Political Economy and Life Course Patterns

We explore the strong linkages between macro changes and the dynamics of educational, occupational, family, and residential careers of young Spanish adults born between 1945 and 1974. We review theory and evidence on macro factors: changes in the welfare system, centrality of the family as a service provider, and the changing role of women. We outline some hypotheses of how life course trajectories, and their heterogeneity, change across cohorts. We build data on sequences of states using FFS. In our analysis, we find an increase in the discontinuity of careers and of the heterogeneity among cohort members, especially for employment. Women's careers are becoming more similar to those of men. Family and household formation is postponed, with a limited spread of post-nuclear family forms.delayed transition to adulthood, life course, postponement of family formation, sequence analysis, Spain, young adults

Development of blood-brain barrier permeable luciferin analogues for in vivo bioluminescent imaging in the brain

La bioluminescence est un procédé que certaines espèces animales utilisent pour se camoufler, attirer des partenaires ou des proies, ou se défendre contre des prédateurs. Pour émettre de la lumière, une protéine appelée luciférase catalyse l'oxydation d'une petite molécule appelée luciférine. Durant cette reaction, cette molécule est excitée et émet un photon pour retourner à son état fondamental. La bioluminescence est utilisée en biologie dans de nombreuses applications, comme pour détecter l'expression d'un gène, quantifier l'activité d'une enzyme, ou pour étudier le développement de tumeurs. Une des limitation de cette technique est que la luciférine peut difficilement atteindre le cerveau. En effet, le cerveau est protégé par la barrière hémato-encéphalique ou blood-brain barrier (BBB). Ce projet a pour but le developpement et l'évaluation de derivés de la luciférine permettant d'améliorer le passage de cette molécule à travers la BBB. Notre approche consiste à attacher par estérification un acide gras au groupe hydroxy de la luciférine afin de la rendre plus lipophile. Cette propriété permet à cette nouvelle molécule de passer plus facilement par diffusion à travers la bicouche lipidique. Une fois entrée dans la cellule, la liaison ester est hydrolysée, libérant ainsi la luciférine. Nous avons donc synthétisé et caractérisé une nouvelle classe de dérivés alkylés de D-luciférine et de son précurseur, le 6-hydroxy-2-cyanobenzothiazole (OH-CBT). Ces composés ont été obtenus par estérification avec des acides gras d'une longueur de chaîne de 5 ou 9 carbones, l'acide pentanoïque et l'acide nonanoïque. Les composés correspondants C5-luciférine, C9-luciférine, C5-CBT et C9-CBT ont été obtenus. Ces nouveaux composés ont montré qu'ils sont de mauvais substrats pour la luciférase en solution, avec pour résultat une faible émission de lumière. En revanche l'hydrolyse de l'acide gras sous l'action d'estérases présentes dans un lysat de cellules permet la libération de la luciférine et ainsi la production de bioluminescence. La bioluminescence observée in vitro dans des cellules exprimant la luciferase est supérieure à la luciférine pour nos composés C5-luciférine et C9-luciférine. Après reaction avec la D-cystéine pour former la luciférine correspondante, le C5-CBT présente également une meilleure bioluminescence que le OH-CBT dont il est dérivé. Nous supposons donc que la plus grande lipophilicité de nos composés alkylés facilite leur diffusion vers l'intérieur des cellules. Les expériences in vivo n'ont pas montré de supériorité des composés alkylés. En effet, l'intensité du signal lumineux émis depuis la region de la tête de la souris n'est pas améliorée par l'utilisation de ces nouvelles molécules. L'utilisation d'une lignée de souris qui experiment la luciferase uniquement dans le cerveau pourrait permettre une meilleure evaluation de l'aptitude des composés à traverser la BBB. Nos molécules présentent toutefois des propriétés nouvelles avec une cinétique de bioluminescence plus lente, ce qui peut être un avantage lors d'expérience nécessitant un temps d'imagerie plus important. Les prochaines étapes de ce projet consisteront à modifier la D-luciférine et le OH-CBT afin de permettre un transport actif et non passif au travers de la BBB. Il serait possible par exemple d'attacher la D-luciférine à une molécule ou à un peptide transporté de manière active vers le parenchyme cérébral

Perception of climate change, loss of social capital and mental health in two groups of migrants from African countries

AbstractIntroduction. The negative effects of climate change affect community subsistencemodels, thus determining an increase in social conflicts, a loosening of social capital, anincrease in the incidence of traumas and diseases, and a push for migration.Aim. This exploratory research compares the perception of climate change, as well as thereduction of social capital and mental health, in two groups of migrants arriving in Italyfrom African countries with high or extreme vulnerability to climate change.Methods. The perception of climate change and the degree of social capital were assessedwith a semi-structured interview. The psychological condition was investigatedthrough a clinical psychological interview and tests.Results. The group of migrants coming from countries with extreme exposure to climatechange perceive greater vulnerability of their country and reports a greater loss of socialcapital. The level of education does not seem to affect the ability to perceive climatechange. In the entire sample, there is a strong correlation between the perception ofchange and the loss of social capital, and between the loss of social capital and emotionaldisorders.Conclusions. The study suggests that actions to preserve the social capital of a communitystrongly exposed to climate change can mitigate the impact of change on mentalhealth

