Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

Social Context in Developmental Psychopathology: Recommendations for Future Research from the MacArthur Network on Psychopathology and Development

Accumulating evidence suggests that social contexts in early life have important and complex effects on childhood psychopathology. Spurred by the lack of an explicit operational definition that could guide the study of such effects, we define a social context operationally as “a set of interpersonal conditions, relevant to a particular behavior or disorder and external to, but shaped and interpreted by, the individual child.” Building on this definition, we offer a series of recommendations for future research, based on five theoretically derived propositions: (a) Contexts are nested and multidimensional; (b) contexts broaden, differentiate, and deepen with age, becoming more specific in their effects; (c) contexts and children are mutually determining; (d) a context's meaning to the child determines its effects on the child and arises from the context's ability to provide for fundamental needs; and (e) contexts should be selected for assessment in light of specific questions or outcomes. As reflected in an increasingly rich legacy of literature on child development and psychopathology, social contexts appear to influence emerging mental disorders through dynamic, bidirectional interactions with individual children. Future research will benefit from examining not only statistical interactions between child- and context-specific factors, but also the actual transactions between children and contexts and the transduction of contextual influences into pathways of biological mediation. Because adverse contexts exert powerful effects on the mental health of children, it is important for the field to generate new, more theoretically grounded research addressing the contextual determinants of psychological well-being and disorder

Baroreflex Modeling in the Genesis of Stress Reactivity Using Sigmoidal Characteristic

Abstract-According to a physiological hypothesis, children are separated into the two groups, (1)non-reactive and (2)highreactive based on their different autonomic reactivity characteristic. In the non-reactive group, blood pressure(BP) and heart rate(HR) are regulated in a timely manner following external disturbances such as a stressful condition. However, this regulation process does not operate properly, or may even behave in an opposite direction for at least a period of the process in the high-reactive group. The purpose of this research is to analyze and compare the behavioral differences of the autonomic reactivity characteristic, represented by the shortterm blood pressure regulation system (STBPRS), between these two groups of individuals. Similar to any regulation system, each component of this system has a specific role. For example, the autonomic nervous system (ANS) can be considered a controller while the heart and vasculature can be considered a plant under control. The arterial baroreceptor nerves -fiber endings in the arterial walls -play the role of sensor and feedback path. The STBPRS is called as baroreflex or baroreceptor reflex including the ANS and baroreceptors. We applied the Windkessel model and sigmoidal function as the model structures of the vasculature and baroreflex, respectively. To obtain the most similar simulated HR in comparison with measured HR, an optimization problem was defined. Due to the non-convex nature of the optimization problem, a genetic algorithm (GA) was applied to identify all of the corresponding unknown parameters for each component of the system. The obtained results of the system identification problem, verify the mentioned physiological hypothesis. Moreover, these results lead to a better understanding of the deficient baroreflex in highreactive children. Furthermore, necessities of invasive blood pressure measurement in baroreflex studies is eliminated by using our proposed method

Synthesis of Interface-Driven Tunable Bandgap Metal Oxides

Mixed bandgap and bandgap tunability in semiconductors is critical in expanding their use. Composition alterations through single-crystal epitaxial growth and the formation of multilayer tandem structures are often employed to achieve mixed bandgaps, albeit with limited tunability. Herein, self-assembled one-dimensional coordination polymers provide facile synthons and templates for graphitic C-doped mesoporous oxides, gC-β-Ga2O3 or gC-In2O3 via controlled oxidative ligand ablation. These materials have mixed bandgaps and colors, depending on amount of gC present. The carbon/oxide interface leads to induced gap states, hence, a stoichiometrically tunable band structure. Structurally, a multiscale porous network percolating throughout the material is realized. The nature of the heat treatment and the top-down process allows for facile tunability and the formation of mixed bandgap metal oxides through controlled carbon deposition. As a proof of concept, gC-β-Ga2O3 was utilized as a photocatalyst for CO2 reduction, which demonstrated excellent conversion rates into CH4 and CO

Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure

Failure properties and microstructure of healthy and aneurysmatic human thoracic aortas subjected to uniaxial extension with a focus on the media

Current clinical practice for aneurysmatic interventions is often based on the maximum diameter of the vessel and/or on the growth rate, although rupture can occur at any diameter and growth rate, leading to fatality. For 27 medial samples obtained from 12 non-aneurysmatic (control) and 9 aneurysmatic human descending thoracic aortas we examined: the mechanical responses up to rupture using uniaxial extension tests of circumferential and longitudinal specimens; the structure of these tissues using second-harmonic imaging and histology, in particular, the content proportions of collagen, elastic fibers and smooth muscle cells in the media. It was found that the mean failure stresses were higher in the circumferential directions (Control-C 1474 kPa; Aneurysmatic-C 1446 kPa), than in the longitudinal directions (Aneurysmatic-L 735kPa; Control-L 579 kPa). This trend was the opposite to that observed for the mean collagen fiber directions measured from the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C), thus suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. The difference in the mean values of the out-of-plane dispersion in the radial/longitudinal plane between the control and aneurysmatic groups was significant. The difference in the mean values of the mean fiber angle from the circumferential direction was also significantly different between the two groups. Most specimens showed delamination zones near the ruptured region in addition to ruptured collagen and elastic fibers. This study provides a basis for further studies on the microstructure and the uniaxial failure properties of (aneurysmatic) arterial walls towards realistic modeling and prediction of tissue failure