Implementing Smart Specialisation Strategies: A Handbook

Smart Specialisation represents the most comprehensive industrial policy experiment being implemented in Europe. Conceived within the reformed Cohesion policy of the European Commission, Smart Specialisation is a place-based policy promoting economic transformation and investment in innovative activities in selected areas of the socio-economic system in order to achieve a smart, inclusive and sustainable growth. Drawing on empirical evidence, the Smart Specialisation Implementation Handbook is targeted at policy-makers and regional development professionals who are crafting their innovation policy according to a common set of principles and methodologies. The handbook aims at taking stock of the Smart Specialisation experience and presenting its current state of the art, both in terms of conceptual developments and practical implementation. It addresses five key milestones of the implementation process: 1) The Entrepreneurial Discovery Process (EDP) cycle: from priority selection to strategy implementation 2) Good governance: principles and challenges 3) From priorities to projects: selection criteria and selection process 4) Transnational cooperation and value chains 5) MonitoringJRC.B.3-Territorial Developmen

Epigenetic Silencing of Peroxisome Proliferator-Activated Receptor γ Is a Biomarker for Colorectal Cancer Progression and Adverse Patients' Outcome

The relationship between peroxisome proliferator-activated receptor γ (PPARG) expression and epigenetic changes occurring in colorectal-cancer pathogenesis is largely unknown. We investigated whether PPARG is epigenetically regulated in colorectal cancer (CRC) progression. PPARG expression was assessed in CRC tissues and paired normal mucosa by western blot and immunohistochemistry and related to patients' clinicopathological parameters and survival. PPARG promoter methylation was analyzed by methylation-specific-PCR and bisulphite sequencing. PPARG expression and promoter methylation were similarly examined also in CRC derived cell lines. Chromatin immunoprecipitation in basal conditions and after epigenetic treatment was performed along with knocking-down experiments of putative regulatory factors. Gene expression was monitored by immunoblotting and functional assays of cell proliferation and invasiveness. Methylation on a specific region of the promoter is strongly correlated with PPARG lack of expression in 30% of primary CRCs and with patients' poor prognosis. Remarkably, the same methylation pattern is found in PPARG-negative CRC cell lines. Epigenetic treatment with 5′-aza-2′-deoxycytidine can revert this condition and, in combination with trichostatin A, dramatically re-activates gene transcription and receptor activity. Transcriptional silencing is due to the recruitment of MeCP2, HDAC1 and EZH2 that impart repressive chromatin signatures determining an increased cell proliferative and invasive potential, features that can experimentally be reverted. Our findings provide a novel mechanistic insight into epigenetic silencing of PPARG in CRC that may be relevant as a prognostic marker of tumor progression

Notulae to the Italian native vascular flora: 8

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions for taxa in the genera Ajuga, Chamaemelum, Clematis, Convolvulus, Cytisus, Deschampsia, Eleocharis, Epipactis, Euphorbia, Groenlandia, Hedera, Hieracium, Hydrocharis, Jacobaea, Juncus, Klasea, Lagurus, Leersia, Linum, Nerium, Onopordum, Persicaria, Phlomis, Polypogon, Potamogeton, Securigera, Sedum, Soleirolia, Stachys, Umbilicus, Valerianella, and Vinca. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1

Compétition bactérienne dans la colonisation de la muqueuse nasale chez l'homme : rôle de la compétition d'adhésion sur les éléments de la matrice extracellulaire

REIMS-BU Santé (514542104) / SudocSudocFranceF

Pure shear dominated high-strain zones in basement terranes

High-strain zones are common in basement terranes, and understanding their tectonic significance requires quantitative knowledge of deformation kinematics. We report on strained rocks from different tectonic settings that record pure shear dominated (W m \u3c 0.4) deformations. Mylonitic rocks derived from Mesoproterozoic basement granitoids are exposed in the Lawhorne Mill high-strain zone in the Virginia Blue Ridge. Chemical and mineralogical differences between the leucogranitoid protolith and mylonite are consistent with ∼50% volume loss during deformation. Minimum finite strains in XZ sections range from 4:1 to 7:1, and three-dimensional strains plot in the field of apparent flattening; however, with volume loss these rocks likely experienced bulk plane strain. The R s /Θ and quartz c-axis vorticity gauges yield Wm values of 0.0-0.6. Fabric asymmetries normal to both foliation and lineation are consistent with modest triclinic deformation symmetry. Mylonitic rocks from the Lawhorne Mill high-strain zone record a pure shear dominated deformation that produced ∼70% contraction across the zone with only minimal displacement parallel to the zone (\u3c0.5 km). Pure shear dominated high-strain zones occur in a variety of mid-crustal settings. Ultramylonites from metamorphic core complexes in Arizona record very low vorticity values (W m \u3c 0.4). Well-foliated, steeply dipping, upper amphibolite facies rocks from the Coast shear zone in British Columbia are characterized by orthorhombic fabrics formed during pure shear dominated deformation that accommodated crustal contraction. These zones differ from simple and general shear zones because displacement across these zones is minimal relative to the overall finite strain. However, zonenormal shortening and zone-parallel stretching are significant in pure shear dominated zones. Steeply dipping zones formed in contractional settings serve to effectively shorten and thicken the crust across basement massifs, whereas gently dipping zones formed in extensional settings thin the crust. © 2007 The Geological Society of America. All rights reserved

MicroRNA-130b Promotes Tumor Development and Is Associated with Poor Prognosis in Colorectal Cancer

MicroRNA-130b (miR-130b) is involved in several biologic processes; its role in colorectal tumorigenesis has not been addressed so far. Herein, we demonstrate that miR-130b up-regulation exhibits clinical relevance as it is linked to advanced colorectal cancers (CRCs), poor patients' prognosis, and molecular features of enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. miR-130b high-expressing cells develop large, dedifferentiated, and vascularized tumors in mouse xenografts, features that are reverted by intratumor injection of a specific antisense RNA. In contrast, injection of the corresponding mimic in mouse xenografts from miR-130b low-expressing cells increases tumor growth and angiogenic potential while reduces the epithelial hallmarks. These biologic effects are reproduced in human CRC cell lines. We identify peroxisome proliferator-activated receptor γ (PPARγ) as an miR-130b direct target in CRC in vitro and in vivo. Notably, the effects of PPARγ gain- and loss-of-function phenocopy those due to miR-130b down-regulation or up-regulation, respectively, underscoring their biologic relevance. Furthermore, we provide mechanistic evidences that most of the miR-130b-dependent effects are due to PPARγ suppression that in turn deregulates PTEN, E-cadherin, Snail, and vascular endothelial growth factor, key mediators of cell proliferation, EMT, and angiogenesis. Since higher levels of miR-130b are found in advanced tumor stages (III–IV), we propose a novel role of the miR-130b-PPARγ axis in fostering the progression toward more invasive CRCs. Detection of onco-miR-130b and its association with PPARγ may be useful as a prognostic biomarker. Its targeting in vivo should be evaluated as a novel effective therapeutic tool against CRC

Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism

The circadian gene Timeless (TIM) provides a molecular bridge between circadian and cell cycle/DNA replication regulatory systems and has been recently involved in human cancer development and progression. However, its functional role in colorectal cancer (CRC), the third leading cause of cancer-related deaths worldwide, has not been fully clarified yet. Here, the analysis of two independent CRC patient cohorts (total 1159 samples) reveals that loss of TIM expression is an unfavorable prognostic factor significantly correlated with advanced tumor stage, metastatic spreading, and microsatellite stability status. Genome-wide expression profiling, in vitro and in vivo experiments, revealed that TIM knockdown induces the activation of the epithelial-to-mesenchymal transition (EMT) program. Accordingly, the analysis of a large set of human samples showed that TIM expression inversely correlated with a previously established gene signature of canonical EMT markers (EMT score), and its ectopic silencing promotes migration, invasion, and acquisition of stem-like phenotype in CRC cells. Mechanistically, we found that loss of TIM expression unleashes ZEB1 expression that in turn drives the EMT program and enhances the aggressive behavior of CRC cells. Besides, the deranged TIM-ZEB1 axis sets off the accumulation of DNA damage and delays DNA damage recovery. Furthermore, we show that the aggressive and genetically unstable 'CMS4 colorectal cancer molecular subtype' is characterized by a lower expression of TIM and that patients with the combination of low-TIM/high-ZEB1 expression have a poorer outcome. In conclusion, our results as a whole suggest the engagement of an unedited TIM-ZEB1 axis in key pathological processes driving malignant phenotype acquisition in colorectal carcinogenesis. Thus, TIM-ZEB1 expression profiling could provide a robust prognostic biomarker in CRC patients, supporting targeted therapeutic strategies with better treatment selection and patients' outcomes

Notulae to the Italian native vascular flora: 7

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations and status changes to the Italian administrative regions for taxa in the genera Acer, Alchemilla, Andrachne, Bromus, Clinopodium, Colchicum, Damasonium, Erodium, Festuca, Hieracium, Hyparrhenia, Ipomoea, Linaria, Lolium, Narcissus, Ranunculus, Sisymbrium, Stipa, Valerianella, Vicia, and Zannichellia. New combinations in the genus Ziziphora (Z. sardoa and Z. corsica) and the new subspecies Ulmus minor susbp. canescens are proposed. Furthermore, the name Calamintha alpina var. sardoa is here lectotypified. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1