Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.

Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy

Experimental evidences of a large extrinsic spin Hall effect in AuW alloy

We report an experimental study of a gold-tungsten alloy (7% at. W concentration in Au host) displaying remarkable properties for spintronics applications using both magneto-transport in lateral spin valve devices and spin-pumping with inverse spin Hall effect experiments. A very large spin Hall angle of about 10% is consistently found using both techniques with the reliable spin diffusion length of 2 nm estimated by the spin sink experiments in the lateral spin valves. With its chemical stability, high resistivity and small induced damping, this AuW alloy may find applications in the nearest future

The mysterious bird outbreak of 1779 in southeastern Iberian peninsula: a massive irruption of the Spanish sparrow Passer hispaniolensis from Africa?

Several current and past bibliographical references mention the sudden pest outbreak of a mysterious sparrow–like bird in the southeastern Iberian peninsula in 1779. Based on these references, we investigated unpublished documentary sources from various historical archives that reflected the actions carried out by public authorities against the bird pest. Some narratives come from direct witnesses who sometimes provided relevant data on the origin and biology of the birds involved. From the analysis and interpretation of these data, it was clear that the bird outbreak was caused by an unusual passerine in southeastern Iberia. In May 1779, birds irrupted in large numbers into several localities in the current provinces of Alicante, Murcia and Almería, probably coming from North Africa. Damage caused to cereal crops was meaningful and the extraordinary alarm generated in the people motivated the intervention of both local authorities and government institutions. The birds formed large arboreal colonies, building multiple nests per tree. We discuss different hypotheses related to the taxonomic position of these birds within the Ploceidae and Passeridae families. The bird species whose distribution, morphology, life characteristics and behaviour agrees best with the testimonies analysed is the Spanish sparrow Passer hispaniolensis. We propose that this sparrow could be the protagonist of this historic bird pest outbreak

Efectos del daño de la mosca del olivo y del atroje sobre la microflora en pasta y la acidez del aceite virgen de oliva

The effects of olive fly damage, olive storage, harvest date, olive grove plot and their interactions on the microflora associated with olive paste and oil acidity were studied. Microflora and oil acidity were significantly affected by the four studied factors and by several interactions between them. Fly damage and olive storage interacted sinergically increasing oil acidity. The relationship between fly damage and oil acidity was lineal although sometimes it was not significant depending on microflora populations. The relationship between microflora populations and oil acidity fitted to a logarithmic model. Major microorganisms in olive paste were bacteria (Xanthomonas), yeasts (mostly Torulopsis and Candida) and in a smaller measure moulds (mainly Fusarium and Penicillium). Results overall suggest that a qualitative damage threshold based on the percentage of damaged fruits in order to infer oil acidity may be unfeasible in most instances.Se estudiaron los efectos del daño de mosca, atroje, fecha de recolección, parcela de olivo y de sus interacciones, sobre la microflora asociada a la pasta de aceituna y la acidez del aceite obtenido. Microflora y acidez se vieron significativamente afectados por los cuatro factores estudiados y por varias de sus interacciones. Daño y atroje interactuaron sinérgicamente para incrementar la acidez. La relación entre el daño de mosca y la acidez fue lineal aunque a veces no fue significativa dependiendo de la microflora. La relación entre la microflora y la acidez se ajustó a un modelo logarítmico. Los microorganismos predominantes en la pasta fueron bacterias (Xanthomonas), levaduras (fundamentalmente Torulopsis y Candida) y en menor medida otros hongos (principalmente Fusarium y Penicillium). Los resultados sugieren que un umbral de daño cualitativo basado en el porcentaje de frutos picados para inferir la acidez del aceite es de difícil implementación

Antifungal effect of volatile organic compounds produced by Bacillus amyloliquefaciens CPA-8 against fruit pathogen decays of cherry

The present work focuses on the antifungal effect of volatile organic compounds (VOCs) produced by Bacillus amyloliquefaciens CPA-8 against Monilinia laxa, M. fructicola and Botrytis cinera, three postharvest fruit pathogens of sweet cherry fruit. VOCs were evaluated with a double petri dish assay against mycelial and colony growth of target pathogens. For this purpose, CPA-8 was grown on different media and cultured for 24 and 48 h at 30 °C before assays. Data showed that mycelial growth inhibition was higher when CPA-8 was grown on Tryptone Soya Agar (TSA) while no differences were generally observed when CPA-8 was cultured for either, 24 and 48 h. Moreover, no effects were observed on colony growth. The main volatile compounds emitted by CPA-8 were identified by solid-phase microextraction (SPME)-gas chromatography as 1,3 pentadiene, acetoin (3-hydroxy-2-butanone) and thiophene. Pure compounds were also tested in vitro on mycelial growth inhibition and their EC50 values against the three pathogens were estimated. Thiophene was the most effective VOC, showing more than 82% suppression of mycelial growth at the highest concentration (1.35 μL/mL headspace) and EC50 values ranging from 0.06 to 6.67 μL/mL headspace. Finally, the effectiveness of thiophene and CPA-8 VOCs was evaluated against artificially inoculated cherry fruits. Among the target pathogens, M. fructicola was clearly controlled by CPA-8 with less than 25% of rotten fruits compared to the control (65% disease incidence) and for all pathogens, less than 37.5% of CPA-8 treated decayed fruits produced spores (disease sporulation). Otherwise, pure thiophene showed no effect against any pathogen on disease incidence and disease sporulation. The results indicated that VOCs produced by B. amyloliquefaciens CPA-8 could develop an additive antifungal effect against postharvest fruit pathogens on stone fruit.This research was supported by the European project BIOCOMES FP7-612713 and by the Catalan government (Generalitat de Catalunya) for the PhD grant 2016-FI-B2 00143 (Amparo M. Gotor)

