RECONSTRUCTION OF A LOST CARBONATE FACTORY BASED ON ITS BIOGENIC DETRITUS (TERNATE-TRAVEDONA FORMATION AND GONFOLITE LOMBARDA GROUP - NORTHERN ITALY)

This work reconstructs a now completely eroded late Eocene to earliest Oligocene carbonate factory of Northern Italy, through the analysis of a carbonate deep-water-fan sequence (Ternate-Travedona Formation) and the limestone detritus dispersed into the late Oligocene clastic-wedge of the Gonfolite Lombarda Group. Textural characteristics and skeletal assemblages of the Gonfolite pebbles were studied and compared to those of the Ternate-Travedona Formation. The same skeletal assemblage and the same taxa were found in samples from both areas, suggesting their common origin. Whereas the Ternate-Travedona Formation skeletal grains were reworked during transport, the Gonfolite Lombarda Group pure-limestone pebbles are pristine fragments of the carbonate platform, that was uplifted and eroded from the late Eocene to the early Oligocene. Using both these sources of information it was possible to reconstruct the late Eocene environment and its facies distribution. The areas undergoing high hydrodynamic energy were dominated by free-living coralline-algal branches, rhodoliths and larger thick-tested benthic foraminifera. A coralline framework, associated with thin-tested benthic foraminifera and boxwork rhodoliths, was present in slightly deeper and sheltered environments. Episodic debris flows, mainly triggered by river floods, supplied the sub-marine fan of the Ternate-Travedona Formation. These events were able to down-cut through the narrow platform and rip off large fragments of the substrate. River runoff probably also supplied large quantities of organic matter, leading to local oxygen-depletion and preservation of organic matter. The combined stressful effects of bottom instability and riverine discharge probably excluded corals from the association. The integrated study of the Ternate-Travedona Formation, and of the limestone pebbles in the Gonfolite Group, have enabled the reconstruction of this otherwise lost Eocene carbonate factory

Mechanical behaviour and phase transition mechanisms of a shape memory alloy by means of a novel analytical model

The aim of the present paper is to examine both the fatigue behaviour and the phase transition mechanisms of an equiatomic pseudo-elastic NiTi Shape Memory Alloy through cyclic tests (up to 100 loading cycles). More precisely, miniaturised dog-bone specimens are tested by using a customised testing machine and the contents of both austenite and martensite phase are experimentally measured by means of X-Ray diffraction (XRD) analyses. On the basis of such experimental results in terms of martensite content, an analytical model is here formulated to correlate the stress-strain relationship to the phase transition mechanisms. Finally, a validation of the present model by means of experimental data pertaining the stress-strain relationship is performed

Cognitive reserve in dementia: Implications for cognitive training

open9noCognitive reserve (CR) is a potential mechanism to cope with brain damage. The aim of this study was to evaluate the effect of CR on a cognitive training (CT) in a group of patients with dementia. Eighty six participants with mild to moderate dementia were identified by their level of CR quantified by the CR Index questionnaire (CRIq) and underwent a cycle of CT. A global measure of cognition mini mental state examination (MMSE) was obtained before (T0) and after (T1) the training. Multiple linear regression analyses highlighted CR as a significant factor able to predict changes in cognitive performance after the CT. In particular, patients with lower CR benefited from a CT program more than those with high CR. These data show that CR can modulate the outcome of a CT program and that it should be considered as a predictive factor of neuropsychological rehabilitation training efficacy in people with dementia.openMondini, Sara; Madella, Ileana; Zangrossi, Andrea; Bigolin, Angela; Tomasi, Claudia; Michieletto, Marta; Villani, Daniele; Di Giovanni, Giuseppina; Mapelli, DanielaMondini, Sara; Madella, Ileana; Zangrossi, Andrea; Bigolin, Angela; Tomasi, Claudia; Michieletto, Marta; Villani, Daniele; Di Giovanni, Giuseppina; Mapelli, Daniel

High blood levels of IL-6 nicely correlate with animal survival in trained C26 bearing mice

