Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancy

AIMS AND BACKGROUND: The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. METHODS: In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. RESULTS: Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. CONCLUSIONS: These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice

A comprehensive molecular phylogeny of Afrotropical white-eyes (Aves: Zosteropidae) highlights prior underestimation of mainland diversity and complex colonisation history

White-eyes (Zosterops) are a hyper-diverse genus of passerine birds that have rapidly radiated across the Afrotropics and Southeast Asia. Despite their broad range, a disproportionately large number of species are currently recognised from islands compared to the mainland. Described species-level diversity of this ‘great speciator’ from continental Africa-Arabia is strikingly low, despite the vast size and environmental complexity of this region. However, efforts to identify natural groups using traditional approaches have been hindered by the remarkably uniform morphology and plumage of these birds. Here, we investigated the phylogenetic relationships and systematics of Afrotropical Zosterops, including the Gulf of Guinea and western Indian Ocean islands. We included exceptional sampling (∼160 individuals) from all except one subspecies of the 54 taxa (31 species, plus 22 additional named sub-species) currently recognized throughout the region, in addition to a subset of extra-Afrotropical taxa, by exploiting blood and archival samples. Employing a multi-locus phylogenetic approach and applying quantitative species delimitation we tested: 1) if there has been a single colonisation event of the Afrotropical realm; 2) if constituent mainland and island birds are monophyletic; and 3) if mainland diversity has been underestimated. Our comprehensive regional phylogeny revealed a single recent colonisation of the Afrotropical realm c.1.30 Ma from Asia, but a subsequent complex colonisation history between constituent island and mainland lineages during their radiation across this vast area. Our findings suggest a significant previous underestimation of continental species diversity and, based on this, we propose a revised taxonomy. Our study highlights the need to densely sample species diversity across ranges, providing key findings for future conservation assessments and establishing a robust framework for evolutionary studies

A feature selection approach for identification of signature genes from SAGE data

<p>Abstract</p> <p>Background</p> <p>One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements.</p> <p>Results</p> <p>A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology.</p> <p>Conclusion</p> <p>The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.</p

Development and validation of exhaled breath condensate microRNAs to identify and endotype asthma in children

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment.Authors gratefully acknowledge the funding by Fundação para a Ciência e Tecnologia through the Project NORTE-01-0145-FEDER-000010 - Health, Comfort and Energy in the Built Environment (HEBE), cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Europeu de Desenvolvimento Regional (FEDER) and EXALAR 21 project financed by FEDER/FNR and by Fundação para a Ciência e Tecnologia (EXALAR 21 02/SAICT/2017 - Project nº 30193). FCM kindly acknowledges the scholarship SFRH/BD/144563/2019 granted by Fundação para a Ciência e Tecnologia, as well as the Fulbright Research Grant 2019/2020 granted by Fulbright Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Bound State S-matrix of the Deformed Hubbard Chain

In this work we use the q-oscillator formalism to construct the atypical (short) supersymmetric representations of the centrally extended Uq (su(2|2)) algebra. We then determine the S-matrix describing the scattering of arbitrary bound states. The crucial ingredient in this derivation is the affine extension of the aforementioned algebra.Comment: 44 pages, 3 figures. v2: minor correction

Emancipation under the great recession in Spain.

ABSTRACT: In this paper we document the behavior of emancipation over one of the biggest boom–bust cycles experienced by the Spanish economy. In principle, the economic difficulties faced by the Spanish youth during the last recession would have hampered a normal emancipation pace. However, we find that the proportion living away from parents among those aged 18–40 has not decreased but increased from 44 % during the boom (2005–2008) to 46 % during the bust (2009–2013). A simple decomposition reveals that this is mainly driven by the substantial rise in the emancipation rate among the full-time employed workers during the bust. To explain this change we discuss several factors such as macroeconomic conditions, rental subsidy policy, higher labor mobility, selection bias, reverse causation, timelag in adjustment and secular trend.MEC(IP: María Paz Espinosa Alejos, UPV