Happiness, Health and Well-Being in a Life Course Perspective : Quantitative Data Collection and Analysis of Sequences of Subjective Indicators

MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2014-2018)Forming a Social Well-being Research Consortium in AsiaSubjective information has recently made a remarkable breakthrough into quantitative data collection and analysis in demography. Seen as a complement to hard statistics, the new perspective it opens seems promising. In the study of life-event histories, pioneering sociologists have developed the qualitative analysis of turning-points based on qualitative life-course narratives; we here present quantitative surveys which recorded factual individual life-event histories together with perceptions of subjective well-being, self-rated health indicators and financial situation over the life course. The interest of this approach is to explore variations in the subjective indicators along individual life courses rather than their absolute level at any point in time; and to confront facts and perceptions in order to better grasp the interpretation of social, familial, health transitions that take place along the life course. We here present how demographers collect such data and how they validate the subjective information against factual data. Some examples of the analysis of individual histories of subjective well-being are then presented and discussed

Phenotype clustering of breast epithelial cells in confocal images based on nuclear protein distribution analysis

Background: The distribution of the chromatin-associatedproteins plays a key role in directing nuclear function. Previously, wedeveloped an image-based method to quantify the nuclear distributions ofproteins and showed that these distributions depended on the phenotype ofhuman mammary epithelial cells. Here we describe a method that creates ahierarchical tree of the given cell phenotypes and calculates thestatistical significance between them, based on the clustering analysisof nuclear protein distributions. Results: Nuclear distributions ofnuclear mitotic apparatus protein were previously obtained fornon-neoplastic S1 and malignant T4-2 human mammary epithelial cellscultured for up to 12 days. Cell phenotype was defined as S1 or T4-2 andthe number of days in cultured. A probabilistic ensemble approach wasused to define a set of consensus clusters from the results of multipletraditional cluster analysis techniques applied to the nucleardistribution data. Cluster histograms were constructed to show how cellsin any one phenotype were distributed across the consensus clusters.Grouping various phenotypes allowed us to build phenotype trees andcalculate the statistical difference between each group. The resultsshowed that non-neoplastic S1 cells could be distinguished from malignantT4-2 cells with 94.19 percent accuracy; that proliferating S1 cells couldbe distinguished from differentiated S1 cells with 92.86 percentaccuracy; and showed no significant difference between the variousphenotypes of T4-2 cells corresponding to increasing tumor sizes.Conclusion: This work presents a cluster analysis method that canidentify significant cell phenotypes, based on the nuclear distributionof specific proteins, with high accuracy

Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium

<p>Abstract</p> <p>Background</p> <p>Basoapical polarity in epithelia is critical for proper tissue function, and control of proliferation and survival. Cell culture models that recapitulate epithelial tissue architecture are invaluable to unravel developmental and disease mechanisms. Although factors important for the establishment of basal polarity have been identified, requirements for the formation of apical polarity in three-dimensional tissue structures have not been thoroughly investigated.</p> <p>Results</p> <p>We demonstrate that the human mammary epithelial cell line-3522 S1, provides a resilient model for studying the formation of basoapical polarity in glandular structures. Testing three-dimensional culture systems that differ in composition and origin of substrata reveals that apical polarity is more sensitive to culture conditions than basal polarity. Using a new high-throughput culture method that produces basoapical polarity in glandular structures without a gel coat, we show that basal polarity-mediated signaling and collagen IV are both necessary for the development of apical polarity.</p> <p>Conclusion</p> <p>These results provide new insights into the role of the basement membrane, and especially collagen IV, in the development of the apical pole, a critical element of the architecture of glandular epithelia. Also, the high-throughput culture method developed in this study should open new avenues for high-content screening of agents that act on mammary tissue homeostasis and thus, on architectural changes involved in cancer development.</p

