Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

LEO 1.0 - a computer software-based maintenance strategy for reinforced concrete structures undergoing rebar corrosion

Peer reviewed: YesNRC publication: Ye

Bats (Mammalia, Chiroptera) of an urban park in the metropolitan area of Rio de Janeiro, southeastern Brazil

Some bat species are able to adapt to urban areas, where they find food and roosts. Despite the high number of parks in Brazilian cities, they did not yet raise the interest of most zoologists, except for some surveys of birds and butterflies. The objectives of the present study were: (i) to inventory the bat species of Quinta da Boa Vista (QBV), a large (25 ha) urban park centrally located in densely populated Rio de Janeiro, which is Brazil's second largest metropolis; (ii) to compare the species richness observed in roosts with the richness recorded through mist netting in flight routes and near fruiting fig trees; and (iii) to analyze recaptures of bats marked in this park and recaptured in other sites and vice-versa. Sampling totaled 104 sampling nights resulting in 3,256 captures (including 133 recaptures) between April 1989 and December 2004. We also sampled roosts and received some specimens from park visitors and city workers. We documented 21 bat species, predominantly large frugivores. The number of expected species for this park was 24.0 ± 4.6, and the total sampled represented 87.5% of the expected. The recapture of bats marked in surrounding forest fragments and in QBV shows the importance of urban parks for the maintenance of bat diversity. Inspection of roosts produced two species that had not been captured with other methods. Sampling near fruiting fig trees did not differ in terms of richness from sampling carried out far from these trees or during their non-fruiting periods

Can endotracheal bioimpedance cardiography assess hemodynamic response to passive leg raising following cardiac surgery?

The utility of endotracheal bioimpedance cardiography (ECOM) has been scarcely reported. We tested the hypothesis that it could be an alternative to pulse contour analysis for cardiac index measurement and prediction in fluid responsiveness

Sevoflurane- and desflurane-induced human myocardial post-conditioning through Phosphatidylinositol-3-kinase/Akt signalling

BACKGROUND: The role of phosphatidylinositol-3-kinase (PI3K) in sevoflurane- and desflurane-induced myocardial post-conditioning remains unknown. METHODS: We recorded isometric contraction of isolated human right atrial trabeculae (oxygenated Tyrode's at 34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by a 60-min reoxygenation period. At the onset of reoxygenation, muscles were exposed to 5 min of sevoflurane 1%, 2%, and 3%, and desflurane 3%, 6%, and 9%. In separate groups, sevoflurane 2% and desflurane 6% were administered in the presence of 100 nM wortmannin, a PI3K inhibitor. Recovery of force after the 60-min reoxygenation period was compared between groups (mean +/- SD). RESULT: As compared with the Control group (49 +/- 7% of baseline) PostC by sevoflurane 1%, 2%, and 3% (78 +/- 4%, 79 +/- 5%, and 85 +/- 4% of baseline, respectively) and desflurane 3%, 6%, and 9% (74 +/- 5%, 84 +/- 4%, and 86 +/- 11% of baseline, respectively) enhanced the recovery of force. This effect was abolished in the presence of wortmannin (56 +/- 5% of baseline for sevoflurane 2%+wortmannin; 56 +/- 3% of baseline for desflurane 6%+wortmannin). Wortmannin alone had no effect on the recovery of force (57 +/- 7% of baseline). CONCLUSION: In vitro, sevoflurane and desflurane post-conditioned human myocardium against hypoxia through activation of phosphatidylinositol-3-kinase

Soil type determines how root and rhizosphere traits relate to phosphorus acquisition in field-grown maize genotypes

Aims Phosphorus (P) is frequently limiting crop production in agroecosystems. Large progress was achieved in understanding root traits associated with P acquisition efficiency (PAE, i.e. P uptake achieved under low P conditions). Most former studies were performed in controlled environments, and avoided the complexity of soil-root interactions. This may lead to an oversimplification of the root-soil relations. The aim of the present study was, therefore, to identify the dominant root and rhizosphere-related traits determining PAE, in contrasting soil conditions in the field. Methods Twenty-three maize hybrids were grown at two contrasting P levels of a long-term P-fertilizer trial in two adjacent soil types: alkaline and neutral. Bulk soil, rhizosphere and root parameters were studied in relation to plant P acquisition. Results Soil type had robust effect on PAE. Hybrids\u2019 performance in one soil type was not related to that in the other soil type. In the neutral soil, roots exhibited higher specific root length, higher root/shoot ratio but lower PAE. Best performing hybrids in the neutral soil were characterized by top soil exploration, i.e., greater root surface and topsoil foraging. In contrast, in the alkaline soil, PAE and foraging traits were not correlated, P availability in the rhizosphere was greater than the bulk soil and phosphatase activity was higher, suggesting a \u2018mining strategy\u2019 in that case (i.e. traits that facilitate elevated P availability). Conclusions These results indicate the key role of environmental factors for roots traits determining high PAE. The study highlights the need to consider soil properties when breeding for high PAE, as various soil types are likely to require different crop ideotypes

Role of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase-3 beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning in isolated human right atria

Desflurane during early reperfusion has been shown to postcondition human myocardium. Whether it involves "reperfusion injury salvage kinase" pathway remains incompletely studied. The authors tested the involvement of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase (GSK)-3beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning

Una splendida cinquantenne. La Quinta Repubblica francese

Raccolta di saggi originali scritti da autori italiani e francesi per valutare la Costituzione, le istituzioni, i partiti dei cinquant\u2019anni della Quinta Repubblica e i mutamenti avvenuti nella cultura politica dei francesi