Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea

Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.

Anti-Atherogenic Effects of a Phenol-Rich Fraction from Brazilian Red Wine (Vitis labrusca L.) in Hypercholesterolemic Low-Density Lipoprotein Receptor Knockout Mice

Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr-/- mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.

Contribution of AT-, GC-, and methylated cytidine-rich DNA to chromatin composition in Malpighian tubule cell nuclei of Panstrongylus megistus (Hemiptera, Reduviidae)

The Malpighian tubule cell nuclei of male Panstrongylus megistus, a vector of Chagas disease, contain one chromocenter, which is composed solely of the Y chromosome. Considering that different chromosomes contribute to the composition of chromocenters in different triatomini species, the aim of this study was to determine the contribution of AT-, GC-, and methylated cytidine-rich DNA in the chromocenter as well as in euchromatin of Malpighian tubule cell nuclei of P. megistus in comparison with published data for Triatoma infestans. Staining with 4',6-diamidino-2-phenylindole/actinomycin D and chromomycin A(3)/distamycin, immunodetection of 5-methylcytidine and AgNOR test were used. The results revealed AT-rich/GC-poor DNA in the male chromocenter, but equally distributed AT and GC DNA sequences in male and female euchromatin, like in T. infestans. Accumulation of argyrophilic proteins encircling the chromocenter did not always correlate with that of GC-rich DNA. Methylated DNA identified by immunodetection was found sparsely distributed in the euchromatin of both sexes and at some points around the chromocenter edge, but it could not be considered responsible for chromatin condensation in the chromocenter, like in T. infestans. However, unlike in T. infestans, no correlation between the chromocenter AT-rich DNA and nucleolus organizing region (NOR) DNA was found in P. megistus. (c) 2011 Elsevier GmbH. All rights reserved.

Ab-initio calculations for a realistic sensor: A study of CO sensors based on nitrogen-rich carbon nanotubes

The use of nanoscale low-dimensional systems could boost the sensitivity of gas sensors. In this work we simulate a nanoscopic sensor based on carbon nanotubes with a large number of binding sites using ab initio density functional electronic structure calculations coupled to the Non-Equilibrium Green's Function formalism. We present a recipe where the adsorption process is studied followed by conductance calculations of a single defect system and of more realistic disordered system considering different coverages of molecules as one would expect experimentally. We found that the sensitivity of the disordered system is enhanced by a factor of 5 when compared to the single defect one. Finally, our results from the atomistic electronic transport are used as input to a simple model that connects them to experimental parameters such as temperature and partial gas pressure, providing a procedure for simulating a realistic nanoscopic gas sensor. Using this methodology we show that nitrogen-rich carbon nanotubes could work at room temperature with extremely high sensitivity. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. [http://dx.doi.org/10.1063/1.4739280]

Characterization of selectivity and pharmacophores of type 1 sea anemone toxins by screening seven Na-v sodium channel isoforms

During their evolution, animals have developed a set of cysteine-rich peptides capable of binding various extracellular sites of voltage-gated sodium channels (VGSC). Sea anemone toxins that target VGSCs delay their inactivation process, but little is known about their selectivities. Here we report the investigation of three native type 1 toxins (CGTX-II, delta-AITX-Bcg1a and delta-AITX-Bcg1b) purified from the venom of Bunodosoma cangicum. Both delta-AITX-Bcg1a and delta-AITX-Bcg1b toxins were fully sequenced. The three peptides were evaluated by patch-clamp technique among Nav1.1-1.7 isoforms expressed in mammalian cell lines, and their preferential targets are Na(v)1.5 > 1.6 > 1.1. We also evaluated the role of some supposedly critical residues in the toxins which would interact with the channels, and observed that some substitutions are not critical as expected. In addition, CGTX-II and delta-AITX-Bcg1a evoke different shifts in activation/inactivation Boltzmann curves in Nav1.1 and 1.6. Moreover, our results suggest that the interaction region between toxins and VGSCs is not restricted to the supposed site 3 (S3-54 linker of domain IV), and this may be a consequence of distinct surface of contact of each peptide vs. targeted channel. Our data suggest that the contact surfaces of each peptide may be related to their surface charges, as CGTX-II is more positive than delta-AITX-Bcg1a and delta-AITX-Bcg1b. (C) 2011 Elsevier Inc. All rights reserved.

