mTORC2 regulates PGE2-mediated endothelial cell survival and migration.

Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.

IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies-A Price Comparison with Sanger Sequencing.

The molecular diagnosis of retinal dystrophies (RD) is difficult because of genetic and clinical heterogeneity. Previously, the molecular screening of genes was done one by one, sometimes in a scheme based on the frequency of sequence variants and the number of exons/length of the candidate genes. Payment for these procedures was complicated and the sequential billing of several genes created endless paperwork. We therefore evaluated the costs of generating and sequencing a hybridization-based DNA library enriched for the 64 most frequently mutated genes in RD, called IROme, and compared them to the costs of amplifying and sequencing these genes by the Sanger method. The production cost generated by the high-throughput (HT) sequencing of IROme was established at CHF 2,875.75 per case. Sanger sequencing of the same exons cost CHF 69,399.02. Turnaround time of the analysis was 3 days for IROme. For Sanger sequencing, it could only be estimated, as we never sequenced all 64 genes in one single patient. Sale cost for IROme calculated on the basis of the sale cost of one exon by Sanger sequencing is CHF 8,445.88, which corresponds to the sale price of 40 exons. In conclusion, IROme is cheaper and faster than Sanger sequencing and therefore represents a sound approach for the diagnosis of RD, both scientifically and economically. As a drop in the costs of HT sequencing is anticipated, target resequencing might become the new gold standard in the molecular diagnosis of RD.

Taller de teatre socioeducatiu per a dones maltractades

Projecte que presenta una base teòrica construida a partir de l'animació sociocultural com a àmbit d'intervenció de l'educació social, passant per l'educació no formal, l'educació d'adults i l'educació en el temps lliure i l'oci i el teatre socioeducatiu. Aquesta base teòrica ha servit per idear i desenvolupar el taller de teatre per a dones maltractades

Biological markers of alcohol consumption in alcoholised drivers: Comparison of capillary electrophoresis (CZE CDT) and a direct immunoassay (N Latex CDT) with the traditional method of anion-exchange chromatography-immunoturbidimetry (%CDT TIA).

Objectives: The aim of this study was to compare specificity and sensitivity of different biological markers that can be used in a forensic field to identify potentially dangerous drivers because of their alcohol habits. Methods: We studied 280 Swiss drivers after driving while under the alcohol influence. 33 were excluded for not having CDT N results, 247 were included (218 men (88%) and 29 women (12%). Mean age was 42,4 (SD:12, min: 20 max: 76). The evaluation of the alcohol consumption concerned the month before the CDT test and was considered as such after the interview: Heavy drinkers (>3 drinks per day): 60 (32.7%), < 3 drinks per day and moderate: 127 (51.4%) 114 (46.5%), abstinent: 60 (24.3%) 51 (21%). Alcohol intake was monitored by structured interviews, self-reported drinking habits and the C-Audit questionnaire as well as information provided by their family and general practitioner. Consumption was quantified in terms of standard drinks, which contain approximately 10 grams of pure alcohol (Ref. WHO). Results: comparison between moderate (less or equal to 3 drinks per day) and excessive drinkers (more than 3 drinks) Marker ROC area 95% CI cut-off sensitivity specificity CDT TIA 0.852 0.786-0917 2.6* 0.93 LR+1.43 0.35 LR-0.192 CDT N latex 0.875 0.821-0.930 2.5* 0.66 LR+ 6.93 0.90 LR- 0.369 Asialo+disialo-tf 0.881 0.826-0.936 1.2* 0.78 LR+4.07 0.80 LR-0.268 1.7° 0.66 LR+8.9 0.93 LR-0.360 GGT 0.659 0.580-0.737 85* 0.37 LR+2.14 0.83 LR-0.764 * cut-off point suggested by the manufacturer ° cut-off point suggested by our laboratory Conclusion: With the cut-off point established by the manufacturer, CDT TIA performed poorly in term of specificity. N latex CDT and CZE CDT were better, especially if a 1.7 cut-off is used with CZE

Pääjohtaja Erkki Raatikainen 19/2 1975

Kirje 19.2.1975

Plan I Investigaciones de anchoveta desarrollo del programa: estructura de la población. Los experimentos de marcación de anchoveta

Describe los procedimientos de marcar peces como método útil para estudiar los movimientos de dispersión, migraciones, edad, crecimiento y estimar la densidad de la población, los efectos de la pesca en los stocks y la estructura de las poblaciones.

Interlocking directorates in Spanish banking in the twentieth century

Spanish banking historiography asserts that the largest banks performed in the twentieth century as though they constituted a monopoly. One of their main coordination schemes would have been a network of interlocking bank directors that would include most of the financial firms. Evidence available for the 1920s and 1960s seems to confirm the veracity of this hypothesis. In this paper, more systematic evidence is presented to cover the whole twentieth century with the aim of checking whether these networks persisted over the entire period or they were by-products of temporary situations. Our results show that no general network remained for more than a decade. Therefore, it should be ruled out that interlocking directorates worked as a coordination device of an alleged banking cartel.

Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome.

Many currently used and candidate vaccine adjuvants are particulate in nature, but their mechanism of action is not well understood. Here, we show that particulate adjuvants, including biodegradable poly(lactide-co-glycolide) (PLG) and polystyrene microparticles, dramatically enhance secretion of interleukin-1beta (IL-1beta) by dendritic cells (DCs). The ability of particulates to promote IL-1beta secretion and caspase 1 activation required particle uptake by DCs and NALP3. Uptake of microparticles induced lysosomal damage, whereas particle-mediated enhancement of IL-1beta secretion required phagosomal acidification and the lysosomal cysteine protease cathepsin B, suggesting a role for lysosomal damage in inflammasome activation. Although the presence of a Toll-like receptor (TLR) agonist was required to induce IL-1beta production in vitro, injection of the adjuvants in the absence of TLR agonists induced IL-1beta production at the injection site, indicating that endogenous factors can synergize with particulates to promote inflammasome activation. The enhancement of antigen-specific antibody production by PLG microparticles was independent of NALP3. However, the ability of PLG microparticles to promote antigen-specific IL-6 production by T cells and the recruitment and activation of a population of CD11b(+)Gr1(-) cells required NALP3. Our data demonstrate that uptake of microparticulate adjuvants by DCs activates the NALP3 inflammasome, and this contributes to their enhancing effects on innate and antigen-specific cellular immunity.

New multicomponent capsules for immunoisolation.

A new generation of microcapsules based on the use of oligomers which participate in polyelectrolyte complexation reactions has been developed. These freeze-thaw stable capsules have been applied as a bioartificial pancreas and have resulted in normoglycemia for periods of six months in concordant xenotransplantations. The new chemistry permits the control of permeability and mechanical properties over a wide range and can be adapted both to microcapsule and hollow fiber geometries rendering it a robust tool for encapsulation in general. Methods, and metrics, for the characterization of the mechanical properties and permeability of microcapsules are presented.

Correlação linear e espacial entre o rendimento de grãos do feijoeiro e a resistência mecânica à penetração em um Latossolo Vermelho distrófico

A resistência mecânica à penetração apresentada pelo solo exerce grande influência sobre o desenvolvimento vegetal, uma vez que o crescimento das raízes, assim como o rendimento das culturas, varia de forma inversamente proporcional ao seu valor. No ano agrícola de 2001/2002, na Fazenda Experimental de Ensino e Pesquisa da Faculdade de Engenharia/UNESP - Campus de Ilha Solteira, foram analisados o rendimento de grãos do feijoeiro (PG) e a resistência mecânica à penetração (R), de um Latossolo Vermelho distrófico. O objetivo foi apurar diretrizes relacionadas com o aumento da produtividade agrícola em questão, estudando a correlação linear e a espacial entre a PG e a R. Foi instalada uma rede geoestatística para a coleta dos dados do solo e da planta, estabelecida com espaçamentos de 5 x 5 m e 2,5 x 2,5 m, que continham 120 pontos amostrais distribuídos numa área de 1.875 m². A correlação linear entre a PG e a R foi praticamente nula, uma vez que, dependendo das profundidades estudadas do solo, apresentou coeficientes de correlação (r) menores do que 0,20. A análise geoestatística apresentou boa estrutura de dependência espacial, tanto para a PG quanto para a R, quando analisadas isoladamente. Entretanto, a análise espacial conjunta de tais atributos apresentou-se inconsistente. Assim, com o aumento da resistência mecânica à penetração, em determinada região do solo ocorreu ora aumento, ora diminuição do rendimento de grãos do feijoeiro.