Constitutively Activated PI3K Accelerates Tumor Initiation and Modifies Histopathology of Breast Cancer

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α had predominantly sarcomatoid features, whereas two copies of myr-p110α resulted in tumors with a carcinoma phenotype. This novel model provides experimental support for importance of active p110α in breast tumor initiation, and shows that the amount of PI3K activity can affect the rate of tumor initiation and modify the histological phenotype of breast cancer

Satb1 overexpression drives tumor-promoting activities in cancer-associated dendritic cells

Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.Fil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Perales Puchal, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Payne, Kyle K.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Wickramasinghe, Jayamanna. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Tchou, Julia. University of Pennsylvania; Estados UnidosFil: Borowsky, Mark E.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Conejo Garcia, José R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unido

Silicon quantum dots in photovoltaic devices: device fabrication, characterization and comparison of materials

The realization of crystalline silicon tandem solar cells relies on silicon nanocrystal (Si NC) quantum dots as the absorber of the top solar cell. Quantum confinement of charge carriers within the nanocrystals permits to achieve a band gap up to 2 eV which can be adjusted according to the size of the nanocrystals. This enables the construction of all-crystalline Si tandem solar cells, and increases the theoretical efficiency limit from 33 % to 42.5 % due to the addition of a second band gap. In this work, the electrical and photovoltaic properties of Si NC films are assessed and the most prominent material systems (SiO2, Si3N4, SiC) are compared. P-i-n solar cells are presented which feature Si NC as the intrinsic absorber layer and permit to characterize quantum confinement electrically on device level. P-i-n solar cells with Si NC in SiC in the i-region have yielded open circuit voltages of up to 370mV

Plant communities of Italy. The vegetation prodrome

The Vegetation Prodrome of Italy was promoted in 2012 by the Italian "Ministry of Environment, Land and Sea Protection", in collaboration with the "Italian Society of Botany", to provide a comprehensive and systematic catalogue and description of Italian plant communities. The Prodrome that is presented in this paper is the first full organic synthesis of the vegetation of Italy at the alliance syntaxonomic level. It fulfils several needs, the main one being a unified and comprehensive national framework that may make an important contribution to the definition of the European Vegetation Prodrome. Syntaxonomy, as well as taxonomy, is sometimes based on considerations that may in part diverge: several authors tend to favour models that are divisive or aggregative to a greater or lesser extent in terms of flora, biogeography and ecology. These different points of view stimulate the scientific debate and allow the adoption of a framework that is more widely supported. The Prodrome includes 75 classes, 2 subclasses, 175 orders, 6 suborders and 393 alliances. The classes were grouped into nine broad categories according to structural, physiognomic and synecological elements rather than to syntaxonomic criteria. The rank, full valid name, any synonymies and incorrect names are provided for each syntaxon. The short declaration highlights the physiognomy, synecology, syndynamics and distribution of the plant communities that belong to the syntaxon. The Prodrome of the Italian Vegetation is linked to the European Strategy for Biodiversity, the European Habitats Directive and the European Working Groups related to the ecosystems and their services. In addition to basic applications, the Prodrome can be used as a framework for scientific research related to the investigation of the relationships between plant communities and the environmental factors that influence their composition and distribution

Is it the Income Distribution or Redistribution that Affects Growth?

Hervorming Sociale Regelgevin

the forest vegetation of the tolfa ceriti mountains northern latium central italy

The Forest Vegetation of the Tolfa-Ceriti Mountains (Northern Latium - Central Italy)The forests of the Tolfa-Ceriti mountains (Latium, central Italy) were investigated through a phytosociological approach. 249 relevés were performed and treated with multivariate analysis. 13 woodland communities were identified, of which 7 belong toQuercetalia pubescenti-petraeae, 1 toFagetalia sylvaticae, 1 toPopuletaliaand 4 toQuercetalia ilicis. The thermophilous Turkey oak-forests occurring on the trachytic hills of the Ceriti Mountains and on the flysch substrates of the Tolfa Mountains were included inRubio peregrinae-Quercetum cerridisass. nova.Quercus cerrisandFraxinus angustifoliasubsp.oxycarpawoodland communities of the footslopes have been ascribed toFraxino oxycarpae-Quercetum cerridis, while the widespread mesophilus Turkey oak forests have been ascribed toMelico-Quercetum cerridis. Cephalantero longifoliae-Quercetum cerridishas been restricted to acid and oligotrophic soils.Quercus petraeawoodlands, occurring on trachytic substrates have been described as a new association namedCarici olbiensis-Quercetum petraeaeass. nova. All these mixed oak woods have been included in the allianceCrataego laevigatae-Quercion cerridisArrigoni 1997. The nomenclatural problems concerning the prior nameTeucrio siculi-Quercion cerridisUbaldi 1988 are also discussed. The beech forests of the higher altitudes have been included inFraxino orni-Fagetum sylvaticae, while theAlnus glutinosaravine woodlands have been described as belonging to the new associationPolysticho setiferi-Alnetum glutinosae. Secondary communities ofAcer monspessulanumandAcer campestredeveloped on flysch substrates, and ofErica arboreaandArbutus unedo(Erico-Arbutetum unedonis) developed on trachytic substrates, have also been identified. Finally two types ofQuercus ilexwood have been identified:Cyclamino repandi-Quercetum ilicis, on sandstones, and the new associationArbuto unedonis-Quercetum ilicisass. nova on volcanic soils. This latter community can be considered as a coenological and geographical vicariant in central Italy of the sicilianErico-Quercetum ilicis