Signalling pathways from NADPH oxidase-4 to idiopathic pulmonary fibrosis

This review focuses on the roles of NADPH oxidase/NOX proteins in idiopathic pulmonary fibrosis (IPF) pathophysiology and in the signalling pathways involved in IPF. NOX proteins are membrane-associated multi-unit enzymes that catalyze the reduction of oxygen using NADPH as an electron donor. Recent studies indicate that NOX4 is induced in pulmonary fibroblasts in response to TGF-β. TGF-β or PDGF induce myofibroblast proliferation, differentiation, migration, contractility and extracellular matrix production, through NOX4 and reactive oxygen species dependent SMAD2/3 phosphorylation. NOX4 is increased in pulmonary fibroblasts from IPF patients and deletion of Nox4 in mice prevents bleomycin-induced pulmonary fibrosis. These data strongly suggest that targeting of NOX4 could be a step forward in the treatment of fibrotic lung diseases, by specifically targeting myofibroblasts, a major player in this disease.     

Lack of association of CD36 SNPs with early onset obesity: a meta-analysis in 9,973 European subjects

A recent study suggested that four CD36 polymorphisms (namely rs3211867, rs3211883, rs3211908, and rs1527483) were associated with an increased risk of obesity, an increased BMI and percentage of body fat in European adolescents. We first attempted to confirm these results in three independent case-control genome-wide association studies (GWAS) data totaling 3,509 subjects of French and German origin, but we were unable to find any association of these variants with early onset obesity risk. We then genotyped the four CD36 single-nucleotide polymorphisms (SNPs) in a large population-based study of 4,667 Finnish subjects and we did not replicate any of the recently reported associations with BMI. By combining all available data in a meta-analysis (N = 9,973), we found no evidence for an association of the reported four variants in CD36 with increased obesity risk or increased BMI (0.07 ≤ P values ≤ 0.93). Finally, we assessed the contribution of the full CD36 locus gene variation to obesity risk in 3,509 subjects and we did not detect any significant association with obesity after correction for multiple testing. In summary, we were unable to confirm the recently reported association of variants in CD36 with early onset obesity in populations of European ancestry.     

Genetic analysis of durable resistance to yellow rust in bread wheat

Yellow rust, caused by Puccinia striiformis, is one of the most damaging diseases affecting bread wheat in temperate regions. Although resistance to yellow rust is frequently overcome by new virulent races, a durable form of resistance in the French bread wheat Camp Rémy (CR) has remained effective since its introduction in 1980. We used 217 F₇ recombinant inbred lines (RILs) derived from the cross between CR and the susceptible cultivar Récital to identify and map quantitative trait loci (QTLs) involved in durable yellow rust resistance. Six significant QTLs that were stable over a 4-year period were detected. Two QTLs, denoted QYr.inra-2DS and QYr.inra-5BL.2, were located on the short arm of chromosome 2D and the long arm of chromosome 5B, respectively. Each explained on average 25–35% of the observed phenotypic variation and were probably inherited from Cappelle Desprez, a parent of CR that confers durable adult plant resistance to yellow rust. QYr.inra-2DS probably corresponds to the Yr16 gene. The most consistent QTL, designated QYr.inra-2BL, was located on the centromeric region of chromosome 2B and explained 61% of the phenotypic variation in 2003. This QTL was responsible for seedling-stage resistance and may correspond to a cluster of genes, including Yr7. The remaining QTLs were mapped to the short arm of chromosome 2B (R²=22–70%) and to the long arm of chromosomes 2A (R²=0.20–0.40) and 5B (R²=0.18–0.26). This specific combination of seedling and adult plant resistance genes found in CR and CD may constitute the key to their durable resistance against yellow rust.     

Multiple origins for Mediterranean olive (Olea europaea L. ssp. europaea) based upon mitochondrial DNA polymorphisms

A study of nuclear and cytoplasmic genetic diversity of cultivated olive, oleaster and other taxa belonging to the complex O. europaea was performed. Nuclear DNA polymorphism (RAPDs) in oleaster displays a gradient between the east and west of the Mediterranean Basin. In cultivars, the gradient is less visible owing to their diffusion and selection. Furthermore, three mitotypes (ME1, MOM and MCK) were detected in both cultivated olive and oleaster. A fourth mitotype, ME2, was unique to some cultivars. The preponderant mitotype, ME1, marks the Near Eastern origin of olive in oleaster. In the west of the Mediterranean, another mitotype, MOM, was found in most oleaster. and a few cultivars. The third, MCK, was found in a few oleaster from the west and in cultivars originating in Kabylie and Languedoc. We argue that MCK marks an ancestral Mediterranean population. The mitotypes mark independent cultivated olive origins which were not detected with DNA nuclear diversity.     

A complete collection of single‐gene deletion mutants of Acinetobacter baylyi ADP1

We have constructed a collection of single‐gene deletion mutants for all dispensable genes of the soil bacterium Acinetobacter baylyi ADP1. A total of 2594 deletion mutants were obtained, whereas 499 (16%) were not, and are therefore candidate essential genes for life on minimal medium. This essentiality data set is 88% consistent with the Escherichia coli data set inferred from the Keio mutant collection profiled for growth on minimal medium, while 80% of the orthologous genes described as essential in Pseudomonas aeruginosa are also essential in ADP1. Several strategies were undertaken to investigate ADP1 metabolism by (1) searching for discrepancies between our essentiality data and current metabolic knowledge, (2) comparing this essentiality data set to those from other organisms, (3) systematic phenotyping of the mutant collection on a variety of carbon sources (quinate, 2‐3 butanediol, glucose, etc.). This collection provides a new resource for the study of gene function by forward and reverse genetic approaches and constitutes a robust experimental data source for systems biology approaches.     

Comparative sensitivity of larval mosquitoes to vegetable polyphenols versus conventional insecticides

The larvicidal effects of polyphenols of natural crude decomposed alder leaf litter and commercially available tannic acid were experimentally compared with those of two common conventional insecticides (Bacillus thuringiensis ssp. israelensis: microbial insecticide; temephos: organophosphate insecticide). Comparative standard bioassays using third instar larval Aedes aegypti, A. albopictus, Culex pipiens and Coquillettidia richiardii as references indicated that Aedes and Culex taxa are far more sensitive to alder leaf litter than to tannic acid and conventional insecticides. C. richiardii is far more resistant to conventional insecticides than Aedes and Culex taxa, but its sensitivity to tannic acid is close to that of those taxa. Dietary vegetable polyphenols are thus proposed as new, practical, alternative chemicals for mosquito control when conventional insecticides are difficult and costly to be used (e.g., in the management of Aedes and Culex populations in man-made breeding sites and Coquillettidia control strategy).