Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5mM lithium. Although ineffective when used at 0.5mM, lithium at higher concentrations (2mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β)

The geothermal potential of Campanian volcanoes: evaluation and opportunities.

x

Tectonic stress and renewed uplift at Campi Flegrei caldera, southern Italy: New insights from caldera drilling

Deep drilling is a key tool for the investigation of active volcanoes in the modern Earth Sciences, as this provides the only means to obtain direct information on processes that occur at depth. Data acquired from drilling projects are fundamental to our understanding of volcano dynamics, and for mitigation of the hazards they pose for millions of people who live close to active volcanoes. We present here the first borehole measurement of the stress field in the crust of Campi Flegrei (southern Italy), a large active caldera, and one of the highest risk volcanoes worldwide. Measurements were performed to depths of ∼500 m during a pilot study for the Campi Flegrei Deep Drilling Project. These data indicate an extensional stress field, with a minimum horizontal stress of ca. 75% to 80% of the maximum horizontal stress, which is approximately equal to the vertical stress. The deviation from lithostatic conditions is consistent with a progressive increase in applied horizontal stress during episodes of unrest, since at least 1969. As the stress field is evolving with time, the outcome of renewed unrest cannot be assessed by analogy with previous episodes. Interpretations of future unrest must therefore accommodate the possibility that Campi Flegrei is approaching conditions that are more favourable to a volcanic eruption than has previously been the case. Such long-term accumulation of stress is not expected to be unique to Campi Flegrei, and so might provide a basis for improved forecasts of eruptions at large calderas elsewhere

Phase angle: A possible biomarker to quantify inflammation in subjects with obesity and 25(OH)D deficiency

Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI (p 14 ng/mL (p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation

Sex differences of vitamin D status across BMI classes: An observational prospective cohort study

Growing evidence reported that vitamin D deficiency is a common finding in obesity. Vitamin D status also seems to be sex-related, although little is known regarding this association. Therefore, the aim of this study was to investigate the sex-related differences of serum 25OH vitamin D (25OHD) concentrations across body mass index (BMI) classes and, if there were any differences, whether they could be explained by sex-related differences in body composition. We enrolled 500 subjects (250 males, age 37.4 ± 11.8 years; 250 females, age 36.6 ± 11.8 years). Body composition was assessed by bioelectrical impedance analysis (BIA) phase-sensitive system. Serum 25OHD concentration was quantified by a direct, competitive chemiluminescence immunoassay. Vitamin D deficiency was defined as a serum 25OHD concentrations < 20 ng/mL (50 nmol/L). Stratifying the sample population according to sex and BMI categories, 25OHD concentrations were significantly higher in males compared to females in all BMI classes and decreased along with the increase of BMI values. Females with vitamin D deficiency had higher fat mass (FM) % compared to males with vitamin D deficiency. The 25OHD concentrations inversely correlated with FM % in both sexes. In a multiple regression analysis model, sex, FM %, and BMI were predictive factors of 25OHD concentration. In conclusion, our study suggests that 25OHD concentrations were lower in females than males across all BMI categories. Given the tight correlation between 25OHD concentrations and FM %, it can be hypothesized that the lower 25OHD concentrations in females than males can be explained by the fact that females have a higher amount of fat than males

Cepheid metallicity in the Leavitt law (C-MetaLL) survey -- III. Simultaneous derivation of the Gaia parallax offset and Period-Luminosity-Metallicity coefficients

Classical Cepheids (DCEPs) are the most important standard candles in the extra-galactic distance scale thanks to the Period-Luminosity ($\rm PL$), Period-Luminosity-Color ($\rm PLC$) and Period-Wesenheit ($\rm PW$) relations that hold for these objects. The advent of the {\it Gaia} mission, and in particular the Early Data Release 3 (EDR3) provided accurate parallaxes to calibrate these relations. In order to fully exploit {\it Gaia} measurements, the zero point (ZP) of {\it Gaia} parallaxes should be determined with an accuracy of a few $\rm \mu as$. The individual ZP corrections provided by the {\it Gaia} team depend on the magnitude and the position on the sky of the target. In this paper, we use an implicit method that relies on the Cepheid $\rm PL$ and $\rm PW$ relations to evaluate the ensemble {\it Gaia} parallax zero point. The best inferred estimation of the offset value needed to additionally correct (after the {\it Gaia} team correction) the {\it Gaia} parallaxes of the present DCEP sample, amounts to $\rm -22\pm 4\, \mu as$. This value is in agreement with the most recent literature values and confirms that the correction proposed by the {\it Gaia} team over-corrected the parallaxes.\\ As a further application of our results, we derive an estimate of the Large Magellanic Cloud distance ($\rm \mu_0=18.49\pm 0.06\, mag$), in very good agreement with the currently accepted value obtained through geometric methods.Comment: 12 pages, 12 figures, accepted for publication in MNRA

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature

Purpose: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. Methods: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. Results: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00–1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. Conclusions: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA

V363 Cas: a new lithium rich Galactic Cepheid

Classical Cepheids (DCEPs) are important astrophysical objects not only as standard candles in the determination of the cosmic distance ladder, but also as a testbed for the stellar evolution theory, thanks to the strict connection between their pulsation [period(s), amplitudes] and stellar (luminosity, mass, effective temperature, metallicity) parameters. We aim at unveiling the nature of the Galactic DCEP V363 Cas and other DCEPs showing cosmic abundances of lithium in their atmospheres. We have collected three epochs high-resolution spectroscopy for V363 Cas with HARPS-N@TNG. Accurate stellar parameters: effective temperatures, gravities, micro-turbulences, radial velocities, and metal abundances were measured for this star. We detected a lithium abundance of A(Li)=2.86+-0.10 dex, along with iron, carbon and oxygen abundances of [Fe/H]=-0.30+-0.12 dex, [C/H]=-0.06+-0.15 dex and [O/H]=0.00+-0.12 dex. V363 Cas is the fifth among the Milky Way DCEPs to exhibit a Li-rich feature. An analysis of historical time-series spanning a hundred year interval shows that the period of V363 Cas is increasing, with a sharp acceleration after HJD=2453000. This is a clear hint of first crossing of the instability strip. Our results favour the scenario in which the five Galactic Li-rich DCEPs are first-crossing the instability strip having had slowly-rotating progenitors during their main sequence phase.Comment: Accepted on Astronomy and Astrophysics (Letter). 5 Page

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5 mM lithium. Although ineffective when used at 0.5 mM, lithium at higher concentrations (2 mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3b (GSK-3b