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Pulmonary adenoma susceptibility 1 (Pas1) is the major locus responsible for lung tumor susceptibility in mice; among the six genes mapping in this locus, Kras is considered the best candidate for Pas1 function although how it determines tumor susceptibility remains unknown. In an (A/J×C57BL/6)F4 intercross population treated with urethane to induce lung tumors, Pas1 not only modulated tumor susceptibility (LOD score = 48, 69% of phenotypic variance explained) but also acted, in lung tumor tissue, as an expression quantitative trait locus (QTL) for Kras-4A, one of two alternatively spliced Kras transcripts, but not Kras-4B. Additionally, Kras-4A showed differential allelic expression in lung tumor tissue of (A/J×C57BL/6)F4 heterozygous mice, with significantly higher expression from the A/J-derived allele; these results suggest that cis-acting elements control Kras-4A expression. In normal lung tissue from untreated mice of the same cross, Kras-4A levels were also highly linked to the Pas1 locus (LOD score = 23.2, 62% of phenotypic variance explained) and preferentially generated from the A/J-derived allele, indicating that Pas1 is an expression QTL in normal lung tissue as well. Overall, the present findings shed new light on the genetic mechanism by which Pas1 modulates the susceptibility to lung tumorigenesis, through the fine control of Kras isoform levels. [ABSTRACT FROM AUTHOR]

Background: Food supplements, and in particular those containing botanicals (plant food supplements, PFS), have in recent decades been of great interest both to consumers and to food/pharmaceutical industries. Objectives: The aim of this paper is to examine replies by Italian consumers to the PlantLIBRA consumers' survey in order to: 1) assess the behaviour of an Italian population with respect to the use of PFS, and to compare it with that of other 5 countries involved in the whole survey; 2) identify different habits in the 4 Italian cities selected according to their geographical distribution; 3) collect independent information on the actual intake of PFS and consumers' behaviour. Subjects/setting: 397 Italian consumers enrolled, 187 males (49.5%) and 191 female (50.5%). The distribution of subjects among the 4 cities included was: Milan 99; Venice 90; Rome 96 and Catania 96. Results: The interest in PFS in Italy is high, the prevalence of "regular" consumers being 22.7%. Some differences were observed between the 4 cities involved: the pattern of use during the year was specific to each city; consumers in Milan reported reasons to use PFS significantly different from those in the whole Italian sample and did not indicate supermarkets as an important place of purchase; respondents from Rome and Catania more frequently used family doctors and pharmacists as a source of recommendation. Some significant difference among cities, sex and age groups were observed when the most frequently used botanicals were ranked. Conclusions: The results provide new insights on the socio-economic characteristics and lifestyle of Italian PFS consumers, on their reasons for and pattern of use, and on their behaviour and expectations. The value of this information is not restricted to the specific country (Italy) but allows for a more general evaluation of the pattern of use, according to habits and geographical area. [ABSTRACT FROM AUTHOR]

Background: Sex and age strongly influence the pathophysiology of human lungs, but scarce information is available about their effects on pulmonary gene expression. Methods: We followed a discovery-validation strategy to identify sex- and age-related transcriptional differences in lung. Results: We identified transcriptional profiles significantly associated with sex (215 genes; FDR < 0.05) and age at surgery (217 genes) in non-involved lung tissue resected from 284 lung adenocarcinoma patients. When these profiles were tested in three independent series of non-tumor lung tissue from an additional 1,111 patients, we validated the association with sex and age for 25 and 22 genes, respectively. Among the 17 sex-biased genes mapping on chromosome X, 16 have been reported to escape X-chromosome inactivation in other tissues or cells, suggesting that this mechanism influences lung transcription too. Our 22 age-related genes partially overlap with genes modulated by age in other tissues, suggesting that the aging process has similar consequences on gene expression in different organs. Finally, seven genes whose expression was modulated by sex in non-tumor lung tissue, but no age-related gene, were also validated using publicly available data from 990 lung adenocarcinoma samples, suggesting that the physiological regulatory mechanisms are only partially active in neoplastic tissue. Conclusions: Gene expression in non-tumor lung tissue is modulated by both sex and age. These findings represent a validated starting point for research on the molecular mechanisms underlying the observed differences in the course of lung diseases among men and women of different ages. [ABSTRACT FROM AUTHOR]