61 research outputs found

    Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease

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    Unacylated ghrelin (UnAG) may lower skeletal muscle oxidative stress, inflammation, and insulin resistance in lean and obese rodents. UnAG-induced autophagy activation may contribute to these effects, likely involving removal of dysfunctional mitochondria (mitophagy) and redox state maintenance. In chronic kidney disease (CKD) oxidative stress, inflammation and insulin resistance may negatively influence patient outcome by worsening nutritional state through muscle mass loss. Here we show in a 5/6 nephrectomy (Nx) CKD rat model that 4 d s.c. UnAG administration (200 \ub5g twice a day) normalizes CKD-induced loss of gastrocnemius muscle mass and a cluster of high tissue mitochondrial reactive oxygen species generation, high proinflammatory cytokines, and low insulin signaling activation. Consistent with these results, human uremic serum enhanced mitochondrial reactive oxygen species generation and lowered insulin signaling activation in C2C12 myotubes while concomitant UnAG incubation completely prevented these effects. Importantly, UnAG enhanced muscle mitophagy in vivo and silencing RNA-mediated autophagy protein 5 silencing blocked UnAG activities in myotubes. UnAG therefore normalizes CKD-induced skeletal muscle oxidative stress, inflammation, and low insulin signaling as well as muscle loss. UnAG effects are mediated by autophagy activation at the mitochondrial level. UnAG administration and mitophagy activation are novel potential therapeutic strategies for skeletal muscle metabolic abnormalities and their negative clinical impact in CKD.-Gortan Cappellari, G., Semolic, A., Ruozi, G., Vinci, P., Guarnieri, G., Bortolotti, F., Barbetta, D., Zanetti, M., Giacca, M., Barazzoni, R. Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease

    Zefiro - Technology and Innovation against Covid-19

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    Zefiro in an electro-ventilated mask made up of custom designed elements and other widely-available components. Specifically, the frame has been designed as structural element that ensures the correct positioning of the mask. The other standard components perform the functions of isolation and individual protection, as well as introducing air into the mask

    A VLBI experiment using a remote atomic clock via a coherent fibre link

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    We describe a VLBI experiment in which, for the first time, the clock reference is delivered from a National Metrology Institute to a radio telescope using a coherent fibre link 550 km long. The experiment consisted of a 24-hours long geodetic campaign, performed by a network of European telescopes; in one of those (Medicina, Italy) the local clock was alternated with a signal generated from an optical comb slaved to a fibre-disseminated optical signal. The quality of the results obtained with this facility and with the local clock is similar: interferometric fringes were detected throughout the whole 24-hours period and it was possible to obtain a solution whose residuals are comparable to those obtained with the local clock. These results encourage further investigation of the ultimate VLBI performances achievable using fibre dissemination at the highest precision of state-of-the-art atomic clocks

    The Northern Cross Fast Radio Burst project -- III. The FRB-magnetar connection in a sample of nearby galaxies

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    Fast radio bursts (FRBs) are millisecond radio transients observed at cosmological distances. The nature of their progenitors is still a matter of debate, although magnetars are invoked by most models. The proposed FRB-magnetar connection was strengthened by the discovery of an FRB-like event from the Galactic magnetar SGR J1935+2154. In this work, we aim to investigate how prevalent magnetars such as SGR J1935+2154 are within FRB progenitors. We carried out an FRB search in a sample of seven nearby (< 12 Mpc) galaxies with the Northern Cross radio telescope for a total of 692 h. We detected one 1.8 ms burst in the direction of M101 with a fluence of 58±558 \pm 5 Jy ms. Its dispersion measure of 303 pc cm−3^{-3} places it most-likely beyond M101. Considering that no significant detection comes indisputably from the selected galaxies, we place a 38 yr−1^{-1} upper limit on the total burst rate (i.e. including the whole sample) at the 95\% confidence level. This upper limit constrains the event rate per magnetar λmag<0.42\lambda_{\rm mag} < 0.42 magnetar−1^{-1} yr−1^{-1} or, if combined with literature observations of a similar sample of nearby galaxies, it yields a joint constraint of λmag<0.25\lambda_{\rm mag} < 0.25 magnetar−1^{-1} yr−1^{-1}. We also provide the first constraints on the expected rate of FRBs hypothetically originating from ultraluminous X-ray (ULX) sources, since some of the galaxies observed during our observational campaign host confirmed ULXs. We obtain <13< 13 yr−1^{-1} per ULX for the total sample of galaxies observed. Our results indicate that bursts with energies E>1034E>10^{34} erg from magnetars like SGR J1935+2154 appear more rarely compared to previous observations and further disfavour them as unique progenitors for the cosmological FRB population, leaving more space open to the contribution from a population of more exotic magnetars, not born via core-collapsed supernovae.Comment: 9 pages, 4 figures, published in A&

    Comparing Remote Atomic Clocks via VLBI Networks and Fiber Optic Links: the LIFT/MetGeSp Perspective

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    Very Long Baseline Interferometry experiments require an extremely precise synchronization between the atomic clocks keeping the time and frequency standards at radiotelescope observatories. Recently the availability of fiber optic links from a few radio observatories and their national metrological institutes has made the streaming of extremely stable frequency standards via optical atomic clocks possible (even two orders of magnitudes better than Rubidium or Hydrogen maser standards). Firstly, we present the infrastructure of the Italian Link for Frequency and Time (LIFT) and results of the MetGeSp project aimed at finally creating a common clock between two of the antennas of the VLBI Italian Network. Secondly, the results are shown from VLBI experiments in which the rms phase noise was used to accurately compare the synchronicity of atomic clocks located at a few European stations (Medicina, Noto, Yebes, Torun, and Matera). VLBI clock timing proves a valid alternative to satellite-based techniques such as the Global Navigation Satellite System or the Two-Way Satellite Time and Frequency Transfer

    Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies

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    Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing

    The First Geodetic VLBI Field Test of LIFT: a 550-km-long Optical Fiber Link for Remote Antenna Synchronization

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    We present the first field test of the implementation of a coherent optical fiber link for remote antenna synchronization realized in Italy between the Italian Metrological Institute (INRIM) and the Medicina radio observatory of the National Institute for Astrophysics (INAF). The Medicina VLBI antenna participated in the EUR137 experiment carried out in September 2015 using, as reference systems, both the local H-maser and a remote H-maser hosted at the INRIM labs in Turin, separated by about 550 km. In order to assess the quality of the remote clock, the observed radio sources were split into two sets, using either the local or the remote H-maser. A system to switch automatically between the two references was integrated into the antenna field system. The observations were correlated in Bonn and preliminary results are encouraging since fringes were detected with both time references along the full 24 hours of the session. The experimental set-up, the results, and the perspectives for future radio astronomical and geodetic experiments are presented

    A Coherent Optical Fiber Link for Very Long Baseline Interferometry

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    We realize a phase-stabilised optical fiber backbone that connects the Italian National Metrology Institute with two radio telescopes over a 600 km baseline. This allows referencing of Very Long Baseline Interferometry (VLBI) facilities with the best atomic frequency standards available today and the implementation of a common-clock architecture, which we are now using to assess VLBI ultimate performances
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