Niraparib in ovarian cancer. results to date and clinical potential

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened

DNA methylation alterations caused by Leishmania infection may generate a microenvironment prone to tumour development

DNA methylation is an epigenetic signature consisting of a methyl group at the 5' cytosine of CpG dinucleotides. Modifications in DNA methylation pattern have been detected in cancer and infectious diseases and may be associated with gene expression changes. In cancer development DNA methylation aberrations are early events whereas in infectious diseases these epigenetic changes may be due to host/pathogen interaction. In particular, in leishmaniasis, a parasitic disease caused by the protozoan Leishmania, DNA methylation alterations have been detected in macrophages upon infection with Leishmania donovani and in skin lesions from patients with cutaneous leishmaniasis. Interestingly, different types of cancers, such as cutaneous malignant lesions, lymphoma and hepatocellular carcinoma, have been diagnosed in patients with a history of leishmaniasis. In fact, it is known that there exists an association between cancer and infectious diseases. Leishmania infection may increase susceptibility to develop cancer, but the mechanisms involved are not entirely clear. Considering these aspects, in this review we discuss the hypothesis that DNA methylation alterations induced by Leishmania may trigger tumorigenesis in long term infection since these epigenetic modifications may enhance and accumulate during chronic leishmaniasis

Scuola ed educazione di genere

Affrontare oggi il tema Scuola significa toccare un argomento spinoso. Se poi al tema Scuola abbiniamo quello della Teoria Gender otteniamo binomio oltremodo discusso. Tante, spesso contraddittorie, sono le informazioni che possiamo trovare sul Web e parlare con gli addetti ai lavori è molto difficile. Difficile, ma non impossibile, soprattutto se si fa riferimento alle fonti e agli autori di questa “Buona Scuola”, oggetto dell’ennesima Riforma-Controriforma che si voglia intendere, testo molto discusso nelle piazze d’Italia non solo dai sindacati o dagli insegnanti precari, ma anche dalle associazioni dei genitori

Cyberbullismo 2.0: una ricerca qualitativa del fenomeno

Denso è il dibattito nel mondo scientifico su come l’uso delle tecnologie stia cambiando il modo di approcciarsi all’Altro delle nuove generazioni e di come si sta modificando il loro modus agendi della componente emotiva, sempre più contrassegnata dell’aggressività: il fenomeno del bullismo così come tutte le fenomenologie devianti, messe in atto da minori, destano infatti una preoccupazione crescente. A questa va aggiunta l’apprensione di molti genitori davanti al ‘ritiro sociale’, che sempre più minori adottano per isolarsi dal mondo reale e rifugiarsi in quello virtuale. Strettamente correlato al bullismo, il cyberbullismo consiste in reiterati atteggiamenti e comportamenti finalizzati ad offendere, spaventare, umiliare la vittima tramite mezzi elettronici. Necessaria, quindi si fa un’analisi delle peculiarità possedute dai comportamenti aggressivi online, elementi strettamente connessi alle caratteristica proprie del cyberspace, che possa rendere più preparati, coloro che sono chiamati ad educare

An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that aects social interaction and communication, with restricted interests, activity and behaviors. ASD is highly familial, indicating that genetic background strongly contributes to the development of this condition. However, only a fraction of the total number of genes thought to be associated with the condition have been discovered. Moreover, other factors may play an important role in ASD onset. In fact, it has been shown that parental conditions and in utero and perinatal factors may contribute to ASD etiology. More recently, epigenetic changes, including DNA methylation and micro RNA alterations, have been associated with ASD and proposed as potential biomarkers. This review aims to provide a summary of the literature regarding ASD candidate genes, mainly focusing on synapse formation and functionality and relevant epigenetic and environmental aspects acting in concert to determine ASD onset

PLAGL1 gene function during hepatoma cells proliferation

Hepatocellular carcinoma develops as a multistep process, in which cell cycle deregulation is a central feature, resulting in unscheduled proliferation. The PLAGL1 gene encodes a homonym zinc finger protein that is involved in cell-proliferation control. We determined the genomic profile and the transcription and expression level of PLAGL1, simultaneously with that of its molecular partners p53, PPARγ and p21, in cell-lines derived from patients with liver cancer, during in vitro cell growth. Our investigations revealed that genomic and epigenetic changes of PLAGL1 are also present in hepatoma cell-lines. Transcription of PLAGL1 in tumor cells is significantly lower than in normal fibroblasts, but no significant differences in terms of protein expression were detected between these two cell-types, indicating that there is not a direct relationship between the gene transcriptional activity and protein expression. RT-PCR analyses on normal fibroblasts, used as control, also showed that PLAGL1 and p53 genes transcription occurs as an apparent orchestrated process during normal cells proliferation, which gets disturbed in cancer cells. Furthermore, abnormal trafficking of the PLAGL1 protein may occur in hepatocarcinogenesis.Fil: Vega Benedetti, Ana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Saucedo, Cinthia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Zavattari, Patrizia. University of Cagliari; ItaliaFil: Vanni, Roberta. University of Cagliari; ItaliaFil: Royo, Felix. CIC BioGUNE CIBERehd; EspañaFil: LLavero, Freancisco. Universidad del País Vasco; España. IKERBASQUE; EspañaFil: Zugaza, José L.. Universidad del País Vasco; España. IKERBASQUE; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

Soil bacterial community response to differences in agricultural management along with seasonal changes in a Mediterranean region

Land-use change is considered likely to be one of main drivers of biodiversity changes in grassland ecosystems. To gain insight into the impact of land use on the underlying soil bacterial communities, we aimed at determining the effects of agricultural management, along with seasonal variations, on soil bacterial community in a Mediterranean ecosystem where different land-use and plant cover types led to the creation of a soil and vegetation gradient. A set of soils subjected to different anthropogenic impact in a typical Mediterranean landscape, dominated by Quercus suber L., was examined in spring and autumn: a natural cork-oak forest, a pasture, a managed meadow, and two vineyards (ploughed and grass covered). Land uses affected the chemical and structural composition of the most stabilised fractions of soil organic matter and reduced soil C stocks and labile organic matter at both sampling season. A significant effect of land uses on bacterial community structure as well as an interaction effect between land uses and season was revealed by the EP index. Cluster analysis of culture-dependent DGGE patterns showed a different seasonal distribution of soil bacterial populations with subgroups associated to different land uses, in agreement with culture-independent T-RFLP results. Soils subjected to low human inputs (cork-oak forest and pasture) showed a more stable bacterial community than those with high human input (vineyards and managed meadow). Phylogenetic analysis revealed the predominance of Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes phyla with differences in class composition across the site, suggesting that the microbial composition changes in response to land uses. Taken altogether, our data suggest that soil bacterial communities were seasonally distinct and exhibited compositional shifts that tracked with changes in land use and soil management. These findings may contribute to future searches for bacterial bio-indicators of soil health and sustainable productivity. X Maite Sampedro Pellicer, Affiliation: ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development) Casaccia Research Center, Technical Unit for Sustainable Development and Innovation of Agro-Industrial System, Rome, Italy X Maria Cristiana Papaleo, Affiliation: Laboratory of Microbial and Molecular Evolution, Department of Biology, University of Florence, Florence, Italy X Alessio Mengoni, Affiliation: Laboratory of Microbial and Molecular Evolution, Department of Biology, University of Florence, Florence, Italy X Luigi Ledda, Affiliation: Dipartimento di Agraria, University of Sassari, Sassari, Italy X Renato Fani, Affiliation: Laboratory of Microbial and Molecular Evolution, Department of Biology, University of Florence, Florence, Italy X Anna Benedetti, Affiliation: Consiglio per la Ricerca e la Sperimentazione in Agricoltura - Research Centre for the Soil-Plant System, Rome, Italy X Claudia Dalmastr

Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue

DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology

Holstein model in infinite dimensions at half-filling

The normal state of the Holstein model is studied at half-filling in infinite dimensions and in the adiabatic regime. The dynamical mean-field equations are solved using perturbation expansions around the extremal paths of the effective action for the atoms. We find that the Migdal-Eliashberg expansion breaks down in the metallic state if the electron-phonon coupling $\lambda$ exceeds a value of about 1.3 in spite of the fact that the formal expansion parameter $\lambda \omega_0/E_F$ ($\omega_0$ is the phonon frequency, $E_F$ the Fermi energy) is much smaller than 1. The breakdown is due to the appearance of more than one extremal path of the action. We present numerical results which illustrate in detail the evolution of the local Green's function, the self-energy and the effective atomic potential as a function of $\lambda$.Comment: Revtex + 17 postscript figures include