Voltage-dependent anion channels: different isoforms for different functions

The Voltage-dependent anion channel (VDAC) is the most abundant protein of the outer mitochondrial membrane (OMM) and mediates the flow of ions and metabolites between the cytoplasm and the mitochondrial network. Here we reveal novel and unexpected roles of this protein in the regulation of Ca2+ signaling, cell death and autophagy, throwing light on the differential contribution of the three mammalian isoforms in these cellular processes. In particular, we show that: i) VDAC is physically linked to the endoplasmic reticulum Ca2+ release channel inositol-1,4,5-trisphosphate receptor (IP3R), through the molecular chaperone grp75 and the functional coupling of these channel directly enhances Ca2+ accumulation in mitochondria; ii) the different VDAC isoforms share common Ca2+ channelling properties in living cells but VDAC1 is the only isotype selectively coupled to the ER Ca2+ releasing machinery, thus laying the foundations for a preferential route specifically transmitting Ca2+-mediated cell death signals between the two organelles; iii) VDAC2 is selectively required for the induction of the autophagic process through the establishment of specific protein-protein interactions and the consequent assembly of macromolecular complexes at the OMM level involved in nutrient sensing mediated by the mammalian Target Of Rapamycin (mTOR) signaling pathway. These data highlight the pleiotropic functions of VDAC and its role as central regulator of cell patho-physiology

Reversals in nature and the nature of reversals

The asymmetric shape of reversals of the Earth's magnetic field indicates a possible connection with relaxation oscillations as they were early discussed by van der Pol. A simple mean-field dynamo model with a spherically symmetric $\alpha$ coefficient is analysed with view on this similarity, and a comparison of the time series and the phase space trajectories with those of paleomagnetic measurements is carried out. For highly supercritical dynamos a very good agreement with the data is achieved. Deviations of numerical reversal sequences from Poisson statistics are analysed and compared with paleomagnetic data. The role of the inner core is discussed in a spectral theoretical context and arguments and numerical evidence is compiled that the growth of the inner core might be important for the long term changes of the reversal rate and the occurrence of superchrons.Comment: 24 pages, 12 figure

AN ALGORITHM FOR CONSTRUCTING CERTAIN DIFFERENTIAL OPERATORS IN POSITIVE CHARACTERISTIC

Given a non-zero polynomial f in a polynomial ring R with coefficients in a finite field of prime characteristic p, we present an algorithm to compute a differential operator delta which raises 1/f to its pth power. For some specific families of polynomials, we also study the level of such a differential operator delta, i.e., the least integer e such that delta is R-pe -linear. In particular, we obtain a characterization of supersingular elliptic curves in terms of the level of the associated differential operator

The monitoring program of grapevine phytoplasmas in Tuscany (Italy): Results of a four year survey

Quantitative PCR protocols for phytoplasma detection were used to monitor grapevine yellows (GY) in 373 vineyards located in nine Tuscan districts. Among more than 70,000 plants visually monitored, 1.867 plants were sampled and “flavescence dorée” phytoplasmas (FD) were detected in 122 plants and mainly identified as trains belonging to 16SrV-C subgroup. The “bois noir” (BN) phytoplasma was found in 734 samples, with prevalence of tufB type-b strains. The 2013–2015 monitoring program was strongly influenced by the first survey (2012) in which FD was found consistently in the North West (15 samples), whereas only a few cases were observed in the East territory (2 samples). Both areas were thoroughly monitored in the following years: few foci were found in the East (2 in 2014, 1 in 2015), while several infected areas were found in the North West (6, 10 and 22 foci in 2013, 2014 and 2015, respectively). Definitely, the novel FD foci detected in the survey (17, 6, 12 and 23 in each year of survey) and the widespread of BN, suggest a dangerous distribution of GY in Tuscan

A Pig Model of Hemivascular Liver Occlusion for The Study of Ischemia-Reperfusion Injury: Use of an Infrared System for Detecting Ischemic Areas

