Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in tripeptidyl peptidase-1 (TPP-1)-deficient fibroblasts

NCLs (neuronal ceroid lipofuscinoses) form a group of eight inherited autosomal recessive diseases characterized by the intralysosomal accumulation of autofluorescent pigments, called ceroids. Recent data suggest that the pathogenesis of NCL is associated with the appearance of fragmented mitochondria with altered functions. However, even if an impairement in the autophagic pathway has often been evoked, the molecular mechanisms leading to mitochondrial fragmentation in response to a lysosomal dysfunction are still poorly understood. In this study, we show that fibroblasts that are deficient for the TPP-1 (tripeptidyl peptidase-1), a lysosomal hydrolase encoded by the gene mutated in the LINCL (late infantile NCL, CLN2 form) also exhibit a fragmented mitochondrial network. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 (Bcl2/adenovirus E1B 19 kDa interacting protein 3) as well as a decrease in the abundance of mitofusins 1 and 2, two proteins involved in mitochondrial fusion. Using RNAi (RNA interference) and quantitative analysis of the mitochondrial morphology, we show that the inhibition of BNIP3 expression does not result in an increase in the reticulation of the mitochondrial population in LINCL cells. However, this protein seems to play a key role in cell response to mitochondrial oxidative stress as it sensitizes mitochondria to antimycin A-induced fragmentation. To our knowledge, our results bring the first evidence of a mechanism that links TPP-1 deficiency and oxidative stress-induced changes in mitochondrial morphology

An Adaptive Filtering-based Adjustment Method for Reliability Parameters of Vehicle Systems During Their Lifecycle

The paper considers a problem of difficult accessibility and low quality of data on the reliability parameters of the vehicle system components and the difficulties arising from this problem to estimate the reliability parameters of the systems themselves as statutorily required and in terms of international standards (e.g. ISO 26262). As a problem solution, the paper proposes a method for adjustment of the system reliability estimates based on the field observation of system failures. The method based on a Kalman filter uses non-parametric definition of the failure probability distribution (quantile «folding» of the distribution) with subsequent «unfolding» via Monte Carlo.A mathematical model shows how to use this method.  For clarity, the estimates of reliability parameters are given at the time of rollout (100 % of systems are in working order) and upon the failure of 25%, 50%, 75% and 100% of produced systems, respectively. A КК plot shows that the reliability estimates gradually become close to the field reliability data.The method allows, by varying filter parameters, a more conservative estimate of the reliability parameters or an estimate, which is more in accord with the field data. Thus, the results can be used at all stages of the system lifecycle, namely when developing, manufacturing and upon completing production for the aftermarket services.</p

General relation between spatial coherence and absorption

International audienceDespite the fact that incandescent sources are usually spatially incoherent, it has been known for some time that a proper design of a thermal source can modify its spatial coherence. A natural question is whether it is possible to extend this analysis to electroluminescence and photoluminescence. A theoretical framework is needed to explore these properties. In this paper, we extend a general coherence-absorption relation valid at equilibrium to two non-equilibrium cases: luminescent bodies and anisothermal bodies. We then use this relation to analyse the differences between the isothermal and anisothermal cases and to study the near-field emission of an electroluminescent source

Efficient simulation of large irregular arrays on a finite ground plane

An efficient method is presented to take into account the radiation pattern deformation due to the presence of a finite ground plane lying under an antenna array and above a layered dielectric medium. The interactions between the antennas and the ground plane are computed using two main algorithms: on one hand, the near-field interactions are carried out using inhomogeneous plane waves, and on the other hand, a new formulation based on an analytical Hankel transform is derived to handle the intermediate-field interactions. This formulation expresses the electric field as a finite series of Hankel functions and associated Anger-Weber functions. The method is validated here for the second version of the square kilometer array (SKA) log-periodic Antenna (SKALA2) and then applied to an SKA low-frequency station (SKA1-LOW)

Validation of the Analytical Procedure for the Determination of Malondialdehyde and Three Other Aldehydes in Vegetable Oil Using Liquid Chromatography Coupled to Tandem Mass Spectrometry (LC-MS/MS) and Application to Linseed Oil

Secondary oxidation products of fatty acids, mainly aldehydes, are susceptible to cause significant deterioration in chemical, sensory and nutritional food properties, as well as adverse health effects. An analytical method involving separation by liquid chromatography coupled to the detection by tandem mass spectrometry (LC-MS/MS) has been developed to evaluate the concentration of four aldehydes in oil samples: malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE) and 2,4-decadienal (2,4-DECA). The optimisation of the extraction, derivation, detection and quantification has been finalised for coconut oil, used as a model of vegetable oils. The method has been validated according to the criteria and procedure described in international standards. The evaluated parameters include specificity/selectivity, recovery, precision, accuracy, uncertainty, limits of detection and quantification, using the concept of accuracy profiles. These parameters have been evaluated during experiments planned on different non-consecutive days with coconut oil spiked at different levels of concentration. The validation of the developed analytical method showed that it is possible to analyse MDA, 4-HHE, 4-HNE and 2,4-decadienal in oil samples, in the same run, with a very good accuracy for MDA, and a defined accuracy at specified concentrations for the three other aldehydes. The accuracy profile of MDA showed a recovery rate of 100 % (±1) and a maximum coefficient of variation for the intermediate precision of 14 % at 0.15 mg kg−1. For the three other aldehydes, recovery rates ranged between 79 and 101 % and coefficient of variation for the intermediate precision between 13 and 23 %. In first pressure linseed oil, stored for several days at 60 °C according to the Schaal oven test, it was shown that 4-HHE was the most produced aldehyde, reaching levels of 85 and 382 μmol kg−1 after 12 and 24 days, respectively, versus levels of 18 and 28 μmol MDA kg−1 of oil, respectively, and 17 and 51 μmol 4-HNE kg−1 of oil. © 2014, Springer Science+Business Media New York

Meiotic sex in Chagas disease parasite Trypanosoma cruzi

Genetic exchange enables parasites to rapidly transform disease phenotypes and exploit new host populations. Trypanosoma cruzi, the parasitic agent of Chagas disease and a public health concern throughout Latin America, has for decades been presumed to exchange genetic material rarely and without classic meiotic sex. We present compelling evidence from 45 genomes sequenced from southern Ecuador that T. cruzi in fact maintains truly sexual, panmictic groups that can occur alongside others that remain highly clonal after past hybridization events. These groups with divergent reproductive strategies appear genetically isolated despite possible co-occurrence in vectors and hosts. We propose biological explanations for the fine-scale disconnectivity we observe and discuss the epidemiological consequences of flexible reproductive modes. Our study reinvigorates the hunt for the site of genetic exchange in the T. cruzi life cycle, provides tools to define the genetic determinants of parasite virulence, and reforms longstanding theory on clonality in trypanosomatid parasites