Determinants of the Use of Safety Restraint Systems in Italy

Wearing a safety restraint system is one of the most effective measures to substantially reduce the risk of serious or fatal accidents. Despite their benefits, a survey in 2015 revealed that on average 62 out of 100 Italian front car occupants wore their seat belt and only 15% of the rear seat passengers were regularly wearing their seat belt. According to several studies, one's (driving) behaviour is based on a combination of attitudes toward the behaviour, subjective norm and perceived behavioural control. The present study aims at understanding factors contributing to the low wearing rates in Italy. The data used are based on a questionnaire survey carried out among a representative sample of more than 1.000 Italian drivers within the ESRA project (European Survey of Road users' safety Attitudes). The survey involved 17 European countries and covered several themes on (un)safe traffic behaviour and attitudes among which those related to the use of seat belts and child restraint systems. Two methods of investigation were adopted: the comparison between the Italian situation with the European best performers, pointing out the relevant difference with the included selected European Countries, and the use of regression models to study the association between several explanatory variables and self-declared behaviours related to the use of safety restraint systems. The main results show a high acceptability of risky behaviour in Italy and a relevant contribution of age and gender in shaping attitudes towards unsafe traffic behaviours. A number of recommendations are proposed to change people's unsafe behaviour and attitudes in Italy, providing both enforcement and voluntary (e.g. campaigns, education and training, incentives) measures

Proneural-Mesenchymal Transition: Phenotypic Plasticity to Acquire Multitherapy Resistance in Glioblastoma

Glioblastoma (GBM) is an extremely aggressive tumor of the central nervous system, with a prognosis of 12\u201315 months and just 3\u20135% of survival over 5 years. This is mainly because most patients suffer recurrence after treatment that currently consists in maximal resection followed by radio- and chemotherapy with temozolomide. The recurrent tumor shows a more aggressive behavior due to a phenotypic shift toward the mesenchymal subtype. Proneural-mesenchymal transition (PMT) may represent for GBM the equivalent of epithelial\u2013mesenchymal transition associated with other aggressive cancers. In this review we frame this process in the high degree of phenotypic inter- and intra-tumor heterogeneity of GBM, which exists in different subtypes, each one characterized by further phenotypic variability in its stem-cell compartment. Under the selective pressure of different treatment agents PMT is induced. The mechanisms involved, as well as the significance of such event in the acquisition of a multitherapy resistance phenotype, are taken in consideration for future perspectives in new anti-GBM therapeutic options

Improving sustainable mobility in university campuses. The case study of Sapienza University

The pursue of sustainable mobility is one of the greatest environmental challenges nowadays. It requires a people mind shift, where the use of private vehicles give way to different modes of public transport like buses, bicycles, car sharing, electric cars, and walking lanes. This new call to make mobility sustainable has already been undertaken by policymakers and public managers in many urban contexts around the world, as well as, more recently, by the managers of university systems. The paper shows the work developed in 2018 for the Sapienza Sustainable University Mobility Plan (SUMP). The study stems from the need to understand and improve, in the sustainability direction, modes of travel for the students and staff of one of the oldest universities in the world, and one of the largest in Europe (112,142 students enrolled and 23,101 between academic staff and no academic staff), with its premises located in a complex and challenging urban context such as the city of Rome. The SUMP has been developed in two phases. The first one investigated travel patterns and the reasons for the modal shift and highlighted the main issues. The second phase defined strategies and interventions to be implemented in the short, medium, and long term to make students and staff's mobility more environmentally sustainable. The methodology used in the fact-finding stage was the online survey that was carried out through the use of a diversified questionnaire for staff and students of the University. The sample of students who participated in the survey amounted to 14,719 units, while the sample of faculty and staff was 9,403. The main questionnaire outcomes showed that the attitudes recorded were largely different between faculty and staff and students. While for the first ones the choice of private vehicles is the first option (36%), for students public transport is the prevailing preference (78%). According to the critical aspects found in this first stage, the SUMP objectives were defined, leading to the identification of macro-areas of intervention and specific actions. At a policy and strategic level, the attention was focused on the guidelines issued by the United Nations, the European Commission, and the Network of Universities for Sustainable Development, of which Sapienza University is a member. For this reason, the identification of strategies and interventions results from the combination of the first phase analysis, the Sapienza Governance objectives, and the national and international context in which the SUMP was drafted. Five macro-areas of intervention have been identified: Smart Strategies, Pedestrian Mobility, Cycling, Local Public Transport, Private Transport, and for each one specific intervention to be implemented in different time frames have been defined

HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells

Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers

The High Mobility Group A1 (HMGA1) Chromatin Architectural Factor Modulates Nuclear Stiffness in Breast Cancer Cells

