Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases

Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.     

The inhibition of tube formation in a collagen-fibrinogen, three-dimensional gel by cleaved kininogen (HKa) and HK domain 5 (D5) is dependent on Src family kinases

Cleaved high molecular weight kininogen (HKa), as well as its domain 5 (D5), inhibits migration and proliferation induced by angiogenic factors and induces apoptosis in vitro. To study its effect on tube formation we utilized a collagen-fibrinogen, three-dimensional gel, an in vitro model of angiogenesis. HKa, GST-D5 and D5 had a similar inhibitory effect of tube length by 90+/-4.5%, 86+/-5.5% and 77+/-12.9%, respectively. D5-derived synthetic peptides: G440-H455 H475-H485 and G486-K502 inhibited tube length by 51+/-3.7%, 54+/-3.8% and 77+/-1.7%, respectively. By a comparison of its inhibitory potency and its sequences, a functional sequence of HKa was defined to G486-G496. PP2, a Src family kinase inhibitor, prevented tube formation in a dose-dependent manner (100-400 nM), but PP3 at 5 microM, an inactive analogue of PP2, did not. HKa and D5 inhibited Src 416 phosphorylation by 62+/-12.3% and 83+/-6.1%, respectively. The C-terminal Src kinase (Csk) inhibits Src kinase activity. Using a siRNA to Csk, expression of Csk was down-regulated by 86+/-7.0%, which significantly increased tube length by 27+/-5.8%. The addition of HKa and D5 completely blocked this effect. We further showed that HKa inhibited Src family kinase activity by disrupting the complex of uPAR, alphavbeta3 integrin and Src. Our results indicate that the anti-angiogenic effect of HKa and D5 is mediated at least in part through Src family kinases and identify a potential novel target for therapeutic inhibition of neovascularization in cancer and inflammatory arthritis.     

Maternal Control of PIN1 Is Required for Female Gametophyte Development in Arabidopsis

Land plants are characterised by haplo-diploid life cycles, and developing ovules are the organs in which the haploid and diploid generations coexist. Recently it has been shown that hormones such as auxin and cytokinins play important roles in ovule development and patterning. The establishment and regulation of auxin levels in cells is predominantly determined by the activity of the auxin efflux carrier proteins PIN-FORMED (PIN). To study the roles of PIN1 and PIN3 during ovule development we have used mutant alleles of both genes and also perturbed PIN1 and PIN3 expression using micro-RNAs controlled by the ovule specific DEFH9 (DEFIFICENS Homologue 9) promoter. PIN1 down-regulation and pin1-5 mutation severely affect female gametophyte development since embryo sacs arrest at the mono- and/or bi-nuclear stages (FG1 and FG3 stage). PIN3 function is not required for ovule development in wild-type or PIN1-silenced plants. We show that sporophytically expressed PIN1 is required for megagametogenesis, suggesting that sporophytic auxin flux might control the early stages of female gametophyte development, although auxin response is not visible in developing embryo sacs.     

Anadromous trout threatened by whitefish gill‐net fisheries in the northern Baltic Sea

We estimated the effect of the gill‐net fisheries targeted at whitefish (Coregonus sp.) on anadromous sea trout, Salmo trutta, in the Gulf of Bothnia, Baltic Sea using separate data for fish species. The analysis of sea trout captures was based on tagging and recapture data collected in 1998–2011, while whitefish data were derived from individual samples of commercial fisheries from the same period. The mesh sizes used in gill‐net fishing and the seasonal and temporal distributions of recaptured sea trout and sampled whitefish were compared in the northern and southern Gulf of Bothnia. The trout had typically spent 1–2 years at sea, and they were mainly immature with a median body length of 40–43 cm at the time of recapture in gill nets. Despite the increase in the minimum permitted landing size from 40 to 50 cm in 2008, the median length of recaptured trout remained unchanged during the study period. Most (59%) of the gillnetted trout were caught in the southern Gulf of Bothnia in gill nets with mesh sizes of 40–45 mm, which were also used in the whitefish fishery (72%). In the northern Gulf of Bothnia, nets with a smaller mesh size of 25–39 mm took 83% of the whitefish catch and 39% from recaptured trout. In both areas, the overlap in mesh sizes used to gill‐net catch whitefish and sea trout increased during the study period. There were clear seasonal and areal differences in the relative probability of sea trout being captured in gill nets, suggesting that carefully tailored spatial and temporal restrictions on gill‐net fisheries could provide a tool to protect young sea trout without causing intolerable difficulties for the fisheries targeting other species.     

Epichloë endophyte effects on leaf blotch pathogen (Rhynchosporium sp.) of tall fescue (Schedonorus phoenix) vary among grass origin and environmental conditions

ABSTRACT

Background

Systemic Epichloë endophytes are common fungal symbionts of many cool-season grasses. They are known for their capability of increasing host plant tolerance against biotic and abiotic stressors, including grass pathogens. However, results on endophyte-mediated disease resistance have been ambiguous, and the underlying mechanisms of disease resistance remain unknown.     

Bilingual Education: Teachers' Narratives

Bilingual Education: Teachers' Narratives. Nancy Lemberger. Mahwah, NJ: Lawrence Erlbaum Associates, 1997. 206 pp.