C'est la plume qui fait le conte : "Die sechs Schwäne" des frères Grimm et "De vilde Svaner" de Hans Christian Andersen

Dans De vilde Svaner (Les cygnes sauvages), conte des Eventyr, fortalte for Børn (Contes, racontés aux enfants), H. C. Andersen raconte une histoire très proche de celle de Die sechs Schwäne (Les six cygnes), des Kinder- und Hausmärchen (Contes de l'enfance et du foyer) des Grimm. On peut fort justement se demander si l'auteur danois ne réécrit pas le Märchen de 1812 lorsqu'il publie son eventyr, en 1838. Mais l'étude de plusieurs récits d'enfants transformés en cygnes - de l'histoire du septième sage du Dolopathos de Jean de Haute-Seille, à la fin du xiie siècle, et Die sieben Schwäne, un Feen-Märchen de 1801, à De elleve Svaner de Winther, en 1823 - montre qu'Andersen réécrit vraisemblablement ce dernier texte danois et que le dialogue intertextuel avec les Grimm s'effectue sur un autre mode. L'auteur des Eventyr, fortalte for Børn se positionne par rapport aux Kinder- und Hausmärchen, développant ainsi une nouvelle conception du genre qui ressort de la comparaison des manières de raconter propres à chaque auteur, leur plume. It is the pen which makes the tale. the Grimm brothers' Die sechs Schwäne and Christian Andersen's De vilde Svaner In De vilde Svaner, a tale from Eventyr, fortale for Børn, H. C. Andersen tells a story that is very close to that of Die sechs Schwäne from the Grimms' Kinder- und Hausmärchen. One could legitimately wonder whether the Danish author was inspired by the 1812 Märchen when he published his own eventyr in 1838. The study of other narratives about children transformed into swans (including the story of the seventh wise man in Jean de Haute-Seille's Dolopathos at the end of the twelth century; Die sieben Schwäne, a Feen-Märchen from 1801; and Winther's 1823 De elleve Svaner) shows that Andersen rewrote this last Danish text and that the intertextual dialogue with the Grimms takes place at another level. Andersen distinguishes himself from the Grimms by developing a new conception of the genre, which becomes clear in his very different way of telling a tale.

Heritability of blood pressure in the swiss population: the family-based skipogh study

Objective: Blood pressure is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. Moreover, little is known on the heritability of the white-coat effect. We investigated the heritability of various blood pressure (BP) traits in a Swiss population-based sample. Methods: SKIPOGH (Swiss Kidney Project on Genes in Hypertension) is a family-based multi-centre (Lausanne, Bern, Geneva) cross-sectional study that examines the role of genes in determining BP levels. Office and 24-hour ambulatory BP were measured using validated devices (A&D UM-101 and Diasys Integra). We estimated the heritability of systolic BP (SBP), diastolic BP (DBP), heart rate (HR), pulse pressure (PP), proportional white-coat effect (i.e. [office BP-mean ambulatory daytime BP]/mean ambulatory daytime BP), and nocturnal BP dipping (difference between mean ambulatory daytime and night-time BP) using a maximum likelihood method implemented in the SAGE software. Analyses were adjusted for age, sex, body mass index (BMI), and study centre. Analyses involving PP were additionally adjusted for DBP. Results: The 517 men and 579 women included in this analysis had a mean (}SD) age of 46.8 (17.8) and 47.8 (17.1) years and a mean BMI of 26.0 (4.2) and 24.2 (4.6) kg/m2, respectively. Heritability estimates (}SE) for office SBP, DBP, HR, and PP were 0.20}0.07, 0.20}0.07, 0.39}0.08, and 0.16}0.07 (all P<0.01). Heritability estimates for 24-hour ambulatory SBP, DBP, HR, and PP were, respectively, 0.39}0.07, 0.30}.08, 0.19}0.09, and 0.25}0.08 (all P<0.05). The heritability of the white-coat effect was 0.29}0.07 for SBP and 0.31}0.07 for DBP (both P<0.001). The heritability of nocturnal BP dipping was 0.15}0.08 for SBP and 0.22}0.07 for DBP (both P<0.05). Conclusions: We found that the white-coat effect is significantly heritable. Our findings show that BP traits are moderately heritable in a multi-centric study in Switzerland, in line with previous population-based studies, justifying the ongoing search for genetic determinants in this field.

How do Swiss Gastroenterologists assess Activity of Inflammatory Bowel Disease in Daily Practice: by Clinical Indices, Endoscopic Activity, or Biomarkers?

