plans and developing the spatial structure.
The main theme of this search is to show the characteristics of the regional transportation network in Iraq and to determine the most important effective spatial characteristics and the dimension of that effect negatively or positively. Further this search tries to draw an imagination for the connection between network as a spatial phenomenon and the surrounded natural and human variables within the spatial structure. This search aiming also to determine the nat