PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ(2) domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA-mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS-PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.

Macromicets de l'illa de Menorca.II.

Donem a conèixer els resultats de les prospeccions micològiques realitzades a Menorca entre els anys 1980 i 1988, i els presentem en forma de catàleg. S'han estudiat 193 tàxons (10 Ascomycetes i 183 Basidiomycetes), dels quals 127 creiem corresponen a citacions noves per a l'illa, entre els quals destaquem: Agaricus pequinii (Boud.) Konr. & Maubl., Amanita boudieri Barla, Dermoloma pseudocuneifolium Henrink, Hebeloma sarcophyllum (Peck) Sacc., Inocybe tenebrosa Quél., Psathyrella ammophila (Dur. & Lev.) Orton, Lactarius cistophilus Bon & Trimb. Russula seperina Dupain i Battarraea phalloides (Dicks.) Pers

Fungos micorrízicos arbusculares e adubação fosfatada em mudas de mangabeira

O objetivo deste trabalho foi avaliar os efeitos de fungos micorrízicos arbusculares (FMA) e da adubação fosfatada em mudas de mangabeira (Hancornia speciosa Gomes). O experimento, em casa de vegetação, utilizou delineamento inteiramente casualizado em fatorial com dois tratamentos de solo nativo oriundo de pomar com mangabeiras, desinfestado com brometo de metila e não-desinfestado, seis doses de P (3*, 3, 48, 93, 138 e 183 mg dm-3) e três tratamentos de inoculação, Gigaspora albida Schenck & Smith, Glomus etunicatum Becker & Gerdemann e controle sem inoculação, com quatro repetições. O tratamento 3* não recebeu solução nutritiva e os demais receberam solução nutritiva de Hoagland sem fósforo por ocasião da inoculação. Após 150 dias, observou-se aumento na altura, biomassa e área foliar nos tratamentos com G. albida, em solo desinfestado. Respostas à inoculação ocorreram nas mudas cultivadas com a menor dose de P, nos dois tratamentos de solo. A mangabeira mostrou-se dependente da micorrização apenas na menor dose de P em solo desinfestado. Nos demais níveis de P, a dependência variou em função do FMA e da condição do solo. A associação com G. albida proporcionou melhor desenvolvimento das mudas de mangabeira.

Evolució de la construcció del coneixement científic a l'educació primària

Aquest és un treball d'investigació sobre la construcció del coneixement científic, concretament del concepte de densitat a través de la flotabilitat. La investigació es basa en la teoria escrita i les idees prèvies dels alumnes d'una escola primària sobre aquest concepte. Aquest alumnes són una mostra representativa, 10 alumnes de 2n, 4t i 6è respectivament, per intentar reflectir les idees que tenen els alumnes al llarg de l'etapa de educació primària. Per a dur a terme aquesta investigació els alumnes han respost a dos qüestionaris on havien de predir el comportament de diferents materials dins l'aigua. També es van portar a terme unes activitats manipulatives sobre flotabilitat per poder recollir més dades. Finalment hi ha els resultats i comentaris que n'extrec sobre la teoria i les dades recollides.

Consommation de cannabis : quels sont les risques?

