PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy

Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ΔΨm and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy

A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

Phononic and photonic band gap structures: modelling and applications

AbstractPhotonic crystals (PhCs) are artificial materials with a permittivity which is a periodic function of the position, with a period comparable to the wavelength of light. The most interesting characteristic of such materials is the presence of photonic band gaps (PBGs). PhCs have very interesting properties of light confinement and localization together with the strong reduction of the device size, orders of magnitude less than the conventional photonic devices, allowing a potential very high scale of integration. These structures possess unique characteristics enabling to operate as optical waveguides, high Q resonators, selective filters, lens or superprism. The ability to mould and guide light leads naturally to novel applications in several fields.Band gap formation in periodic structures also pertains to elastic wave propagation. Composite materials with elastic coefficients which are periodic functions of the position are named phononic crystals. They have properties similar to those of photonic crystals and corresponding applications too. By properly choosing the parameters one may obtain phononic crystals (PhnCs) with specific frequency gaps. An elastic wave, whose frequency lies within an absolute gap of a phononic crystal, will be completely reflected by it. This property allows realizing non-absorbing mirrors of elastic waves and vibration-free cavities which might be useful in high-precision mechanical systems operating in a given frequency range. Moreover, one can use elastic waves to study phenomena such as those associated with disorder, in more or less the same manner as with electromagnetic waves.The authors present in this paper an introductory survey of the basic concepts of these new technologies with particular emphasis on their main applications, together with a description of some modelling approaches

Thermo-mechanical behaviour of a compacted swelling clay

Compacted unsaturated swelling clay is often considered as a possible buffer material for deep nuclear waste disposal. An isotropic cell permitting simultaneous control of suction, temperature and pressure was used to study the thermo-mechanical behaviour of this clay. Tests were performed at total suctions ranging from 9 to 110 MPa, temperature from 25 to 80 degrees C, isotropic pressure from 0.1 to 60 MPa. It was observed that heating at constant suction and pressure induces either swelling or contraction. The results from compression tests at constant suction and temperature evidenced that at lower suction, the yield pressure was lower, the elastic compressibility parameter and the plastic compressibility parameter were higher. On the other hand, at a similar suction, the yield pressure was slightly influenced by the temperature; and the compressibility parameters were insensitive to temperature changes. The thermal hardening phenomenon was equally evidenced by following a thermo-mechanical path of loading-heating-cooling-reloading

Theoretical investigation on the scale factor of a triple ring cavity to be used in frequency sensitive resonant gyroscopes

In this paper we study a multi-ring resonant structure including three evanescently coupled ring resonators (named triple ring resonator,TRR), with different ring radii and coupling coefficients, and coupled to two bus waveguides. The potential application of a TRR as a rotationsensor is analyzed and its advantages over a single ring resonator (SRR) under rotation conditions are also highlighted. When the coupledrings have different size and their inter-ring coupling coefficients are lower than the ring-bus coupling coefficients, the resonance frequencydifference between two counter-propagating beams induced by rotation is enhanced with respect to that of a single ring resonator (SRR)with the same footprint. The scale factor of the rotating TRR, which depends on the structural parameters (i.e. inter-ring and ring-buscoupling coefficients, lengths of the rings, overall propagation loss within the rings), is up to 1.88 times the value of the scale factor of aSRR, which depends only on the ring radius, by assuming that the waveguide structure in both configurations is the same. This promisingnumerical achievement results in a reduction of the sensor footprint of about two times, with respect to a single ring with the same scalefactor. The results obtained may be useful to define new configurations of frequency sensitive optical gyros in low-loss technology, havinga small volume. In fact, by properly choosing the structural parameters, the spectral response of the TRR is forced to assume a shape moresensitive to the resonant frequency shift due to the rotation with respect to that one of a SRR

Mannheim Peritonitis Index (MPI) and elderly population: Prognostic evaluation in acute secondary peritonitis

Introduction. Acute Secondary Peritonitis due to abdominal visceral perforation is characterized by high mortality and morbidity risk. Risk stratification allows prognosis prediction to adopt the best surgical treatment and clinical care support therapy. In Western countries elderly people represent a significant percentage of population Aim. Evaluation of Mannheim Peritonitis Index (MPI) and consideration upon old people. Patients and methods. Retrospective study on 104 patients admitted and operated for \ue2\u80\u9cAcute Secondary Peritonitis due to visceral perforation\ue2\u80\u9d. MPI was scored. In our study we want to demonstrate efficacy of MPI and the possibility to consider older age an independent prognostic factor. Results. Mortality was 25.96%. Greatest sensitivity and specificity for the MPI score as a predictor of mortality was at the score of 20. MPI score of 22. Patients with MPI score 17-21 had 0.46 times lower risk of mortality compared to patients with MPI score >21. In the group of patients with MPI score of >20 the mortality rate was 48.5% for patients older than 80 years old and 12.1% for younger patients (p < 0.005); in the group with MPI score of < 20 mortality rate was respectively 8.4% and 1.4% (p < 0.005). Discussion and conclusions. Data confirm the accuracy of the test. MPI score and age over 80 years old resulted independent predictors of mortality at multivariate analysis

Investigation of refractive index sensing based on Fano resonance in fiber Bragg grating ring resonators.

In this paper we theoretically investigate a ring resonant cavity obtained by closing on itself a pi-shifted fiber Bragg grating, to be used for refractive index sensing applications. Differently from a conventional pi-shifted fiber Bragg grating, the spectral structure of this cavity is characterized by an asymmetric splitting doublet composed by a right side resonance having an asymmetric Fano profile and a left side resonance having a symmetric Lorentzian profile. The right side resonance shows a narrower and sharper peak than all the other kinds of resonance achievable with both conventional ring resonators and pi-shifted fiber Bragg gratings. A reduction of the resonant linewidth with respect to a conventional pi-shifted Fiber Bragg grating and a fiber ring resonator, having the same physical parameters, is theoretically proved, achieving up to five orders of magnitude improvement with respect to the usual ring resonator. Due to these resonance features, the pi-shifted Bragg grating ring resonator results suitable for RI sensing applications requiring extremely narrow resonances for high resolution measurements. In particular, by assuming a refractive index sensing to detect the presence of sugar in water, the sensor can show a theoretical resolution better than 10(-9) RIU. (C)2015 Optical Society of Americ

Applications of biopolymers to processes of environmental control

Two new methods of insolubilizing in cellulose triacetate membranes, natural or synthetic polyelectrolytes, able to bind heavy metal ions, were experimented and discussed. The efficiency of the obtained membranes was tested by monitoring the cupric ion adsorption with a copper ion selective electrode (ISE