Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice

Scavenger receptor BI (SR-BI) is a selective uptake receptor for HDL cholesterol but is also involved in the catabolism of apolipoprotein (apo)B-containing lipoproteins. However, plasma levels of apoB-containing lipoproteins increase following hepatic SR-BI overexpression, suggesting that SR-BI not solely mediates their catabolism. We therefore tested the hypothesis that hepatic SR-BI impacts on VLDL production. On day 7 following adenovirus (Ad)-mediated overexpression of SR-BI, VLDL-triglyceride and VLDL-apoB production rates were significantly increased (P < 0.001), whereas VLDL production was significantly lower in SR-BI knockout mice compared with controls (P < 0.05). In mice injected with AdSR-BI, hepatic cholesterol content increased (P < 0.001), microsomal triglyceride transfer protein activity was higher (P < 0.01) and expression of sterol-regulatory element binding protein (SREBP)2 and its target genes was decreased (P < 0.01). Conversely, in SR-BI knockout mice, microsomal triglyceride transfer protein activity was lower and expression of SREBP2 target genes was increased (P < 0.01). Finally, we demonstrate in vitro in isolated primary hepatocytes as well as in vivo that cholesterol derived from HDL and taken up via SR-BI into the liver can be resecreted within VLDL. These data indicate that hepatic SR-BI expression is linked to VLDL production, and within liver, a metabolic shunt might exist that delivers HDL cholesterol, at least in part, to a pool from which cholesterol is mobilized for VLDL production. These results might have implications for HDL-based therapies against atherosclerotic cardiovascular disease, especially with SR-BI as target.     

灰树花胞外多糖对四氯化碳致小鼠肝损伤的保护作用

四氯化碳可导致小鼠急性肝损伤,采用灰树花胞外多糖(GFP)防治后,对其血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和过氧化氢酶活力(CAT)以及肝组织匀浆中的丙二醛(MDA)和乳酸脱氢酶(LDH)进行测定,与模型组相比较,灰树花胞外多糖治疗组ALT、AST、MDA、LDH活力明显降低,而CAT活力明显升高。通过组织切片染色可以直观的看出灰树花胞外多糖能显著减轻肝组织病理变化程度。结果显示GFP对CCL4致小鼠急性肝损伤具有保护作用。     

Somatic mosaicism in cases with small supernumerary marker chromosomes

Somatic mosaicism is something that is observed in everyday lives of cytogeneticists. Chromosome instability is one of the leading causes of large-scale genome variation analyzable since the correct human chromosome number was established in 1956. Somatic mosaicism is also a well-known fact to be present in cases with small supernumerary marker chromosomes (sSMC), i.e. karyotypes of 47,+mar/46. In this study, the data available in the literature were collected concerning the frequency mosaicism in different subgroups of patients with sSMC. Of 3124 cases with sSMC 1626 (52%) present with somatic mosaicism. Some groups like patients with Emanuel-, cat-eye- or i(18p)- syndrome only tend rarely to develop mosaicism, while in Pallister-Killian syndrome every patient is mosaic. In general, acrocentric and non-acrocentric derived sSMCs are differently susceptible to mosaicism; non-acrocentric derived ones are hereby the less stable ones. Even though, in the overwhelming majority of the cases, somatic mosaicism does not have any detectable clinical effects, there are rare cases with altered clinical outcomes due to mosaicism. This is extremely important for prenatal genetic counseling. Overall, as mosaicism is something to be considered in at least every second sSMC case, array-CGH studies cannot be offered as a screening test to reliably detect this kind of chromosomal aberration, as low level mosaic cases and cryptic mosaics are missed by that.     

Interaction of silver nanoparticles with Tacaribe virus

Background  

Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent.     

Copper-cobalt oxide ceramic thin films from single source precursors: Preparation and characterization

Two heterobimetallic coordination complexes [Co(acac)Cu₂(bdmap)₂Cl₃]·C₇H₈ (1) and [Co(acac)Cu₂(bdmap)₂Cl₃]·3CH₂Cl₂ (2) [bdmap = 1,3-Bis(dimethylamino)-2-propanol and acac = 2,4-pentanedionate], have been synthesized by simple chemical technique and characterized by their melting points, elemental composition, FT-IR spectroscopy, mass spectrometry and single crystal X-ray analysis. Thermograms of both the precursors indicated their facile decomposition at relatively low temperature of 454 °C to give stable residual mixture of Cu and CoO. Both the precursors are utilized for the deposition of Cu-CoO thin films by aerosol-assisted chemical vapor deposition (AACVD) equipment at 450 °C on glass substrates that were subsequently characterized for their morphology and composition of the ceramic material. The scanning electron microscopy of copper-cobalt oxide films grown from both the precursors describe highly compact and smooth morphology with homogenously dispersed spherical particles with excellent adhesion properties to the substrates. The EDX analysis shows homogeneous distribution of metallic elements with Cu:Co ratio close to 2:1. Powder X-ray diffraction analysis of the films shows that they are composed of Cu/CoO composite and are crystalline in nature having particle size in the range of 0.3-0.8 μm.     