Political economy and life course patterns: the heterogeneity of occupational, family and household trajectories of young spaniards

We explore the strong linkages between macro changes and the dynamics of educational, occupational, family, and residential careers of young Spanish adults born between 1945 and 1974. We review theory and evidence on macro factors: changes in the welfare system, centrality of the family as a service provider, and the changing role of women. We outline some hypotheses of how life course trajectories, and their heterogeneity, change across cohorts. We build data on sequences of states using FFS. In our analysis, we find an increase in the discontinuity of careers and of the heterogeneity among cohort members, especially for employment. Women´s careers are becoming more similar to those of men. Family and household formation is postponed, with a limited spread of post-nuclear family forms.

Lowest low fertility in an urban context: when migration plays a key role

In countries with so-called "lowest-low" fertility, the lowest fertility levels are seen in the cities. The main reasons for this development is the difference in the cost of living expenses, combined with income constraints in cities, as compared to these same aspects in rural areas. If we focus our attention on the center of an urban area, migration needs to be taken into account, since it can contribute to particularly low yield fertility. In this paper we use the Turin Longitudinal Study, which has data on all people who have ever been residents in Turin (Italy) during the period 1971-2001. We study the interdependencies between fertility and out-migration choices for a selected group, from the 1956 birth-cohort. In order to fully understand fertility, we need to consider how fertility acts on out-migration choices. Our findings underline the important role of economic resources and life cycle events in such a context which seem to guide both fertility and migration behaviors. Moreover, while having a child significantly hampers long-distance migration, it also has a lower impact on short-distant moves.

Shaping the interaction landscape of bioactive molecules

Motivation: Most bioactive molecules perform their action by interacting with proteins or other macromolecules. However, for a significant fraction of them, the primary target remains unknown. In addition, the majority of bioactive molecules have more than one target, many of which are poorly characterized. Computational predictions of bioactive molecule targets based on similarity with known ligands are powerful to narrow down the number of potential targets and to rationalize side effects of known molecules. Results: Using a reference set of 224 412 molecules active on 1700 human proteins, we show that accurate target prediction can be achieved by combining different measures of chemical similarity based on both chemical structure and molecular shape. Our results indicate that the combined approach is especially efficient when no ligand with the same scaffold or from the same chemical series has yet been discovered. We also observe that different combinations of similarity measures are optimal for different molecular properties, such as the number of heavy atoms. This further highlights the importance of considering different classes of similarity measures between new molecules and known ligands to accurately predict their targets. Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

SwissSidechain: a molecular and structural database of non-natural sidechains

Amino acids form the building blocks of all proteins. Naturally occurring amino acids are restricted to a few tens of sidechains, even when considering post-translational modifications and rare amino acids such as selenocysteine and pyrrolysine. However, the potential chemical diversity of amino acid sidechains is nearly infinite. Exploiting this diversity by using non-natural sidechains to expand the building blocks of proteins and peptides has recently found widespread applications in biochemistry, protein engineering and drug design. Despite these applications, there is currently no unified online bioinformatics resource for non-natural sidechains. With the SwissSidechain database (http://www.swisssidechain.ch), we offer a central and curated platform about non-natural sidechains for researchers in biochemistry, medicinal chemistry, protein engineering and molecular modeling. SwissSidechain provides biophysical, structural and molecular data for hundreds of commercially available non-natural amino acid sidechains, both in l- and d-configurations. The database can be easily browsed by sidechain names, families or physico-chemical properties. We also provide plugins to seamlessly insert non-natural sidechains into peptides and proteins using molecular visualization software, as well as topologies and parameters compatible with molecular mechanics softwar

Compatibility of children and work preferences: two European cases.

Nowadays female participation in the labor market and motherhood are competing and the conciliation between them can be solved in different ways. In this paper we analyze children and work preferences in two European countries with very different behaviour: Italy and France. Italy shares with Spain the lowest fertility level (the TFR is around 1.25) whereas French TFR reaches the highest level (1.89) among the European Community countries. Moreover female employment rate in Italy is about 40% whereas in France reaches 70%. In these two contexts, using data from the European Community Household Panel, we model jointly fertility and female participation in the labor market, taking into account the potential correlation across unobserved heterogeneity in children and work preferences

SwissDock, a protein-small molecule docking web service based on EADock DSS

Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours