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.
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 MoreThe 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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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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Objective(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
The world is moving towards greening business in general and production systems in particular. At the same time, economic units seek to enhance their productivity and find any variables that can contribute to improving their elements. Economic units should not ignore the green dimension of cost management techniques because of its role in containing the green dimension of the production system and the product. However the few researches dealt with the subject of the green kaizen showed its role in reducing costs and improving the environment. Those researches did not address its contribution to raising the level of productivity. Productivity is an important indicator of economic units that expresses their level of success and progre
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To investigate the relationship between increased lipid peroxidation, and the lowering of both plasma total proteins and albumin in lead-exposed workers, and the effectiveness of antioxidants (vit. C and E) in modulating oxidative stress in those workers.
Thirty male and females workers employed in the Iraqi storage battery (age range 20-40 years) were participating in this study. Additionally, 11 healthy subjects were served as healthy controls, with the same age range compared to workers group, to avoid the effects of age variations on the studied parameters. Blood lead levels, erythrocytes and plasma MDA, erythrocytes and plasma GSH, total protein and albumin levels in healthy controls and lead-exposed workers pre- and post-tr
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The research aims to study and analysis of concurrent engineering (CE) and cost optimization (CO), and the use of concurrent engineering inputs to outputs to improve the cost, and the statement of the role of concurrent engineering in improving the quality of the product, and achieve savings in the design and manufacturing time and assembly and reduce costs, as well as employing some models to determine how much the savings in time, including the model (Lexmark) model (Pert) to determine the savings in design time for manufacturing and assembly time.
To achieve the search objectives, the General Company for Electrical and Electronic Industries \ Refrigerated Engine
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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
... Show MoreBackground: This study aimed to determine the gender of a sample of Iraqi adults utilizing the mesio-distal width of maxillary canines, inter-canine width and standard maxillary canine index, and to determine the percentage of dimorphism as an aid in forensic odontology. Materials and methods: The sample included 200 sets of study models belong to 200 subjects (100 males and 100 females) with an age ranged between 17-23 years. The mesio-distal crown dimension was measured manually, from the contact points for the maxillary canines (both sides), in addition to the inter-canine width using digital vernier. Descriptive statistics were obtained for the measurements for both genders; independent samples t-test was performed to evaluate the gende
... Show MoreThe aim of the research is to clarify the role of service quality through its dimensions represented by (tangibility, reliability, safety, response, empathy) in tax compliance with taxpayers, i.e. performance of the duties and obligations of the taxpayer through its dimensions (registration, accounting, payment of the amount of tax), and to know For this role, a sample was taken from the taxpayers of the branches of the General Authority for Taxes spread in the governorate of Baghdad and its affiliated districts, which amount to (15) tax branches, as (215) questionnaires were distributed to know the impressions and reactions of the taxpayers regarding the level of service quality through the aforementioned dimensions. Using the statistic
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