Early-Life Socioeconomic Status and Adult Physiological Functioning: A Life Course Examination of Biosocial Mechanisms

A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life SES and adult SES varied across young, mid, and late adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course at which interventions might be most effective in preventing disease and premature mortality.     

合成生物学及其在生物技术中的应用进展

合成生物学是一门21世纪生物学的新兴学科,它着眼生物科学与工程科学的结合,把生物系统当作工程系统"从下往上"进行处理,由"单元"(unit)到"部件"(device)再到"系统"(system)来设计,修改和组装细胞构件及生物系统.合成生物学是分子和细胞生物学、进化系统学、生物化学、信息学、数学、计算机和工程等多学科交叉的产物.目前研究应用包括两个主要方面:一是通过对现有的、天然存在的生物系统进行重新设计和改造,修改已存在的生物系统,使该系统增添新的功能.二是通过设计和构建新的生物零件、组件和系统,创造自然界中尚不存在的人工生命系统.合成生物学作为一门建立在基因组方法之上的学科,主要强调对创造人工生命形态的计算生物学与实验生物学的协同整合.必须强调的是,用来构建生命系统新结构、产生新功能所使用的组件单元既可以是基因、核酸等生物组件,也可以是化学的、机械的和物理的元件.本文跟踪合成生物学研究及应用,对其在DNA水平编程、分子修饰、代谢途径、调控网络和工业生物技术等方面的进展进行综述.     

Homology and the hierarchy of biological systems

Homology is the similarity between organisms due to common ancestry. Introduced by Richard Owen in 1843 in a paper entitled "Lectures on comparative anatomy and physiology of the invertebrate animals", the concept of homology predates Darwin's "Origin of Species" and has been very influential throughout the history of evolutionary biology. Although homology is the central concept of all comparative biology and provides a logical basis for it, the definition of the term and the criteria of its application remain controversial. Here, I will discuss homology in the context of the hierarchy of biological organization. I will provide insights gained from an exemplary case study in evolutionary developmental biology that indicates the uncoupling of homology at different levels of biological organization. I argue that continuity and hierarchy are separate but equally important issues of homology.     

Sexual dimorphism in the XXI(st) century

A new definition of sexual dimorphism is required. The divergent biology of the sexes is still largely ignored, overshadowed by sociocultural considerations and confined to its hormonal organizational and activational effects, while the genes unequally expressed by the sex chromosomes play an important role much earlier, after conception, to set the stage and throughout life. These different components have independent and parallel effects that can interact in a synergistic or antagonistic manner on differentiation and response processes to trigger or erase sex-specific differences. The epigenetic marks and machinery represent the perfect tools to keep the memory of which sex is ours from the very beginning of life. Within the context of the developmental origin of adult health and diseases (DOHaD), owing to their flexibility to the environment, epigenetic marks also represent a support to archive the effects of environments during development, according to the sex of the parent, in a sex-specific mode. In all tissues, including gonads and brain, different trajectories of genes and pathways are used at the basal levels and to modulate/dictate responses according to sex and gender. It is urgent to emphasize the need to take into consideration this new knowledge and to apply less sex-biased approaches in research, medicine and society, to enhance women health and well-being. A critical review and realization of gender-specific social constraints, an indeniably but slowly on-going process, should allow us to "set free our sex biology" while detracting the delusion of hierarchy of the complex mechanisms involved.     

A bird's-eye view of the C-value enigma: genome size, cell size, and metabolic rate in the class aves

For half a century, variation in genome size (C-value) has been an unresolved puzzle in evolutionary biology. While the initial "C-value paradox" was solved with the discovery of noncoding DNA, a much more complex "C-value enigma" remains. The present study focuses on one aspect of this puzzle, namely the small genome sizes of birds. Significant negative correlations are reported between resting metabolic rate and both C-value and erythrocyte size. Cell size is positively correlated with both nucleus size and C-value in birds, as in other vertebrates. These findings shed light on the constraints acting on genome size in birds and illustrate the importance of interactions among various levels of the biological hierarchy, ranging from the subchromosomal to the ecological. Following from a discussion of the mechanistic bases of the correlations reported and the processes by which birds achieved and/or maintain small genomes, a pluralistic approach to the C-value enigma is recommended.     

