Identification of SPLUNC1's ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airways.

The epithelial sodium channel (ENaC) is responsible for Na+ and fluid absorption across colon, kidney, and airway epithelia. We have previously identified SPLUNC1 as an autocrine inhibitor of ENaC. We have now located the ENaC inhibitory domain of SPLUNC1 to SPLUNC1's N terminus, and a peptide corresponding to this domain, G22-A39, inhibited ENaC activity to a similar degree as full-length SPLUNC1 (∼2.5 fold). However, G22-A39 had no effect on the structurally related acid-sensing ion channels, indicating specificity for ENaC. G22-A39 preferentially bound to the β-ENaC subunit in a glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic fibrosis (CF) lung disease. Addition of G22-A39 to CF human bronchial epithelial cultures (HBECs) resulted in an increase in airway surface liquid height from 4.2±0.6 to 7.9±0.6 μm, comparable to heights seen in normal HBECs, even in the presence of neutrophil elastase. Our data also indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase, which suggests that it may still be active during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC by the G22-A39 peptide suggests that this peptide may be suitable for treating CF lung disease.

Dépistage néonatal systématique de la mucoviscidose en Suisse: dès janvier 2011 [Implementation of the neonatal cystic fibrosis screening program in Switzerland: beginning January 2011].

The diagnosis of cystic fibrosis (CF) is often delayed because of the nonspecificity of a wide variety of clinical symptoms at disease onset. Newborn screening for CF has been advocated to reduce delays in diagnosis, facilitating preventive care for early respiratory and nutritional involvement. According to American and European consensus and experience of existing programs, a Swiss Nationwide Cystic Fibrosis Newborn Screening Program started in January 2011. Screening strategy combines two steps: an immunoreactive trypsinogen assay and DNA mutation analysis in dried blood samples at day 4 (Guthrie cards).

Rubber Buffings for Bridge Approach Expansion Joints, MLR-01-01, 2001

Many of the bridges in the state of Iowa have type ‘CF���, ‘EE’, or ‘EF’ expansion joints installed in the bridge approach slabs. These joints, which are typically 4” wide, are currently filled with a foam expansion joint material that is covered with a sealant. Over time the sealant begins to pull off of the walls of the joint and it ultimately fails. The joint, which is now exposed to the weather, is then filled with water and solids. The foam joint material, which is lighter than water, floats out of the joint onto the highway. This foam resembles a large 4” X 6” plank and poses a threat to motorists. A possible solution to this problem would be to replace the foam material with rubber buffings. Rubber buffings are a by-product of the tire retread industry.

Rituel à l'usage d'une abbaye de femmes.

Acquis le 15 mai 1830 d'Armans-Alexis Monteil parmi 80 ouvrages pour le prix global de 2400 francs; cf. B.n.F., département des Manuscrits, registre des acquisitions 1828-1833, n° 65/29.

Extrait du "Registrum curiae".

Entré à la Bibliothèque du roi en 1719 parmi les mss. d'Étienne Baluze; cf. Delisle, Cab. des mss., I, 364-367; Omont, Concordances des mss. latins, 38-42

