Peroxisomes contribute to the acylcarnitine production when the carnitine shuttle is deficient

Fatty acid β-oxidation may occur in both mitochondria and peroxisomes. While peroxisomes oxidize specific carboxylic acids such as very long-chain fatty acids, branched-chain fatty acids, bile acids, and fatty dicarboxylic acids, mitochondria oxidize long-, medium-, and short-chain fatty acids. Oxidation of long-chain substrates requires the carnitine shuttle for mitochondrial access but medium-chain fatty acid oxidation is generally considered carnitine-independent. Using control and carnitine palmitoyltransferase 2 (CPT2)- and carnitine/acylcarnitine translocase (CACT)-deficient human fibroblasts, we investigated the oxidation of lauric acid (C12:0). Measurement of the acylcarnitine profile in the extracellular medium revealed significantly elevated levels of extracellular C10- and C12-carnitine in CPT2- and CACT-deficient fibroblasts. The accumulation of C12-carnitine indicates that lauric acid also uses the carnitine shuttle to access mitochondria. Moreover, the accumulation of extracellular C10-carnitine in CPT2- and CACT-deficient cells suggests an extramitochondrial pathway for the oxidation of lauric acid. Indeed, in the absence of peroxisomes C10-carnitine is not produced, proving that this intermediate is a product of peroxisomal β-oxidation. In conclusion, when the carnitine shuttle is impaired lauric acid is partly oxidized in peroxisomes. This peroxisomal oxidation could be a compensatory mechanism to metabolize straight medium- and long-chain fatty acids, especially in cases of mitochondrial fatty acid β-oxidation deficiency or overload.     

Asymmetric reduction of (4S)-(+)-carvone catalyzed by baker's yeast: A green method for monitoring the conversion based on liquid–liquid–liquid microextraction with polypropylene hollow fiber membranes

The α,β-unsaturated carbonyl compound (4S)-(+)-carvone was selectively reduced to (1R,2R,4S)-iso-dihydrocarveol using baker's yeasts. The conversion of the bioreduction reaction was monitored using a green hollow-fiber liquid–liquid–liquid microextraction (HF-LLLME) technique. Several parameters which may affect the bioreduction of (4S)-(+)-carvone, such as temperature, time, substrate/enzyme ratio, pH and buffer concentration, were evaluated. The effect of some additives, such as trehalose, DMSO and the ionic liquid [BMIm][PF₆], was also studied. The (1R,2R,4S)-iso-dihydrocarveol was recovered with 52.7% conversion and diastereoisomeric excess >99% after 48 h of reaction at 40 °C in an aqueous monophasic system, with 0.1 mol L^?1 buffer concentration (pH 7.5) and a substrate/yeast cell mass ratio of 8.0 mg g^?1. The HF-LLLME microextraction technique allowed the optimization of the reaction with a reduction of over 99.5% in relation to the use of organic solvents.     

Productivity: key factor affecting grazing exclusion effects on vegetation and soil

In this study, we inquire into the effects of short-term goat grazing abandonment on plant species and functional composition, bare ground and net primary productivity (NPP) in two traditionally grazed pastures located in the Canarian Network of Natural Protected Areas and the Natura 2000 Network. In addition, we analyse soil chemical properties, biomass tannin content and energetic value to find out how grazing abandonment affects soil fertility and forage quality of these agroecosystems. Grazing exclusion effects on plant species and functional composition, as well as on soil fertility depended on the productivity of the studied pasture. Erect forbs and shrubs (endemic to Macaronesian region and native) were favoured by grazing removal in the most productive pasture, while soil fertility decreased in the driest and least productive site. An increase in NPP after exclusion was consistent among study sites. Although we consider goat grazing as necessary for maintaining traditional agroecosystems, we also suggest controlling it over time, allowing some periods of rest to give endemic shrub species time to recover from near propagule sources.     

Genetic divergence between Melipona quadrifasciata Lepeletier (Hymenoptera,Apidae) populations

Melipona quadrifasciata is a stingless bee widely found throughout the Brazilian territory, with two recognized subspecies, M. quadrifasciata anthidioides, that exhibits interrupted metasomal stripes, and M. quadrifasciata quadrifasciata, with continuous metasomal stripes. This study aimed to estimate the genetic variability of these subspecies. For this purpose, 127 colonies from 15 Brazilian localities were analyzed, using nine species-specific microsatellite primers. At these loci, the number of alleles ranged from three to 15 (mean: 7.2), and the observed heterozygosity (H_o) ranged from 0.03–0.21, while the expected heterozygosity (H_e) ranged from 0.23–0.47. The genetic distances among populations ranged from 0.03–0.45. The F_ST multilocus value (0.23) indicated that the populations sampled were structured, and the clustering analysis showed the formation of two subgroups and two more distant populations. The first group contained the subspecies M. quadrifasciata quadrifasciata, and the other, the subspecies M. quadrifasciata anthidioides and the two M. quadrifasciata populations with continuous metasomal stripes from northern Minas Gerais. These results confirmed that the yellow metasomal stripes alone are not a good means for correctly identifying the different subspecies of M. quadrifasciata.     

Does rearing an aphid parasitoid on one host affect its ability to parasitize another species?

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River Ecosystem Response to Prescribed Vegetation Burning on Blanket peatland

Catchment-scale land-use change is recognised as a major threat to aquatic biodiversity and ecosystem functioning globally. In the UK uplands rotational vegetation burning is practised widely to boost production of recreational game birds, and while some recent studies have suggested burning can alter river water quality there has been minimal attention paid to effects on aquatic biota. We studied ten rivers across the north of England between March 2010 and October 2011, five of which drained burned catchments and five from unburned catchments. There were significant effects of burning, season and their interaction on river macroinvertebrate communities, with rivers draining burned catchments having significantly lower taxonomic richness and Simpson’s diversity. ANOSIM revealed a significant effect of burning on macroinvertebrate community composition, with typically reduced Ephemeroptera abundance and diversity and greater abundance of Chironomidae and Nemouridae. Grazer and collector-gatherer feeding groups were also significantly less abundant in rivers draining burned catchments. These biotic changes were associated with lower pH and higher Si, Mn, Fe and Al in burned systems. Vegetation burning on peatland therefore has effects beyond the terrestrial part of the system where the management intervention is being practiced. Similar responses of river macroinvertebrate communities have been observed in peatlands disturbed by forestry activity across northern Europe. Finally we found river ecosystem changes similar to those observed in studies of wild and prescribed forest fires across North America and South Africa, illustrating some potentially generic effects of fire on aquatic ecosystems.     

Paradoxical Regulation of Hypoxia Inducible Factor-1α (HIF-1α) by Histone Deacetylase Inhibitor in Diffuse Large B-Cell Lymphoma

Hypoxia inducible factor (HIF) is important in cancer, as it regulates various oncogenic genes as well as genes involved in cell survival, proliferation, and migration. Elevated HIF-1 protein promotes a more aggressive tumor phenotype, and greater HIF-1 expression has been demonstrated to correlate with poorer prognosis, increased risk of metastasis and increased mortality. Recent reports suggest that HIF-1 activates autophagy, a lysosomal degradation pathway which may promote tumor cell survival. We show here that HIF-1α expression is constitutively active in multiple diffuse large B cell lymphoma (DLBCL) cell lines under normoxia and it is regulated by the PI3K/AKT pathway. PCI-24781, a pan histone deacetylase inhibitor (HDACI), enhanced accumulation of HIF-1α and induced autophagy initially, while extended incubation with the drug resulted in inhibition of HIF-1α. We tested the hypothesis that PCI-24781- induced autophagy is mediated by HIF-1α and that inhibition of HIF-1α in these cells results in attenuation of autophagy and decreased survival. We also provide evidence that autophagy serves as a survival pathway in DLBCL cells treated with PCI-24781 which suggests that the use of autophagy inhibitors such as chloroquine or 3-methyl adenine in combination with PCI-24781 may enhance apoptosis in lymphoma cells.     

Mechanisms Involved in the Nociception Triggered by the Venom of the Armed Spider Phoneutria nigriventer

Background

The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV).

Methodology/Principal Findings

Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.). The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv), local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT₄) and vanilloid receptors (TRPV1). We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B₂ was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na⁺ channels, acid-sensitive ion channels (ASIC) and TRPV1 receptors.

Conclusion/Significance

Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B₂, TRPV1, 5-HT₄ or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of interest not only for better treating poisoning by P. nigriventer but also appreciating the diversity of targets triggered by PNV toxins.