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

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

Exosome levels in human body fluids: A tumor marker by themselves?

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up

Recurrence quantification analysis of heart rate variability to detect both ventilatory thresholds

Aims of this study were: To verify if Recurrence Quantification Analysis (RQA) of Heart Rate Variability (HRV) time series could determine both ventilatory thresholds in individuals with different fitness levels, and to assess the validity of RQA method compared to gasexchange method (GE). The two thresholds were estimated in thirty young individuals during incremental exercise on cycle-ergometer: Heart rate (HR), Oxygen consumption (VO2) and Workload were measured by the two methods (RQA and GE). Repeated measures ANOVA was used to assess main effects of methods and methods-by-groups interaction effects for HR, VO2 and Workload at aerobic (AerT) and anaerobic (AnT) thresholds. Validity of RQA at both thresholds was assessed for HR, VO2 and Workload by Ordinary Least Products (OLP) regression, Typical Percentage Error (TE), Intraclass Correlation Coefficients (ICC) and the Bland Altman plots. No methods-by-groups interaction effects were detected for HR, VO2 and Workload at AerT and AnT. The OLP analysis showed that at both thresholds RQA and GE methods had very strong correlations (r >0.8) in all variables (HR, VO2 and Workload). Slope and intercept values always included the 1 and the 0, respectively. At AerT the TE ranged from 4.02% (5.48 bpm) to 10.47% (8.53 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.85). At AnT the TE ranged from 2.53% (3.98 bpm) to 6.64% (7.81 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.90). Therefore, RQA of HRV time series is a new valid approach to determine both ventilatory thresholds in individuals with different physical fitness levels, it can be used when gas analysis is not possible or not convenient

Activity of bacterial seed endophytes of landrace durum wheat for control of Fusarium foot rot

Five bacterial endophytic isolates obtained from durum wheat seeds (Iandrace "Timilia reste nere") and identified as belonging to Pantoea (isolates A1, F7, F15 and GI) and Paenibacillus (isolate B) genera on the basis of 16S rDNA gene sequences, were assayed in vitro and in vivo for their ability to inhibit Fusarium culmorum growth and the disease (Fusarium foot rot) it causes in durum wheat. All isolates significantly reduced in vitro growth of F. culmorum in comparison with the control. After 120 hours of incubation, isolates B and GI showed the greatest mycelial growth inhibition, i.e., respectively, 76 and 74%. When durum wheat "Simeto" seeds were treated with bacterial isolates singly or in combinations and then inoculated with F. culmorum, all treatments with endophytes showed increased, but not statistically significant, seed germination. Except for isolate Al, all bacterial isolates stimulated vegetative parameters of durum wheat seedlings. Mixture of isolates F7 + F15 was the most effective in improving shoot height (+94%), root length (+47%) and vigour index (+81%). Mixture of isolates A1 + B reduced Fusarium foot rot incidence (-21%) and severity (-30%), and isolate A1 reduced incidence (-15%) and severity (-16%) of the disease. These results indicate potential of bacterial seed endophytes, identified in this study, for control of Fusarium foot rot and suggest that bacterial seed endophytes may provide a new biocontrol agent for an environmentally sustainable durum wheat disease management programme

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

AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways

Hexavalent chromium release over time from a pyrolyzed Cr-bearing tannery sludge

Pyrolysis in an inert atmosphere is a widely applied route to convert tannery wastes into reusable materials. In the present study, the Cr(III) conversion into the toxic hexavalent form in the pyrolyzed tannery waste referred to as KEU was investigated. Ageing experiments and leaching tests demonstrated that the Cr(III)–Cr(VI) inter-conversion occurs in the presence of air at ambient temperature, enhanced by wet environmental conditions. Microstructural analysis revealed that the Cr-primary mineral assemblage formed during pyrolysis (Cr-bearing srebrodolskite and Cr-magnetite spinel) destabilized upon spray water cooling in the last stage of the process. In the evolution from the higher to the lower temperature mineralogy, Cr is incorporated into newly formed CrOOH flakes which likely react in air forming extractable Cr(VI) species. This property transforms KEU from an inert waste to a hazardous material when exposed to ordinary ambient conditions

Association between Hashimoto's thyroiditis and papillary thyroid carcinoma: A retrospective analysis of 305 patients

Background: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a controversial question that is still under debate, its pathological significance and the eventual clinical implications of this association remaining unclear. Methods: The data regarding 305 patients were retrospectively analyzed. The patients were divided in two different groups. A first group made up of 142 patients undergoing surgery for differentiated thyroid carcinoma was compared to a control group of 142 analogous subjects operated for normofunctioning goiter. A second group was made up of 163 patients who had undergone total thyroidectomy (TT) with pre-operative diagnosis of HT. Results: In the first group of patients an association with HT was found in 28,6% of the patients with final histopathological diagnosis of PTC versus 7,7% of the patients with histopathological diagnosis of multinodular goiter, which was a significant difference (p < 0.001). In the second group, the association with PTC was found in 43 (40,2%) cases of HT nodular variant and in 3 cases (8,1%) of HT diffuse variant (p < 0.001). Conclusions: The relationship between HT and PTC is still far from clear and represents an unresolved issue. Our own study has underlined the frequent coexistence of these two pathologies, an aspect not to be neglected in clinical practice. Patients receiving HT diagnosis should undergo careful follow-up and, especially those with the nodular variant, should undergo a frequent both clinical and cytological evaluation of the nodular lesions, taking always into great consideration the surgical approach of total thyroidectomy

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development