Welcome to the revolution: integrative biology and assessing the impact of endocrine disruptors on environmental and public health

Concern continues to grow over the negative impact of endocrine disrupting chemicals on environmental and public health. The number of identified endocrine disrupting chemicals is increasing, but biological endpoints, experimental design, and approaches for examining and assessing the impact of these chemicals are still debated. Although some workers consider endocrine disruption an "emerging science," I argue here that it is equally, a "merging science" developing in the tradition of integrative biology. Understanding the impact of endocrine disruptors on humans and wildlife is an examination of "context dependent development" and one that Scott Gilbert predicted would require a "new synthesis" or a "revolution" in the biological sciences. Here, I use atrazine as an example to demonstrate the importance of an integrative approach in understanding endocrine disruptors.Atrazine is a potent endocrine disruptor that chemically castrates and feminizes amphibians and other wildlife. These effects are the result of the induction of aromatase, the enzyme that converts androgens to estrogens, and this mechanism has been confirmed in all vertebrate classes examined (fish, amphibians, reptiles, birds, and mammals, including humans). To truly assess the impact of atrazine on amphibians in the wild, diverse fields of study including endocrinology, developmental biology, molecular biology, cellular biology, ecology, and evolutionary biology need to be invoked. To understand fully the long-term impacts on the environment, meteorology, geology, hydrology, chemistry, statistics, mathematics and other disciplines well outside of the biological sciences are required.     

Honeybee Associative Learning Performance and Metabolic Stress Resilience Are Positively Associated

Background

Social-environmental influences can affect animal cognition and health. Also, human socio-economic status is a covariate factor connecting psychometric test-performance (a measure of cognitive ability), educational achievement, lifetime health, and survival. The complimentary hypothesis, that mechanisms in physiology can explain some covariance between the same traits, is disputed. Possible mechanisms involve metabolic biology affecting integrity and stability of physiological systems during development and ageing. Knowledge of these relationships is incomplete, and underlying processes are challenging to reveal in people. Model animals, however, can provide insights into connections between metabolic biology and physiological stability that may aid efforts to reduce human health and longevity disparities.

Results

We document a positive correlation between a measure of associative learning performance and the metabolic stress resilience of honeybees. This relationship is independent of social factors, and may provide basic insights into how central nervous system (CNS) function and metabolic biology can be associated. Controlling for social environment, age, and learning motivation in each bee, we establish that learning in Pavlovian conditioning to an odour is positively correlated with individual survival time in hyperoxia. Hyperoxia induces oxidative metabolic damage, and provides a measure of metabolic stress resistance that is often related to overall lifespan in laboratory animals. The positive relationship between Pavlovian learning ability and stress resilience in the bee is not equally established in other model organisms so far, and contrasts with a genetic cost of improved associative learning found in Drosophila melanogaster.

Conclusions

Similarities in the performances of different animals need not reflect common functional principles. A correlation of honeybee Pavlovian learning and metabolic stress resilience, thereby, is not evidence of a shared biology that will give insight about systems integrity in people. Yet, the means to resolve difficult research questions often come from findings in distant areas of science while the model systems that turn out to be valuable are sometimes the least predictable. Our results add to recent findings indicating that honeybees can become instrumental to understanding how metabolic biology influences life outcomes.     

Synthetic biology advancing clinical applications

The 'omics' era, with its identification of genetic and protein components, has combined with systems biology, which provided insights into network structures, to set the stage for synthetic biology, an emerging interdisciplinary life science that uses engineering principles. By capitalizing on an iterative design cycle that involves molecular and computational biology tools to assemble functional designer devices from a comprehensive catalogue of standardized biological components with predictable functions, synthetic biology has significantly advanced our understanding of complex control dynamics that program living systems. Such insights, collected over the past decade, are priming a variety of synthetic biology-inspired biomedical applications that have the potential to revolutionize drug discovery and production technologies, as well as treatment strategies for infectious diseases and metabolic disorders.     

The Clock Is Ticking

The “biological clock” serves as a powerful metaphor that reflects the constraints posed by female reproductive biology. The biological clock refers to the progression of time from puberty to menopause, marking the period during which women can conceive children. Findings from two experiments suggest that priming the passage of time through the sound of a ticking clock influenced various aspects of women’s (but not men’s) reproductive timing. Moreover, consistent with recent research from the domain of life history theory, those effects depended on women’s childhood socioeconomic status (SES). The subtle sound of a ticking clock led low (but not high) SES women to reduce the age at which they sought to get married and have their first child (Study 1), as well as the priority they placed on the social status and long-term earning potential of potential romantic partners (Study 2). Findings suggest that early developmental sensitization processes can interact with subtle environmental stimuli to affect reproductive timing during adulthood.     

Modularity: a new perspective in biology

Several decades of research in biochemistry and molecular biology have been devoted for studies on isolated enzymes and proteins. Recent high throughput technologies in genomics and proteomics have resulted in avalanche of information about several genes, proteins and enzymes in variety of living systems. Though these efforts have greatly contributed to the detailed understanding of a large number of individual genes and proteins, this explosion of information has simultaneously brought out the limitations of reductionism in understanding complex biological processes. The genes or gene products do not function in isolation in vivo. A delicate and dynamic molecular architecture is required for precision of the chemical reactions associated with "life". In future, a paradigm shift is, therefore, envisaged, in biology leading to exploration of molecular organizations in physical and genomic context, a subtle transition from conventional molecular biology to modular biology. A module can be defined as an organization of macromolecules performing a synchronous function in a given metabolic pathway. In modular biology, the biological processes of interest are explored as complex systems of functionally interacting macromolecules. The present article describes the perceptions of the concept of modularity, in terms of associations among genes and proteins, presenting a link between reductionist approach and system biology.     

Metabolic engineering in the -omics era: elucidating and modulating regulatory networks.

The importance of regulatory control in metabolic processes is widely acknowledged, and several enquiries (both local and global) are being made in understanding regulation at various levels of the metabolic hierarchy. The wealth of biological information has enabled identifying the individual components (genes, proteins, and metabolites) of a biological system, and we are now in a position to understand the interactions between these components. Since phenotype is the net result of these interactions, it is immensely important to elucidate them not only for an integrated understanding of physiology, but also for practical applications of using biological systems as cell factories. We present some of the recent "-omics" approaches that have expanded our understanding of regulation at the gene, protein, and metabolite level, followed by analysis of the impact of this progress on the advancement of metabolic engineering. Although this review is by no means exhaustive, we attempt to convey our ideology that combining global information from various levels of metabolic hierarchy is absolutely essential in understanding and subsequently predicting the relationship between changes in gene expression and the resulting phenotype. The ultimate aim of this review is to provide metabolic engineers with an overview of recent advances in complementary aspects of regulation at the gene, protein, and metabolite level and those involved in fundamental research with potential hurdles in the path to implementing their discoveries in practical applications.     

Parts plus pipes: synthetic biology approaches to metabolic engineering

Synthetic biologists combine modular biological "parts" to create higher-order devices. Metabolic engineers construct biological "pipes" by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design.     

"Positive biology": the centenarian lesson

ABSTRACT: The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies.Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. To discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series. The aim is to realize, through a" positive biology" approach (rather than making diseases the central focus of research, "positive biology" seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.     

Lipid mimetics: A versatile toolbox for lipid biology and beyond

Being the principal component of biological membranes lipids are essential building blocks of life. Given their huge biological importance, the investigation of lipids, their properties, interactions and metabolic pathways is of prime importance for the fundamental understanding of living cells and organisms as well as the emergence of diseases. Different strategies have been applied to investigate lipid-mediated biological processes, one of them being the use of lipid mimetics. They structurally resemble their natural counterparts but are equipped with functionality that can be used to probe or manipulate lipid-mediated biological processes and biomembranes. Lipid mimetics therefore constitute an indispensable toolbox for lipid biology and membrane research but also beyond for potential applications in medicine or synthetic biology. Herein, we highlight recent advances in the development and application of lipid-mimicking compounds.     

Biology of size and gravity]

Gravity is a force that acts on mass. Biological effects of gravity and their magnitude depend on scale of mass and difference in density. One significant contribution of space biology is confirmation of direct action of gravity even at the cellular level. Since cell is the elementary unit of life, existence of primary effects of gravity on cells leads to establish the firm basis of gravitational biology. However, gravity is not limited to produce its biological effects on molecules and their reaction networks that compose living cells. Biological system has hierarchical structure with layers of organism, group, and ecological system, which emerge from the system one layer down. Influence of gravity is higher at larger mass. In addition to this, actions of gravity in each layer are caused by process and mechanism that is subjected and different in each layer of the hierarchy. Because of this feature, summing up gravitational action on cells does not explain gravity for biological system at upper layers. Gravity at ecological system or organismal level can not reduced to cellular mechanism. Size of cells and organisms is one of fundamental characters of them and a determinant in their design of form and function. Size closely relates to other physical quantities, such as mass, volume, and surface area. Gravity produces weight of mass. Organisms are required to equip components to support weight and to resist against force that arise at movement of body or a part of it. Volume and surface area associate with mass and heat transport process at body. Gravity dominates those processes by inducing natural convection around organisms. This review covers various elements and process, with which gravity make influence on living systems, chosen on the basis of biology of size. Cells and biochemical networks are under the control of organism to integrate a consolidated form. How cells adjust metabolic rate to meet to the size of the composed organism, whether is gravity responsible for this feature, are subject we discuss in this article. Three major topics in gravitational and space biology are; how living systems have been adapted to terrestrial gravity and evolved, how living systems respond to exotic gravitational environment, and whether living systems could respond and adapt to microgravity. Biology of size can contribute to find a way to answer these question, and answer why gravity is important in biology, at explaining why gravity has been a dominant factor through the evolutional history on the earth.     

The challenges for molecular nutrition research 3: comparative nutrigenomics research as a basis for entering the systems level

Human nutrition and metabolism may serve as the paradigm for the complex interplay of the genome with its environment. The concept of nutrigenomics now enables science with new tools and comprehensive analytical techniques to investigate this interaction at all levels of the complexity of the organism. Moreover, nutrigenomics seeks to better define the homeostatic control mechanisms, identify the de-regulation in the early phases of diet-related diseases, and attempts to assess to what extent an individual's sensitizing genotype contributes to the overall health or disease state. In a comparative approach nutrigenomics uses biological systems of increasing complexity from yeast to mammalian models to define the general rules of metabolic and genetic mechanisms in adaptations to the nutritional environment. Powerful information technology, bioinformatics and knowledge management tools as well as new mathematical and computational approaches now make it possible to study these molecular mechanisms at the cellular, organ and whole organism level and take it on to modeling the processes in a "systems biology" approach. This review summarizes some of the concepts of a comparative approach to nutrigenomics research, identifies current lacks and proposes a concerted scientific effort to create the basis for nutritional systems biology.     

Disrupted seasonal biology impacts health,food security and ecosystems

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.     

Quantifying the Socio-Economic Benefits of Reducing Industrial Dietary Trans Fats: Modelling Study

Background

Coronary Heart Disease (CHD) remains a leading cause of UK mortality, generating a large and unequal burden of disease. Dietary trans fatty acids (TFA) represent a powerful CHD risk factor, yet to be addressed in the UK (approximately 1% daily energy) as successfully as in other nations. Potential outcomes of such measures, including effects upon health inequalities, have not been well quantified. We modelled the potential effects of specific reductions in TFA intake on CHD mortality, CHD related admissions, and effects upon socioeconomic inequalities.

Methods & Results

We extended the previously validated IMPACTsec model, to estimate the potential effects of reductions (0.5% & 1% reductions in daily energy) in TFA intake in England and Wales, stratified by age, sex and socioeconomic circumstances. We estimated reductions in expected CHD deaths in 2030 attributable to these two specific reductions. Output measures were deaths prevented or postponed, life years gained and hospital admissions. A 1% reduction in TFA intake energy intake would generate approximately 3,900 (95% confidence interval (CI) 3,300–4,500) fewer deaths, 10,000 (8,800–10,300) (7% total) fewer hospital admissions and 37,000 (30,100–44,700) life years gained. This would also reduce health inequalities, preventing five times as many deaths and gaining six times as many life years in the most deprived quintile compared with the most affluent. A more modest reduction (0.5%) would still yield substantial health gains.

Conclusions

Reducing intake of industrial TFA could substantially decrease CHD mortality and hospital admissions, and gain tens of thousands of life years. Crucially, this policy could also reduce health inequalities. UK strategies should therefore aim to minimise industrial TFA intake.     

TinkerCell: modular CAD tool for synthetic biology

Background

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks.

Results

An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com.

Conclusion

An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology.