Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure

Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.     

Characterization of new microsatellite loci isolated from Santiria trimera (Burseraceae)

? Premise of the study: To study the genetic structure among three morphotypes of an African rainforest tree species, Santiria trimera, nuclear microsatellite markers were isolated and characterized. ? Methods and Results: Seven polymorphic loci were isolated using a pyrosequencing-based protocol and successfully amplified on three different morphotypes of S. trimera. For six of the seven loci, there is at least one private allele for one of the three morphotypes. The mean effective number of alleles is about four for each of the three morphotypes. ? Conclusions: These microsatellite markers are promising to explore the genetic delimitation among sympatric morphotypes found in Gabonese forests and to study the spatial genetic structure within each gene pool.     

Biomechanical analysis of pedalling for rehabilitation purposes: experimental results on two pathological subjects and comparison with non-pathological findings

In this paper the experimental results obtained by means of a prototype measuring device dedicated to the evaluation of the rehabilitation level of the lower limb are presented. The analysis of the experimental data collected on non-pathological subjects allows the identification of the characteristic meaning of the most significant parameters typical of healthy subjects. These data have been employed for a systematic comparison with the same parameters measured on two pathological subjects, in order to define quantitative indicators of the rehabilitation degree of the lower limbs and indicators of the "quality" of the movement.     

Statistical methods in genetics

In recent years, a very large variety of statistical methodologies, at various levels of complexity, have been put forward to analyse genotype data and detect genetic variations that may be responsible for increasing the susceptibility to disease. This review provides a concise account of a number of selected statistical methods for population-based association mapping, from single-marker tests of association to multi-marker data mining techniques for gene-gene interaction detection.     

Design and analysis issues in genome-wide somatic mutation studies of cancer

The availability of the human genome sequence and progress in sequencing and bioinformatic technologies have enabled genome-wide investigation of somatic mutations in human cancers. This article briefly reviews challenges arising in the statistical analysis of mutational data of this kind. A first challenge is that of designing studies that efficiently allocate sequencing resources. We show that this can be addressed by two-stage designs and demonstrate via simulations that even relatively small studies can produce lists of candidate cancer genes that are highly informative for future research efforts. A second challenge is to distinguish mutated genes that are selected for by cancer (drivers) from mutated genes that have no role in the development of cancer and simply happened to mutate (passengers). We suggest that this question is best approached as a classification problem and discuss some of the difficulties of more traditional testing-based approaches. A third challenge is to identify biologic processes affected by the driver genes. This can be pursued by gene set analyses. These can reliably identify functional groups and pathways that are enriched for mutated genes even when the individual genes involved in those pathways or sets are not mutated at sufficient frequencies to provide conclusive evidence as drivers.     

<Emphasis Type="Italic">Isospora lopesi</Emphasis> n. sp. (Apicomplexa: Eimeriidae) from the eastern white-throated spadebill <Emphasis Type="Italic">Platyrinchus mystaceus</Emphasis> Vieillot (Passeriformes: Tyranni: Tyrannidae) in South America

A species of Isospora Schneider, 1881 (Protozoa: Apicomplexa: Eimeriidae) considered as new to science is described and characterised molecularly from the eastern white-throated spadebill Platyrinchus mystaceus Vieillot in the Parque Nacional do Itatiaia, southeastern Brazil. Isospora lopesi n. sp. has oöcysts that are subspheroidal to ovoidal, 18–24 × 18–22 (20.6 × 19.7) µm, with smooth, bilayered wall, c.1.5 μm thick. Micropyle and oöcyst residuum are absent, but one polar granule is present. Sporocysts are ellipsoidal, 12–16 × 8–11 (14.4 × 8.6) µm. The Stieda body is flattened to half-moon-shaped and sub-Stieda body is rounded. Sporocyst residuum is present, consisting of numerous spherules of different sizes. Sporozoites are vermiform with anterior and posterior refractile bodies and nucleus. Molecular analysis was conducted at the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. This new isolate exhibited similarity greater than 98% with Isospora spp. isolates from spectacled warblers Sylvia conspicillata Temminck, 1820. This is the fourth isosporoid coccidian described from New World tyrannid birds, but is the first to have a complementary molecular characterisation.