First evidence of protein modulation by polystyrene microplastics in a freshwater biological model

Microplastics (MPs)are now one of the major environmental problems due to the large amount released in aquatic and terrestrial ecosystems, as well as their diffuse sources and potential impacts on organisms and human health. Still the molecular and cellular targets of microplastics\u2019 toxicity have not yet been identified and their mechanism of actions in aquatic organisms are largely unknown. In order to partially fill this gap, we used a mass spectrometry based functional proteomics to evaluate the modulation of protein profiling in zebra mussel (Dreissena polymorpha), one of the most useful freshwater biological model. Mussels were exposed for 6 days in static conditions to two different microplastic mixtures, composed by two types of virgin polystyrene microbeads (size = 1 and 10 \u3bcm)each one. The mixture at the lowest concentration contained 5 7 105 MP/L of 1 \u3bcm and 5 7 105 MP/L of 10 \u3bcm, while the higher one was arranged with 2 7 106 MP/L of 1 \u3bcm and 2 7 106 MP/L of 10 \u3bcm. Proteomics\u2019 analyses of gills showed the complete lack of proteins\u2019 modulation after the exposure to the low-concentrated mixture, while even 78 proteins were differentially modulated after the exposure to the high-concentrated one, suggesting the presence of an effect-threshold. The modulated proteins belong to 5 different classes mainly involved in the structure and function of ribosomes, energy metabolism, cellular trafficking, RNA-binding and cytoskeleton, all related to the response against the oxidative stress

Expression and subcellular localization of the bromodomain-containing protein 7 is a prognostic biomarker in breast cancer

Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family. Previous studies suggest that BRD7 is predominantly localized in the nucleus, wherein it functions as a transcriptional regulator. Several lines of evidence imply a tumour suppressor function for BRD7. However, the importance of BRD7 in the pathogenesis of breast cancer is not well understood. We have investigated the expression, CpG island methylation and subcellular localization of BRD7 in breast cancer cell lines and clinical cases and thereby assessed its prognostic significance by correlating with clinical-pathological features and time-dependent clinical outcomes. We show that nuclear exclusion of BRD7 occurs commonly in breast cancer and is strongly associated with cases expressing wild-type p53. Moreover, clinical outcomes are significantly less favourable in cases with nuclear exclusion or loss of expression than those in which there is nuclear expression of BRD7. Methylation of the CpG island of BRD7 increases in breast cancer relative to normal breast tissue, but there is not an obvious correlation between methylation and reduced expression or between methylation and clinical outcomes. Overall, our results suggest that nuclear exclusion, rather than transcriptional silencing, is a common mechanism by which the tumour suppressor function of wild-type p53 is inhibited in breast cancer, and show that BRD7 is a promising candidate biomarker in breast cancer

Analysis of new control applications

This document reports the results of the activities performed during the first year of the CRUTIAL project, within the Work Package 1 "Identification and description of Control System Scenarios". It represents the outcome of the analysis of new control applications in the Power System and the identification of critical control system scenarios to be explored by the CRUTIAL project

First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration

Imatinib in combination with everolimus in patients with progressive advanced chordoma: results form an Italian phase 2 clinical trial

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Changing prevalence of asthma in Turin school children between 1994 and 1999

Beckground: Asthma is a widespread chronic disorder in children and its prevalence has been on the increase in Europe. Only few studies have described the prevalence variation in respiratory symptoms in Italian regions. The aim of this study, conducted in Turin during the 1998/1999 school year, is to investigate the distribution of respiratory symptoms in a sample of Turin school children and to compare the obtained results with the findings of the SIDRIA study performed in 1994-95. Methods: the sample in study is composed of all the children attending to three elementary schools in Turin. All of the selected schools had already participated in the 94-95 ISAAC-SIDRIA study. A total of 448 pupils aged 6- 10 years received a standardised questionnaire to be filled by parents. Results: response rate is higher than 97% in all the studies. In 1999 we found that the prevalence of wheezing in the past 12 months was 7.3%. The 13.3% of children had asthma at least once in life and the 5.3% reported an attack in the last year. The comparison of our study results with the ISAACSIDRIA (1994-95) shows that the prevalence of asthma and asthma-like symptoms is rather stable among children, while the prevalence of bronchitis reveals a reduction of about 5.5%, but not statistically significant (p=0.094; 95%CI:-11.9;0.9). A considerable reduction in exposure to parents' passive smoke is shown: ΔP%=-4.7 (95%CI: -9.4;-0.1) for maternal smoking in pregnancy, ΔP%=-8.2 and -15.2, respectively for maternal and paternal smoking in the first two years of life. Conclusions: The results indicate a stable prevalence rate in asthma symptoms in children. A possible explanation of slight variation in asthma prevalence may be due to a reduced exposure to outdoor and indoor risk factors as reported in the questionnaires

Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3

ABSTRACT In normal subjects the main form of circulating insulin-like growth factor (IGF) is the 150-kDa complex. This complex is formed by the IGF peptide, the acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS). Experimental and clinical data have demonstrated that ALS is primarily under the control ofGHand plays a critical role in maintaining constant levels of circulating IGF-I. In this study we evaluated ALS, IGF-I, and IGFBP-1, -2, and -3 in 45 acromegalic patients in basal conditions and, in 37 of these, twice after surgical therapy compared with 100 age- and sex-matched control subjects to estimate their value as parameter of GH secretory state. The results demonstrated that in acromegaly before treatment all parameters (ALS, 523 6 26; IGF-I, 129 6 6; IGFBP-1, 0.7 6 0.1; IGFBP-3, 234 6 21; nmol/L; mean 6 SEM) but IGFBP-2 were significantly different (P , 0.0001) from those in healthy subjects (ALS, 281 6 4; IGF-I, 22 6 1; IGFBP-1, 1.6 6 0.1; IGFBP-3, 91 6 3). IGF-I was more sensitive (100%) than ALS (89%), and both were more predictive of disease status than IGFBP-3, in that 27% of the patients had IGFBP-3 levels within the normal range. Considering the ALS/ IGFBP-3 molar ratio, almost 55% of ALS circulated in a free form in active acromegaly. Before treatment, the IGF-I/IGFBPs (21122 1 23) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 6 0.06; P , 0.0001) compared with that in control subjects (0.23 6 0.01). After surgery, all 10 patients with controlled disease showed normalization of ALS (100% sensitivity), whereas 9 of them had normal IGFBP-3; reevaluation after varying lengths of time showed all these parameters within the normal range. In the 27 patients with active disease, IGF-I and ALS were more predictive of disease status (91% and 83% negative predictive values, respectively) than IGFBP-3 (53%).The basal ALS concentration correlated only with IGFBP-3 (r 5 0.70; P , 0.001). In postsurgery samples (first control) a statistically significant (P , 0.001) correlation was found between mean GH values as well as minimum GH after oral glucose tolerance test and ALS (r 5 0.72 and 0.83, respectively), IGF-I (r 5 0.69 and 0.77), IGFBP-3 (r 5 0.50 and 0.72), and IGFBP-2 (r 5 20.36 and 20.63). Similarly, IGF-I, IGFBP-3, and ALS were positively correlated among themselves and negatively correlated with IGFBP-2 (P , 0.001). In conclusion, in the diagnosis of acromegaly, the measurement of total IGF-I appears to be the most sensitive parameter among the subunits of the 150K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite sensitive and appears to be a useful parameter in reassessment after surgical treatment

Methodologies synthesis

This deliverable deals with the modelling and analysis of interdependencies between critical infrastructures, focussing attention on two interdependent infrastructures studied in the context of CRUTIAL: the electric power infrastructure and the information infrastructures supporting management, control and maintenance functionality. The main objectives are: 1) investigate the main challenges to be addressed for the analysis and modelling of interdependencies, 2) review the modelling methodologies and tools that can be used to address these challenges and support the evaluation of the impact of interdependencies on the dependability and resilience of the service delivered to the users, and 3) present the preliminary directions investigated so far by the CRUTIAL consortium for describing and modelling interdependencies

Sex-specific eNOS activity and function in human endothelial cells

Clinical and epidemiological data show that biological sex is one of the major determinants for the development and progression of cardiovascular disease (CVD). Impaired endothelial function, characterized by an imbalance in endothelial Nitric Oxide Synthase (eNOS) activity, precedes and accelerates the development of CVD. However, whether there is any sexual dimorphism in eNOS activity and function in endothelial cells (ECs) is still unknown. Here, by independently studying human male and female ECs, we found that female ECs expressed higher eNOS mRNA and protein levels both in vitro and ex vivo. The increased eNOS expression was associated to higher enzymatic activity and nitric oxide production. Pharmacological and genetic inhibition of eNOS affected migratory properties only in female ECs. In vitro angiogenesis experiments confirmed that sprouting mostly relied on eNOS-dependent migration in female ECs. At variance, capillary outgrowth from male ECs was independent of eNOS activity but required cell proliferation. In this study, we found sex-specific differences in the EC expression, activity, and function of eNOS. This intrinsic sexual dimorphism of ECs should be further evaluated to achieve more effective and precise strategies for the prevention and therapy of diseases associated to an impaired endothelial function such as CVD and pathological angiogenesis

Electrical Properties of Meso-Porous Silicon: from a surface effect to Coulomb Blockade and more

Abstract: since the Volker Lehmann's paper "Resistivity of Porous Silicon: a surface effect" published in 1995 [1], a great deal of efforts has been produced in understanding the basic mechanisms ruling the electron transport in Si mesostructures and how these phenomena are affected by external environment. After more than 10 years, new experimental evidences and physical insights have been obtained, like gas sensitivity [2], chemisorption phenomena [3], Coulomb blockade [4] and glassy dynamics In the first half of the '90s, the most studied porous silicon morphology was from high resistivity p-type wafers, because of the high luminescence efficiency. The Lehmann's paper on electrical properties of porous silicon from p+ doped wafers, addressed few unanswered crucial questions regarding resistivity, impurity role, carrier freeze out and surface conditioning proposing a microscopic model of transport in mesoPS, in analogy to submicron channels of CMOS devices, whose figures of telegraph noise are affected by single charge trapping at the oxide-semiconductor interface. In 1999, the first report of strong interaction between mesoporous p+ silicon was announced in Strasbourg, EMRS by our group The successive years were so devoted to a fundamental study of mesoporous silicon in interaction with gas, by means of IR spectroscopy, ESR, NMR and ab-initio calculations Since the former paper of 1999 other groups contributed to study the phenomenon of NO 2 interaction with detailed papers on IR spectroscopy and Drude effect due to free carriers restored by nitrogen dioxid