53 research outputs found

    The emerging landscape of dynamic DNA methylation in early childhood

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    Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho <1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.Peer reviewe

    Synthesising Corporate Responsibility on Organisational and Societal Levels of Analysis: An Integrative Perspective

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    This article develops an integrative perspective on corporate responsibility by synthesising competing perspectives on the responsibility of the corporation at the organisational and societal levels of analysis. We review three major corporate responsibility perspectives, which we refer to as economic, critical, and politico-ethical. We analyse the major potential uses and pitfalls of the perspectives, and integrate the debate on these two levels. Our synthesis concludes that when a society has a robust division of moral labour in place, the responsibility of a corporation may be economic (as suggested under the economic perspective) without jeopardising democracy and sustainability (as reported under the critical perspective). Moreover, the economic role of corporations neither signifies the absence of deliberative democratic mechanisms nor business practices extending beyond compliance (as called for under the politico-ethical perspective). The study underscores the value of integrating different perspectives and multiple levels of analysis to present comprehensive descriptions and prescriptions of the responsibility phenomenon

    Back on track – On the role of the microtubule for kinesin motility and cellular function

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    The evolution of cytoskeletal filaments (actin- and intermediate-filaments, and the microtubules) and their associated motor- and non-motor-proteins has enabled the eukaryotic cell to achieve complex organizational and structural tasks. This ability to control cellular transport processes and structures allowed for the development of such complex cellular organelles like cilia or flagella in single-cell organisms and made possible the development and differentiation of multi-cellular organisms with highly specialized, polarized cells. Also, the faithful segregation of large amounts of genetic information during cell division relies crucially on the reorganization and control of the cytoskeleton, making the cytoskeleton a key prerequisite for the development of highly complex genomes. Therefore, it is not surprising that the eukaryotic cell continuously invests considerable resources in the establishment, maintenance, modification and rearrangement of the cytoskeletal filaments and the regulation of its interaction with accessory proteins. Here we review the literature on the interaction between microtubules and motor-proteins of the kinesin-family. Our particular interest is the role of the microtubule in the regulation of kinesin motility and cellular function. After an introduction of the kinesin–microtubule interaction we focus on two interrelated aspects: (1) the active allosteric participation of the microtubule during the interaction with kinesins in general and (2) the possible regulatory role of post-translational modifications of the microtubule in the kinesin–microtubule interaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42588/1/10974_2005_Article_9052.pd

    The Social Dimensions of Biological Invasions in South Africa

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    Thischapterexaminescurrentknowledgerelatingtothehumanandsocial dimensions of biological invasions in South Africa. We do so by advancing 12 propo- sitions and examining the evidence for or against each using South African literature. The propositions cover four broad issues: how people cause invasions; how they conceptualise them; effects of invasive species on people; and peoples’ responses to them. The propositions we assess include: (1) intentional introductions were and continue to reflect the social ethos of the time; (2) people go to great lengths to ensure that newly introduced species establish themselves; (3) human-mediated modifications help invasive species to establish; (4) how people think about and study invasive species is strongly shaped by social-ecological contexts; (5) knowledge and awareness of invasive species is low amongst the general public; (6) personal values are the primary factor affecting perceptions of invasive alien species and their control; (7) specific social-ecological contexts mediate how invasive species affect people; (8) research on social effects of invasive species primarily focuses on negative impacts; (9) the negative social impacts of invasive species on local livelihoods are of more concern to people than impacts on biodiversity; (10) people are less willing to manage species regarded as ‘charismatic’; (11) social heterogeneity increases conflicts around the management of biological invasions; and (12) engagement with society is key to successful manage- ment. By advancing and questioning propositions, we were able to determine what is known, provide evidence for where gaps lie, and thus identify areas for future research

    Nuclear brinkmanship: a study in non-linguistic communication

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    This article examines meaning making with nuclear bombs and military manoeuvres. The data is verbatim audio recordings from the White House during the Cuban Missile Crisis. The analysis uses concepts from impression management and dialogism. It is found that actions often speak louder than words and that even non-linguistic communication with nuclear weapons is often oriented to third-parties, in this case, world opinion. A novel process of 'staging the other' is identified, that is, when one side tries to create a situation which will force the other side to act in a way which will create a negative impression on world opinion. Staging the other is a subtle form of meaning making for it entails shaping how third parties will view a situation without those third parties being aware of the intentionality of the communication

    Maternal occupation during pregnancy, birth weight, and length of gestation: combined analysis of 13 European birth cohorts

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    Objectives We assessed whether maternal employment during pregnancy overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. Methods We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. Results Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (ORadj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (ORadj, 0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (ORadj 1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts. Conclusions This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development
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