Intraovarian sperm storage in Helicolenus dactylopterus dactylopterus fertilitzation, crypt formation and maintenance of stored sperm

The females of the bluemouth rockfish, Helicolenus dactylopterus dactylopterus (DelaRoche, 1809), store sperm within their ovaries for periods of up to 10 months. Twenty six females with standard lengths between 152 and 257 mm and six males with standard lengths between 253 and 209 mm were caught storage crypts with stored spermatozoa and to describe their evolution over the year. After internal fertilization and once sperm reaches the ovary, a crypt forms probably by an epithelial inclusion at the base of the lamellae of one or several spermatozoa groups that are floating freely in the interlamellar space of the ovarian lumen. Stored spermatozoa have a large cytoplasm bag surrounding their heads. This bag could serve as a nutritive reservoir during the long storage period. Many desmosonal and tight junctions between the crypt cells ensure tha male sex cells are protected against the female immune system

A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans.

Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus,we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.

Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.

Pathways for the synthesis of polyesters in plants; cutin, suberin, and polyhydroxyalkanoates

Plants naturally produce the lipid-derived polyester cutin, which is found in the plant cuticle that is deposited at the outermost extracellular matrix of the epidermis covering nearly all aboveground tissues. Being at the interface between the cell and the external environment, cutin and the cuticle play important roles in the protection of plants from several stresses. A number of enzymes involved in the synthesis of cutin monomers have recently been identified, including several P450s and one acyl-CoA synthetase, thus representing the first steps toward the understanding of polyester formation and, potentially, polyester engineering to improve the tolerance of plants to stresses, such as drought, and for industrial applications. However, numerous processes underlying cutin synthesis, such as a controlled polymerization, still remain elusive. Suberin is a second polyester found in the extracellular matrix, most often synthesized in root tissues and during secondary growth. Similar to cutin, the function of suberin is to seal off the respective tissue to inhibit water loss and contribute to resistance to pathogen attack. Being the main constituent of cork, suberin is a plant polyester that has already been industrially exploited. Genetic engineering may be worth exploring in order to change the polyester properties for either different applications or to increase cork production in other species. Polyhydroxyalkanoates (PHAs) are attractive polyesters of 3-hydroxyacids because of their properties as bioplastics and elastomers. Although PHAs are naturally found in a wide variety of bacteria, biotechnology has aimed at producing these polymers in plants as a source of cheap and renewable biodegradable plastics. Synthesis of PHA containing various monomers has been demonstrated in the cytosol, plastids, and peroxisomes of plants. Several biochemical pathways have been modified in order to achieve this, including the isoprenoid pathway, the fatty acid biosynthetic pathway, and the fatty acid β-oxidation pathway. PHA synthesis has been demonstrated in a number of plants, including monocots and dicots, and up to 40% PHA per gram dry weight has been demonstrated in Arabidopsis thaliana. Despite some successes, production of PHA in crop plants remains a challenging project. PHA synthesis at high level in vegetative tissues, such as leaves, is associated with chlorosis and reduced growth. The challenge for the future is to succeed in synthesis of PHA copolymers with a narrow range of monomer compositions, at levels that do not compromise plant productivity. This goal will undoubtedly require a deeper understanding of plant biochemical pathways and how carbon fluxes through these pathways can be manipulated, areas where plant "omics" can bring very valuable contributions.

Sequential analysis of trans-SNARE formation in intracellular membrane fusion.

SNARE complexes are required for membrane fusion in the endomembrane system. They contain coiled-coil bundles of four helices, three (Q(a), Q(b), and Q(c)) from target (t)-SNAREs and one (R) from the vesicular (v)-SNARE. NSF/Sec18 disrupts these cis-SNARE complexes, allowing reassembly of their subunits into trans-SNARE complexes and subsequent fusion. Studying these reactions in native yeast vacuoles, we found that NSF/Sec18 activates the vacuolar cis-SNARE complex by selectively displacing the vacuolar Q(a) SNARE, leaving behind a Q(bc)R subcomplex. This subcomplex serves as an acceptor for a Q(a) SNARE from the opposite membrane, leading to Q(a)-Q(bc)R trans-complexes. Activity tests of vacuoles with diagnostic distributions of inactivating mutations over the two fusion partners confirm that this distribution accounts for a major share of the fusion activity. The persistence of the Q(bc)R cis-complex and the formation of the Q(a)-Q(bc)R trans-complex are both sensitive to the Rab-GTPase inhibitor, GDI, and to mutations in the vacuolar tether complex, HOPS (HOmotypic fusion and vacuolar Protein Sorting complex). This suggests that the vacuolar Rab-GTPase, Ypt7, and HOPS restrict cis-SNARE disassembly and thereby bias trans-SNARE assembly into a preferred topology.

Bilan de santé à 50 ans: formation des médecins praticiens en prévention clinique

En 1994, l'entreprise Ciba SC située à Monthey (canton du Valais, Suisse) a décidé d'élargir ses actions de promotion de la santé en offrant à ses collaborateurs de 50 ans une consultation médicale intitulée "Bilan de santé". 1.1. Historique. 1.2. Prolongation du projet auprès des praticiens. 2. Population et méthodes. 2.1. Médecins et module de formation : Réalisation du "Module de consultation des 50 ans en pratique ambulatoire, remboursement, évaluation du module de formation. 2.2. Collaborateurs des usines de Monthey. 2.3. Réalisation pratique et déroulement de la consultation. 2.4. Evaluation de l'impact du projet. 3. Résultats. 3.1. Participation, habitudes de vie et santé des participants : tabagisme, alimentation, activité physique, alcool, drogues, médicaments, situation de vie et état psychique, prévention routière, vaccinations, hypercholestérolémie, données cliniques, facteurs de risques identifiés et reportés par le médecin. 3.2. Evaluation, l'opinion des patients : satisfaction, conséquences sur les habitudes de vie. 3.3. Evaluation, l'opinion des praticiens : satisfaction, impact et souhaits perçus chez les médecins, déroulement de la consultation, examens de laboratoire, rémunération. 4. Discussion. 5. Conclusion.

