Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter.

Abstract Mitochondrial Ca2 + uptake regulates a wide array of cell functions, from stimulation of aerobic metabolism and ATP production in physiological settings, to induction of cell death in pathological conditions. The molecular identity of the Mitochondrial Calcium Uniporter (MCU), the highly selective channel responsible for Ca2 + entry through the IMM, has been described less than five years ago. Since then, research has been conducted to clarify the modulation of its activity, which relies on the dynamic interaction with regulatory proteins, and its contribution to the pathophysiology of organs and tissues. Particular attention has been placed on characterizing the role of MCU in cardiac and skeletal muscles. In this review we summarize the molecular structure and regulation of the MCU complex in addition to its pathophysiological role, with particular attention to striated muscle tissues. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou

Treatment options for PNET liver metastases. a systematic review

Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs

Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages

<p>Abstract</p> <p>Background</p> <p>Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the molecular aspects underlying muscle atrophy have received increased attention, the fine mechanisms controlling muscle degeneration are still incomplete. In this study we applied meta-analysis on gene expression signatures pertaining to different types of muscle atrophy for the identification of novel key regulatory signals implicated in these degenerative processes.</p> <p>Results</p> <p>We found a general down-regulation of genes involved in energy production and carbohydrate metabolism and up-regulation of genes for protein degradation and catabolism. Six functional pathways occupy central positions in the molecular network obtained by the integration of atrophy transcriptome and molecular interaction data. They are TGF-β pathway, apoptosis, membrane trafficking/cytoskeleton organization, NFKB pathways, inflammation and reorganization of the extracellular matrix. Protein degradation pathway is evident only in the network specific for muscle short-term response to atrophy. TGF-β pathway plays a central role with proteins SMAD3/4, MYC, MAX and CDKN1A in the general network, and JUN, MYC, GNB2L1/RACK1 in the short-term muscle response network.</p> <p>Conclusion</p> <p>Our study offers a general overview of the molecular pathways and cellular processes regulating the establishment and maintenance of atrophic state in skeletal muscle, showing also how the different pathways are interconnected. This analysis identifies novel key factors that could be further investigated as potential targets for the development of therapeutic treatments. We suggest that the transcription factors SMAD3/4, GNB2L1/RACK1, MYC, MAX and JUN, whose functions have been extensively studied in tumours but only marginally in muscle, appear instead to play important roles in regulating muscle response to atrophy.</p

Testing the weak equivalence principle

AbstractThe discovery of Dark Energy and the fact that only about 5% of the mass of the universe can be explained on the basis of the current laws of physics have led to a serious impasse. Based on past history, physics might indeed be on the verge of major discoveries; but the challenge is enormous. The way to tackle it is twofold. On one side, scientists try to perform large scale direct observations and measurements – mostly from space. On the other, they multiply their efforts to put to the most stringent tests ever the physical theories underlying the current view of the physical world, from the very small to the very large. On the extremely small scale very exciting results are expected from one of the most impressive experiments in the history of mankind: the Large Hadron Collider. On the very large scale, the universe is dominated by gravity and the present impasse undoubtedly calls for more powerful tests of General Relativity – the best theory of gravity to date. Experiments testing the Weak Equivalence Principle, on which General Relativity ultimately lies, have the strongest probing power of them all; a breakthrough in sensitivity is possible with the "Galileo Galilei" (GG) satellite experiment to fly in low Earth orbit

Biochemical and neuropathological findings in a Creutzfeldt-Jakob Disease patient with the rare Val180Ile-129Val haplotype in the prion protein gene

Genetic Creutzfeldt-Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians

Abatement of thermal noise due to internal damping in 2D oscillators with rapidly rotating test masses.

Mechanical oscillators can be sensitive to very small forces. Low frequency effects are up-converted to higher frequency by rotating the oscillator. We show that for 2-dimensional oscillators rotating at frequency much higher than the signal the thermal noise force due to internal losses and competing with it is abated as the square root of the rotation frequency. We also show that rotation at frequency much higher than the natural one is possible if the oscillator has 2 degrees of freedom, and describe how this property applies also to torsion balances. In addition, in the 2D oscillator the signal is up-converted above resonance without being attenuated as in the 1D case, thus relaxing requirements on the read out. This work indicates that proof masses weakly coupled in 2D and rapidly rotating can play a major role in very small force physics experiments

The MURAVES muon telescope: technology and expected performances

The MURAVES project aims to study the inner structure of the upper part of the Mt. Vesuvius volcano by muon radiography (muography) technique. Very high energy muons, produced by cosmic rays in the at- mosphere, can penetrate large thickness of rocks. By measuring the at- tenuation of the muons flux trough the volcano cone is possible to obtain a 2D image of the density structure. Internal discontinuities, with a spa- tial resolution of about 10 m, can be, in principle, resolved. An absolute average density measurement can be provided too. The project, funded by the Italian Ministry of University, Research and Education (MIUR), is led by INGV and INFN. In this article the mechanical structure of the de- tectors and background suppression techniques are reported

Anomalous high-temperature superconductivity in YH6_6

Pressure-stabilized hydrides are a new rapidly growing class of high-temperature superconductors which is believed to be described within the conventional phonon-mediated mechanism of coupling. Here we report the synthesis of yttrium hexahydride Im3m-YH$_6$ that demonstrates the superconducting transition with T$_c$ = 224 K at 166 GPa, much lower than the theoretically predicted (>270 K). The measured upper critical magnetic field B$_c$$_2$(0) of YH$_6$ was found to be 116-158 T, which is 2-2.5 times larger than the calculated value. A pronounced shift of T$_c$ in yttrium deuteride YD$_6$ with the isotope coefficient 0.4 supports the phonon-assisted superconductivity. Current-voltage measurements showed that the critical current I$_c$ and its density J$_c$ may exceed 1.75 A and 3500 A/mm$^2$ at 0 K, respectively, which is comparable with the parameters of commercial superconductors, such as NbTi and YBCO. The superconducting density functional theory (SCDFT) and anharmonic calculations suggest unusually large impact of the Coulomb repulsion in this compound. The results indicate notable departures of the superconducting properties of the discovered YH$_6$ from the conventional Migdal-Eliashberg and Bardeen-Cooper-Schrieffer theories.Comment: arXiv admin note: text overlap with arXiv:1902.1020