Oculopalatal Tremor : Variations on a theme by Guillain and Mollaret

Le trémor oculo-palatin (TOP) est une complication tardive et rare faisant suite à une lésion au niveau du tronc cérébral. Il est caractérisé par des contractions involontaires du voile du palais (pratiquement toujours asymptomatique), synchronisées avec un nystagmus pendulaire à environ 2 Hz (toujours symptomatique, se manifestant par des oscillopsies). Un hypersignal du noyau de l'olive inférieure (HNOI) est visible en IRM ; l'HNOI persiste au fil des ans. Notre objectif était de mieux définir le profil clinique des patients avec un TOP. Pour ceci nous avons effectué une étude rétrospective de 8 patients présentant un TOP et avons compilé ces résultats avec les 82 cas que nous avons retrouvé dans la littérature mondiale (revue PubMed). L'âge moyen était de 54 ans, avec une prédominance masculine. L'étiologie la plus fréquente était une lésion vasculaire du tronc cérébral (80%). Un nystagmus pendulaire principalement vertical a été retrouvé dans 90% des cas. Un nystagmus dissocié était principalement associé à une HNOI controlatérale et unilatérale sur l'IRM. Un nystagmus bilatéral et symétrique résultait d'une HNOI bilatérale dans la majorité des cas. Trois singularités ont été retrouvées parmi nos 8 patients : 1) une HNOI ipsilatérale à un nystagmus dissocié ; 2) la persistance du nystagmus en cas de disparition de l'HNOI ; 3) la découverte d'un micronystagmus asymptomatique. Le profil clinique du TOP reste assez stéréotypé, malgré quelques variations possibles (cf nos trois singularités). Les oscillopsies sont parfois handicapantes et il n'existe pas à ce jour de traitement spécifique du TOP.

Time invested in the global respiratory care of cystic fibrosis paediatrics patients.

INTRODUCTION: Respiratory therapy is a keystone of the treatment for cystic fibrosis (CF) lung disease, but it is time consuming. OBJECTIVES: We aimed to assess the total time spent on respiratory therapy, including chest physiotherapy (CPT) and physical activity (PA), as well as inhalation therapy (IT) and maintenance of materials (MM) to rationalise and optimise treatment. METHODS: A cross-sectional prospective study in a paediatric CF cohort. A questionnaire was developed to look at the time spent on respiratory care over 3 months. Enrolled in this study are all CF patients aged from 6 to 16 years (the exclusion criterion was lung transplantation). RESULTS: Of the 40 enrolled patients, 22 participated (13 boys and 9 girls), with a mean age of 11 years. The patients spent approximately 19.46 h per week (standard deviation ± 7.53, 8.00-35.25 h) on therapy: CPT (30.58%), IT (15.11%), PA (50%) and MM (4.32%), without statistical significance between sexes. CONCLUSION: In our cohort, CF patients spent an average of nearly 20 h a week in respiratory therapy, within a wide range of between 8 h to almost 36 h a week. PA consumes almost half of the time. Physicians have to take into consideration the burden of the treatment, to optimise the therapy.

Morphology in phonology : introduction

This fourth volume of Catalan Journal of Linguistics is devoted to a topic discussed at length in the literature but which nevertheless remains a challenge for any view of phonology: the morphology-phonology interaction. The papers collected address two related issues, the role of morphological information in phonology and the role of phonological information in morphology. The first six articles (i.e. McCarthy, Wheeler, Downing, van Oostendorp, José and Auger, and Rice) deal with the former topic; the last three (i.e. Bertinetto and Jetchev, Pérez Saldanya and Vallès, and Viaplana), with the latter. Several papers (Wheeler, van Oostendorp, Rice, Bertinetto and Jetchev, Pérez Saldanya and Vallès, and Viaplana) further discuss the role and concept of paradigms, an old Neogrammarian notion to which renewed attention has been payed both from the phonological perspective (cf. work by Benua 1995, 1997; Burzio 1994 and subsequent work; Kenstowicz 1996, 2002; Steriade 2000, and the articles in the recent volume edited by Downing et al. 2005, among others) and from the morphological perspective (cf. work by Aronoff 1994; Bauer 1997, 2001; Carstairs-McCarthy 1994, 1998; Stump 1991, 1997; van Marle 1985, 1994; Wurzel 1989, and several articles in the recent volume edited by Boucher 2002, among others).

Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

Seguimiento de la Pradera de Posidonia oceanica de las Islas Medas. Ejercicio de 1999

Siguiendo la metodología de años anteriores(ver informes de seguimiento previos), durantelos meses de octubre a diciembre de 1999 setomaron una serie de medidas de vitalidad de lapradera de Posidonia oceanica de las islas Medes,así como de macrofauna asociada.Los resultados se presentan en las tablas quese adjuntan.No se han detectado cambios notables en losdescriptores de vitalidad de la planta (densidad ycobertura).No se han detectado inflorescencias.La población de erizos de la pradera se mantieneestable.Las nacras (Pinna cf. nobilis) han experimentadoun crecimiento significativo en anchura y enaltura, no habiéndose detectado ninguna mortalidaden la población estudiada en 1999. Se hanidentificado en el presente ejercicio tres individuosnuevos, de los que uno corresponde probablementea un recluta.Del seguimiento detallado del balizamientodel calvero se desprende que no hay cambiosimportantes en los límites de esta estructura

Validation et normes du SF-36 dans la population du canton de Vaud

[Table des matières] 1. Patients et méthodes. 1.1. Enquête dans la population générale : population, modalités d'envoi, taux de réponse. 1.2. Questionnaire SF-36 et questionnaire Medical Outcome Study (MOS) : PF physical functioning = activité physique (fonctionnement) ; RP role physical = limitations (du rôle) liées à la santé physique ; BP bodily pain = douleur physique ; GH General Health = santé générale ; VT vitality = vitalité (énergie/fatigue) ; SF social functioning = fonctionnement ou bien-être social ; RE role éemotional = limitations (du rôle) liées à la santé mentale ; MH mental health = santé mentale ; CF cognitive functioning = fonctionnement cognitif (dimension absente du SF-36 classique) ; HT eported health transition = modification perçue de l'état de santé ("dimension" annexe, = item 2 ou Q2). 1.3. Analyse : calcul des scores du SF-36 et du SF-36 + CF, cohérence des réponses, fiabilité de l'instrument, validité. 1.4. Analyse statistique. 2. Résultats commentés de l'enquête dans la population générale. 2.1. Fréquence des non-réponses par item et par question. 2.2. Cohérence des réponses. 2.3. Scores d'état de santé par dimension : description et comparaison avec une population américaine, comparaison des scores vaudois et genevois. 2.4. Existe-t-il une concentration des bons et des mauvais scores chez les mêmes répondants ? 2.5. Fiabilité. 2.6. Validité : validité convergente et discriminante, analyse factorielle, validation en fonction de variables externes. 3. Discussion. 3.1. Evaluation du questionnaire. 3.2. Mesure de la qualité de vie liée à l'état de santé perçu dans la population générale. 3.3. Adjonction de la dimension "fonctionnement cognitif". 3.4. Conclusions et recommandations.

Cellular delivery of pyrenyl-arene ruthenium complexes by a water-soluble arene ruthenium metalla-cage.

Three pyrenyl-arene ruthenium complexes (M(1)-M(3)) of the general formula [Ru(η(6)-arene-pyrenyl)Cl(2)(pta)] (pta = 1,3,5-triaza-7-phosphaadamantane) have been synthesised and characterised. Prior to the coordination to ruthenium, pyrene was connected to the arene ligand via an alkane chain containing different functional groups: ester (L(1)), ether (L(2)) and amide (L(3)), respectively. Furthermore, the pyrenyl moieties of the M(n) complexes were encapsulated within the hydrophobic cavity of the water soluble metalla-cage, [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) (tpt = 2,4,6-tri-(pyridin-4-yl)-1,3,5-triazine; donq = 5,8-dioxydo-1,4-naphthoquinonato), while the arene ruthenium end was pointing out of the cage, thus giving rise to the corresponding host-guest systems [M(n)⊂Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) ([M(n)⊂cage](6+)). The antitumor activity of the pyrenyl-arene ruthenium complexes (M(n)) and the corresponding host-guest systems [M(n)⊂cage][CF(3)SO(3)](6) were evaluated in vitro in different types of human cancer cell lines (A549, A2780, A2780cisR, Me300 and HeLa). Complex M(2), which contains an ether group within the alkane chain, demonstrated at least a 10 times higher cytotoxicity than the reference compound [Ru(η(6)-p-cymene)Cl(2)(pta)] (RAPTA-C). All host-guest systems [M(n)⊂cage](6+) showed good anticancer activity with IC(50) values ranging from 2 to 8 μM after 72 h exposure. The fluorescence of the pyrenyl moiety allowed the monitoring of the cellular uptake and revealed an increase of uptake by a factor two of the M(2) complex when encapsulated in the metalla-cage [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+).