Background a nd A ims: There is a n ongoing d ebate which i sthe most appropriate w ay t o measure inflammatory boweldisease (IBD) activity (be it b y clinical i ndices, e ndoscopy, orbiomarkers). Accumulating evidence associates m ucosalhealing with a reduction in I BD-related s urgery andhospitalizations. We a imed to i nvestigate which outcomeparameters are used in daily practice for IBD monitoring.Methods: A q uestionnaire was sent in J uly 2010 t o all boardcertified gastroenterologists in S witzerland to evaluate t heassessment strategy of IBD activity, t he items on whichtherapeutic decisions w ere based upon, and the kind ofbiomarkers used for monitoring IBD activity.Results: Response rate was 57% (153/270). Mean physician'sage was 5 0±9years, mean duration o f gastroenterologicpractice 1 4±8years, 52% of them were working in p rivatepractice a nd 48% in h ospitals. S eventy-eight percent usedclinical activity i ndices as g old standard for IBD activityassessment, followed by 15% choosing endoscopic activity, and7% favouring biomarkers. Gastroenterologists based theirtherapeutic decisions in 70% on clinical activity indices, 24% onendoscopic activity, a nd 6% o n biomarkers. Most frequentlyused biomarkers were C-reactive protein (94%), complete bloodcount (78%) and fecal calprotectin (74%).Conclusions: I n daily p ractice, most IBD patients a remonitored based u pon t heir clinical a ctivity. B iomarkers a reperceived as l ess important compared to clinical andendoscopic activity. S imilar to activity a ssessment, alsotherapeutic decisions a re mostly made on the basis of clinicalactivity indices. The upcoming scientific evidence on the impactof mucosal h ealing does n ot yet seem to influence the dailypractice of gastroenterologists.

PixFRET, an ImageJ plug-in for FRET calculation that can accommodate variations in spectral bleed-throughs.

Fluorescence resonance energy transfer (FRET) allows the user to investigate interactions between fluorescent partners. One crucial issue when calculating sensitized emission FRET is the correction for spectral bleed-throughs (SBTs), which requires to calculate the ratios between the intensities in the FRET and in the donor or acceptor settings, when only the donor or acceptor are present. Theoretically, SBT ratios should be constant. However, experimentally, these ratios can vary as a function of fluorophore intensity, and assuming constant values may hinder precise FRET calculation. One possible cause for such a variation is the use of a microscope set-up with different photomultipliers for the donor and FRET channels, a set-up allowing higher speed acquisitions on very dynamic fluorescent molecules in living cells. Herein, we show that the bias introduced by the differential response of the two PMTs can be circumvented by a simple modeling of the SBT ratios as a function of fluorophore intensity. Another important issue when performing FRET is the localization of FRET within the cell or a population of cells. We hence developed a freely available ImageJ plug-in, called PixFRET, that allows a simple and rapid determination of SBT parameters and the display of normalized FRET images. The usefulness of this modeling and of the plug-in are exemplified by the study of FRET in a system where two interacting nuclear receptors labeled with ECFP and EYFP are coexpressed in living cells.

Reference values and factors associated with renal resistive index in a family-based population study.

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

Transcriptome of a mouse kidney cortical collecting duct cell line: effects of aldosterone and vasopressin.

Aldosterone and vasopressin are responsible for the final adjustment of sodium and water reabsorption in the kidney. In principal cells of the kidney cortical collecting duct (CCD), the integral response to aldosterone and the long-term functional effects of vasopressin depend on transcription. In this study, we analyzed the transcriptome of a highly differentiated mouse clonal CCD principal cell line (mpkCCD(cl4)) and the changes in the transcriptome induced by aldosterone and vasopressin. Serial analysis of gene expression (SAGE) was performed on untreated cells and on cells treated with either aldosterone or vasopressin for 4 h. The transcriptomes in these three experimental conditions were determined by sequencing 169,721 transcript tags from the corresponding SAGE libraries. Limiting the analysis to tags that occurred twice or more in the data set, 14,654 different transcripts were identified, 3,642 of which do not match known mouse sequences. Statistical comparison (at P < 0.05 level) of the three SAGE libraries revealed 34 AITs (aldosterone-induced transcripts), 29 ARTs (aldosterone-repressed transcripts), 48 VITs (vasopressin-induced transcripts) and 11 VRTs (vasopressin-repressed transcripts). A selection of the differentially-expressed, hormone-specific transcripts (5 VITs, 2 AITs and 1 ART) has been validated in the mpkCCD(cl4) cell line either by Northern blot hybridization or reverse transcription-PCR. The hepatocyte nuclear transcription factor HNF-3-alpha (VIT39), the receptor activity modifying protein RAMP3 (VIT48), and the glucocorticoid-induced leucine zipper protein (GILZ) (AIT28) are candidate proteins playing a role in physiological responses of this cell line to vasopressin and aldosterone.