13siPlasticity is an essential condition for cancer cells to invade surrounding tissues. The nucleus is the most rigid cellular organelle and it undergoes substantial deformations to get through environmental constrictions. Nuclear stiffness mostly depends on the nuclear lamina and chromatin, which in turn might be affected by nuclear architectural proteins. Among these is the HMGA1 (High Mobility Group A1) protein, a factor that plays a causal role in neoplastic transformation and that is able to disentangle heterochromatic domains by H1 displacement. Here we made use of atomic force microscopy to analyze the stiffness of breast cancer cellular models in which we modulated HMGA1 expression to investigate its role in regulating nuclear plasticity. Since histone H1 is the main modulator of chromatin structure and HMGA1 is a well-established histone H1 competitor, we correlated HMGA1 expression and cellular stiffness with histone H1 expression level, post-translational modifications, and nuclear distribution. Our results showed that HMGA1 expression level correlates with nuclear stiffness, is associated to histone H1 phosphorylation status, and alters both histone H1 chromatin distribution and expression. These data suggest that HMGA1 might promote chromatin relaxation through a histone H1-mediated mechanism strongly impacting on the invasiveness of cancer cells-openopenSenigagliesi B, Penzo C, Severino LU, Maraspini R, Petrosino S, Morales-Navarrete H, Pobega E, Ambrosetti E, Parisse P, Pegoraro S, Manfioletti G, Casalis L, Sgarra RSenigagliesi, Beatrice; Penzo, C; Severino, Lu; Maraspini, R; Petrosino, Sara; Morales-Navarrete, H; Pobega, E; Ambrosetti, E; Parisse, P; Pegoraro, S; Manfioletti, G; Casalis, L; Sgarra,

Keratin 8 expression in colon cancer associates with low faecal butyrate levels

<p>Abstract</p> <p>Background</p> <p>Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton <it>in vitro</it>. These and other data suggest a link between the role of diet and the implication of a central role for the keratin 8 (K8) as guardian of the colorectal epithelium.</p> <p>Methods</p> <p>In this cross-sectional study possible links between butyrate levels, field effects and keratin expression in cancer were addressed directly by analysing how levels of expression of the IF protein K8 in tumours, in adjacent fields and at a distant landmark site may be affected by the level of butyrate in the colon microenvironment. An immunohistochemical scoring protocol for K8 was developed and applied to samples, findings were further tested by immunoblotting.</p> <p>Results</p> <p>Levels of K8 in colorectal tumours are lower in subjects with higher levels of faecal butyrate. Immunoblotting supported this finding.Although there were no significant relationships with butyrate on the non-tumour tissues, there was a consistent trend in all measures of extent or intensity of staining towards a reduction in expression with elevated butyrate, consistent with the inverse association in tumours.</p> <p>Conclusions</p> <p>The data suggest that butyrate may associate with down-regulation of the expression of K8 in the cancerized colon. If further validated these findings may suggest the chemopreventive value of butyrate is limited to early stage carcinogenesis as low K8 expression is associated with a poor prognosis.</p

Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation

The molecular pathogenesis of gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) remains to be elucidated. High-mobility group A (HMGA) proteins play important roles in the regulation of transcription, differentiation, and neoplastic transformation. In this study, the expression of HMGA1 and HMGA2 was studied in 55 GEP NETs. Overexpression of HMGA1 and 2 was frequently detected in GEP NETs compared with normal tissues. Nuclear immunostaining of HMGA1 and 2 was observed in GEP NETs (38 of 55, 69%; 40 of 55, 73%, respectively). High-mobility group A2 expression increased from well-differentiated NET (WNET) to well-differentiated neuroendocrine carcinoma (WNEC) and poorly differentiated NEC (PNEC) (P<0.005) and showed the highest level in stage IV tumours (P<0.01). In WNECs, the expression of HMGA1 and 2 was significantly higher in metastatic tumours than those without metastasis (P<0.05). Gastroenteropancreatic NETs in foregut showed the highest level of HMGA1 and 2 expressions. MIB-1 labelling index (MIB-1 LI) correlated with HMGA1 and 2 overexpression (R=0.28, P<0.05; R=0.434, P<0.001; respectively) and progressively increased from WNETs to WNECs and PNECs (P<0.001). Let-7 expression was addressed in 6 normal organs, 30 tumour samples, and 24 tumour margin non-tumour tissues. Compared with normal tissues, let-7 downregulation was frequent in NETs (19 of 30, 63%). Higher expression of HMGA1 and 2 was frequently observed in tumours with let-7 significant reduction (53, 42%, respectively). The reverse correlation could be detected between HMGA1 and let-7 (P<0.05). Our findings suggested that HMGA1 and 2 overexpression and let-7 downregulation might relate to pathogenesis of GEP NETs

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

Background The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein. Methods To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns. Results Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-κB-target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells. Conclusions We conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas

Self-exciting jumps in the oil market: Bayesian estimation and dynamic hedging

In this paper we propose a novel self-exciting jump-diffusion model for oil price dynamics based on a Hawkes-type process. In particular, the jump intensity is stochastic and path dependent, implying that the occurrence of a jump will increase the probability of observing a new jump and this feature of the model aims at explaining the jumps clustering effect. Moreover, volatility is described by a stochastic process, which can jump simultaneously with prices. The model specification is completed by a stochastic convenience yield. In order to estimate the model we apply the two-stage Sequential Monte Carlo (SMC) sampler (Fulop and Li, 2019) to both spot and futures quotations. From the estimation results we find evidence of self-excitation in the oil market, which leads to an improved fit and a better out of sample futures forecasting performance with respect to jump-diffusion models with constant intensity. Furthermore, we compute and discuss two optimal hedging strategies based on futures trading. The optimality of the first hedging strategy proposed is based on the variance minimization, while the second strategy takes into account also the third-order moment contribution in considering the investors attitudes. A comparison between the two strategies in terms of hedging effectiveness is provided