Zeolitized tuffs in pedotechnique for quarry restoration: evaluation of phytonutritional efficiency in ^AUP model horizons

A study was started aiming at assessing the suitability of zeolitized tuff as optimal mineral Human Transported Materials (HTMs) in pedotechnologies for quarry restoration

Genetic predictors of response to treatment of chronic hepatitis C virus infection in patients from southern Italy

Various clinical and genetic factors affect response to antiviral treatment of chronic hepatitis C virus (HCV) infection. The IL28B single-nucleotide polymorphism (SNP) rs12979860 is associated with a sustained viral response (SVR), and the suppressor cytokine signaling 3 (SOCS3) gene is over-expressed in HCV-1b non-responders. The aim of this study was to look for correlations between genetic, clinical and viral factors implicated in response to antiviral treatment in chronic HCV infection. We evaluated 190 controls and 148 HCV-infected patients (102 HCV-1 and 46 HCV-2). Demographic, metabolic and histological features related to antiviral treatment were recorded. Univariate and multivariate analyses were used to identify correlations between the genetic and non-genetic features examined and response to antiviral treatment. IL28B expression was higher in CC SNPs versus other alleles in controls (P=0.01) and this difference was associated with viral infection (HCV vs controls P=0.006), particularly in HCV-2 patients (P=0.003). SOCS3 and IL28B expression was correlated with controls (P=0.011), whereas there was an inverse correlation between the expression of the two genes in HCV patients and HCV-1b non-responders (P=0.014 and P=0.03, respectively). Multivariate analysis showed that the only independent SVR predictive factor was rapid virological response. The frequency of IL28B rs12979860 SNP alleles in controls (C allele=71.1% and T allele= 28.9%) was comparable to that of the HCV population (C allele=66.6% and T allele=33.4%). Rapid virological response seems to be the only significant independent predictor of an SVR to antiviral treatment. The inverse correlation between SOCS3 and IL28B expression in genotype 1b non-responders suggests that SOCS3 may affect IL28B expression thereby influencing response to antiviral therapy

Ccdc6 knock-in mice develop thyroid hyperplasia associated to an enhanced CREB1 activity

CCDC6 was originally identified upon rearrangement with RET in human thyroid papillary carcinomas generating the RET/PTC1 oncogene. We have previously reported that CCDC6 interacts with CREB1 and represses its transcriptional activity. Since the function of at least one allele of CCDC6 is lost following RET/PTC1 rearrangements, we aimed at the generation of mice, carrying a CCDC6 mutant gene. Previous studies suggested that the coiled-coil domain of CCDC6, mainly encoded by human exon 2, is required for the protein function. Therefore, we engineered a murine Ccdc6 construct, carrying a deletion of the exon 2, that was able to exert only a mild repression on CREB1 transcriptional activity, with respect to the wild type Ccdc6. Subsequently, we generated Ccdc6-ex2 knock-in mice. These mice developed thyroid hyperplasia associated with an enhanced CREB1 activity and an increased expression of the CREB-1 regulated genes. These results strongly support a CCDC6 promoting role, ascribed to its functional impairment, in the development of thyroid papillary carcinomas harboring the RET/PTC1 oncogene

The cl2/dro1/ccdc80 null mice develop thyroid and ovarian neoplasias

We have previously reported that the expression of the CL2/CCDC80 gene is downregulated in human papillary thyroid carcinomas, particularly in follicular variants. We have also reported that the restoration of CL2/CCDC80 expression reverted the malignant phenotype of thyroid carcinoma cell lines and that CL2/CCDC80 positively regulated E-cadherin expression, an ability that likely accounts for the role of the CL2/CCDC80 gene in thyroid cancer progression. In order to validate the tumour suppressor role of the CL2/CCDC80 gene in thyroid carcinogenesis we generated cl2/ccdc80 knock-out mice. We found that embryonic fibroblasts from cl2/ccdc80(-/-) mice showed higher proliferation rate and lower susceptibility to apoptosis. Furthermore, cl2/ccdc80(-/-) mice developed thyroid adenomas and ovarian carcinomas. Finally, ret/PTC1 transgenic mice crossed with the cl2/ccdc80 knock-out mice developed more aggressive thyroid carcinomas compared with those observed in the single ret/PTC1 transgenic mice. Together, these results indicate CL2/CCDC80 as a putative tumour suppressor gene in human thyroid carcinogenesis

Hypomorphic mutations of SEC23B gene account for mild phenotypes of congenital dyserythropoietic anemia type II

AbstractCongenital dyserythropoietic anemia type II, a recessive disorder of erythroid differentiation, is due to mutations in SEC23B, a component of the core trafficking machinery COPII. In no case homozygosity or compound heterozygosity for nonsense mutation(s) was found. This study represents the first description of molecular mechanisms underlying SEC23B hypomorphic genotypes by the analysis of five novel mutations. Our findings suggest that reduction of SEC23B gene expression is not associated with CDA II severe clinical presentation; conversely, the combination of a hypomorphic allele with one functionally altered results in more severe phenotypes. We propose a mechanism of compensation SEC23A-mediated which justifies these observations

miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene

We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity

Successful hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia type II

Abstract CDA are a group of inherited, rare diseases that are characterized by dyserythropoiesis and ineffective erythropoiesis associated with transfusion dependency in approximately 10% of cases. For these latter patients, the only curative treatment is HSCT. There are very limited data on HSCT experience in this rare disease. Herein, we report a five-yr six-month-old girl with compound heterozygous mutations in SEC23B gene, who was diagnosed to have CDA type II and underwent successful HSCT from her matched sibling donor.Wo

Zeolitized tuffs in pedotechnique for the reclamation of abandoned quarries: a case study in the Campania region (Italy)

The present study aims to assess the evolution of different proto-horizons as embryonic soils built by pedotechnologies for the reclamation and management of derelict and damaged lands, such as abandoned quarries. The model proto-horizons were assembled by utilizing coarse limestone gravel or zeolitized Phlegraean Yellow Tuff (PYT) as mineral components and commercial compost-amendments or a phosphorite-poultry manure mixture as organic matrices for growth of a pasture-grass under controlled conditions. The evolution of the model proto-horizons was followed by an evaluation of the stability and modification of the organic matter (OM) with reference to plant development. The results suggest that the natural carbonatic substrate occurring in limestone quarries was unable to sustain significant plant growth, while the PYT was suitable and efficient as a pedogenic substrate because it supported plant growth and induced a conspicuous accumulation of OM due to root activity. In particular, OM, including humic and non-humic components, greatly increased in the PYT treatment with the phosphorite-poultry manure mixture showing a concurrent trend toward humification. Conversely, an overall tendency toward degradation of OM was detected in the PYT model proto-horizon treated with commercial compost. Feasibility estimates show that quarry restoration costs appear reasonable where environmental impacts are high

Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low-and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients