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\
Dealing economic units at the present time with an industrial environment characterized by competitiveness and the pace of change and its strength as a result of this changing environment shall be on those who made it to adopt strategies that allow them to confront these variables and work in order to meet the market requirements of quality and price appropriate products to suit and the demand for those products and conditions to maintain
its competitive position and its development.
As a result, it became the subject of competitiveness in recent years and enjoys widespread attention at the global level. And in order to keep up
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The Study aims to show the role of Flexible Budget in planning and control The Factory over head.
The study consists four reaserchs the First introduction for the role of Budget in planning and control The second definition Flexible Badget the Third Factory overhed cost variances Analysis The four conclusions and recommendations.
The factory overhead cost represents great ratio from product cost so the management must planning and control on cost Through the year by the Budget of factory over head in the beginning of the year and determind overhead rater.
The study of the concepts of "democracy" and "human rights" and their impact on development, has taken a prominent place in the context of general political and cultural concerns, or in specialized studies even though researchers and scholars do not agree on defining the concepts: Democracy, Human Rights, Development or deriving a global definition hindering them, and that because of the importance of this topic, which proceeds from a number of considerations standing in the forefront, of which:
First: What the world witnesses today in the first decade of this century of consecration of the unipolar theory, trying to give its concepts and perceptions through the law ((excessive force)) to the power of international
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الاستثمار الاجنبي المباشر في العراق ودوره في تحقيق التنمية الاقتصادية
Periodontitis is a persistent bacterial-causing disease which damages the supporting periodontium of the teeth. The complexity of supporting tissue structure makes the regeneration a challenge for periodontists. Early investigations were focused on discovering therapeutic substitutes that are biocompatible, simple to prepare and economic. This might cause a local release of growth factors that accelerate the healing process of the soft and hard tissue. Recently, platelet-rich fibrin (PRF) has received a wide attention as a biocompatible regenerative material in both dental and medical fields. PRF is a natural fibrin-derived biomaterial, and it is easy to obtain. It can be gotten from individual blood without the use of any external anticoag
... Show MoreThis study aimed to clarify the importance of ecological taxation in achieving sustainable development, by analyzing a set of economic measures such as taxes, taxes levied by the legislation in the field of ecology, to fight against pollution. And we tried to evaluate this initiative in Algeria. The results of the study showed that economic measures of ecological taxation contribute to achieving sustainable development, and Although Algeria has adopted a series of ecological tax mechanisms, it is far from keeping pace with developments in this area.
Gender mainstreaming is a goal for building a society characterized by justice and equality. Gender mainstreaming requires a clear understanding of the concept. Therefore, the research focuses on the concept of gender and how it was addressed in the literature through which the concepts related to gender were extracted which is represented by the role and social status through which the relationship of gender can be measured. In order to find out the basis for the different status and roles of both sexes in societies, the interpreted theories of gender were addressed, through which the most important factors affecting gender relations, such as biological, social and economic factors, as well as political systems, were discussed. Due to t
... Show MoreAbstract: This research aims to investigate and analyze the most pressing issues facing the Iraqi economy, namely economic stability and inclusive growth Consequently, the present study investigates the effect of inflation and unemployment, which are significant contributors to economic instability, on inclusive growth dimensions such as GDP, education, health, governance, poverty, income inequality, and environmental performance. From 1991 to 2021, secondary data were collected using World Bank Indicators (WDI) and Organization for Economic Cooperation and Development (OECD) databases. The researchers also employed the autoregressive distributed lag (ARDL) model to determine the relationship between variables. The study revealed that fluct
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Background: Dorsal plication on each side of the penis at the 2 and 10-o’clock positions had been a mainstay for correction of ventral penile curvature. However, because only the 12-o’clock position proved to be a nerve-free zone, dorsal plication at the 12-o’clock position can be advocated.
Objectives: To evaluate tunica albuginea plication with and without neurovascular bundle mobilization in patients with ventral penile curvature. Type of the study: A prospective study.
Methods: A 34 patients with a mean age of (4.8 ± 0.54) years, Who still
Examining of 80 feces samples showed that 31 samples of the house and stray cats harbored either single or mixed infection with eight species of parasites and protozoa with a total infection rate 38.75 %.The results on parasite classes are: Toxocara cati (5%), Ancylostoma tubeforme (3.75%), Capillaria felis(3.75%), Isospora sp.(10%), Cryptosporidium parvum(3.75%), Cryptosporidium muris (6.25%), Toxoplasma gondi (3.75%), Giardia sp.(2.5%) infection from feces of cats that showed single, double and triple infections. Our findings revealed the risk for public health, thus preventive measures should be implemented.