New Isomers in the Full Seniority Scheme of Neutron-Rich Lead Isotopes: The Role of Effective Three-Body Forces

The neutron-rich lead isotopes, up to Pb-216, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond Pb-208.

Discovery and cross-section measurement of neutron-rich isotopes in the element range from neodymium to platinum with the FRS

Using the high-resolution performance of the fragment separator FRS at GSI we have discovered 60 new neutron-rich isotopes in the atomic number range of 60 <= Z <= 78. The new isotopes were unambiguously identified in reactions with a U-238 beam impinging on a Be target at 1 GeV/nucleon. The production cross-section for the new isotopes have been measured down to the pico-barn level and compared with predictions of different model calculations. For elements above hafnium fragmentation is the dominant reaction mechanism which creates the new isotopes, whereas fission plays a dominant role for the production of the new isotopes up to thulium. (C) 2012 Elsevier B.V. All rights reserved.

Platelet-rich plasma stimulates cytokine expression and alkaline phosphatase activity in osteoblast-derived osteosarcoma cells

Objective: The aim of this study was to investigate the effects of PRP on SAOS-2 cells in terms of cytokine expression, cell activity and oxidative stress. Design: Cell line SAOS-2 (1 x 10(5) cells/mL) were grown in culture medium alpha-MEM with 10% FBS for 24 h and stimulated (or not) with PRP at concentrations of 3, 10 and 20%, LPS (E. coli, 10 g/mL) and IL-1 beta (1 mg/mL) for 24 h. The supernatant was collected and analyzed for the expression of cytokines in a panel array, ALP using a commercial kit and NO2- with Griess reaction method. Also, the cells were analyzed using Western blot for RANKL and slot blotting for nitrotyrosine expression. Result: There were no significant differences amongst the groups in terms of NO2-, protein nitrotyrosine content and RANKL expression. However, all stimuli increased ALP activity and in case of PRP, it was in a dose-dependent manner (p < 0.001). Also, all stimuli induced an increase in cytokines and chemokines expression, but only PRP promoted an increase of component C5, sICAM-1 and RANTES expression. Whilst IL-1 receptor antagonist (IL-1ra) expression was down-regulated by PRP, both LPS and IL-1 beta caused up-regulation of this cytokine. Conclusions: PRP can stimulate osteoblast activity and cytokine/chemokine release, as well as indicate some of the mediators that can (and cannot) be involved in this activation. (C) 2012 Elsevier Ltd. All rights reserved.

Liquid-liquid equilibria for systems composed of rice bran oil and alcohol-rich solvents: Application to extraction and deacidification of oil

The liquid-liquid equilibria of systems composed of rice bran oil, free fatty acids, ethanol and water were investigated at temperatures ranging from 10 to 60 degrees C. The results of the present study indicated that the mutual solubility of the compounds decreased with an increase in the water content of the solvent and a decrease in the temperature of the solution. The experimental data set was correlated by applying the UNIQUAC model. The average variance between the experimental and calculated compositions was 0.35%, indicating that the model can accurately predict behavior of the compounds at different temperatures and degrees of hydration. The adjustment of interaction parameters enables both the simulation of liquid-liquid extractors for deacidification of vegetable oil and the prediction of phase compositions for the oil and alcohol-rich phases that are generated during cooling of the stream exiting the extractor (when using ethanol as the solvent). (C) 2012 Elsevier Ltd. All rights reserved.

A gymnosperm homolog of SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE-1 (SERK1) is expressed during somatic embryogenesis

The physiological and molecular processes controlling zygotic and somatic embryo development in angiosperms are mediated by a hierarchically organized program of gene expression. Despite the overwhelming information available about the molecular control of the embryogenic processes in angiosperms, little is known about these processes in gymnosperms. Here we describe the cloning and characterization of the expression pattern of the Araucaria angustifolia putative homolog of a SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) gene family member, designated as AaSERK1. The Araucaria AaSERK1 gene encodes a leucine-rich repeat receptor-like kinase showing significant similarity to angiosperm homologs of SERK1, known to be involved in early somatic and zygotic embryogenesis. Accordingly, RT-PCR results showed that AaSERK1 is preferentially expressed in Araucaria embryogenic cell cultures. Additionally, in situ hybridization results showed that AaSERK1 transcripts initially accumulate in groups of cells at the periphery of the embryogenic calli and then are restricted to the developing embryo proper. Our results indicate that AaSERK1 might have a role during somatic embryogenesis in Araucaria, suggesting a potentially conserved mechanism, involving SERK-related leucine-rich repeat receptor-like kinases, in the embryogenic processes among all seed plants.

Availability of a rich source of sodium during the perinatal period programs the fluid balance restoration pattern in adult offspring

Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine environmental changes during the perinatal period, differentially programming the developing offspring and affecting them even in adulthood. The aim of this study was to evaluate whether availability of hypertonic sodium solution during the perinatal period may induce a differential programming in adult offspring osmoregulatory mechanisms. With this aim, we studied water and sodium intake after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium solution from 1 week before mating until postnatal day 28 of the offspring, used as a perinatal manipulation model [PM-Na group]. In these animals, we also identified the cell population groups in brain nuclei activated by Furosemide-sodium depletion treatment, analyzing the spatial patterns of Fos and Fos-vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake were significantly lower in the PM-Na group vs. animals without access to hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the volumes consumed of both solutions in each PM group, our data show the expected significant differences between both solutions ingested in the PM-Ctrol group, which makes an isotonic cocktail: however, in the PM-Na group there were no significant differences in the volumes of both solutions consumed after Furosemide-sodium depletion, and therefore the sodium concentration of total fluid ingested by this group was significantly higher than that in the PM-Ctrol group. With regard to brain Fos immunoreactivity, we observed that Furosemide-sodium depletion in the PM-Na group induced a higher number of activated cells in the subfornical organ, ventral subdivision of the paraventricular nucleus and vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals. Moreover, along the brainstem, we found a decreased number of sodium depletion-activated cells within the nucleus of the solitary tract of the PM-Na group. Our data indicate that early sodium availability induces a long-term effect on fluid drinking and on the cell activity of brain nuclei involved in the control of hydromineral balance. These results also suggest that availability of a rich source of sodium during the perinatal period may provoke a larger anticipatory response in the offspring, activating the vasopressinergic system and reducing thirst after water and sodium depletion, as a result of central osmosensitive mechanism alterations. (C) 2011 Elsevier Inc. All rights reserved.

Study of CuO/CeO2 catalyst with for preferential CO oxidation reaction in hydrogen-rich feed (PROX-CO)

The CuO/CeO2 system was investigated as a catalyst for preferential CO oxidation reaction in hydrogen-rich feed (PROX-CO). The catalysts were prepared by deposition-precipitation (DEP) and co-precipitation (COP) methods and the catalytic performance reveals that the preparation method influences the properties of solids prepared, where a direct consequence is the difference in behavior of the catalysts in the PROX-CO reaction. A high specific area and a better dispersion of the metallic phase were obtained in the catalyst prepared by co-precipitation. The redox properties during the reaction were reported by measures of temperature programmed reduction (TPR), OSC measurements and X-ray absorption near edge structure (XANES-TPR) in situ showed the relationship between the preparation method, the physicochemical characteristics and redox properties in the PROX-CO reaction. By this means, the good dispersion of CuO and the best oxygen capacity are the response of the high performance of CuO/CeO2-COP catalysts for the PROX-CO reaction. Crown Copyright (c) 2012 Published by Elsevier B.V. All rights reserved.

