The tectonic puzzle of the Messina area (Southern Italy): Insights from new seismic reflection data

The Messina Strait, that separates peninsular Italy from Sicily, is one of the most seismically active areas of the Mediterranean. The structure and seismotectonic setting of the region are poorly understood, although the area is highly populated and important infrastructures are planned there. New seismic reflection data have identified a number of faults, as well as a crustal scale NE-trending anticline few km north of the strait. These features are interpreted as due to active right-lateral transpression along the north-eastern Sicilian offshore, coexisting with extensional and right-lateral transtensional tectonics in the southern Messina Strait. This complex tectonic network appears to be controlled by independent and overlapping tectonic settings, due to the presence of a diffuse transfer zone between the SE-ward retreating Calabria subduction zone relative to slab advance in the western Sicilian side

Antamanide, a Derivative of Amanita phalloides, Is a Novel Inhibitor of the Mitochondrial Permeability Transition Pore

Antamanide is a cyclic decapeptide derived from the fungus Amanita phalloides. Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D. Indeed, (i) permeability transition pore inhibition by antamanide is not additive with the cyclophilin D-binding drug cyclosporin A, (ii) the inhibitory action of antamanide on the pore requires phosphate, as previously shown for cyclosporin A; (iii) antamanide is ineffective in mitochondria or cells derived from cyclophilin D null animals, and (iv) abolishes CyP-D peptidyl-prolyl cis-trans isomerase activity. Permeability transition pore inhibition by antamanide needs two critical residues in the peptide ring, Phe6 and Phe9, and is additive with ubiquinone 0, which acts on the pore in a cyclophilin D-independent fashion. Antamanide also abrogates mitochondrial depolarization and the ensuing cell death caused by two well-characterized pore inducers, clotrimazole and a hexokinase II N-terminal peptide. Our findings have implications for the comprehension of cyclophilin D activity on the permeability transition pore and for the development of novel pore-targeting drugs exploitable as cell death inhibitors

CK2 activity is modulated by growth rate in Saccharomyces cerevisiae

CK2 is a highly conserved protein kinase controlling different cellular processes. It shows a higher activity in proliferating mammalian cells, in various types of cancer cell lines and tumors. The findings presented herein provide the first evidence of an in vivo modulation of CK2 activity, dependent on growth rate, in Saccharomyces cerevisiae. In fact, CK2 activity, assayed on nuclear extracts, is shown to increase in exponential growing batch cultures at faster growth rate, while localization of catalytic and regulatory subunits is not nutritionally modulated. Differences in intracellular CK2 activity of glucose- and ethanol-grown cells appear to depend on both increase in molecule number and k(cat). Also in chemostat cultures nuclear CK2 activity is higher in faster growing cells providing the first unequivocal demonstration that growth rate itself can affect CK2 activity in a eukaryotic organism

What is the best technique to extract bacterial DNA from sputum?

Introduction: There is no consensus on which is the best method to extract bacterial DNA from sputum. We aimed at comparing 20 different DNA extraction techniques on both mock community and sputum samples. Methods: One mock was built and 5 sputa from cystic fibrosis and bronchiectasis patients were evaluated at the Policlinico Hospital in Milan, Italy. 20 techniques for sputum bacterial DNA extraction were compared, including two enzyme-based (Roche and Zymo) and two beads-based (Mobio and QIAGEN) techniques which were tested with/without Dithiothreitol (DTT) and with/without lysostaphin (0.18 and 0.36 mg/mL) steps. Extractions were performed in duplicate to evaluate the variability among samples. DNA was quantified and, then, tested using Real time PCR for 16S rDNA and S. aureus. Results: Although 16S rDNA was similarly detected across all the different techniques in 20 ng of extract (range 19-21 Ct), Roche kit gave the highest DNA yield in both mock and sputa (see figure). The mean standard deviation between replicates was lower in DTT-treated vs non-treated samples (0.17 vs 0.47 Ct, respectively). In both enzymatic-based techniques, the lowest Ct values for Real time PCR for S. aureus in both mock and sputa was identified when lysostaphin was added. Conclusion: An enzyme-based kit with the addition of both DTT treatment and lysostaphin steps seems to be the preferred technique for DNA bacterial extraction on sputum

Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data☆

International audienceBackground: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy.Patients and methods: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out.Results: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI.Conclusion: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution

An educational campaign toward epilepsy among Italian primary school teachers: 1. Survey on knowledge and attitudes.

A questionnaire survey was undertaken to assess the impact of a nationwide educational campaign about epilepsy on the knowledge and attitudes toward the disease among Italian primary school teachers. Five hundred and eighty-two teachers participated. All interviewees were aware of the existence of epilepsy, and most of them had direct experience with the disease. Answers about frequency, causes, outcome, and response to treatments were variable and not correlated with age, residency, and years of experience. Teachers had positive attitudes toward epilepsy, except for the idea that driving and sports can be safe for people with epilepsy. Epilepsy and its treatment were considered a source of learning disability and social disadvantages. Several teachers declared themselves being unable to help a child having seizures. Calling an ambulance was a frequent action. Knowledge and attitudes toward epilepsy are improved compared with those reported in our previous studies. Although this may be a positive reflection of the increasing knowledge and the greater availability of information on epilepsy, there are still areas of uncertainty and incorrect behaviors. Copyright © 2014 Elsevier Inc. All rights reserved

An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program.

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors