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.

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.

The Swiss Willensnation at Risk: Teachers in the Cultural Gap during the First World War

As a neutral and multilingual country, Switzerland struggled with major domestic political conflicts during the First World War due to the two cultures of the French-speaking and German-speaking parts of the country. The divided cultural loyalties ('fossé moral', 'Röstigraben'), consisting of Swiss-Germans supporting Germany and Swiss-French supporting France, were discussed intensively in both of the main teachers' journals in Switzerland. Teachers felt the need to react and to promote unity from the beginning of the war. Despite the fact that the cantons are responsible for public education and, therefore, for the education of their students, teachers considered themselves called to educate their students to be national citizens rather than to be members of a language group. This threefold citizenship - communal, cantonal and national - was not scrutinised, but national unity became crucial due to the critical political circumstances. How did teachers promote and constitute citizenship for themselves and for their students in a nation united by free will during the First World War, a time of severe internal political conflicts?

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.

Teachers' remarks about their salaries in 1800 in the Helvetic Republic

For centuries, teachers have complained about their salaries. In the Stapfer inquiry of 1799, some teachers made remarks about financial issues, particularly their low incomes. This inquiry is the main source for the arguments presented here regarding teachers' low salary during this period of the Helvetic Republic. The disparity between the lowest and the highest income was huge in 1799. This fact invites investigations about the people who complained. The evidence indicates incoherence between the complaints regarding low salary and the real income that was earned by these teachers. However, in order for this thesis to be wholly understood, the salaries must be explained; at the time of the Stapfer inquiry, salaries were paid in different currencies, as wages in kind and using divergent measurements. The present article aims to determine who these teachers were and why they complained. The arguments presented by the teachers shed light on the topics of political appeals, the social status of teachers in 1800 and the professionalisation of teachers.

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.