A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection

Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet

Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable

Patrimoine immobilier et retraite : regard sur les couples

Les choix en matière d’accumulation du patrimoine font partie des grandes décisions qui ponctuent la vie d’un couple. En reconstituant l’histoire résidentielle des couples, l’objet de cet article est de comprendre ce qui se passe (ou ce qui s’est passé) au moment de la retraite en termes de choix de logement. Des entretiens qualitatifs ont été menés en 2010 auprès de 24 couples résidant en Île-de-France, chaque conjoint étant interrogé au même moment, mais séparément. Il en découle toute une série d’arbitrages et de négociations entre conjoints résultant du type de relations conjugales, du poids des deux lignées d’origine, du milieu social et de la construction des identités selon le genre. Pour les générations plus récentes, l’entrée massive des femmes sur le marché du travail a modifié la place de ces dernières au sein de la famille et les rapports de force entre conjoints. Ayant gagné en autonomie, elles sont plus à même de peser dans les arbitrages en matière de type de logement ou de localisation et de développer des stratégies propres pour faire face aux incertitudes liées à la retraite et l’avancée en âge

La fin de carrière professionnelle : une affaire de couple

Dans le contexte français de la réforme des retraites qui vise à prolonger la vie active, les fins de carrière des hommes et des femmes se sont considérablement complexifiées. L'enquête PARC (Passage à la retraite des couples, enquête qualitative Ined/Cnav) réalisée en 2010 auprès des 36 membres de 18 couples âgés de plus de 50 ans, permet d'étudier le vécu des fins de carrière de chacun des conjoints. Pour les générations les plus âgées, les fins de carrière se sont déroulées selon des schémas plutôt traditionnels, privilégiant le parcours de l'homme. Pour les générations plus jeunes, on voit déjà les effets de la percée des femmes au sein de la population active et un certain équilibre entre les conjoints apparaît lorsqu'il est question des conditions de départ et des projets de retraite. L'analyse des entretiens révèle que certains couples ont d'ores et déjà intégré le durcissement des conditions de départ à la retraite et mettent en place des stratégies visant à limiter les risques de dégradation de leurs conditions de vie à l'heure de la retraite, ou tout au moins, une diminution de leur niveau de vie. D'autres voient dans la nécessité de se maintenir au travail l'occasion de compenser ou d'inverser les investissements passés de l'un et l'autre des conjoints dans l'univers professionnel ou familial. Ainsi les femmes mettent en avant les aspects de modes de conciliation entre vie familiale et vie professionnelle.Retirement reforms in France have pushed back the age of retirement, and these reforms have consequences for the timing of retirement among couples. The PARC study (retirement transitions among couples, a qualitative study undertaken by Ined/Cnav in 2010) interviewed 36 partners from 18 couples, in which one member of the couple was aged between 50 and 70. For the eldest generations, the end of working life was characterized by a traditional relationship within the couple, with men’s careers taking priority. For the youngest generations, the consequences of the emergence of women in the labour market are observed in the timing of retirement when both partners are working; this is subject to negotiation within the couple. Analysis reveals that some couples have adopted strategies that respond to the new retirement legislation. Some have also extended their working life to compensate for past decisions regarding the balance between work and family life, a situation that is particularly relevant for women

Transitions in Later Life and the Re-configuration of Family Relationships in the Third Age: The Case of the Baby Boomers

In this chapter, we examine the consequences of demographic and social transformations on the reconfiguration of conjugal and family relationships in later life. In order to understand how ageing individuals and their families reshape these relationships the focus is on the ‘third age’ and, in particular, the experience of the 1946–1954 birth cohort of baby boomers. This generation took an active part in all the transformations that marked the second half of the twentieth century: the important growth of affluence and consumption, increased education, and women’s emancipation with entry in large numbers of women into professional occupations. These trends were accompanied by a rise in individualism and quests for new self-identities which in turn impacted on family life with the rise of unmarried cohabitation, and that of the rise of divorces and remarriages. Aspirations of autonomy and freedom that have been characteristic of the baby boomer generation are tempered with existing and new family obligations in later life. The baby boomer generation, which has now entered the period of the life course associated with the third age, has sought compromises between self-aspirations and intergenerational family solidarity

La fin de carrière professionnelle : une affaire de couple

Dans le contexte français de la réforme des retraites qui vise à prolonger la vie active, les fins de carrière des hommes et des femmes se sont considérablement complexifiées. L'enquête PARC (Passage à la retraite des couples, enquête qualitative Ined/Cnav) réalisée en 2010 auprès des 36 membres de 18 couples âgés de plus de 50 ans, permet d'étudier le vécu des fins de carrière de chacun des conjoints. Pour les générations les plus âgées, les fins de carrière se sont déroulées selon des schémas plutôt traditionnels, privilégiant le parcours de l'homme. Pour les générations plus jeunes, on voit déjà les effets de la percée des femmes au sein de la population active et un certain équilibre entre les conjoints apparaît lorsqu'il est question des conditions de départ et des projets de retraite. L'analyse des entretiens révèle que certains couples ont d'ores et déjà intégré le durcissement des conditions de départ à la retraite et mettent en place des stratégies visant à limiter les risques de dégradation de leurs conditions de vie à l'heure de la retraite, ou tout au moins, une diminution de leur niveau de vie. D'autres voient dans la nécessité de se maintenir au travail l'occasion de compenser ou d'inverser les investissements passés de l'un et l'autre des conjoints dans l'univers professionnel ou familial. Ainsi les femmes mettent en avant les aspects de modes de conciliation entre vie familiale et vie professionnelle

Épigénomique nutritionnelle du syndrome métabolique

The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with metabolic syndrome (MetS)--combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper "epigenetic programing" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their life-time. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display "transgenerational effects" via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in) activation should provide us with the means to he obsolete human thrifty genotype into a "squandering" phenotype

A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic peptides from tumor associated antigens: Design of universal neo-antigen like tumor vaccines for HLA-B*0702 positive patients

International audienceTumor Associated Antigens (TAAs) are the privileged targets of almost all the cancer vaccines tested to date. Unfortunately all these vaccines failed to show a clinical efficacy. The main reason for this failure is the immune tolerance to TAAs that are self-proteins expressed by normal and cancer cells. Self-tolerance to TAAs is directed against their dominant rather than against their cryptic epitopes. The best way to overcome self-tolerance to TAAs would therefore be to target their cryptic epitopes. However, because of their low HLA-I affinity, cryptic peptides are non-immunogenic and cannot be used to stimulate an antitumor immune response unless their immunogenicity has been previously enhanced. In this paper we describe a general approach to enhance immunogenicity of almost all the HLA-B*0702 restricted cryptic peptides derived from TAAs. It consists in substituting residues at position 1 or 9 of low HLA-B*0702 affinity cryptic peptides by an Alanine or a Leucine respectively. These substitutions increase affinity of peptides for HLA-B*0702. These optimized cryptic peptides are strongly immunogenic and very importantly CTL they stimulate recognize their native counterparts. TAAs derived optimized cryptic peptides can be considered as universal antitumor vaccine since they escape self-tolerance, are immunogenic and are not patient specific

Lock-in thermography for characterization of nuclear materials

A simplified procedure of lock-in thermography was developed and applied for characterization of nuclear materials. The possibility of thickness and thermal diffusivity measurements with the accuracy better than 90% was demonstrated with different metals and Zircaloy-4 claddings