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.
Time crosses one of the most important principles that are agreed upon in contracts, because the temporal dimension has a significant impact on all contract provisions and is not limited to a certain group of them. French and Arab legal jurists alike called for this dimension to be given special attention. That is the term of the contract term; To try to limit the temporal elements, clarify their provisions and distinguish between them, but in the Arab world it did not receive the same attention that it received in the West.
This research seeks to study the role of military bases in activating defense diplomacy, with a focus on studying the case of France in the African continent, which relied on its military bases as a tool to implement its foreign policy. The research explains the concept of defense diplomacy and its relationship to military bases as an effective tool to strengthening bilateral relations between the state's parties. The research focuses on studying the effectiveness of military bases as a tool for activating French defense diplomacy, and studying the goals that French foreign policy seeks to achieve through its intervention or presence in the African continent. In addition to the geopolitical reasons that prompted France to move to
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The business environment is witnessing tremendous developments in the field of production and technology, which requires the development of production methods to go in line with these developments and the increasing competition, which has gone beyond the economic aspects to extend to the environmental aspects, as economic units tended to adopt a cleaner production strategy and through what they achieve by producing environmentally friendly products and achieving economic efficiency. Reducing costs, providing a safe and clean environment for workers, and reducing waste from production operations.
The process of employing modern technology in a consistent manner is what the researcher is interested in, and the psychological role of the sound effect in enhancing psychopathic representations in cinematic characters, which had a wide resonance in the field of cinematic films, and after the predominance of digital technology in the production of contemporary films, the sound effect has a higher efficiency And a good level of advanced aesthetic and dramatic expression in film employment, so many directors resorted to this type of films by using various new and advanced techniques and technological programs in their industry, since the traditional construction does not achieve the dazzling that the viewer desires.
Accordingly, th
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Music has a significant role in shaping the artistical, musical and national identity of individuals. The resources of the cultural identity can be divers according to the multiplicity of the social component. In Iraq, there is a unique ethnical and sacred diversity, which is rather than playing a positive role in shaping the cultural and national identity, on contrast, it is establishing to create many local identities in the same society. Each identity reflects the culture of individual ethnic or religious group, which makes people make their own decisions according to their background rather than according to the benefit of the country.Music as an important cultural source has a social function in forming an artistical identity with n
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The economic dimensions of environmental issues are complex and unclear in many cases, there is a kind of confusion in the real relationship between economic growth and environmental regulations. Many of the negative environmental impacts are accompanied by human activities and urban and industrial development in the city, and that many of the projects that did not take into account the environmental factors during the planning and implementation of them can be detrimental, as well as natural environments, archeological sites, historical or scientific value, aesthetic or educational. It also describes the Global Environment Outlook that if current trends continue, population growth, economic growth and consumption patterns, the p
... Show MoreObjective(s): To evaluate of nurses practice toward orthopaedic wound infection and to determine the
relationship between orthopaedic nurses practice and their demographic data characteristic
Methodology: A descriptive study was carried out at orthopaedic wards of Baghdad Teaching Hospital started
from February 1
st, 2011 to August 30th, 2011. A non-probability sample of (39) orthopaedic nurses who were
working in orthopaedic wards were selected from Baghdad Teaching Hospital. The data were collected through
the use of questionnaire , which consists of two parts (1)Demographic data form that consists of a(10) items
and (2) orthopaedic nurses practice form that consists of (4)sections contain (69) items, by mean of di
Introduction: Syphilis is a sexually transmitted disease, that may be transferred from mothers to infants during pregnancy if it is left untreated. Method: This study was conducted among 65 women who suffered from recurrent abortions in Iraq. Syphilis screening recombinant (IgM + IgG) level by ELISA, RADIM (Italy) and rapid plasma reagin (RPR) (positive and negative results) tests were used to analyse the data. Results: A non-significant association was observed with age (p=0.989), and the number of healthy births (p=0.643). Non-significant differences were observed in comparisons between smoker and non-smoker percentages in the study group. The rapid test for syphilis confirmation was applied using Rapid Plasma Reagin (RPR) tests.
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The understanding exchange rate policy is fundamental in order to identify the mechanism by which works out macroeconomic, And the vital for macroeconomic analysis and empirical work to differentiate between the de facto regimes and de jure regimes, Where the proved surveys and studies issued by the international monetary fund that there is divergence between the de facto regime (Regime of exchange applied by the country actually) and between the de jure regime (Regime de jure through the documents and formal writings of officials of the central bank), And launched studies on the de facto regime (Being a the basis of evaluating monetary policy) Stabilized (peg-like)arrangements or
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Aim: The purpose of this study is to compare the effect of epineurotomy of median nerve with just division of the transverse carpal ligament in the treatment of carpal tunnel syndrome. Patients & Methods: We conducted a prospective, random study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were selected randomly into two groups: group I had a release of the transverse carpal ligament alone, and group II had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age group, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological e
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