Innovation through withdrawal. Contribution to a sociology of detachment

To develop the understanding of innovation processes conceptualized in terms of asso- ciation through the "sociology of translation" (cf. actor-network theory) studies, this article analyses innovation processes in terms of dissociation and detachment mechanisms, exami- ning innovation through "withdrawal;" that is, innovation based on reducing or withdrawing use of a practice-"subtracting," "detaching"-a given artefact. Specifically, it focuses on the shift to farming techniques that have eliminated ploughing, bringing to light four major mechanisms constitutive of dissociation: centrifugal association; making entities and asso- ciations visible; making other entities and associations invisible; bringing together or "asso- ciating" new entities. The study helps refine our understanding of the detachment processes at work in innovation, shedding light in this particular case on transfers between public research institutes, industrial companies, farmers and citizens seeking to develop new farm production models.

[Registre de la trésorerie secrète de Paul III. IIème volume (3 novembre 1543 - 1 janvier 1545)].

Ed. d'après ces mss. par Léon Dorez, "La cour du pape Paul III", Paris, 1932, 2 vol in-4°, cf. ms. italien 2325

Horae ad usum romanum.

F. 1-12v. Calendrier d’Autun en français, inscrit à l’or et à l’encre, alternativement rouge et bleue : 1er juin, « s. Reverien » [év. d’Autun] ; 12 juin, en or : « s. Nazaire » [révélation] ; 28 juil., « ss. Nazaire et Celse » ; 4 août, « s. Cassien [év. d’Autun] » ; 1er sept., « s. Ladre » [Lazare] ; 5 sept., «ste Royne » [Reine d’Alise] ; 19 sept., « s. Soigne » [Seine] ; 24 sept., « Andoche » [év. d’Autun] ; 2 oct., « Legier » [év. d’Autun] ; 20 oct., « revelacion s. Ladre » ; 17 déc., « s. Lazaire » ; 20 déc., « s. Nasaire » [21 déc., dédicace de Saint-Nazaire d’Autun]. F. 13-18. Péricopes évangéliques : Io 1, 1-14, suivi du suffrage adressé à l’apôtre ; Mt 2, 1-12 ; Lc 1, 26-38 ; Mc 16, 14-20. Les évangiles de Mathieu et de Luc sont incomplets du début par suite de la perte du premier fol. F. 19-78v. Heures de la Vierge à l’usage de Rome. Les heures de tierce, sexte, none et vêpres sont incomplètes du début par suite de la perte du premier feuillet. F. 79-82v. “Obsecro te…”, prière au masculin (éd. Leroquais, Livres d’heures, II, 347). F. 83-86v. Office de la Croix « De sancta cruce ». F. 87-90v. Office du Saint Esprit « De sancto Spiritu ». F. 91-107v. Psaumes de la pénitence , suivis des Litanies, incomplet du premier feuillet. A noter, parmi les confesseurs, « sancte Ludovice », Louis d’Anjou, év. de Toulouse. F. 107v-154. Office des morts à l’usage de Rome. « In agenda mortuorum ad vesperas ». F. 154v-159. Addition du XVe siècle : « Oraison de saint Sebastien », suffrage ; [Oraison pour les trépassés] « Avete omnes fideles anime quorum corpora… coronemur... Domine Jhesu Christe salus et liberatio animarum... jubeas. Per... » (154v et 159). — Additions du début du XVIe siècle. « Veni creator Spiritus... spiritus. Amen » ; « De s. Johanne Baptista » ; « Salve regina misericordie vita... ostende » ; « Domine non sum digna… animeam meam », à noter la forme féminine (156-158). — Sur le verso du f. 158, a été cousu un petit feuillet de parchemin portant l’oraison « O passio magna, o profunda vulnera, o effusio sanguinis, o dulcis dulcedo, o mortis amaritudo, da michi vitam eternam. Amen. Pater. Ave Maria. Credo ».