Urgences et médecins de premier recours: quelles perspectives? Quelle formation [Emergencies and general practitionners. Which prospects? Which education?].

Professionalisation of emergency medicine and triage before most of emergency consultations led to a major reduction in exposure of general practitionners (GP) to vital emergencies, which participates in reduction of their aptitudes to manage such emergencies. The risk for a GP to face a vital emergency is weak nowaday, but did not totaly disappear. Therefore, it seems important for the GPs to maintain the skills required to manage these emergencies properly. These skills would be capacity in recognizing symptoms and signs of alarm (red flags), applying life support, and sorting the patients correctly. These skills will be all the more important in the future, while the role of the GP could be reinforced in response to requirement of increased efficiency.

A propos de la supervision clinique dans la formation à la psychothérapie cognitive et comportementale : quelques réflexions et commentaires

L'auteur commente deux articles de Clauw et al. (2011a, 2011b) sur la supervision en TCC, en soulignant qu'un des intérêts majeurs de la formation basée sur l'évidence est de légitimer à l'avenir de façon scientifique le rôle d'activités comme la supervision ou l'expérience personnelle en psychothérapie. Les approches transdiagnostiques et transthéoriques en psychothérapie vont conduire à de nouveaux cursus de formation qui ne seront plus liés à une école particulière mais basés sur la connaissance scientifique du fonctionnement humain, de la psychopathologie et de son traitement psychologique. La supervision empiriquement fondée doit explorer de nouvelles manières de mesurer son impact sur la compétence des thérapeutes en formation et sur l'efficacité des traitements conduits auprès des patients. Les instruments mesurant l'adhésion au modèle TCC sont insuffisants. Des listes plus générales de compétences cliniques apparaissent comme des alternatives intéressantes, mais il n'existe pas aujourd'hui de consensus au sujet de leurs contenus. L'auteur s'arrête enfin sur l'importance de maintenir la mission évaluative et contrôlante de la supervision, même si elle peut créer quelque malaise entre supervisé et superviseur. La tendance à la professionnalisation de l'activité de supervision nous conduit à la nécessité de penser une intégration intelligente de ses fonctions pédagogiques et évaluatives. Nous ne devons cependant pas oublier que cette tendance à la professionnalisation ne doit pas être le simple reflet du mouvement économique vers la qualité totale, mais trouver son fondement sur des lacunes objectivement observables dans les cursus de formation actuels.

Didactique de la géographie et formation initiale des enseignants spécialistes : conception et première évaluation du nouveau dispositif de formation initiale des enseignants de géographie du Secondaire supérieur à la HEP Vaud

Geography as a school subject is specifically thought for and by the schools. The contents of the school subject, nowadays, do not reflect the concerns and the evolution of the discipline as such. Nevertheless, official curricula set school objectives that address issues affecting the world and people's lives. These issues are coherent with the ones addressed by geography as a social science, that is to say the study of how people and their environment interact and how societies are interconnected through space. On an every day basis, Geography as a school subject is most of the time reduced to accumulating knowledge outside any given context. This knowledge may even be partially untrue or old and the related activities focus on low cognitive tensions. These practices do not contribute to the learners' understanding of the world because it does not allow them to build a geographical competence, which they. will need as future citizens in order to make responsible choices when they are confronted to questions related to how the locations of human and physical features are influenced by each other and how they interact across space. The central part of the text relies on the ideas and the processes discussed in the publications, which constitute the published file; it is divided into two parts. The first part (chapter 4) presents a didactic approach, which gives meaningful insights into Geography as a school subject and shows a brief account of the theoretical background that supports it. This socio-constructivist approach relies on the main following features: a priming stage (élément déclencheur), which presents geographical knowledge as an issue to be explored, discussed or solved; the issue is given to learners;. the planning of the teaching-learning sequence in small units launched by the main issue in the priming stage ; the interconnections of geographical knowledge with integrative concepts ; the synthetic stage or reporting stage where final concepts and knowledge are put together in order to be learned. Such an approach allows learners to re-invest the knowledge they have built themselves. This knowledge is organised by geographical integrative concepts, which represent true thinking operative tools and with which key issues in the geographical thinking are associated. The second part of the text (chapter 5) displays the didactic principles that governed the conception of the new initial training course for the future upper secondary school teachers at the HEP Vaud. The ambition of this course is to prepare future teachers to plan and realize the teaching of geography that provides pupils with the tools to understand better how people and their environment interact and how societies are interconnected through space. One of the tools for the teachers is the conceptual framework, whose most salient interest is to be relevant at every stage of the preparation and planning of the teaching, including the necessary epistemological reflection that should always be present. The synthesis of the text starts with a short account of the first evaluation of the new course. Various reflections on the future concerns and issues, that the didactics and methodology of Geography will be confronted with, constitute the synthesis.

Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation.

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.