Denis Arnold. Giovanni Gabrieli and the Music of the Venetian High Renaissance. London and New York, Oxford University Press, 1979. viii + 322 pp.

Noble, Jeremy

doi:10.1017/s0261127900000358

Cited by 16 publications

(14 citation statements)

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“…Furthermore, it has become widely appreciated that these separate components and their interactions do not influence phenotypes independent of variations in the micro-cellular or macro-organismal environments (Jirtle et al 2007; Weiss and Buchanan 2009). As Noble (2006, 2008) and Lewontin (2002) have so clearly summarized, the DNA sequence is only part of the material basis of heredity. The biological functions associated with a contiguous region of DNA sequence are determined by the interactions of its effect with the effects of environmental agents, including other regions of DNA sequence, that occur throughout the life cycle from fertilization until death.…”

Section: Discussionmentioning

confidence: 98%

“…It should be widely acknowledged that neither genes nor environments, but their interactions, are the primary biological causes of phenotypic variation (Lewontin 2002; Sing et al 2003; Noble 2006, 2008; Lehner 2011). The primary insights gained from decades of biological research establish that interactions between molecular components of every biological system are pervasive at every level explored to date.…”

Section: Discussionmentioning

confidence: 99%

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Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study

et al. 2014

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Markers of the chromosome 9p21 region are regarded as the strongest and most reliably significant genome-wide association study (GWAS) signals for Coronary heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D Consortium meta-analysis. However, while these associations are significant at the population level, they may not be clinically relevant predictors of risk for all individuals. We describe here the results of a study designed to address the question: What is the contribution of context defined by traditional risk factors in determining the utility of DNA sequence variations marking the 9p21 region for explaining variation in CHD risk? We analyzed a sample of 7,589 (3,869 females and 3,720 males) European American participants of the Atherosclerosis Risk in Communities study. We confirmed CHD-SNP genotype associations for two 9p21 region marker SNPs previously identified by the CARDIoGRAMplusC4D Consortium study, of which ARIC was a part. We then tested each marker SNP genotype effect on prediction of CHD within sub-groups of the ARIC sample defined by traditional CHD risk factors by applying a novel multi-model strategy, PRIM. We observed that the effects of SNP genotypes in the 9p21 region were strongest in a subgroup of hypertensives. We subsequently validated the effect of the region in an independent sample from the Copenhagen City Heart Study. Our study suggests that marker SNPs identified as predictors of CHD risk in large population based GWAS may have their greatest utility in explaining risk of disease in particular sub-groups characterized by biological and environmental effects measured by the traditional CHD risk factors.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study

et al. 2014

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“…With an approximately accurate result they have leverage for improving their model in a more piecemeal but tractable fashion by increasing network complexity. This kind of strategy has been called a “middle-out strategy” (Noble 2008 ). It forms an essential component of the cognitive strategy of “mesoscopic modeling.”…”

Section: Cognitive Constraints and Methodological Choicementioning

confidence: 99%

Modeling complexity: cognitive constraints and computational model-building in integrative systems biology

MacLeod

Nersessian

2018

HPLS

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Modern integrative systems biology defines itself by the complexity of the problems it takes on through computational modeling and simulation. However in integrative systems biology computers do not solve problems alone. Problem solving depends as ever on human cognitive resources. Current philosophical accounts hint at their importance, but it remains to be understood what roles human cognition plays in computational modeling. In this paper we focus on practices through which modelers in systems biology use computational simulation and other tools to handle the cognitive complexity of their modeling problems so as to be able to make significant contributions to understanding, intervening in, and controlling complex biological systems. We thus show how cognition, especially processes of simulative mental modeling, is implicated centrally in processes of model-building. At the same time we suggest how the representational choices of what to model in systems biology are limited or constrained as a result. Such constraints help us both understand and rationalize the restricted form that problem solving takes in the field and why its results do not always measure up to expectations.

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“…It has also been recognized that the pace of such change is sometimes too rapid to be accounted for by natural selection. First Lamarck, and then Waddington, suggested that alternative mechanisms, now termed epigenetics, must also contribute to phenotypic outcomes (Noble 2006 ). Epigenetics encompasses the mechanisms that regulate gene expression without altering the underlying DNA sequence, and the complete epigenetic status of a cell at any given time is termed the epigenome.…”

Section: Introductionmentioning

confidence: 99%

Environmentally induced epigenetic toxicity: potential public health concerns

Marczylo¹,

Jacobs²,

Gant³

2016

Critical Reviews in Toxicology

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Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.

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Denis Arnold. Giovanni Gabrieli and the Music of the Venetian High Renaissance. London and New York, Oxford University Press, 1979. viii + 322 pp.

Cited by 16 publications

References 0 publications

Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study

Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study

Modeling complexity: cognitive constraints and computational model-building in integrative systems biology

Environmentally induced epigenetic toxicity: potential public health concerns

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