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.
It is no secret to everyone that the Arab individual suffers from poor self-awareness and political awareness, which made the state and the importance of its existence and preserving its institutions not among his interests, which made researchers wonder about the possibility of strengthening it and the extent of its impact on the future of building the contemporary Arab state. So, the study attempts to addressing the issue of community awareness and its impact on building the state through a clear intellectual vision that blended what is social and political to define the concept of community awareness and highlight its importance and role as a basic pillar in shaping and building modern Arab countries in the Arab world and ways to enha
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Scientists have delved too much into reality and metaphor, and perhaps a topic of Arabic rhetoric has not received the attention and care of scholars as much as the topic of truth and metaphor. The metaphor opens wide horizons of expression in front of the writer so that he has several means by which he can express the one experience, so his imagination takes off depicting the intelligible as tangible, the seen as audible, and the audible as seen. That image presented by the creative writer.
The first thing to note is that the emergence of metaphor as a rhetorical term was at the hands of the Mu'tazila. Muslims differed about the issue of metaphor in the Holy Qur’an, and the beginning of the dispute was about the verses in which the
Praise be to the one who taught the pen. Without the pen, the knowledge of the first two would not have reached the others. Then, praise the one who taught man from the printing industry unless he knew, and prayers and peace be upon those who guide all nations to the invention and the follower in the matter of religion, and to his family and companions.
The use of Qur’anic use is an integrated and important topic that examines the building and the meaning, which are two major titles in the study of Arabic, so the goal of scholars when going into these explanations was to find out the wonderful linguistic miracle of this great book.
Scholars have worked hard to talk
Thanks allah and peace be upon our prophet muhammed and upon his family and his
followers……
Love means in holy quran what comes to people s mind nowadays and what it inspired its
signi ficence is related with sensual desire and it means adore and passion .by the waythe
word (ishiq) adore wasn’t mentioned in holy quran which means that both of their bases are
farfrom each oiter in m eaning.
The significance of love means virtue while adore means the excess and desire so adore is
dis praised . as al askari said (died 395h )between love and adore.adore is the strain of desire
to get the purpose from lovers if it was ahuman who intended to make love affairs.
Today both of love and adore changed in their meani
Twilight is that light appear on the horizon before sunrise and after sunset, Astronomically it is known that sunrise and sunset are effected by high above sea level, but the effect of high above sea level on the time of astronomical twilight still not decided and controversy among astronomers, in This research we studies the effect of high above sea level on the time of astronomical twilight, through adding the equation correct high above sea level to equation computation of twilight and then calculate of changing in the time of twilight for different highest (0-10000) meters above sea level , and the ratio of increase for time with high between (15.45-20.5) minutes. It was found that there was an increase in the time of the twilight along
... Show MoreAl-Wasiti's drawings are the first attempt to document the Arab landscape more than 778 years ago. These drawings were associated with a fine literary material, and the relationships between words and poetic sentences are matched by artistic, aesthetic and color relations in drawing, as they are all outputs of a sense that agreed in creativity and differed in the language of expression. Al-Wasiti was creative in drawing these events. Islamic painting has a goal that differs from the goals of the painting arts that preceded it or its contemporary, as it tends to “beautification” only. This is achieved by true copying from nature, just as it is achieved by drawing what is transmitted from nature, transforming and refining it. The
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ملخص البحث باللغة الإنجليزية
The concept of the phenomenon of nuns: an analytical ideological study
Dr. Samia bint Yassin Al-Badri
Department of Islamic Doctrine & Contemporary Ideologies
College of Shariʿah & Islamic Studies
Qassim University
The study of concepts is one of the main pillars of doctrinal studies, in order to understand the formation of the concept, and to understand its contexts in religious sources, in order to be systematically criticized; So, this research came with the title:
The concept of the phenomenon of nuns, an analytical doctrinal study
The study concluded with resu
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The major of DDoS attacks use TCP protocol and the TCP SYN flooding attack is the most common one among them. The SYN Cookie mechanism is used to defend against the TCP SYN flooding attack. It is an effective defense, but it has a disadvantage of high calculations and it doesn’t differentiate spoofed packets from legitimate packets. Therefore, filtering the spoofed packet can effectively enhance the SYN Cookie activity. Hop Count Filtering (HCF) is another mechanism used at the server side to filter spoofed packets. This mechanism has a drawback of being not a perfect and final solution in defending against the TCP SYN flooding attack. An enhanced mechanism of Integrating and combining the SYN Cookie with Hop Count Filtering (HCF) mech
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Background: Dental implants are a suitable option for the replacement of some or all missing teeth. The successful insertion of a biocompatible material into living tissue with little to no evidence of rejection has revolutionized medicine and dentistry. An increase in bone response was observed with local administration of growth hormone around dental implants. Growth hormone may act as a bone stimulant in the placement of endosseous dental implants and enhances osseointegration. The aim of the study was to evaluate immunohistochemically the effect of the topical application of growth hormone on the osseointegration of cpTi implant. Materials and Methods: Eighty titanium screw implants were inserted in the tibia of the forty adult rabbits.
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