Génération d'une souris dépourvue du gène VIT32 de manière conditionnelle: étude du phénotype rénal chez les souris dépourvues de RGS2

Résumé Dans le rein, la vasopressine possède un rôle essentiel dans la régulation fine du transport d'eau et participe au contrôle de la réabsorption du sodium. Cette action est conduite par l'activation du récepteur à la vasopressine V2R situé dans l'anse de Henle, dans le tubule connecteur et dans le canal collecteur du néphron des rongeurs et conduit à la formation d'AMPc entraînant un mécanisme d'action caractérisé par deux phases distinctes. Le premier effet de la vasopressine est non génomique et a lieu rapidement après l'activation du récepteur, la deuxième phase est plus tardive et possède la caractéristique de moduler la transcription d'un réseau de gènes. Parmi ces gènes, plusieurs sont directement impliqués dans le transport d'eau et de sodium, comme l'Aqp2 et 3, ENaC et la Na,K-ATPase. L'identification des effets de la voie de signalisation de la vasopressine représente un point crucial pour la compréhension des mécanismes moléculaires de la réabsorption de l'eau et du sodium dans le néphron. L'analyse en série de l'expression de gènes (SAGE) réalisée en 2001 dans notre laboratoire a permis de caractériser le transcriptome dépendant de la vasopressine dans la lignée cellulaire mpkCCDc14,a dérivée du canal collecteur cortical (CCD) de souris. Deux des transcrits induits par la vasopressine (VIT) ont fait l'objet des études de ce travail de thèse. Le premier est VIT32 (Vasopressin induced transcript 32) qui code pour une protéine ne possédant aucune homologie avec des domaines protéiques dont la fonction est connue. Dans le système d'expression de l'ovocyte de Xenopus laevis, VIT32 induit la maturation des ovocytes et diminue le courant sensible à l'amiloride de manière dépendante de la voie des MAPK. Dans les mpkCCDc14, l'inhibition de la voie des MAPK diminue le courant sodique en diminuant l'activité de la Na,K-ATPase, mais sans modifier le courant d'ENaC. Ainsi la voie de signalisation des MAPK peut avoir des cibles différentes suivant le système dans lequel elle est étudiée. C'est pourquoi nous avons décidé de poursuivre l'étude de VIT32 dans un contexte physiologique en créant une souris dépourvue du gène codant pour VIT32 de manière conditionnelle (conditional knockout). La première partie de cette thèse a donc consisté à générer cette souris. Le deuxième transcrit induit par la vasopressine qui a été étudié dans cette thèse est RGS2 (Regulator of G protein Signaling 2). In vitro, il a été montré que RGS2 inhibe des voies de signalisation dépendantes de récepteurs couplés à des protéines Gq et Gs. Dans notre étude, nous avons montré que dans le néphron de rein de souris, RGS2 est colocalisé avec V2R. In vivo, la vasopressine sécrétée lors d'une restriction en eau imposée à des souris augmente l'expression de RGS2. De plus, l'accumulation d'AMPc engendrée par l'action de la vasopressine sur les canaux collecteurs est significativement plus grande chez les souris dépourvues de RGS2 (rgs2 -/-). Cette induction de la signalisation de la vasopressine est corrélée à une augmentation de la réabsorption d'eau chez les souris rgs2 -/-. Ainsi RGS2 serait impliqué dans le rétrocontrôle négatif de la voie de signalisation de la vasopressine. Abstract In the kidney, vasopressin plays a key role in the control of water balance and participates in salt reabsorption. These actions are induced by the activation of V2 vasopressin receptor (V2R) located in the loop of Henle, in the connecting tubule and in the collecting duct leading to an increase in intracellular cAMP levels. The V2R-mediated vasopressin action elicits a rapid, non-genomic effect, during which water and salt reabsorption is rapidly increased and a late or genomic effect characterised by the long-term regulation of water and salt reabsorption through the transcriptional activation of a gene network that includes Aqp2, Aqp3, ENaC and Na,K-ATPase. Serial analysis of gene expression (SAGE) performed in 2001 in our laboratory characterised the vasopressin induced transcripts (VIT) in the mpkCCDc14 cell line. Two of them are studied in this thesis. The first one is VIT32 (Vasopressin induced transcript 32) that encodes a protein that has no homology with any protein domain of known function. In the Xenopus laevis oocyte, VIT32 induces oocyte maturation and downregulates the ENaC amiloride sensitive current via the activation of the MAPK pathway. In mpkCCDc14 cell line, the MAPK pathway inhibition leads to a decrease of Na,K-ATPase activity without affecting ENaC current. Therefore, the MAPK pathway can act on different targets