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.
God Almighty set out to build mosques, and he commanded to seek their architecture, and the competition for them, and allocate them with types of worship that are not valid in others, and to preserve their sanctity and not to be degraded and taken for mundane purposes and special benefits, because they are considered one of the most prominent features of Islam and the rituals of Islamic society, so this research came to show the rule Sharia in various and contemporary issues that are needed by the imams of the mosques, their rulers, and those responsible for them. Among the issues in which they have examined comparative juristic research and reached the most correct opinion are:
Building mosques over or under buildings and factories i
(4)
(2)
Back ground: In the present study Pinealoctomy
was used to study the sympathetic innervations of
the pineal gland by the superior cervical ganglion
(SCG) of the albino rat.
Objective: Following Pinealoctomy, it is
expected to observe the Chromatolysis reaction in
some neurons of the SCG if they were to innervate
the pineal gland (i.e. retrograde Chromatolysis
changes).
Methods: Fifty albino rats were used in this study,
Pinealoctomy was done, then after a different time
interval ganglionectomy was done, in order to
study the Chromatolysis in their cell body.
Result: The present study has demonstrated that
the most obvious Chromatolysis reaction in the
neurons which innervate the pineal gland a
In the construction of buildings usually, problems occur because of the causes of change orders. The main causer of change orders is the owners, consultants, and contractors. These changes lead to conflicts among them which result in influencing building projects. Therefore, it is necessary to analyze the causes of change orders to reduce them and facilitate management. This paper determines the most critical factors that cause change orders from a different point of view, a consulting owner and a contractor, and a study of the reality of the management of change orders when constructing public buildings. The method employed in this research is a field survey using interviews with experts working in the construction of p
... Show More
(4)
The research deals with A very important two subjects, computer aided process planning (CAPP) and Quality of product with its dimintions which identified by the producer organization, the goal of the research is to Highlight and know the role of the CAPP technology to improve quality of the product of (rotor) in the engines factory in the general company for electrical industries, The research depends case study style by the direct visits of researcher to the work location to apply the operational paths generated by specialized computer program designed by researcher, and research divides into four axes, the first regard to the general structure of the research, the second to the theoretical review, the t
... Show More
The global health crisis resulting from the spread of the Corona virus, which the World Health Organization described on January 30, 2020 as a public health emergency of international concern, then returned to describe it as a pandemic on March 11, 2020, and the measures and procedures taken by government authorities in different countries of the world, whether at the highest level of imposing a comprehensive curfew or what is called globally home quarantine and thus disrupting all sectors and activities in the state, whether public or private (with the exception of some sectors such as the health, media and security sectors), or at a lower level than that, such as reducing work rates in different sectors by rates that vary from one country
... Show MorePraise be to God, Lord of the worlds, and prayers and peace be upon our master and beloved Muhammad, the wise guide and great teacher, the guide to a straight path, the one sent as a mercy to the worlds, and upon his good and chosen family, his chosen companions, the working scholars, and those who follow them in righteousness until the Day of Judgment.
And after:
One of the important controversial topics shared between the sciences of the Noble Hadith and the Fundamentals of God is the issue of the innovator in terms of accepting and rejecting his narration and testimony, and the difference in it leads to disagreement in many branches of jurisprudence that were based on texts narrated by innovated narrators or those accu
... Show MoreGalway Kinnell (1927-) is considered as one of the most important contemporary American poets who brought about a drastic change in the American poetry of the nineteen sixties. Kinnell's poetry is characterized by being simple in style and deep in content. Poetry for him is a means through which he perceives the inner levels of consciousness in an attempt to comprehend the depths of the American self. Therefore, he writes narrative poems in which the emphasis is not on the rhetorical effects, but on the inner transformations through which the poet goes.
"The Bear" (1968) is typical of Kinnell's introspective poetry. It takes the form of a journey in which the rituals of hunting are used allegorically to embody the state of the sp
... Show More
(2)
(1)
This research is considered as the beginning of other studies about the iraqi the public and their relationship with the various state institutions. Recently, such studies used to be almost non-existent. The main characteristic that distinguishes the scientific studies, is the fact that it involves a specific problem that needs to be studied and analysed from multiple aspects, otherwise the definition of problem identification wouldn’t have been narrowing the topic into what the researcher wants to address, also not what the title is referring to as topics which the researcher doesn’t want to address. The problem in this research resides in the lack of well planned scientific programs that aims at building a positive mental picture a
... Show More