Aim: Different animals are used as experimental models for the hepatic Ischemia- Reperfusion (IR) injury investigations and for each one of these animal models, many different surgical approaches have been performed. The aim of our study was to establish a new surgical pig model in which a hemi-liver is used to study the pathophysiology of hepatic IR injury. Contro-lateral hemi- liver is used as an internal control in the same animal. Methods: Liver ischemia was performed in six pigs by clamping the hepatic artery and vein and the portal vein to isolate the left hepatic lobe. Four hours of warm ischemia were followed by 4-hourrs of reperfusion. Biochemical and hematological analyses were performed throughout the experiments. Needle biopsies were obtained prior to ischemia and then hourly during the reperfusion for evaluation of tissue damage. To assess local temperature gradients on the liver surface a focal plane array detector camera was used. Results: Four hours ischemia induced mild signs of hepatic damage on the left ischemic lobe while more dramatic changes were evidenced after 2-hours reperfusion. Absence of tissue damage was detected on the right lobe. The liver functional test reached their maximum value at 2-4 hours after reperfusion. Conclusion: Our model is easy to perform, feasible and reproducible. This surgical model minimizes biases dependent on the individual response of different animals under the same conditions. In this IR model the new technology of an infrared thermocamera was used to control temperature changes and provide clinically important real-time information during surgery

Dietary patterns and risk of ductal carcinoma of the breast: A factor analysis in Uruguay

Breast cancer (BC) shows very high incidence rates in Uruguayan women. The present factor analysis of ductal carcinoma of the breast, the most frequent histological type of this malignancy both in Uruguay and in the World, was conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases with ductal BC and 222 controls with normal mammograms. A factor analysis was conducted using 39 food groups, allowing retention of six factors analyzed through logistic regression in order to obtain odds ratios (OR) associated with ductal BC. The low fat and non-alcoholic beverage patterns were inversely associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty cheese pattern was positively associated (OR=4.17) as well as the fried white meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary risk patterns as those identified by studies not discriminating between histologic type of breast cancer

Liquefied sites of the 2012 Emilia earthquake: a comprehensive database of the geological and geotechnical features (Quaternary alluvial Po plain, Italy)

This paper presents a comprehensive geological and geotechnical study of the whole area affected by liquefaction following the 2012 Emilia earthquakes, including all the available information from the field reconnaissance surveys, in situ tests, and laboratory analyses. The compilation was performed at 120 liquefied sites to verify and validate the reliability of liquefaction charts in alluvial sediments, and to assess liquefaction induced by the 2012 seismic sequence in the Emilia plain. The results reveal a wide range of grain sizes (from clean sands to sandy silts) and compositional characteristics (quartz-rich to litharenitic) in the 2012 ejecta, and show a strong relationship between the liquefaction and stratigraphic architecture of the subsurface. The availability of in situ tests at the liquefied sites makes it possible to verify and validate the reliability of the liquefaction charts in alluvial sediments with respect to the real observations. For the analyzed Emilia case studies, the use of non-liquefiable crust provides better estimations of the liquefaction manifestations when coupled with the thickness of the liquefiable layer rather than with the liquefaction potential index. Altogether, this work makes available to the international scientific community a consistent liquefaction database for in-depth earthquake studies

Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.

Objective: To examine whether there are differences in the effect of aspirin on the incidence of preterm-PE in the ASPRE trial in subgroups defined according to maternal characteristics and medical and obstetrical history. Study design: This was a secondary analysis of data from the ASPRE trial. In ASPRE women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks’ gestation. Those with an estimated risk for preterm-PE of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. Aspirin was associated with a significant reduction in the incidence of preterm-PE with delivery at 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. Results: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm-PE occurred in 10.2% (5/49) in the aspirin group and in 8.2% (5/61) in the placebo group (adjusted odds ratio 1.29, 95% confidence interval, 0.33 to 5.12); the respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio 0.27, 95% confidence interval, 0.12 to 0.60). In all participants with adherence of >90% the adjusted odds ratio in the aspirin group was 0.24 (95% CI 0.09 to 0.65), in the subgroup with chronic hypertension it was 2.06 (95% CI 0.40 to 10.71) and in those without chronic hypertension it was 0.05 (95% CI 0.01 to 0.41). For the complete data set the test of interaction was not significant at the 5% level (p=0.055), but in those with adherence >90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (p=0.0019). Conclusions: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history