33 research outputs found

    A comparative study on the in vitro antibacterial activity of the pneumatophores of Heritiera fomes and Xylocarpus moluccensis

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    Se evaluó la actividad antibacteriana in vitro de los extractos de etanol de los neumatóforos de Xylocarpus moluccensis (Familia: Meliaceae) y Heritiera fomes (Familia: Sterculiaceae) frente a diversas cepas bacterianas utilizando el ensayo de difusión en disco. Ambos extractos presentaron perfi les antibacterianos similares, y las zonas de inhibición fueron >10 mm en la mayoría de los casos. Estos extractos presentaron la máxima actividad frente a aerógenos Enterobacter, siendo las zonas de inhibición de 19 y 21 mm, respectivamente. La concentración inhibitoria mínima (CIM) se determinó mediante el método de dilución en caldo de cultivo. El extracto de X. moluccensis fue el más potente frente a Shigella boydii y Shigella sonnie (CIM = 200 y 300 μg/mL, respectivamente). Se puede asumir que X. moluccensis y H. fomes podrían ser fuentes potenciales de nuevos descubrimientos para el desarrollo de fármacos.The ethanol extracts of the pneumatophores of Xylocarpus moluccensis (Family: Meliaceae) and Heritiera fomes (Family: Sterculiaceae) were assessed for in vitro antibacterial activities against a number of bacterial strains using the disc diffusion assay. Both extracts showed similar antibacterial profi les, and the zones of inhibitions were >10 mm in the most cases. These extracts exhibited the most prominent activity against Enterobacter aerogenes, with the zones of inhibition of 19 and 21 mm, respectively. The minimum inhibitory concentration (MIC) was determined by the broth dilution method. The extract of X. moluccensis was the most potent against Shigella boydii and Shigella sonnie (MIC = 200 and 300 μg/mL, respectively). It can be assumed that that X. moluccensis and H. fomes could be potential sources for novel ‘lead’ discovery for antibacterial drug development

    Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

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    DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability

    Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

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    DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability

    The effect of autonomy, training opportunities, age and salaries on job satisfaction in the South East Asian retail petroleum industry

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    South East Asian petroleum retailers are under considerable pressure to improve service quality by reducing turnover. An empirical methodology from this industry determined the extent to which job characteristics, training opportunities, age and salary influenced the level of job satisfaction, an indicator of turnover. Responses are reported on a random sample of 165 site employees (a 68% response rate) of a Singaporean retail petroleum firm. A restricted multivariate regression model of autonomy and training opportunities explained the majority (35.4%) of the variability of job satisfaction. Age did not moderate these relationships, except for employees >21 years of age, who reported enhanced job satisfaction with additional salary. Human Capital theory, Life Cycle theory and Job Enrichment theory are invoked and explored in the context of these findings in the South East Asian retail petroleum industry. In the South East Asian retail petroleum industry, jobs providing employees with the opportunity to undertake a variety of tasks that enhanced the experienced meaningfulness of work are likely to promote job satisfaction, reduce turnover and increase the quality of service

    The Behavioral Roots of Information Systems Security:Exploring Key Factors Related to Unethical IT Use

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    Unethical information technology (IT) use, related to activities such as hacking, software piracy, phishing, and spoofing, has become a major security concern for individuals, organizations, and society in terms of the threat to information systems (IS) security. While there is a growing body of work on this phenomenon, we notice several gaps, limitations, and inconsistencies in the literature. In order to further understand this complex phenomenon and reconcile past findings, we conduct an exploratory study to uncover the nomological network of key constructs salient to this phenomenon, and the nature of their interrelationships. Using a scenario-based study of young adult participants, and both linear and nonlinear analyses, we uncover key nuances of this phenomenon of unethical IT use. We find that unethical IT use is a complex phenomenon, often characterized by nonlinear and idiosyncratic relationships between the constructs that capture it. Overall, ethical beliefs held by the individuals, along with economic, social, and technological considerations are found to be relevant to this phenomenon. In terms of practical implications, these results suggest that multiple interventions at various levels may be required to combat this growing threat to IS security

    Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

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    Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

    Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

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    A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

    Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

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    An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

    Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

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    An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)
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