Combining the conservation of biodiversity with the provision of ecosystem services in urban green infrastructure planning. Critical features arising from a case study in the metropolitan area of Rome

A large number of green infrastructure (GI) projects have recently been proposed, planned and implemented in European cities following the adoption of the GI strategy by the EU Commission in 2013. Although this policy tool is closely related to biodiversity conservation targets, some doubts have arisen as regards the ability of current urban GI to provide beneficial effects not only for human societies but also for the ecological systems that host them. The aim of this work is to review the features that should be considered critical when searching for solutions that simultaneously support biodiversity and guarantee the provision of ecosystem services (ES) in urban areas. Starting from a case study in the metropolitan area of Rome, we highlight the role of urban trees and forests as proxies for overall biodiversity and as main ecosystem service providers. We look beyond the individual functional features of plant species and vegetation communities to promote the biogeographic representativity, ecological coherence and landscape connectivity of new or restored GI elements

MESENCHYMAL FEATURES MEDIATED BY TWIST1 IN COLORECTAL CANCER CELLS AND MICROENVIRONMENT

Background. Colorectal cancer (CRC) is a major cause of death for cancer in western countries, ranking third in both sexes. Therapeutic developments in the past decades have extended life expectancy in patients with advanced disease (i.e., stage III), and even for those with distant metastasis (i.e., stage IV). Most treatments for advanced disease nowadays include a combination of chemotherapy with target therapy. Despite advances, the fact that metastatic colorectal cancer remains largely incurable, pushes to pursue a better understanding of the factors underlying cancer progression. Nowadays, a major field of investigation is the relationship between epithelial tumor cells and the surrounding compartment, namely tumor microenvironment, and in particular its contribution to cancer progression. The tumor microenvironment essentially comprises tumor infiltrating cells, vasculature, extracellular matrix, plus other matrix associated molecules. Transformed cells can modulate the functions of stromal cells, likely to facilitate their own growth and survival. In this Darwinian perspective, outgrowth of cancer cells goes together with local changes. Such changes, like clonal ones, are likely progressive, from the stage of local invasion, up to regional lymph-node colonization and finally to the development of distant metastasis. Infiltrating cells are a mix of populations having myeloid or mesenchymal origin, including tumor-associated macrophages, myeloid -derived suppressor cells, mast cells, monocytes, neutrophils, CD3+ T cells, natural killers, dendritic cells, endothelial cells, mesenchymal stem cells and cancer-associated fibroblasts. Taken together, all these players are involved in a double-faced game, in which an anti-tumor effect (such as that exerted by CD3+ cells in early CRC, [1]) is counteracted by a cancer promoting one (e.g., that exerted by macrophages [2]. Currently, this cancer-microenvironment match implies contradictory and controversial data, largely depending upon the investigated cell population and upon the experimental setting. This Ariadnes' thread seems unravelled, mainly because of the contemporaneous evolution of both tumor and microenvironment cells during multi-stage tumor progression. What is certainly perceived today, is that a switch from a genetic to a non-clonal prospective is required to understand tumor evolution. Clearly, the dynamic architecture of the stromal compartment and the interactions therein, need to be reconciled with the evidences concerning genetic irreversible changes in stromal cells. The latter include loss of heterozygosis, microsatellite instability (MSI) [3], trisomy of Chromosome 7 in connective tissues elements of CRC [4], and p53 mutations (in the stroma of breast carcinoma[5]). These surprising results rise the possibility that the stromal compartment contains not only an admixture of non-neoplastic cells, but also cancer cells with an aggressive and invasive phenotype which became able to invade the surrounding tissues by mimicking fibroblast morphology. This metamorphosis would be possible through the re-use of an embryonic program by cancer cells, that is the epithelial to mesenchymal transition (EMT). Originally, in a murine model of spontaneous metastatic breast cancer, Weinberg and Coll. demonstrated that the highest aggressive potential of cancer cell was reached after their transition from an epithelial to a mesenchymal morphology (i.e., EMT), driven by Twist1 gene [6]. Twist1 