80 research outputs found
Costruzioni di paglia
No full textL’uso delle balle di paglia come materiale da costruzione si sta iniziando a diffondere anche in Italia. Questo materiale presenta un basso valore di trasmittanza termica e di conseguenza ben si allinea con l’attuale necessità di avere una struttura poco disperdente. Prove sperimentali hanno dimostrato che un muro in balle di paglia con pochi centimetri di intonaco presenta un basso rischio d’incendio. Negli ultimi anni si sta inoltre iniziando a porre il problema del comportamento sismico di queste costruzioni. Test sperimentali, condotti presso l’Università del Nevada, mostrano che tali strutture hanno una buona capacità di assorbire tali azioni senza collassare. In questo lavoro si riportano i risultati di una indagine sperimentale condotta, presso il Laboratorio di Strutture e Prove Materiali del Dipartimento di Ingegneria Civile dell’Università degli Studi di Roma “Tor Vergata”, su muretti a singola e a doppia balla di paglia impilate una sull’altra, con e senza intonaco. Tutti gli elementi testati sono stati sottoposti a un carico statico incrementale di compressione applicato con un martinetto elettromeccanico e diffuso uniformemente attraverso una piattaforma lignea
MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad
No full textDeregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as "cell competition". With regard to this intimate and dual relationship between MYC and cell death, recent evidence obtained in Drosophila models of cancer has revealed that, in early tumourigenesis, MYC upregulation guides the clonal expansion of mutant cells, while the surrounding tissue undergoes non-cell autonomous death. Apoptosis inhibition in this context was shown to restrain tumour growth and to restore a wild-type phenotype. This suggests that cell-autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may shape tumour growth in different ways, soliciting the need to reconsider the role of cell death in cancer in the light of this new level of complexity. Here we review recent literature about MYC and cell competition obtained in Drosophila, with a particular emphasis on the relevance of cell death to cell competition and, more generally, to cancer. Possible implications of these findings for the understanding of mammalian cancers are also discussed
Enzimi cellulosolitici e competizione per la paglia tra Rhizoctonia solani e due isolati di Trichoderma antagonisti.
No full textNel presente lavoro è stata valutata la capacità di produrre enzimi coinvolti nella degradazione della cellulosa da parte di due isolati fungini antagonisti appartenenti al genere Trichoderma (Trichoderma virens I10 e T. asperellum I252) e da parte di un isolato fitopatogeno di Rhizoctonia solani.
L’idrolisi della cellulosa da parte dei funghi prevede l’azione successiva di tre enzimi: le endoglucanasi che scindono in modo casuale i legami interni β-1,4 liberando molecole di glucosio e cello-oligosaccaridi, le esoglucanasi che attaccano la porzione terminale non riducente della cellulosa liberando cellobiosio e, infine, le β-glucosidasi che liberano due monomeri di glucosio per ogni molecola di cellobiosio prodotta.
Al fine di indurre la produzione degli enzimi cellulosolitici, nelle prove allestite sono state utilizzate porzioni di paglia di grano (Triticum aestivum L.), precedentemente sterilizzate, come fonte naturale di cellulosa. I saggi enzimatici sono stati condotti al fine di individuare l’attività delle cellulasi (EC 3.2.1), delle esoglucanasi (EC 3.2.1.91), endoglucanasi (EC 3.2.1.4) e delle β-glucosidasi (EC 3.2.1.21) in presenza del substrato, confrontando i valori con quelli ottenuti inoculando i funghi su mezzo minerale (Fries) contenente saccarosio come fonte di carbonio. Le attività enzimatiche sono state valutate dopo 9, 12 e 18 giorni d’incubazione ed espresse come U/mL. Al fine di valutare l’accrescimento fungino, è stato determinato il contenuto di proteine miceliari e di proteine totali o solubili, espresse in mg/mL, agli stessi intervalli di tempo. I risultati ottenuti sono riconducibili a due esperimenti indipendenti, condotti durante l’estate 2004.
In generale, in presenza di paglia, rispetto al Fries, i tre isolati hanno mostrato un maggiore accrescimento (espresso come proteine miceliari) senza significative differenze tra isolati.
I dati ottenuti mediante il saggio dell’attività della β-glucosidasi non hanno mostrato differenze statisticamente significative tra i tre isolati.
Dall’analisi della varianza condotta sui dati ottenuti per le esoglucanasi, l’attività è risultata significativamente superiore su paglia rispetto al Fries. Non sono state registrate differenze tra i due isolati antagonisti, sebbene i due Trichoderma abbiano mostrato valori statisticamente superiori rispetto a R. solani. Infine, dall’analisi della varianza dei valori dell’attività dell’endoglucanasi emerge che solamente l’interazione isolato x substrato risulta significativa. Su paglia R. solani presenta un’attività molto bassa rispetto agli isolati di Trichoderma mentre, su Fries, tale attività è decisamente superiore.
Al fine di valutare un’eventuale competizione per la paglia, è stata misurata la Capacità Competitiva Saprofitica (CSA) di T. virens I10, T. asperellum I252 e R. solani, utilizzando pezzetti di paglia come esca. La CSA dei due antagonisti è stata valutata in base alla loro capacità di ridurre la colonizzazione dell’esca da parte di R. solani. Questo isolato è apparso molto rapido nel reagire alla presenza del substrato e, quando inoculato da solo, è stato capace di colonizzare quasi il 100% dei pezzetti di paglia già dopo due giorni di incubazione. Entrambi gli antagonisti sono apparsi in grado di competere con R. solani per il possesso della paglia, anche se limitatamente nel tempo. La popolazione di R. solani ha subito una diminuzione fino all’ottavo giorno di incubazione in presenza di I252 e fino al decimo in presenza di I10. Successivamente, la colonizzazione delle esche da parte di R. solani è nuovamente aumentata anche se a livelli diversi in funzione dell’antagonista presente; nelle tesi contenenti I10 o i due antagonisti insieme sono state registrate percentuali di colonizzazione simili quelle del patogeno da solo, mentre la presenza di I252 ha mantenuto la colonizzazione della paglia da parte di R. solani a livelli inferiori per tutta la durata dell’esperimento.
Da un punto di vista ecologico, R. solani è definito un ruderale (R-selected) e stress-tollerante. Il genere Trichoderma è considerato sia ruderale (R-selected) per la capacità di colonizzare i residui di paglia, ma anche combattivo (C-selected) in quanto capace di mantenere il possesso del substrato o di colonizzare le esche precedentemente occupate dal patogeno. I risultati da noi ottenuti confermano le capacità combattive di Trichoderma in quanto in grado di sostituirsi nella paglia a Rhizoctonia solani, ma anche quella ruderale, visto che a tempi più lunghi la paglia è colonizzata nuovamente da Rhizoctonia solani, che ha come strategia secondaria la tolleranza agli stress
A neurogenic model of adult brain cancer in the fly
No full textInactivation of the tumour suppressor gene PTEN is prevalent in primary Glioblastoma. In mammals, PTEN loss has been associated with the failure of a specific molecular axis, including aPKC and Lgl, responsible for the maintenance of the Glioblastoma Stem Cells (GSCs), a reservoir of self-sustaining cells with characteristics similar to neural progenitors.
Here we developed a neurogenic model of Drosophila brain cancer based on the dysfunction of the PTEN-aPKC-Lgl axis in type II neuroblasts (NB), whose differentiation proceeds through transit-amplifying intermediate precursors, as it is for mammalian neural progenitors. We obtained neurogenic tumours that express high levels of MYC, keep growing in the adult and lead the animal to premature death, summarising several traits typical of human brain cancers.
Recently, our laboratory has demostrated that the physiological phenomenon called MYC-Mediated Cell Competition (MMCC) is conserved in human cancers, where malignant cells are likely to use MYC activity to colonise the organ. Preliminary data will be presented about a possible correlation between MMCC and cell division in brain cancer development
DataSheet1_Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models.pdf
No full textTumor cells exploit multiple mechanisms to evade apoptosis, hence the strategies aimed at reactivating cell death in cancer. However, recent studies are revealing that dying cells play remarkable pro-oncogenic roles. Among the mechanisms promoting cell death, cell competition, elicited by disparities in MYC activity in confronting cells, plays the primary role of assuring tissue robustness during development from Drosophila to mammals: cells with high MYC levels (winners) overproliferate while killing suboptimal neighbors (losers), whose death is essential to process completion. This mechanism is coopted by tumor cells in cancer initiation, where host cells succumb to high-MYC-expressing precancerous neighbors. Also in this case, inhibition of cell death restrains aberrant cell competition and rescues tissue structure. Inhibition of apoptosis may thus emerge as a good strategy to counteract cancer progression in competitive contexts; of note, we recently found a positive correlation between cell death amount at the tumor/stroma interface and MYC levels in human cancers. Here we used Drosophila to investigate the functional role of competition-dependent apoptosis in advanced cancers, observing dramatic changes in mass dimensions and composition following a boost in cell competition, rescued by apoptosis inhibition. This suggests the role of competition-dependent apoptosis be not confined to the early stages of tumorigenesis. We also show that apoptosis inhibition, beside restricting cancer mass, is sufficient to rescue tissue architecture and counteract cell migration in various cancer contexts, suggesting that a strong activation of the apoptotic pathways intensifies cancer burden by affecting distinct phenotypic traits at different stages of the disease.</p
A neurogenic model of adult brain cancer in Drosophila
No full textPrimary brain cancers are characterised by high cellular heterogeneity, with a subset of undifferentiated and highly tumourigenic cells responsible for cancer aggressiveness and relapse. Despite obvious anatomical differences between humans and flies, the structural and functional analogy of the respective nervous systems and the conservation of the cellular and molecular aberrations at the basis of the disease make Drosophila an excellent model for human brain cancer. Early inactivation of the tumour suppressor gene PTEN is frequent in primary glioblastoma, the most aggressive form of adult brain cancer whose origin is still controversial. This results in the inhibition of the polarity protein Lgl1 due to aPKC hyper-activation. Dysregulation of this molecular axis is sufficient to reprogramme human neural progenitors into cancer stem cells.
After having confirmed that the PTEN/aPKC/Lgl axis is conserved in Drosophila, we have disrupted it in type II neuroblasts, a cell population with a lineage comparable to that of mammalian neural stem cells, obtaining aggressive tumours that persist and keep growing in the adult leading the animals to premature death. This neurogenic model recapitulates many phenotypic traits of human brain cancers, included high proliferation rate, accumulation of undifferentiated neural cells, local invasiveness and genetic instability. Work in progress and future perspectives will also be presented
Failure of the PTEN/aPKC/Lgl Axis Primes Formation of Adult Brain Tumours in<i>Drosophila</i>
No full textDifferent regions in the mammalian adult brain contain immature precursors, reinforcing the concept that brain cancers, such as glioblastoma multiforme (GBM), may originate from cells endowed with stem-like properties. Alterations of the tumour suppressor genePTENare very common in primary GBMs. Very recently,PTENloss was shown to undermine a specific molecular axis, whose failure is associated with the maintenance of the GBM stem cells in mammals. This axis is composed of PTEN, aPKC, and the polarity determinant Lethal giant larvae (Lgl):PTENloss promotes aPKC activation through the PI3K pathway, which in turn leads to Lgl inhibition, ultimately preventing stem cell differentiation. To find the neural precursors responding to perturbations of this molecular axis, we targeted different neurogenic regions of theDrosophilabrain. Here we show thatPTENmutation impacts aPKC and Lgl protein levels also inDrosophila. Moreover, we demonstrate that PI3K activation is not sufficient to trigger tumourigenesis, while aPKC promotes hyperplastic growth of the neuroepithelium and a noticeable expansion of the type II neuroblasts. Finally, we show that these neuroblasts form invasive tumours that persist and keep growing in the adult, leading the affected animals to untimely death, thus displaying frankly malignant behaviours.</jats:p
A neurogenic model of adult brain cancer in Drosophila
No full textBACKGROUND:
Glioblastoma multiforme (GBM) is the most common and aggressive adult brain tumour, with a subset of cells identified as GBM stem cells (GSCs). These cells are undifferentiated, highly tumourigenic and play an essential role in malignancy. Alterations of the tumour suppressor gene PTEN are prevalent in primary GBM. Recently, PTEN loss has been associated with the deregulation of a specific molecular axis, responsible for the maintenance of GSCs in mammals. This axis consists of PTEN, aPKC and Lethal giant larvae (Lgl). PTEN loss of function promotes aPKC activation, which in turn leads to Lgl inhibition, known to support GSC maintenance.
METHODS:
Despite the anatomical divergence between humans and fly, several aspects of brain development are conserved. In particular, type II neuroblasts (NBs) have a lineage similar as that of the mammalian neural stem cells. We developed a Drosophila brain cancer model based on the deregulation the of PTEN/aPKC/Lgl axis. These proteins are involved in the growth and polarity of NBs and, for this reason, their genetic manipulation may represent a good starting point for investigating the origin of GBM. Dysfunction of this axis has been specifically induced in type II NBs by the use of a binary expression system that allows gene manipulation in defined cell types..
RESULTS:
Here we show that PTEN mutation impacts on aPKC and Lgl protein levels also in Drosophila. Perturbations of this conserved axis in the fly brain cause an accumulation of type II NBs, which form tumours that persist and keep growing in the adult, leading the animals to premature death.
CONCLUSIONS:
Our neurogenic model of adult brain cancer summarises many traits typical of human brain cancers.
We aim at restricting and possibly identifying the NB lineage the most susceptible to PTEN inactivation, in order to gain more knowledge on the origin and biology of GBM
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