Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: an immunohistochemistry study

Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331microM BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N(2)deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10(8) nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10(8) nucleotides, with a median of 75/10(8) nucleotides. PAH-DNA adduct values above 150/10(8) nucleotides were found in eight samples, and in three samples adducts were non-detectable. There was no correlation between PAH-DNA adduct formation and either smoking or case status. Therefore, PAH-DNA adduct formation as measured by this methodology did not appear related to the increased risk of cervical precancer and cancer among carcinogenic HPV-infected smokers.     

<i>Streptomyces</i> PRIO41 as plant growth promoter of jalapeño pepper plants and as biocontrol agent of <i>Fusarium</i>

Chili pepper is one of the main crops of economic importance in Mexico, and Fusarium wilting is a disease that limits its production. In addition, the inappropriate use of agrochemicals in farming activities generate environmental and health problems. Therefore, in this study the effectiveness of Streptomyces sp PRIO41 was evaluated as a (1) biocontrol agent of Fusarium spp and (2) plant growth promoter bacteria. Assays of pathogenicity and virulence of Fusarium spp. in jalapeño pepper seeds, and interactions of these pathogens with Streptomyces PRIO41 were evaluated under two nutritional conditions. In the greenhouse, the effectiveness of Streptomyces sp. PRIO41 was determined as a (1) biocontrol of Fusarium, and (2) plant growth promoter of wilt of pepper plants. The results showed that all fungal isolates caused symptoms in pepper seeds and seedlings with different degrees of virulence. Interactions in vitro showed that Streptomyces showed the most effective range of virulence against Fusarium isolates in the poor medium (37.6%-100%), with fungicidal effects in some cases. In the greenhouse, Streptomyces PRIO41 reduced Fusarium wilting up to a 40%, and positively affected all vegetative growth parameters, particularly plant height, leaf area, root length, and leaf and root dry biomasses. This study showed the potential of Streptomyces PRIO41 as a biocontrol agent of Fusarium spp., and as a biofertilizer of pepper plants.     

Cis-Amide isosteric replacement in thienobenzoxepin inhibitors of PI3-kinase

Substructural class effects surrounding replacement of a ‘cis’ N-methyl aniline amide within potent and selective thienobenzoxepin PI3-kinase inhibitors are disclosed. While a simple aryl to alkyl switch was not tolerated due to differences in preferred amide conformation, heterocyclic amide isosteres with maintained aryl substitution improved potency and metabolic stability at the cost of physical properties. These gains in potency allowed lipophilic deconstruction of the arene to simple branched alkyl substituents. As such, overall lipophilicity-neutral, MW decreases were realized relative to the aniline amide series. The improved properties for lead compound 21 resulted in high permeability, solubility and bioavailability.     

Environmental factors determining the establishment of the African Long‐legged Buzzard Buteo rufinus cirtensis in Western Europe

Winters have become warmer under the impact of climate change, which has modified the phenology as well as the distribution ranges of birds. The African Long‐legged Buzzard Buteo rufinus cirtensis has recently colonized Europe via the Strait of Gibraltar. We aim to explain the native distribution of this species and to predict favourable areas in newly colonized parts of Europe using geospatial modelling to identify the most influential factors in this process. We applied the favourability function, a generalized linear model describing environmental favourability, for the presence/absence of breeding areas in northern Morocco and the southern Iberian Peninsula, according to a set of variables describing climate, topography, human activity, vegetation and purely spatial trends. A model was built using some known breeding sites in northern Morocco, and was used to forecast future suitable breeding areas in Europe. A second model was built with the available data for northern Morocco and Europe to explain the current distribution of breeding sites. Both models were assessed according to discrimination, calibration and parsimony criteria, and the influence of each factor was analysed using variation partitioning. We conclude that the Iberian Peninsula could provide new suitable areas for the species and facilitate its northward expansion. This result, together with the increasing number of records available, suggests that this species could soon spread throughout Europe. Steady temperatures and abundant but seasonally distributed precipitation showed the strongest predictive power in the models. This indicates a close relationship between the species’ distribution and climate in the study area, and suggests that this species finds its most favourable environments in the Mediterranean biome. Topography and vegetation, specifically cliffs and woods near hunting zones, point to a fine‐scale habitat selection for breeding. As the case of the African Long‐legged Buzzard is not a unique event, our results may be useful to determine whether a northward expansion of the Mediterranean biome could be followed by distribution shifts of bird species that have so far been restricted to Africa.     

MET receptor is overexpressed but not mutated in oral squamous cell carcinomas.

Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF-induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive-metastatic behavior.     

Latitudinal trends in breeding waterbird species richness in Europe and their environmental correlates

We analysed the latitudinal trend in the number of breeding waterbird species in Europe using the main river basins as geographic units. The number of breeding waterbird species decreases southward, but this latitudinal trend is composed of two opposed patterns: a southward increase in the number of resident species (RS) and a southward decline in the number of aestival species (SS). Following both a bivariate and a multivariate approach, we tested nine hypotheses about the environmental causes of these trends. Using Partial Regression Analysis and Path Analysis, we found that SS richness depends on the bloom in food availability in areas with high seasonality more than on the other environmental factors; environmental stress due to an excess of energy is the second most important factor involved, whereas the third factor involved in the distribution of SS richness is competition with RS. For RS the factors involved are the climatic stability of the basins and their productivity. We also discuss the suitability of river basins as observational units in this kind of analyses and the marginal influence of their surface area in the latitudinal gradients detected here.