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.
With the growth of democratic thought in our country, widened the trading term
citizenship to the magnitude of the meanings of participation in political life, economic, social
and cultural rights, as the recipe ( citizen ) does not mean only affiliation to the homeland and
link him as a child , but is as such an actor in various fields has his being independent , and
own convictions and the right to freely express his views and personal choices and play a
positive role in public life . Do not correct the democratic structure of any state without the
manifestation of the spirit of citizenship in the relations of each individual citizen to state
institutions.
The current research aims to Pfhom definition of citizen
The research aims at evaluating the illustrations images and determining the availability of good image standards in the illustrations images of the content of the second intermediate stage computer's book for the academic year (2019-2020) as seen by computer teachers. The sample was randomly selected, (30) teachers who are actually teaching the subject in schools within the geographical area of the province of Baghdad (Karkh III). To achieve this goal, ten standards were identified: scientific accuracy, suitability for the level of students, image clarity, image freshness, quality of coloring, suitability of its location of the subject, Matching their content glimpsed, The subject matter is appropriate in terms of area, matching its tit
... Show MoreOn of the psychological disorders that the human encounters is guilty conscience, this feeling is negative and affects on the individual and on those around him and harms the psychological health of the individual.
since the university students slice is one of the important slices in the community which the country dependes on their abilities , their energies and their faculties in the construction and development, the university professors and specialists in the field of education and psychology who are around them should help them in achieving psychological balance and adjustment with themselves and with others, the following research objectives have been set :
... Show MoreThe field of climatic geography focuses on the study of the Earth's surrounding atmosphere, particularly the lower (surface) part close to the Earth's surface. This field examines the interactions within the atmosphere resulting from the solar radiation that reaches the Earth and the subsequent distribution of atmospheric pressure. Consequently, certain surface pressure systems, both high and low, emerge and vary in their temporal and spatial impacts on the climate of the Arabian Peninsula. Therefore, it is essential to conduct a comprehensive and detailed study to understand the causes, development, movement, geographical distribution, and monthly and seasonal recurrence of these pressure systems. For this purpose, a minor climatic
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The investment environment is the incubator for all types of domestic and foreign investments, so if their determinants are encouraging, they increase the levels of investment flows and vice versa, as there is a relationship between the nature of the investment environment and the level of investment flows, and the determinants of the investment environment are numerous and the most important of which are security and political stability, and economic and financial factors that include relative stability In the exchange rate and inflation rates, the availability of banks and their development, transparency and integrity in administrative dealings and the lack of prevalence of administrative and financial corruption, and the clari
... Show MoreHuman witnessed over the centuries many of the important issues faced by the international community was centered on human rights in general and the persecution of refugees, especially according to many forms may be directly or indirectly leaves behind economic crises, social and humanitarian push world countries to rethink the mechanisms and the feasibility of developing agreements and laws and the role of international and regional organizations to protect peoplerefugeestatus.
The current research aims to know the complementary use of the paper book and the digital book by defining the paper book and the digital book and knowing the methods and methods of obtaining each of them and indicating the extent of their use and for what purpose and knowing the difficulties that researchers face in using each of them and which is better using the paper book or the digital book in preparing research Studies and for no reason. The research relied on the descriptive approach and the questionnaire as a tool for data collection, and it was distributed to professors and students of Iraqi universities. The research sample reached (219) individuals and reached a set of results, the most important of which are: Preference for the
... Show MoreAbstract
The phonetic replacement is the process of putting a sound or a linguistic
syllable instead of another in one word that results in changing its meaning . It is one
way of vocabulary varionsness and discrimination because replacement among the
sounds of one expression and changing its image lead to change its meaning , and
accordingly , each replaced sound has its own linguistic value that distinguishes it . In
other words , the phonetic replacement is based on system of phonemic change
which is a general phenomenon in all languages . The linguistic system doesn’t stand
straight for word unless it is based on different standards that work on variousness ,
assortment and relating the phonetic change wi
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Abstract This research deals with the definition of the concept of nodal purposes, And what is related to it, from its aim and importance, And for the purposes of the importance of Streptococcus In trying to understand the nodal truths For different minds, Especially with those who object to the introduction of belief in purposes studies, This research has two requirements: The first requirement: the concept and the aim of contractual purposes,It consists of two branches, The first is in the concept of nodal purposes, And it dealt with the definitions in terms of language and terminology And what we see is proportional to what aim |