A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus

Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.     

Dexamethasone quantification in dried blood spot samples using LC-MS: The potential for application to neonatal pharmacokinetic studies

A high-performance liquid chromatography (LC-MS) method has been developed and validated for the determination of dexamethasone in dried blood spot (DBS) samples. For the preparation of DBS samples whole blood spiked with analyte was used to produce 30μl blood spots on specimen collection cards. An 8mm disc was cut from the DBS sample and extracted using a combination of methanol: water (70:30, v/v) containing the internal standard, triamcinolone acetonide. Extracts were centrifuged and chromatographic separation was achieved using a Zorbax Eclipse Plus C18 column using gradient elution with a mobile phase of acetonitrile and water with formic acid at a flow rate of 0.2ml/min. LC-MS detection was conducted with single ion monitoring using target ions at m/z 393.1 for dexamethasone and 435.1 for the internal standard. The developed method was linear within the tested calibration range of 15-800ng/ml. The overall extraction recovery of dexamethasone from DBS samples was 99.3% (94.3-105.7%). The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. Factors with potential to affect drug quantification measurements such as blood haematocrit, the volume of blood applied onto the collection card and spotting device were investigated. Although a haematocrit related effect was apparent, the assay accuracy and precision values remained within the 15% variability limit with fluctuations in haematocrit of ±5%. Variations in the volume of blood spotted did not appear to affect the performance of the developed assay. Similar observations were made regarding the spotting device used. The methodology has been applied to determine levels of dexamethasone in DBS samples collected from premature neonates. The measured concentrations were successfully evaluated using a simple 1-compartment pharmacokinetic model. Requiring only a microvolume (30μl) blood sample for analysis, the developed assay is particularly suited to pharmacokinetic studies involving paediatric populations.     

Psorantin,a unique methylene linked dimer of vismin and kenganthranol E,two anthranoid derivatives from the fruits of Psorospermum aurantiacum (Hypericaceae)

Two prenylated anthranoids, psorantin and kenganthranol E, were isolated from the fruit of Psorospermum aurantiacum together with the known compounds ferruginin B, vismin, vismion D, haronginanthrone, kenganthranol B, kenganthraquinone, 1,7-dihydroxyxanthone, paradisiol, fridelin, fridelinol and betulinic acid. Their structures were determined on the basis of spectral data and by comparison with data reported in the literature as well as with authentic specimens for the known compounds. The structures of the new compounds were determined as bis-[3,8,9-trihydroxy-6-methyl-4,4-bis-(3,3-dimethylallyl)anthracenyl]methane (1) and 1,8,10-trihydroxy-6-methyl-4,5-bis-(3,3-dimethylallyl)-2,3-(2,2-dimethylpyrano)anthrone (2). Psorantin (1) is a dimer of vismin formed through a methylene linkage. The two new compounds when tested against the microbial strains Bacillus megaterium, Escherichia coli, Chlorella fusca and Microbotryum violaceum showed no activity.     

Retracted: In Bangladesh,overweight individuals have fewer symptoms of depression than nonoverweight individuals

The aim of this study was to examine whether the association between overweight and depression usually found in western societies would also be found in locations where overweight is not stigmatized. A total of 1,271 individuals from rural Bangladesh were randomly selected; the response rate was 76%. Depressive symptoms were measured with the Montgomery‐Åsberg Depression Rating Scale (MADRS). The sum MADRS scores were 13.4 (s.d. = 5.8) and 18.5 (8.1) for overweight vs. nonoverweight (t = 6.6; P < 0.000) men, respectively, and 19.7 (7.8) and 23.2 (7.9) for overweight vs. nonoverweight women, respectively (t = 4.2; P < 0.000). Thus the MADRS score was lower in overweight individuals. After adjusting for sex and age, BMI significantly predicted the MADRS score (β = ?0.3; t = 10.2; P < 0.000). These findings suggest that overweight may be related to fewer depressive symptoms in non western cultures.