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.
A new scheme of plasma-mediated thermal coupling has been implemented which yields the temporal distributions of the thermal flux which reaches the metal surface, from which the spatial and temporal temperature profiles can be calculated. The model has shown that the temperature of evaporating surface is determined by the balance between the absorbed power and the rate of energy loss due to evaporation. When the laser power intensity range is 107 to108 W/cm2 the temperature of vapor could increase beyond the critical temperature of plasma ignition, i.e. plasma will be ignited above the metal surface. The plasma density has been analyzed at different values of vapor temperature and pressure using Boltzmann’s code for calculation of elec
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The aim of the present research is to evaluate the child’s nutritional
method (2-5 years old) which is based on his resistance of the food highly rich
with nutritional elements and his acceptance of the food of a low nutritional
value in addition to his having forbidden food with other mates and making
use of all mates when having food, in establishing the sound social values and
affection since child hood. The required statistical equation have been used
by the researcher namely (Z test).
The sample of the present study consists of (26) children who were selected
intentionally and randomly from the kindergartens of Al-Bayaa region and the
college of Education for women. The questionnaires were d
Abstract:
Recently, there is a widespread attention about the service at the level of each of the research and academic studies, and at the organizational level as well. The subject of orientation towards the service aspect is starting to be of this attention being of the modern subjects, relatively, which appeared at the end of the last century, as well as the link of this subject with the relationship between the organization and its customers, and how to provide high quality services to get their satisfaction. Thus, the specialists from researchers were interested in this field to develop an appropriate scale to measure the organizational orientation toward service, and it was the most prominen
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This study showed the basic features of corporate tax in Iraq by showing what was in the Income Tax Law in force .The study aims of this to indicate the role of tax corprates in tax revenue and then the possibility of strengthening the revenue of this tax as an important source of local funding sources in the form that is with him reduce dependence on oil revenues to finance the general budget in Iraq, the risks and the study found a number of conclusions from the most important: that the corporate tax comes in the introduction to the components of the income tax structure in terms of relative importance and formed a revenue source of prime The gross proceeds of the income tax in Iraq, where it contributed to more than a quarter of that
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The objective of this study was to investigate the levels of depression, anxiety, and stress among dentists during covid-19 lockdown and to investigate the relationship between stress and each mental health state.
A cross-sectional survey on 269 dentists was conducted using DASS-21 and PHQ-9 questionnaires. Bivariate and multivariate models were constructed and the odds ratio (OR) was calculated to assess the strength of the association between an independent categorical variable and the outcome.
Being unsatisfied with the job was as
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AW Tarik, AW Ali T, A Salah, Journal of faculity of medicine Baghdad university, 2014 - Cited by 3
Background: Implant stability is considered one of the most important factors affecting healing and successful osseointegration of dental implants. The aims of the study were to measure the implant stability quotient (ISQ) values during the healing period and to determine the factors that affect implant stability. Materials and methods: Thirty patients enrolled in the study (17 female, 13 male). They received 44 Implantium® Dental Implants located as the following: 22 implants in maxillary jaw, 22 implants in mandibular jaw from them 17 implants in anterior segment and 27 in posterior segment. The bone density determined using interactive CT scan and classified according to the Misch bone density classification (29 implants in (D3), 15 i
... Show MoreThis study measures the indicators of social and environmental performance of the contents of the administration's prepared reports on its social and environmental performance by comparing the actual performance with the indicators set within the standards of the Global Reports Initiative (GRI), In preparing this research, the researchers relied on studying the criteria of the Global Reporting Initiative, which aims to achieve a high level of performance disclosure under sustainability, In light of contemporary global trends towards achieving sustainable development and its disclosure and the orientations of economic institutions and units in different countries towards emphasizing the extent of commitment during practicing its a
... Show MoreDecision-makers in each country work to define a list of internal and external interests, goals and threats to their countries according to the nature of their awareness of these interests, goals and threats.
Hence, Iraq is not an exception to this rule, and the process of evaluating its interests and the objectives of its foreign policy is subject to the pattern of awareness of decision-makers and the influencing forces in defining its basic interests, which often witness some kind of difference in defining them, evaluating their importance and determining the size of the threats they face. And among these interests and threats that have witnessed a difference in the assessment of their
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Urinary tract infections (UTI) are some of the most common infections experienced by humans, exceeded in frequency among ambulatory patient only by respiratory and gastrointestinal infections. It is also the most common cause of nosocomial infection in adults. A total of three hundred urine sample were collected in age (1-69 years old) in both gender, with (UTI) symptoms referred to AL-Yarmok Teaching Hospital at Baghdad city during the period from January 2010 till August 2010. The commonest isolates were Escherichia coli (E.Coli), Proteus mirabilis and Klebsiella pneumoniae (These represented 49.2%, 22 %, and16 % of isolates respectively). The percentage of bacteria incidence in females
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