Lysosomal cholesterol accumulation sensitizes to acetaminophen hepatotoxicity by impairing mitophagy.

The role of lysosomes in acetaminophen (APAP) hepatotoxicity is poorly understood. Here, we investigated the impact of genetic and drug-induced lysosomal cholesterol (LC) accumulation in APAP hepatotoxicity. Acid sphingomyelinase (ASMase)(-/-) mice exhibit LC accumulation and higher mortality after APAP overdose compared to ASMase(+/+) littermates. ASMase(-/-) hepatocytes display lower threshold for APAP-induced cell death and defective fusion of mitochondria-containing autophagosomes with lysosomes, which decreased mitochondrial quality control. LC accumulation in ASMase(+/+) hepatocytes caused by U18666A reproduces the susceptibility of ASMase(-/-) hepatocytes to APAP and the impairment in the formation of mitochondria-containing autolysosomes. LC extraction by 25-hydroxycholesterol increased APAP-mediated mitophagy and protected ASMase(-/-) mice and hepatocytes against APAP hepatotoxicity, effects that were reversed by chloroquine to disrupt autophagy. The regulation of LC by U18666A or 25-hydroxycholesterol did not affect total cellular sphingomyelin content or its lysosomal distribution. Of relevance, amitriptyline-induced ASMase inhibition in human hepatocytes caused LC accumulation, impaired mitophagy and increased susceptibility to APAP. Similar results were observed upon glucocerebrosidase inhibition by conduritol β-epoxide, a cellular model of Gaucher disease. These findings indicate that LC accumulation determines susceptibility to APAP hepatotoxicity by modulating mitophagy, and imply that genetic or drug-mediated ASMase disruption sensitizes to APAP-induced liver injury

Structural mechanical simulation to optimize the sensor arm geometry to be implemented on cranial remodeling orthosis

For the treatment of moderate and severe cases of deformational plagiocephaly, an asymmetrical deformation of the skull, a cranial remodeling orthosis (CRO) is used. For the development of a new CRO concept, a pressure sensor grid is placed inside the orthosis that will allow the monitoring of excessive pressures and incorrect CRO positioning throughout the treatment. To implement the sensor grid in the CRO, high mobility of the sensor arms structure that joins the several sensors of this grid is required, however, it is intended that this procedure does not damage the printed copper tracks on the sensor structure. In this study, computer simulations were performed to optimize the sensor arm structure geometry, minimizing undesirable mechanical behavior in the sensor structure when subjected to tensile forces and displacements applied during its placement in the CRO. It was observed that the different sensor arm structures geometries have different effects on the mechanical behavior of the sensor structure when subjected to tensile forces and tensile displacement. The zigzag curve geometry presents the best performance based on high mobility without intense strain on the structure that could damage the printed copper tracks.511F-603F-4B30 | Francisco MirandaN/

The oxygen abundance distribution in M101

The well-observed spiral galaxy M101 was considered. The radial distributions of oxygen abundances determined in three different ways (with the classic Te - method, with the R23 - method, and with the P -- method) were compared. It was found that the parameters (the central oxygen abundance and the gradient) of the radial O/H(P) abundance distribution are close to those of the O/H(Te) abundance distribution. The parameters of the O/H(R23) abundance distribution differ significantly from those of the O/H(Te) abundance distribution: the central O/H(R23) oxygen abundance is higher by around 0.4dex and the gradient is steeper by a factor of around 1.5 as compared to those values in the O/H(Te) abundance distribution. The dispersion in O/H(P) abundance at fixed radius is rather small, around 0.08 dex, and is equal to that in O/H(Te) abundance. The dispersion in O/H(R23) abundance at fixed radius is appreciably larger, around 0.16 dex, compared to that in O/H(Te) abundance. It has been shown that the extra dispersion in O/H(R23) abundances is an artifact and reflects scatter in excitation parameter P at fixed radius.Comment: 7 pages, 5 figures, accepted for publication in Astronomy and Astrophysic