Résumé - Les cannabinoïdes contenus dans la plante de cannabis ont un double usage et possèdent des propriétés opposées suivant les circonstances et les doses employées. Les cannabinoïdes, essentiellement drogue récréative ou d'abus pourraient, pour certains d'entre eux, devenir des médicaments. Selon les conditions d'utilisation, ils peuvent être neurotoxiques ou neuroprotecteurs, carcinogènes ou anticancéreux, hyper-émétiques ou antiémétiques, pro-inflammatoires ou anti-inflammatoires. . . Les techniques de culture sous serre indoor ainsi que la sélection de variétés de cannabis à fort potentiel de production ont conduit à un accroissement notable des taux de THC. Le cannabis est la drogue illégale la plus fréquemment consommée en Suisse et ailleurs dans le monde occidental. Environ la moitié des jeunes ont déjà expérimenté le cannabis. Environ 10 % des consommateurs le fument quotidiennement et en sont devenus dépendants. Un tiers de ces usagers peut être considéré comme chroniquement intoxiqué. Le THC, la principale substance psychoactive du cannabis, interagit avec le « système endocannabinoïde ». Ce système est composé de récepteurs cellulaires, de ligands endogènes et d'un dispositif complexe de synthèse, de dégradation, de régulation et de messagers intra-cellulaires. Le système endocannabinoïde joue un rôle clé dans le réglage fin du système nerveux. Les endocannabinoïdes régulent la mémorisation, l'apprentissage moteur et la plasticité des liaisons nerveuses. À dose psychoactive, le THC réduit les performances psychomotrices et neurocognitives. Les facultés d'apprentissage et de mémorisation sont diminuées. Le risque d'être responsable d'un accident de circulation est augmenté après prise de cannabis, et ceci d'autant plus que de l'alcool aura été consommé parallèlement. À l'exception des jeunes enfants, la consommation de cannabis n'entraîne pas de risque potentiel d'intoxication mortelle. Toutefois, le cannabis pourrait agir comme facteur déclenchant d'accident cardiovasculaire chez de rares individus prédisposés. Les individus jeunes, et/ou vulnérables ont un risque significativement plus élevé de développer une psychose à l'âge adulte ou de devenir dépendant au cannabis. Des études épidémiologiques ont montré que le risque de développer une schizophrénie à l'âge adulte était augmenté pour les consommateurs de cannabis et ceci d'autant plus que l'âge de début de consommation était précoce. Il en va de même pour le risque de dépression. Les troubles respiratoires pourraient être exacerbés par la prise de cannabis. Les femmes enceintes et celles qui allaitent ne devraient pas consommer de cannabis car le THC traverse la barrière hémato-placentaire, en outre, il se concentre dans le lait maternel. La période de la vie la plus sensible aux effets néfastes du cannabis correspond à celle allant du foetus à l'adolescent. Le système endocannabinoïde sur lequel agit le THC serait en effet un acteur majeur orchestrant le développement des réseaux neuronaux dans le cerveau immature. La prise concomitante d'autres psychotropes comme l'alcool, les benzodiazépines ou la cocaïne conduit à des renforcements mutuels de leurs effets délétères. De plus, il a été montré l'existence d'une sensibilité croisée pour la majorité des psychotropes qui agissent sur le système de la récompense, le cannabis y compris, ce qui augmente ainsi le risque de pharmacodépendance. La prise régulière de doses élevées de cannabis entraîne l'apparition d'une tolérance et de symptômes de sevrage discrets à l'arrêt de la consommation. À part les effets négatifs mentionnés auparavant, le cannabis possède des propriétés médicales originales qui sont l'objet d'études attentives. Plusieurs cannabinoïdes mineurs naturels ou synthétiques, comme l'acide ajulémique, pourraient trouver un jour une place dans la pharmacopée. En usage thérapeutique, des variétés particulières de cannabis sont préférées, par exemple celles riches en cannabidiol non psychoactif. Le mode d'administration diffère de celui utilisé en mode récréatif. Par exemple, la vaporisation des cannabinoïdes à basse température est préférée à l'inhalation du « joint »

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Abstract Background: Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity. Objectives: To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period. Research Design: Randomized controlled trial. Subjects: Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources. Measures: The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15). Results: The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002). Conclusions: Our findings indicate that a 3-month physical activity program linked to community resources is a shortduration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits. Trial Registration: ClinicalTrials.gov NCT00714831

Fluid migration through thrust faults in the Helvetic nappes (Western Swiss Alps)

The delta(18)O, delta(13)C and Sr-87/Sr-86 values of calcite and organic matter were measured for carbonate mylonites from numerous thrusts in the Helvetic Alps. Carbonate mylonites in most of the thrusts retain essentially unaltered protolith delta(18)O and delta(13)C values, consistent with there having been little to no advection of isotopically distinct fluid through these faults. Only carbonate mylonites from the basal thrusts of the largest nappes have delta(18)O and/or delta(13)C values that differ from those of their protoliths. The zone of isotopic alteration/exchange is confined to c. 10 to 20 meters of these fault contacts. We propose the fluids that migrated through these faults contained variable amounts of organically derived carbon and radiogenic strontium, and were probably derived from dewatering of the sedimentary rocks and prograde metamorphic reactions in the nappes' root zones. Apart from the basal thrusts of the largest nappes that behaved as narrow, laterally extensive conduits for fluids, there is little isotopic evidence that large quantities of fluids passed through most of the carbonate-hosted thrusts in the Helvetic Alps.

Collection de copies de pièces sur l'histoire de France, formée par François DE CAMPS, abbé de Signy (1723). II PROVINCES. 57 Lyon et Lyonnais.

