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.
Background: Generally, genetic disorders are a leading cause of spontaneous abortion, neonatal death, increased morbidity and mortality in children and adults as well. They a significant health care and psychosocial burden for the patient, the family, the healthcare system and the community as a whole. Chromosomal abnormalities occur much more frequently than is generally appreciated. It is estimated that approximately 1 of 200 newborn infants had some form of chromosomal abnormality. The figure is much higher in fetuses that do not survive to term. It is estimated that in 50% of first trimester abortions, the fetus has a chromosomal abnormality. Aim of the study: This study aims to shed some light on the results of chromosomal studies per
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This study aims to assess the effect of adding twisted fins in a triple-tube heat exchanger used for latent heat storage compared with using straight fins and no fins. In the proposed heat exchanger, phase change material (PCM) is placed between the middle annulus while hot water is passed in the inner tube and outer annulus in a counter-current direction, as a superior method to melt the PCM and store the thermal energy. The behavior of the system was assessed regarding the liquid fraction and temperature distributions as well as charging time and energy storage rate. The results indicate the advantages of adding twisted fins compared with those of using straight fins. The effect of several twisted fins was also studied to discover
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The imperative of achieving financial stability has transcended national boundaries, necessitating heightened attention from both researchers and policymakers. Consequently, this article delves into an examination of the impact of government debt and public debt on financial development within the context of Iraq. The study employs monetary policy, interest rate, inflation, and population growth as control variables to prognosticate financial development. Utilizing data extracted from the World Development Indicators (WDI) spanning the period from 1995 to 2022, the study employs the dynamic autoregressive distributed lag (DARDL) approach to scrutinize the associations under investigation. The findings underscore a negative association betwe
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شهدت العالم منذ نهايات القرن الماضي وبدايات القرن الواحد والعشرين تطورات دراماتيكية على صعيد الادبيات التنموية ، اذ تحولت التنمية من المفهوم التقليدي الذي اهتم بالنمو الاقتصادي الى رؤية جديدة هي رؤية التنمية البشرية ومن ثم الى التنمية المستدامة التي اعطت للتنمية البعد الانساني وجعلت من مشكلات واحتياجات البشر منطلق لها لتحويل الفرد والمجتمع الى مرحلة جديدة تضمن له العيش الكريم وتحقق معه
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Described the Arabic language being of genius sets by top models of eloquence , rhetoric and clarity of sounds and developments Moreover , it is an important element of our existence and our identity and our survival . That my methods and best in teaching Arabic language what has pursued the easiest ways to learning and teaching and helped learners to be aware of the function linguistic information , and they need it and its impact on their lives , and contributed to unleashing the potential of activism and led them to make the effort to apply them in the form of examples and uses of new life , as well as fits are the capabilities and tendencies of different learners , so the goal of current research into the importance of the curriculum
... Show MoreWhen the Italian fascist party leaded & access to the top of regime, it took Benito
Mussolini as a post of Italian prime minister on 1922, that lead to rise the voices which need
to find colonies of Italy, like other colonial countries, especially that of its colonies in Libya,
Eritrea and Somalia were not achieved its ambitions, was to be the occupation of Ethiopia to
revive her dreams to exert control over the Red sea and the Mediterranean and the
establishment of a vast empire satisfy colonial ambitions.
the Italian invasion of Ethiopia gained particularly important, what led to the
disruption of the balance of political forces is not at the level of local powers in the region,
but at the level of the exten
Abstract
The research aims to identify the role played by the strategic mind of human resources managers in reducing the levels of strategic drift that can face the organization, as the problem of research to overlook the importance of this role in monitoring and follow-up all the changes that may face the organization during the implementation of its strategy, therefore highlights the importance Research in providing a set of solutions to the problems faced by the researched organization and as far as the research variables, the researchers have adopted the descriptive analytical approach in the applied side, as adopted the questionnaire as a main tool for data collection, which was prepared based on a number of ready me
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Endometriosis is an estrogen dependent inflammatory disorder plays a pivotal role in the reproductive system of the females which regarded as one of the most important gynecological disorders due to it is a key cause of infertility for women and also it has a remarkable impact on the women's life quality. Indeed, environmental pollution have an extremely importance in the etiology of endometriosis. Hence, the present article submits an abbreviated literature review to the biochemical role of environmental pollutants in the etiology and development of endometriosis. Anyway, this review article represented the major environmental pollutants: the organic pollutants of air, heavy metals, gaseous pollutants and the particulate matter. Th
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Abstract:
Rabi’a tribe lived on the land of Euphrates since the first century of the
Christ. Then that land becomes her homeland. The Persians tried many times
to drive her away from that land, but with out result.
In the course of time Rabi’a become more knowledgeable of Persia.
This tribe proved her love and sanctification to the land of Euphrates, in the
battle of Dhyqar.
Rabi’a converted to Islam quickly and helped the Muslims to conquer
Iraq with a big number of fighters in many battles like al- Qadisyyah. That
influenced the anger of Mudriat Arab tribes who were their old enemies.
Mudriat tribes did their efforts to reduce the importance of Rabi’a because of
some its branches were among of t
The inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are heterogenous chronic inflammatory disorders of the gastrointestinal tract. The most widely accepted etiopathogenic hypothesis for these disorders suggests an immune mediated process.
Objective: This study was performed to evaluate the role of interleukine-33 in pathogenesis of inflammatory bowel disease and to correlate their levels with the disease activity and/or severity.
Methods: Fifty five subjects with inflammatory bowel disease (41 ulcerative colitis patients and 14 Crohn’s disease patients) their ages range from 16-65 years and 25 apparently healthy volunteers their ages and sexes were matched with the patients were participated i