Patellar Tendon Healing With Platelet-Rich Plasma A Prospective Randomized Controlled Trial

Background: The patellar tendon has limited ability to heal after harvesting its central third. Platelet-rich plasma (PRP) could improve patellar tendon healing. Hypothesis: Adding PRP to the patellar tendon harvest site would improve donor site healing and improve clinical outcome at 6 months after anterior cruciate ligament (ACL) reconstruction with a patellar tendon graft. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Twenty-seven patients were randomly divided to receive (n = 12) or not receive (n = 15) PRP in the patellar tendon harvest site during ACL reconstruction. The primary outcome was magnetic resonance imaging (MRI) assessment of patellar tendon healing (gap area) after 6 months. Secondary outcomes were questionnaires and isokinetic testing of ACL reconstruction with a patellar tendon graft comparing both groups. Results: Patellar tendon gap area was significantly smaller in the PRP group (4.9 +/- 5.3 mm(2); 95% confidence interval [CI], 1.1-8.8) than in the control group (9.4 +/- 4.4 mm(2); 95% CI, 6.6-12.2; P = .046). Visual analog scale score for pain was lower in the PRP group immediately postoperatively (3.8 +/- 1.0; 95% CI, 3.18-4.49) than in the control group (5.1 +/- 1.4; 95% CI, 4.24-5.90; P = .02). There were no differences after 6 months in questionnaire and isokinetic testing results comparing both groups. Conclusion: We showed that PRP had a positive effect on patellar tendon harvest site healing on MRI after 6 months and also reduced pain in the immediate postoperative period. Questionnaire and isokinetic testing results were not different between the groups at 6 months.

New constraints on the genesis and long-term stability of Os-rich alloys in the Earth's mantle

A variety of seemingly unrelated processes, such as core-mantle interaction, desulfurization, and direct precipitation from a silicate melt have been proposed to explain the formation of Ru-Os-Ir alloys (here referred to as osmiridiums) found in terrestrial mantle rocks. However, no consensus has yet been reached on how these important micrometer-sized phases form. In this paper we report the results of an experimental study on the solubilities of Ru, Os and Ir in sulfide melts (or mattes) as a function of alloy composition at 1300 degrees C. Considering the low solubilities of Ru, Os, and Ir in silicate melts, coupled with their high matte/silicate-melt partition coefficients, our results indicate that these elements concentrate initially at the ppm level in a matte phase in the mantle source region. During partial melting, the extraction of sulfur into silicate melt leads to a decrease in fS(2) that triggers the exsolution of osmiridiums from the refractory matte in the residue. The newly formed osmiridiums may persist in the terrestrial mantle for periods exceeding billions of years. (C) 2012 Elsevier Ltd. All rights reserved.

Functional characterization and oligomerization of a recombinant xyloglucan-specific endo-beta-1,4-glucanase (GH12) from Aspergillus niveus

Xyloglucan is a major structural polysaccharide of the primary (growing) cell wall of higher plants. It consists of a cellulosic backbone (beta-1,4-linked glucosyl residues) that is frequently substituted with side chains. This report describes Aspergillus nidulans strain A773 recombinant secretion of a dimeric xyloglucan-specific endo-beta-1,4-glucanohydrolase (XegA) cloned from Aspergillus niveus. The ORF of the A. niveus xegA gene is comprised of 714 nucleotides, and encodes a 238 amino acid protein with a calculated molecular weight of 23.5 kDa and isoelectric point of 4.38. The optimal pH and temperature were 6.0 and 60 degrees C, respectively. XegA generated a xyloglucan-oligosaccharides (XGOs) pattern similar to that observed for cellulases from family GH12, i.e., demonstrating that its mode of action includes hydrolysis of the glycosidic linkages between glucosyl residues that are not branched with xylose. In contrast to commercial lichenase, mixed linkage beta-glucan (lichenan) was not digested by XegA, indicating that the enzyme did not cleave glucan beta-1,3 or beta-1,6 bonds. The far-UV CD spectrum of the purified enzyme indicated a protein rich in beta-sheet structures as expected for GH12 xyloglucanases. Thermal unfolding studies displayed two transitions with mid-point temperatures of 51.3 degrees C and 81.3 degrees C respectively, and dynamic light scattering studies indicated that the first transition involves a change in oligomeric state from a dimeric to a monomeric form. Since the enzyme is a predominantly a monomer at 60 degrees C. the enzymatic assays demonstrated that XegA is more active in its monomeric state. (c) 2012 Elsevier B.V. All rights reserved.