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.
Abstract:
One of the most prominent historical stage feature that is well- known
nowadays in the world is democracy issue. This issue gives man the right to
reflect his concept and notions . It,s the world of freedom , human right and
liberation of women. This leads to the principle of equality between women
and men which is put in the top of liberty and Improvement lists .
Improvement can be defined as a group of means and ways that is
used to direct human work to improve their level of life economically and
socially .
This study contains three sections, the first presents the social state of
women in pre-history period . And the second section presents the theory of
improvement as an important social ph
Background: Infections are common in the children attending daycare centers how act as predisposes to it. Hygienic interventions have a fundamental role in infection control and disease prevention in child care settings.
Objective: - To evaluate the knowledge, attitude, and practice of nurseries workers in infection prevention and control among the children.
Subjects and Methods: A cross-sectional study using the researcher-developed questionnaire validated by two experts and piloted and 100 nurseries-workers had participated in it.
Result: the mean age of participants was 37.5 years±12.1, (37%) aged 18-30 yrs, 58% married, and 57% with higher education, 54% of n
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In this research, the influence of the fermentation treatments and baking in Iraqi’s flour type (Ibaa 99, Al-rashed, Tamus, Abu-grabe) and Turkish flour type (Muaamel) on phytic acid was investigated. In whole wheat flour, the phytic acid was (1500, 1290, 1450, 1230, 1440 ( mg/ 100 g flour respectively, and the inorganic phosphorous was (29.18, 25.15, 23.89, 20.85, 22.83) mg/100 g flour respectively. The dough prepared from flour with a higher phytic acid content also contained higher amount of phytic acid. During fermentation, degradation of phytic acid occurred. The cumulative loss of phytic acid after fermentation in all type of dough was ~ 23, 22, 34, 26 and 27% respectively،While increased of inorganic phosphorous occurred. The c
... Show MoreThis study aimed to provide a theoretical framework for the impact of the Turkish intervention in northern Syria and the extent of its impact on the relations between the two countries.
It also sought to answer the study's main question: What is the impact of the Turkish intervention in northern Syria on Turkish-Syrian relations during the period 2011-2019 ?.
In this study, the historical method, the descriptive method, and the systems analysis method were used, with the aim of arriving at an accurate and realistic understanding of the Turkish-Syrian relations.
The study reached a set of results, the most important of which was that the Syrian-Turkish relations are based on interests, and that all alliances and
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The present paper aims at investigating the linguistic image portrayed by UNICEF reports on the Iraqi child from a critical discourse analysis perspective during Covid19 pandemic (2020). The paper attempts to fill a gap in research literature concerning the linguistic construction of the Iraqi child by the UNICEF reports during the critical health crisis of Covid19. Van Leeuwen’s (2008) approach of social actor representation has been adopted for this purpose. From Van Leeuwen’s approach, the category of determination (single determination and overdetermination) has been selected to be the main analytical tool for its high compatibility with the set of objectives put forward to figure out how such a globally effective and
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Abstract:
In light of globalization and internationalization of financial markets, issues arising from financial crises have become increasingly serious and fundamental, creating a lot of debate among experts around the world. So, many studies have attempted to investigate what measures can be taken to detect and prevent crises before they devastate the economies.
Therefore, this paper examines the Effectiveness of the Monetary Policy (MP) to Avoid, Reduce or Treat the Financial Crisis in Malaysia. Scholars have yet to agree on the issue
... Show MoreGenerally, different propositions show that culture changes because of many factors, and acculturation has emerged out of important operations which lead to cultural change as a result of contact between different societies or cultures. Since the cultural environment with its varying effects plays a major role in the formulation of architectural products, the research defined its research problem as follows: There is need for knowledge to specify the results of acculturation at the level of plans of house architecture belong to Iraqi elites in Baghdad city during the late Ottoman rule in Iraq(1830-1917). The research depends on the comparative procedure to define the acculturation results, so the plans character of
... Show MoreOur study comes up to clarify the role of television in spreading the culture of violence with a child. This study represents one of the important studies that have tried to highlight the impact of these programmes, particularly cartoons, on the child's behaviors, actions and acquired habits.Violence considers a common phenomenon among the people, as the role of the media, particularly TV has a vital role due to its properties, characteristics and its significant impact on different segments and groups in society and in children particularly through exposure to programmes of films.The results of the study have been affected by the rising proportion of females to males, and that the contribution of real life has a big role in the child ac
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