« De la souveraineté des rois de France sur la ville et le comté de Lion » (fol. 2, 93, 120) : pièces justificatives, 942-1320 (132, 183). — Lettre critique sur l'Histoire civile ou consulaire de la ville de Lyon du P. Menestrier (90). — Primatie de Lyon (186). Extraits « ex cartulario episcopatus Diensis, quod est conventus fratrum Minimorum Parisiensium, » 1158-1229 (193). Diplômes de l'empereur Frédéric II, copies extraites des archives du Domaine royal en Languedoc, arm. B (196). Inventaire des chartes du Trésor relatives au Lyonnais (218).

Ultrasound evaluation of synovitis in RA: Correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE: To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS: One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS: In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r=0.41, P<0.0001). The same was true for the PwD score (r=0.41, P<0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r=0.54, P<0.0001 and r=0.46, P<0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS: The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

Avaliação agronômica e econômica da aplicação de biossólido na produção de soja

O objetivo deste trabalho foi definir parâmetros técnicos e econômicos do uso de biossólido como fertilizante para a soja. A resposta da soja à aplicação de biossólido úmido, nas doses 0, 7,5, 15, 30 e 45 Mg ha-1 foi comparada à resposta ao fertilizante mineral, aplicado em quantidades equivalentes de NPK, por dois anos de cultivo, em um Latossolo Vermelho distrófico argiloso. Utilizou-se o delineamento experimental de blocos ao acaso, com nove tratamentos e três repetições. Biossólido e fertilizante mineral foram aplicados somente antes do primeiro cultivo. Na dose de 30 Mg ha-1 de biossólido úmido, as produções de 3.602 e 3.183 kg ha-1 de grãos, no primeiro e segundo cultivo, respectivamente, evidenciaram o efeito imediato e residual do material, o que também foi observado na dose de 45 Mg ha-1. Em termos econômicos, a melhor relação benefício-custo (1,15) foi obtida na dose de 30 Mg ha-1. A eficiência agronômica dos tratamentos com biossólido, em média, foi 18% superior aos tratamentos com fertilizante mineral. Os resultados mostram a viabilidade agronômica e econômica do uso do biossólido em substituição ao fertilizante mineral, na produção de soja.

Mesurer la stigmatisation perçue chez les personnes souffrant de troubles psychiques : traduction française, validation et adaptation de la Stigma Scale [French translation, validation and adaptation of the Stigma Scale].

AIM: People suffering from mental illness are exposed to stigma. However, only few tools are available to assess stigmatization as perceived from the patient's perspective. The aim of this study is to adapt and validate a French version of the Stigma Scale (King et al., 2007 [8]). This self-report questionnaire has a three-factor structure: discrimination, disclosure and positive aspects of mental illness. Discrimination subscale refers to perceived negative reactions of others. Disclosure subscale refers mainly to managing disclosure to avoid discrimination and finally positive aspects subscale taps into how patients are becoming more accepting, more understanding toward their illness. METHOD: In the first step, internal consistency, convergent validity and test-retest reliability of the French adaptation of the 28-item scale were assessed in a sample of 183 patients. Results of confirmatory factor analyses (CFA) did not confirm the hypothesized structure. In the light of the failed attempts to validate the original version, an alternative 9-item short-form version of the Stigma Scale, maintaining the integrity of the original model, was developed based on results of exploratory factor analyses in the first sample and cross-validated in a new sample of 234 patients. RESULTS: Results of CFA did not confirm that the data fitted well to the three-factor model of the 28-item Stigma Scale (χ(2)/df=2.02, GFI=0.77, AGFI=0.73, RMSEA=0.07, CFI=0.77 and NNFI=0.75). Cronbach's α was excellent for discrimination (0.84) and disclosure (0.83) subscales but poor for potential positive aspects (0.46). External validity was satisfactory. Overall Stigma Scale total score was negatively correlated with the score on Rosenberg's Self-Esteem Scale (r=-0.49), and each subscale was significantly correlated with a visual analogue scale that referred to the specific aspect of stigma (0.43≤|r|≤0.60). Intraclass correlation coefficients between 0.68 and 0.89 indicated good test-retest reliability. The results of the CFA demonstrated that the items chosen for the short version of the Stigma Scale have the expected fit properties (χ(2)/df=1.02, GFI=0.98, AGFI=0.98, RMSEA=0.01, CFI=1.0 and NNFI=1.0). Considering the small number (three) of items in each subscale of the short version of the Stigma Scale, α coefficients for discrimination (0.57), disclosure (0.80) and potential positive aspects subscales (0.62) are considered as good. CONCLUSION: Our results suggest that the 9-item French short version of the Stigma Scale is a useful, reliable and valid self-report questionnaire to assess perceived stigmatization in people suffering from mental illness. The time of completion is really short and questions are well understood and accepted by the patients.