depending on the cellular context. Thus, we decided to investigate the function of VIT32 in its physiological environment by performing a conditional knockout mouse of VIT32. The first part of this thesis consisted in generating this mouse. The second studied vasopressin induced transcript is RGS2 (Regulator of G protein Signaling 2). In vitro, RGS2 has been shown to inhibit Gq and Gs protein-coupled receptor pathway. In our study we show that RGS2 is co-localized with V2R in the mouse nephron. In vivo, vasopressin secreted during water restriction up-regulates RGS2 expression. Moreover, vasopressin-dependant accumulation of CAMP is significantly increased in the cortical collecting duct of RGS2 knockout mice. This increase is correlated with an increase in water reabsorption. RGS2 could be involved in the negative feedback regulation of V2R signalling. Résumé tout public Le corps humain est composé d'environ 60% d'eau répartie à l'intérieur et à l'extérieur des cellules de notre organisme. Les cellules, unités fondamentales du vivant, puisent l'oxygène et les nutriments indispensables à leur fonctionnement dans le liquide extracellulaire. La composition du milieu doit être constante, car les variations peuvent perturber considérablement et parfois fatalement la fonction des cellules. Ainsi les organismes pluricellulaires ont développé des mécanismes permettant de contrôler la constance du milieu extracellulaire afin de maintenir l'état d'équilibre nommé homéostasie. Le rein joue un rôle majeur dans cette homéostasie grâce à sa capacité de réabsorber l'eau et les solutés en fonction des besoins de l'organisme. Cette fonction du rein est régulée par différentes hormones comme la vasopressine, qui permet de contrôler la réabsorption fine de l'eau et des solutés. Dans leurs membranes, les cellules possèdent des récepteurs leur permettant de répondre aux signaux extracellulaires comme le sont entre autres les hormones. Ainsi les cellules sensibles à la vasopressine possèdent un récepteur nommé V2R qui permet d'intégrer les signaux de la vasopressine en déclenchant tout une cascade d'événements conduisant à une modification de l'expression de certaines protéines impliquées directement ou non dans la réabsorption de l'eau et des solutés. Une étude précédente élaborée au sein de notre laboratoire a permis de répertorier les protéines dont l'expression est augmentée par de la vasopressine. Deux de ces protéines ont fait l'objet des études de cette thèse. La première protéine induite par la vasopressine est VIT32 (Vasopressin induced transcript 32). Cette protéine est entre autres impliquée dans la réabsorption du sodium, mais la fonction précise de VIT32 dans ce transport n'a pas pu être déterminée. Une des approches possibles pour l'étude de la fonction d'une protéine est de supprimer son expression chez la souris et d'étudier les conséquences de son absence. Ces souris sont appelées des souris knockout, puisque la protéine en question ne peut plus agir. La première partie de cette thèse a donc consisté à générer une souris dépourvue du gène de VIT32. La deuxième protéine étudiée est RGS2 (Regulator of G protein Signaling 2). Cette protéine inhibe certaines voies de signalisation activées par différentes hormones. Dans cette partie du travail de thèse, nous avons pu mettre en évidence que RGS2 agit comme un inhibiteur de la voie de signalisation de la vasopressine. En modifiant cette signalisation, RGS2 serait donc un médiateur du contrôle de la réabsorption d'eau dans les cellules du rein sensibles à la vasopressine.

Complexity of the Paradigms Present in Quality Criteria of Qualitative Research Grids

With qualitative methods being increasingly used in health science fields, numerous grids proposing criteria to evaluate the quality of this type of research have been produced. Expert evaluators deem that there is a lack of consensual tools to evaluate qualitative research. Based on the review of 133 quality criteria grids for qualitative research in health sciences, the authors present the results of a computerized lexicometric analysis, which confirms the variety of intra- and inter-grid constructions, including within the same field. This variety is linked to the authors' paradigmatic references underlying the criteria proposed. These references seem to be built intuitively, reflecting internal representations of qualitative research, thus making the grids and their criteria hard to compare. Consequently, the consensus on the definitions and the number of criteria becomes problematic. The paradigmatic and theoretical references of the grids should be specified so that users could better assess their contributions and limitations.