On the sign of the linear magnetoelectric coefficient in Cr2_2O3_3

We establish the sign of the linear magnetoelectric (ME) coefficient, $\alpha$, in chromia, Cr$_2$O$_3$. Cr$_2$O$_3$ is the prototypical linear ME material, in which an electric (magnetic) field induces a linearly proportional magnetization (polarization), and a single magnetic domain can be selected by annealing in combined magnetic (H) and electric (E) fields. Opposite antiferromagnetic domains have opposite ME responses, and which antiferromagnetic domain corresponds to which sign of response has previously been unclear. We use density functional theory (DFT) to calculate the magnetic response of a single antiferromagnetic domain of Cr$_2$O$_3$ to an applied in-plane electric field at 0 K. We find that the domain with nearest neighbor magnetic moments oriented away from (towards) each other has a negative (positive) in-plane ME coefficient, $\alpha_{\perp}$, at 0 K. We show that this sign is consistent with all other DFT calculations in the literature that specified the domain orientation, independent of the choice of DFT code or functional, the method used to apply the field, and whether the direct (magnetic field) or inverse (electric field) ME response was calculated. Next, we reanalyze our previously published spherical neutron polarimetry data to determine the antiferromagnetic domain produced by annealing in combined E and H fields oriented along the crystallographic symmetry axis at room temperature. We find that the antiferromagnetic domain with nearest-neighbor magnetic moments oriented away from (towards) each other is produced by annealing in (anti-)parallel E and H fields, corresponding to a positive (negative) axial ME coefficient, $\alpha_{\parallel}$, at room temperature. Since $\alpha_{\perp}$ at 0 K and $\alpha_{\parallel}$ at room temperature are known to be of opposite sign, our computational and experimental results are consistent.Comment: 11 pages, 5 figure

The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair

P53-binding protein 1 (53BP1) mediates DNA repair pathway choice and promotes checkpoint activation. Chromatin marks induced by DNA double-strand breaks and recognized by 53BP1 enable focal accumulation of this multifunctional repair factor at damaged chromatin. Here, we unveil an additional level of regulation of 53BP1 outside repair foci. 53BP1 movements are constrained throughout the nucleoplasm and increase in response to DNA damage. 53BP1 interacts with the structural protein NuMA, which controls 53BP1 diffusion. This interaction, and colocalization between the two proteins in vitro and in breast tissues, is reduced after DNA damage. In cell lines and breast carcinoma NuMA prevents 53BP1 accumulation at DNA breaks, and high NuMA expression predicts better patient outcomes. Manipulating NuMA expression alters PARP inhibitor sensitivity of BRCA1-null cells, end-joining activity, and immunoglobulin class switching that rely on 53BP1. We propose a mechanism involving the sequestration of 53BP1 by NuMA in the absence of DNA damage. Such a mechanism may have evolved to disable repair functions and may be a decisive factor for tumor responses to genotoxic treatments

Higher order nuclear organization in growth arrest of human mammary epithelial cells: A novel role for telomere-associated protein TIN2

Summary Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNAse, but not RNAse, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein 1γ

Microenvironment-Cell Nucleus Relationship in the Context of Oxidative Stress

The microenvironment is a source of reactive oxygen species (ROS) that influence cell phenotype and tissue homeostasis. The impact of ROS on redox pathways as well as directly on epigenetic mechanisms and the DNA illustrate communication with the cell nucleus. Changes in gene transcription related to redox conditions also influence the content and structure of the extracellular matrix. However, the importance of microenvironmental ROS for normal progression through life and disease development still needs to be thoroughly understood. We illustrate how different ROS concentration levels trigger various intracellular pathways linked to nuclear functions and determine processes necessary for the differentiation of stem cells. The abnormal predominance of ROS that leads to oxidative stress is emphasized in light of its impact on aging and diseases related to aging. These phenomena are discussed in the context of the possible contribution of extracellular ROS via direct diffusion into cells responsible for organ function, but also via an impact on stromal cells that triggers extracellular modifications and influences mechanotransduction. Finally, we argue that organs-on-a-chip with controlled microenvironmental conditions can help thoroughly grasp whether ROS production is readily a cause or a consequence of certain disorders, and better understand the concentration levels of extracellular ROS that are necessary to induce a switch in phenotype

Intergenerational relationships within families of HIV-infected adults under antiretroviral treatment in Northern Thailand

Thailand has been severely affected by AIDS/HIV. The epidemic has undermined the health of the population of working age, placing stress on intergenerational relations and threatening the social fabric. Older people in families affected by the disease, although not the main victims, have experienced major changes in relationships with their adult children and grandchildren. However, the availability of antiretrovirals has transformed HIV infection from a lethal to a chronic disease. Intergenerational relationships are analysed with data from a quantitative survey of HIV-infected adults currently receiving antiretroviral treatment in Northern Thailand. The introduction of antiretroviral treatment has eased the pressure on families. Where HIV-infected adults are more dependent on their older parents, it is because they are single and childless or single parents. While ageing parents remain a source of support for their adult children, the introduction of antiretroviral treatment has radically changed the prospects for HIV-infected adults and their regained health allows them to work, take care of their family and fulfil their filial duties as expected in Thai society. If Thailand's original aim in introducing health policies in this area was to curtail the HIV epidemic, its positive impact on intergenerational relations is an additional benefit