Exercise is a beneficial adjunct therapy to maintain or enhance quality of life in cancer patients. Recently, few studies demonstrated a correlation between high concentrations of IL-6 and a poor survival. This depends on the equilibrium between the concentrations of IL-6 and sIL-6R. Exercise induces a beneficial increase in circulating IL-6 (1). Fresh fragments of solid C26 tumor were inoculated in healthy 3 months-old mice (n=230, M=115 and F=115). The experimental procedure were 12 weeks long. During the first 6 weeks, mice were randomly assigned to one of the experimental conditions: sedentary (SED) or progressive training (TRP). After the first 6 weeks, all mice were inoculated with a fresh fragment of tumor. All trained adult mice after the tumor inoculation were randomly assigned to a different training program: low intensity training (TRL), moderate intensity training (TRM) and high intensity training (TRH). Mice run 5 days per week on a Rota-Rod following one of the specific training program (TRP ,TRL, TRM and TRH) (2). After tumor inoculation the mice were daily weighted and tumor size monitored until death. Moreover, 8 mice for each group were sacrificed when cachexia occurred (>9% body weight loss), and blood samples were stored for CBA Enhanced flex set flow-cytometric assays (IL-6 and TNF-alpha). The TRM and TRH training protocol performed by trained adult male mice extend the median survival compared to the sedentary adult mice and trained female mice. Interesting the beneficial effect of exercise seemed to be mediated extending the survival days. Significant high blood levels of IL-6 were recorded among the male trained mice (TRM and TRH) groups in comparison with sedentary adult mice and trained female mice (TRM and TRH). The results suggest that endurance exercise as adjuvant therapy is gender and physical training level specific. This effect seems to be mediated by IL-6 blood levels

Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay

The molecular mechanisms by which glioblastoma multiforme (GBM) refracts and becomes resistant to radiotherapy treatment remains largely unknown. This radioresistance is partly due to the presence of hypoxic regions, which are frequently found in GBM tumors. We investigated the radiosensitizing effects of MEK/ERK inhibition on GBM cell lines under hypoxic conditions. Four human GBM cell lines, T98G, U87MG, U138MG and U251MG were treated with the MEK/ERK inhibitor U0126, the HIF-1α inhibitor FM19G11 or γ-irradiation either alone or in combination under hypoxic conditions. Immunoblot analysis of specific proteins was performed in order to define their anti‑oncogenic or radiosensitizing roles in the different experimental conditions. MEK/ERK inhibition by U0126 reverted the transformed phenotype and significantly enhanced the radiosensitivity of T98G, U87MG, U138MG cells but not of the U251MG cell line under hypoxic conditions. U0126 and ERK silencing by siRNA reduced the levels of DNA protein kinase catalytic subunit (DNA-PKcs), Ku70 and K80 proteins and clearly reduced HIF-1α activity and protein expression. Furthermore, DNA-PKcs siRNA-mediated silencing counteracted HIF-1α activity and downregulated protein expression suggesting that ERKs, DNA-PKcs and HIF-1α cooperate in radioprotection of GBM cells. Of note, HIF-1α inhibition under hypoxic conditions drastically radiosensitized all cell lines used. MEK/ERK signal transduction pathway, through the sustained expression of DNA-PKcs, positively regulates HIF-1α protein expression and activity, preserving GBM radioresistance in hypoxic condition

The Accuracy of Three Intraoral Scanners in the Oral Environment with and without Saliva: A Comparative Study

Background: with the emergence of technological innovations in the dental industry, one emerging trend has been the intraoral digitizing of patients by using intraoral scanning systems. Compared to taking conventional impressions, the use of intraoral scanners (IOS) is suitable for capturing direct optical impressions, helping to improve diagnostic efficacy, save time, reduce patient discomfort, and simplify clinical procedures. Intraoral scanning systems appear to have a high potential for providing guidance on proper standards of care. However, one main disadvantage is breathing and saliva secretion, which causes deviations, interfering with the applicability and accuracy of the optical impression. The aim of this study was to compare the validity and accuracy of three commercially available intraoral scanners, performing an analysis exploiting a wet model. Methods: an in vitro experimental study of four permanent teeth (two molars and two premolars) on the accuracy of copings obtained by subgingival preparations was performed, using an oral wet environment model. Two hundred and forty digital impressions were produced from three digital scanners using four samples. Descriptive analysis was performed using mean, standard deviation, and median. ANOVA and F-tests were performed to assess the amount of variability between the groups. For statistical analysis a 95% significance level was chosen. Results: all differences between groups were statistically significant. Conclusions: the present data implicate a huge impact of the oral biological fluids on the accuracy of digital impression to corresponding images, implying a failure of accurate impression under wetness conditions

Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4’-chlorophenyl)thiazol-2-yl] hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells. Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction. Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts. Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers. By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny. In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo. Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC