Indicatori di sostenibilità: la dimensione ‘ambiente’ dello sviluppo sostenibile

Prendendo le mosse dai precedenti studi e progetti di ricerca in tema di indici aggregati di sostenibilità, il presente lavoro ha come obiettivo quello di costruire un indice composito della dimensione ‘Ambiente’ dello sviluppo sostenibile per le regioni italiane, che parte da indicatori elementari di natura ambientale, appropriatamente raggruppati in temi. Una volta definiti gli indicatori elementari, questi vengono normalizzati, ponderati e raggruppati secondo tre livelli di aggregazione: indicatori elementari, indici tematici, indice sintetico di sostenibilità ambientale, EnvIndex. Tale indice è calcolato per le regioni italiane, laddove la maggior parte degli indicatori di sostenibilità sviluppati in letteratura si riferiscono ad un livello di aggregazione territoriale nazionale. La metodologia seguita per la sua costruzione è quella dell’Indice di performance ambientale, che permette di valutare i risultati delle politiche ambientali in termini di percentuale di conseguimento degli obiettivi prefissati, attraverso il metodo della “vicinanza al target”. L’EnvIndex aggrega 23 indicatori elementari, articolati in 4 temi: ‘Qualità dell’ambiente urbano’, ‘Tutela ambientale’, ‘Qualità del suolo’, ‘Qualità dell’acqua’. Ai fini del raggruppamento degli indicatori elementari nei 4 temi e dell’individuazione dei pesi da attribuire a ciascun indicatore nella costruzione degli indici tematici, è stata utilizzata l’analisi delle componenti principali, mentre l’indice sintetico EnvIndex è stato calcolato come somma ponderata dei 4 indici tematici con attribuzione di pesi uguali. Il vincolo costituito dalla difficoltà nel recuperare dati regionali su alcuni aspetti di tali tematiche ha inevitabilmente portato a trascurare elementi rilevanti ai fini della misurazione della sostenibilità ambientale e ciò deve essere tenuto in considerazione nella lettura dei risultati da noi ottenuti. Per questo motivo il presente lavoro si propone principalmente di offrire alcuni strumenti metodologici in tema di costruzione di indicatori sintetici di sostenibilità

Muon Radiography Investigations in Boreholes with a Newly Designed Cylindrical Detector

Muons are constantly produced in cosmic-rays and reach the Earth surface with a flux of about 160 particles per second per square meter. The abundance of muons with respect to other cosmic particles and their capability to cross dense materials with low absorption rate allow them to be exploited for large scale geological or human-made object imaging. Muon radiography is based on similar principles as X-ray radiography, measuring the surviving rate of muons escaping the target and relating it to the mass distribution inside the object. In the course of decades, after the first application in 1955, the methodology has been applied in several different fields. Muography allows us to measure the internal density distribution of the investigated object, or to simply highlight the presence of void regions by observing any excess of muons. Most of these applications require the detector to be installed below the rock being probed. In case that possible installation sites are not easily accessible by people, common instrumentation cannot be installed. A novel borehole cylindrical detector for muon radiography has been recently developed to deal with these conditions. It has been realized with a cylindrical geometry to fit typical borehole dimensions. Its design maximizes the geometrical acceptance, minimizing the dead spaces by the use of arc-shaped scintillators. The details of the construction and preliminary results of the first usage are described in this paper. © 2022 by the authors

CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN

The design, construction and test of a charged particle detector made of scintillation counters read by Silicon Photomultipliers (SiPM) is described. The detector, which operates in vacuum and is used as a veto counter in the NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating charged particles

Analysis of growth factor signaling in genetically diverse breast cancer lines

Background: Soluble growth factors present in the microenvironment play a major role in tumor development, invasion, metastasis, and responsiveness to targeted therapies. While the biochemistry of growth factor-dependent signal transduction has been studied extensively in individual cell types, relatively little systematic data are available across genetically diverse cell lines. Results: We describe a quantitative and comparative dataset focused on immediate-early signaling that regulates the AKT (AKT1/2/3) and ERK (MAPK1/3) pathways in a canonical panel of well-characterized breast cancer lines. We also provide interactive web-based tools to facilitate follow-on analysis of the data. Our findings show that breast cancers are diverse with respect to ligand sensitivity and signaling biochemistry. Surprisingly, triple negative breast cancers (TNBCs; which express low levels of ErbB2, progesterone and estrogen receptors) are the most broadly responsive to growth factors and HER2amp cancers (which overexpress ErbB2) the least. The ratio of ERK to AKT activation varies with ligand and subtype, with a systematic bias in favor of ERK in hormone receptor positive (HR+) cells. The factors that correlate with growth factor responsiveness depend on whether fold-change or absolute activity is considered the key biological variable, and they differ between ERK and AKT pathways. Conclusions: Responses to growth factors are highly diverse across breast cancer cell lines, even within the same subtype. A simple four-part heuristic suggests that diversity arises from variation in receptor abundance, an ERK/AKT bias that depends on ligand identity, a set of factors common to all receptors that varies in abundance or activity with cell line, and an “indirect negative regulation” by ErbB2. This analysis sets the stage for the development of a mechanistic and predictive model of growth factor signaling in diverse cancer lines. Interactive tools for looking up these results and downloading raw data are available at http://lincs.hms.harvard.edu/niepel-bmcbiol-2014/

GRP78 Mediates Cell Growth and Invasiveness in Endometrial Cancer.

Abstract Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown. Here we report that the silencing of GRP78 expression affects both cell growth and invasiveness of Ishikawa and AN3CA cells, analyzed by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell migration assay, respectively. At variance with Ishikawa cells, AN3CA cells showed, besides an endoplasmic reticulum, also a plasma membrane GRP78 localization, evidenced by both immunofluorescence and cell membrane biotinylation experiments. Intriguingly, flow cytometry experiments showed that the treatment with a specific antibody targeting GRP78 C-terminal domain caused apoptosis in AN3CA but not in Ishikawa cells. Induction of apoptosis in AN3CA cells was not mediated by the p53 pathway activation but was rather associated to reduced AKT phosphorylation. Interestingly, immunofluorescence analysis evidenced that endometrioid adenocarcinoma tissues displayed, similarly to AN3CA cells, also a GRP78 plasma membrane localization. These data suggest that GRP78 and its plasma membrane localization, might play a role in endometrial cancer development and progression and might constitute a novel target for the treatment of endometrial cancer

MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner

Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related brain actions. We showed that MDMA dramatically reduced mitochondrial trafficking in hippocampal neurons in a Tau-dependent manner, in which glycogen synthase kinase 3β activity was implicated. Furthermore, we found that these trafficking abnormalities were rescued by over-expression of Mitofusin2 and dynamin-related protein 1, but not of Miro1. Given the relevance of mitochondrial targeting for neuronal function and neurotransmission, our data underscore a novel mechanism of action of MDMA that may contribute to our understanding of how this drug of abuse alters neuronal functioning. © 2014 Springer-Verlag.BFU2008-3980 (“Ministerio de Ciencia e Innovacion” (MICINN), Spain) and a grant from the “Plan Nacional de Drogas” to ES, and by the “Fundação para a Ciência e Tecnologia (FCT),” Portugal (Project PTDC/SAU-FCF/102958/2008), under the framework of the “Programa Operacional Temático Factores de Competitividade (COMPTE) do Quadro Comunitário de Apoio III” and “Fundo Comunitário Europeu (FEDE

The Pervasive Effects of ER Stress on a Typical Endocrine Cell: Dedifferentiation, Mesenchymal Shift and Antioxidant Response in the Thyrocyte

none13noThe endoplasmic reticulum stress and the unfolded protein response are triggered following an imbalance between protein load and protein folding. Until recently, two possible outcomes of the unfolded protein response have been considered: life or death. We sought to substantiate a third alternative, dedifferentiation, mesenchymal shift, and activation of the antioxidant response by using typical endocrine cells, i.e. thyroid cells. The thyroid is a unique system both of endoplasmic reticulum stress (a single protein, thyroglobulin represents the majority of proteins synthesized in the endoplasmic reticulum by the thyrocyte) and of polarized epithelium (the single layer of thyrocytes delimiting the follicle). Following endoplasmic reticulum stress, in thyroid cells the folding of thyroglobulin was disrupted. The mRNAs of unfolded protein response were induced or spliced (X-box binding protein-1). Differentiation was inhibited: mRNA levels of thyroid specific genes, and of thyroid transcription factors were dramatically downregulated, at least in part, transcriptionally. The dedifferentiating response was accompanied by an upregulation of mRNAs of antioxidant genes. Moreover, cadherin-1, and the thyroid (and kidney)-specific cadherin-16 mRNAs were downregulated, vimentin, and SNAI1 mRNAs were upregulated. In addition, loss of cortical actin and stress fibers formation were observed. Together, these data indicate that ER stress in thyroid cells induces dedifferentiation, loss of epithelial organization, shift towards a mesenchymal phenotype, and activation of the antioxidant response, highlighting, at the same time, a new and wide strategy to achieve survival following ER stress, and, as a sort of the other side of the coin, a possible new molecular mechanism of decline/loss of function leading to a deficit of thyroid hormones formation.openUlianich L.; Mirra P.; Garbi C.; Cali G.; Conza D.; Treglia A.S.; Miraglia A.; Punzi D.; Miele C.; Raciti G.A.; Beguinot F.; Consiglio E.; Di Jeso B.Ulianich, L.; Mirra, P.; Garbi, C.; Cali, G.; Conza, D.; Treglia, A. S.; Miraglia, A.; Punzi, D.; Miele, C.; Raciti, G. A.; Beguinot, F.; Consiglio, E.; Di Jeso, B

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMAassociated disruption of Ca2+ homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increasedmitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.Ministerio de Ciencia e Innovacion (MICINN), Spain (BFU2008-3980); Plan Nacional de Drogas, Spain; Fundação para a Ciência e a Tecnologia (Portugal) (FCT)