expression and EMT are strictly associated with the acquisition of a spindle-like fibroblast morphology, the down-regulation of the epithelial marker E-cadherin and the expression of mesenchymal ones (N-cadherin and vimentin), with metastases development, and with the inhibition of the key pathway of senescence p16 driven [7]. Currently, many studies demonstrate that this embryonic program is activated by a set of transcription factors which act pleiotropically. These include Snail, Slug, Zeb1/2, and obviously Twist1. These regulators are expressed in various combination in a number of malignant tumor types and have been shown in experimental models of carcinoma formation to be casually important for programming invasion [8], [9], [10], [11]. The issues. The multi-step process of metastasis development, recapitulated by local invasion, intravasation, extravasation, colonization and growth in distant organs, postulates that cells undergoing EMT should be able to complete each individual step. However, no experimental evidence of the EMT process has been provided for the first step of local invasion (nor for the following ones) in tissues specimens of human malignancies. Similarly, proof of EMT in human epithelial cancer cells remains partial, largely derived from murine models, and based on ectopic expression of EMT regulators, or on stimulation to achieve transient mesenchymal features. Although several studies demonstrate the expression of EMT transcription factors in both the tumoral and stromal compartments of different cancers [12], [13], [14], they do not directly link this expression to the presence of cancer infiltrating cells. The experimental work. We moved from the unexplained evidence of genetic and chromosomal abnormalities in the stromal compartment of solid tumors, and from the role of Twist1 as EMT regulator in cancer cells. Moving by microarray data of a pool of CRC cells, we first show that tumor cells with a permanent mesenchymal signature, in a stable EMT state, can arise from epithelial CRC cells, both in humans and mice. Then we clarify that, within the mesenchymal signature, Twist1 plays a crucial role in the migration and invasion of CRC tumor cells. By a combination of immuno-based and cytogenetic methods we detected in human CRC a Twist1+subpopulation of stromal cells, with a mesenchymal phenotype. This subpopuation was more represented in MS-stable CRC than in less metastatic MS-unstable CRC, and was associated with advanced CRC stage and with worse survival. Additionally, we showed that Twist1 transcript is degraded in MSI CRC, due to a frameshifted 3\u2019-UTR, and propose that this mechanism contributes to the low capability of MSI CRC to exploit EMT to undergo metastasis. Finally, we identified Twist1+, stromal cells which share genetic changes with epithelial cancer cells, establishing a genetic link between epithelial and mesenchymal components of CRC. In summary, we provide data from an original cellular model to tissue studies to prove the occurrence of EMT in human CRC. We demonstrated the presence of tumor cells in the stroma of CRC tumors and we give a method to identify those cells undergone to EMT and able to invade the surrounding tissues. Thus, our results readdress the study approach to the stromal compartment from that of a recipient of non-neoplastic cells to an incubator of cancer EMT cells able to disrupt tissues by mimicking activated fibroblast. The experimental demonstration of human CRC in stable EMT, coupled to the identification of previously postulated tumor cells with mesenchymal morphology in the stromal compartment, add substantial evidence to EMT, translating a model it into a real phenomenon contributing to the metastatic process of human CRC. In a clinical perspective, our study highlights the importance to re-evaluate the target therapy of solid tumors from the epithelial compartment to include the mesenchymal one

Towards alien plant prioritization in Italy: methodological issues and first results

In recent decades, multiple actions have been taken to counteract the relentless expansion of invasive alien species as well as to gain a better understanding of their effects on ecosystems. Here, we describe the approach designed by the Italian Botanical Society that is aimed at selecting a list of candidate alien plants to be subjected to a prioritization procedure. We selected a total of 96 species on the basis of data related to their occurrence on both a national and regional scale, their invasiveness and their potential to invade plant communities and/or habitats of community concern. This list represents the first result obtained by applying this standardized workflow and is a first step towards the identification of those alien species that should be included in the national list according to Regulation (EU) n. 1143/2014

MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

View the MathML source: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. View the MathML source: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor \u3b2 receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. View the MathML source: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. View the MathML source:ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer

IBIS/PICsIT in-flight performances

PICsIT (Pixellated Imaging CaeSium Iodide Telescope) is the high energy detector of the IBIS telescope on-board the INTEGRAL satellite. PICsIT operates in the gamma-ray energy range between 175 keV and 10 MeV, with a typical energy resolution of 10% at 1 MeV, and an angular resolution of 12 arcmin within a \~100 square degree field of view, with the possibility to locate intense point sources in the MeV region at the few arcmin level. PICsIT is based upon a modular array of 4096 independent CsI(Tl) pixels, ~0.70 cm^2 in cross-section and 3 cm thick. In this work, the PICsIT on-board data handling and science operative modes are described. This work presents the in-flight performances in terms of background count spectra, sensitivity limit, and imaging capabilities.Comment: 8 pages, 4 figures. Accepted for publication on A&A, special issue on First Science with INTEGRA

Combined low densities of FoxP3+ and CD3+ tumor-infiltrating lymphocytes identify stage II colorectal cancer at high risk of progression

The densities of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs), combined with TNM (tumor-node-metastasis) staging, have prognostic value for nonmetastatic colorectal cancer (CRC) patients. We compared the prognostic value of CD3+ and FoxP3+ TILs at the invasive front, TNM classifiers, and microsatellite (MS) status in a trial set of patients with stage II-III CRC (n = 413), by recursive partitioning with a classification and regression tree (CART). Significant prognostic factors and interactions were re-assessed by logistic regression and Cox proportional-hazards modeling in the trial and a validation set (n = 215) of patients with stage II CRC. In the trial set, CART indicated that TIL numbers were of value only in predicting recurrence risk for stage II cancers, where low densities of FoxP3+ TILs ranked first and low densities of CD3+ TILs further stratifiying risk. Multivariate analysis showed that TILs interacted with tumor stage (FoxP3+, P = 0.06; CD3+, P = 0.02) and MS instability (FoxP3+; P = 0.02). In stage II MS-stable cancers, concomitant low densities of both FoxP3+ and CD3+ TILs identified patients with the highest progression risk in the trial (HR 7.24; 95%CI, 3.41-15.4; P < 0.001) and the validation (HR 15.16; 95% IC, 3.43-66.9; P < 0.001) sets. FoxP3+ and CD3+ TIL load in CRC was more informative than other prognostic factors before the cancer progressed to lymph nodes. This prognostic information about TILs, including FoxP3+ cells, suggests that randomized controlled trials might be refined to include interactions between TNM status, molecular classifiers, and post-surgical treatments

Floristic analysis of a high-speed railway embankment in a Mediterranean landscape

We analyzed the floristic composition of a 4.5 km-long segment of a high-speed railway in Lazio, central Italy, which travels on an artificial embankment through an intensively-farmed landscape. In total, 287 vascular plant species were recorded. The life-form distribution was found to be similar to that of the regional species pool, with high percentages of therophytes (38%) and phanerophytes (13%). In the chorological spectrum the Mediterranean floristic element prevailed (44%), while alien species were 8% of the flora. The phytosociological spectrum showed a high diversity of characteristic species from the class Stellarietea mediae or its subordinate syntaxa (26%), and in particular from the order Thero-Brometalia (Mediterranean, sub-nitrophilous annual communities). Species from forest syntaxa had a relatively high diversity (9%). These results suggest that the ecological filtering provided by the Mediterranean regional climate controlled species assemblage even in a completely artificial habitat, preventing floristic homogenization: the flora of the studied railway section is only partially »ruderalized«, while it keeps strong links with the regional (semi-) natural plant communities. However, in contrast to what is observed in central and north Europe, the railway sides studied in the present paper do not seem to represent a refugial habitat for rare species from grassland communities, mainly because in Italy semi-natural dry grasslands are still widely represented

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed