Investors' striking migration from growth to value investing over their life cycle

Investors’ striking migration from growth to value investing over their life cycle It happens as they depend less on work, their balance sheets strengthen and their horizons shorten, write Sebastien Betermier, Laurent E. Calvet and Paolo Sodin

Couplage entre introduction et réparation des cassures double brin pendant les réarrangements programmés du génome de Paramecium tetraurelia

L élimination programmée d ADN spécifique de la lignée germinale pour former un nouveau noyau somatique a été décrite chez les eucaryotes. Ces réarrangements sont initiés par l introduction de cassures double brin (CDB) de l ADN et la préservation de l intégrité du génome requiert une réparation efficace. Chez Paramecium tetraurelia, le génome est largement réarrangé pendant le développement du nouveau noyau somatique, après l introduction de milliers de cassures double brin programmées par la transposase domestiquée PiggyMac (Pgm)Ces réarrangements consistent en l excision précise de dizaines de milliers de séquences uniques et non codantes (IES) qui interrompent 47% des gènes dans la lignée germinale ; et l élimination hétérogène de séquences répétées qui mène à des délétions internes de taille variable ou à la fragmentation des chromosomes avec addition de télomères aux extrémités.L implication de la voie du Non Homologous End Joining (NHEJ) dans l excision précise des IES a été prouvée. Dans des cellules déplétées de Ligase IV ou XRCC4, les cassures aux bornes des IES sont introduites normalement mais il n y a pas de jonctions d excision formées et les extrémités cassées s accumulent sans être dégradées. Mais la voie de réparation impliquée dans les réarrangements imprécis est encore inconnue. L hypothèse d une réparation par la voie NHEJ alternative (alt-NHEJ), indépendante de Ku et impliquant la résection des extrémités et l utilisation de microhomologie, a été émise. C est pourquoi pendant ma thèse je me suis intéressé à ma thèse au rôle des protéines Ku.Deux gènes KU70 et trois gènes KU80 ont été identifiés dans le génome de la paramécie. KU70a et KU80c sont spécifiquement induits pendant les réarrangements programmés du génome et les protéines localisent dans les noyaux somatiques en développement. Des expériences d extinction de ces gènes par ARN interférence ont prouvé que ces gènes étaient indispensables. Au niveau moléculaire, l ADN non réarrangé est amplifié dans les cellules déplétées de Ku. De plus, les cassures double brin programmées ne sont pas introduites aux bornes des IES.Mes résultats suggèrent que Ku fait partie d un complexe de pré-excision, avec la transposase domestiquée Pgm, et est nécessaire pour l introduction des cassures double brin programmées pendant les réarrangements programmés du génome.Programmed elimination of germline specific DNA has been described in several eukaryotic organisms. These rearrangements are initiated through introduction of DNA double strand breaks (DSB). To ensure genome integrity, efficient repair is needed. In Paramecium tetraurelia, the genome is widely rearranged during development of a new somatic nucleus after introduction of tens of thousands of DSBs by the domesticated transposase PiggyMac (Pgm)These rearrangements consist in: the precise excision of thousands of unique and non coding sequences called IESs that interrupt 47% of genes in the germline; and the heterogeneous elimination of repeated sequences. It leads to internal deletions of variable sizes or to chromosome fragmentation with telomere addition at DNA ends.Implication of the Non Homologous End Joining Pathway (NHEJ) in precise IES excision has been proved. In cells depleted for Ligase IV or XRCC4, DSBs at IES boundaries are introduced normally but broken DNA ends accumulate without being repaired nor degraded. The repair pathway implicated in heterogeneous rearrangements is still unknown. An hypothesis would be that heterogeneous rearrangements involve a Ku independent alternative NHEJ (alt-NHEJ) pathway characterized by end resection and use of microhomologies. During my thesis I studied the role of Ku proteins in programmed genome rearrangements.Two KU70 genes and three KU80 genes has been identified in the Paramecium genome. KU70a and KU80c are specifically induced during programmed genome rearrangements. Encoded proteins localize in developing somatic nuclei. Gene extinction by RNA interference experiments proved that these genes are necessary for programmed genome rearrangements. At molecular level, non rearranged DNA is amplified in cells depleted for Ku. And more surprisingly, no programmed DSBs are introduced at IES boundaries in these cells.My results indicate that Ku is a part of a pre excision complex with the domesticated transposase Pgm and necessary for the introduction of programmed DSB during programmed genome rearrangements.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Why Do Homeowners Invest the Bulk of their Wealth in their Home?

Despite the well-known benefits of diversification, homeowners invest mostly in their home. A common explanation for this pattern is that homeowners are constrained to fully own the home they want to live in. We refute this explanation and show that the predominance of housing stems from its distinct investment value. We then provide clarity on the value of the housing investment. Because owning a home provides a steady stream of housing consumption, it is equivalent to purchasing a perpetual bond indexed to that home. Housing thus plays a special role in the portfolio as one of the homeowner’s risk-free assets

Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage

SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways

Functional specialization of Piwi proteins in Paramecium tetraurelia from post-transcriptional gene silencing to genome remodelling

Proteins of the Argonaute family are small RNA carriers that guide regulatory complexes to their targets. The family comprises two major subclades. Members of the Ago subclade, which are present in most eukaryotic phyla, bind different classes of small RNAs and regulate gene expression at both transcriptional and post-transcriptional levels. Piwi subclade members appear to have been lost in plants and fungi and were mostly studied in metazoa, where they bind piRNAs and have essential roles in sexual reproduction. Their presence in ciliates, unicellular organisms harbouring both germline micronuclei and somatic macronuclei, offers an interesting perspective on the evolution of their functions. Here, we report phylogenetic and functional analyses of the 15 Piwi genes from Paramecium tetraurelia. We show that four constitutively expressed proteins are involved in siRNA pathways that mediate gene silencing throughout the life cycle. Two other proteins, specifically expressed during meiosis, are required for accumulation of scnRNAs during sexual reproduction and for programmed genome rearrangements during development of the somatic macronucleus. Our results indicate that Paramecium Piwi proteins have evolved to perform both vegetative and sexual functions through mechanisms ranging from post-transcriptional mRNA cleavage to epigenetic regulation of genome rearrangements