Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.     

Retrospective evaluation of the results of the microbiological meat examination (MFU) from calves and cows

The microbiological meat examination (MFU), consisting of a bacteriological analysis and a testing for antibiotic residues, is one of several additional analyses used for an edibility rating of carcasses made during meat inspection. Reasons for performing a microbiological meat examination and procedures in the laboratory are defined in the Swiss ordinance for meat examination (FUV). The aim of this study was to analyze the data of 313 microbiological meat examinations from calves and 2882 microbiological meat examinations from cows carried out at the Institute for Food Safety and Hygiene during a period of 8 years. Reasons for microbiological meat examinations as reported by the meat inspectors were mainly classified to the category of "inflammation and necroses" (FUV, Annex 4, Pt 1.2; calves: 73%, cows: 48%). As declarations of the age of the pathological-anatomical changes (that influences directly the probability of detection of pathogens) were generally missing, it is not surprising that the compliance between a particular pathological-anatomical change and a specific detection of pathogens is poor (calves: 19%, cows: 18% of all MFU). About 18% (calves) and 45% (cows) of the reasons for microbiological meat examinations did not correspond to one of the reasons mentioned in the ordinance for meat examination. However, according to the data set, some reasons require a microbiological meat examination due to an often-found specific detection of pathogens. Otherwise, a remarkable number of reasons mentioned were missing the link to bacteriological etiology. Moreover, 14% (calf) and 7% (cow) of microbiological meat examinations with the declaration "no pretreatment" as well as 15% (calf) and 11% (cow) of microbiological meat examinations without declaration showed a positive result in the testing for antibiotic residues.     

Composition, enantiomeric distribution, and antibacterial activity of the essential oil of Achillea ligustica All. from Corsica

The essential oil of Achillea ligustica from Corsica was investigated by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of 82 compounds representing 94.0% of the oil were tentatively identified. The main constituents were the camphane derivatives, representing >30% (camphor, 21.3%; borneol, 6.2%; bornyl acetate, 3.5%) of the whole oil, and santolina alcohol (19.3%). The enantiomeric distribution of 8 chiral constituents was determined by GC-MS using two enantioselective stationary phases (DIME-beta-CD and Lipodex-E). Racemic santolina alcohol, required for optimization of the enantioselective GC conditions, was prepared by an original two-step synthesis from 2,5-dimethylhexa-2,4-diene. The whole essential oil was tested for its antibacterial activity against a wide range of bacteria using a paper disk method. The results show a promising activity against Streptomyces species.     

Impact features on Stardust: implications for comet 81P/Wild 2 dust

Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.     

BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling

Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca2+). Under normal cellular conditions, BKCa channel activation requires Ca2+ concentrations that typically occur in close proximity to Ca2+ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional "Ca2+ nanodomain" where Ca2+ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system.     

Hydrogen isotopes in Eocene river gravels and paleoelevation of the Sierra Nevada

We determine paleoelevation of the Sierra Nevada, California, by tracking the effect of topography on precipitation, as recorded in hydrogen isotopes of kaolinite exposed in gold-bearing river deposits from the Eocene Yuba River. The data, compared with the modern isotopic composition of precipitation, show that about 40 to 50 million years ago the Sierra Nevada stood tall (>/=2200 meters), a result in conflict with proposed young surface uplift by tectonic and climatic forcing but consistent with the Sierra Nevada representing the edge of a pre-Eocene continental plateau.     

The application of sexual coral recruits for the sustainable management of ex situ populations in public aquariums to promote coral reef conservation — SECORE Project

• 1. SECORE (SExual COral REproduction) Project is an initiative of public aquariums and research institutions to produce and exchange sexual coral recruits for the sustainable management of ex situ populations. Here we present the results of the initial three years (2002–2004).
• 2. Primary polyps (n=501) of corals (Acropora tenuis, Agaricia humilis, Favia fragum) were transported from Rotterdam Zoo to Cologne, Burgers', Hagenbeck and London Zoos, where development of juveniles was monitored for 10 months. All polyps were produced at Rotterdam Zoo from laboratory colonies (A. humilis, F. fragum), and from larvae generated from field collected gametes at Akajima, Okinawa, Japan (A. tenuis). Additionally, planulae of A. tenuis (n=1440) were transported from Rotterdam Zoo to Burgers' Zoo and to London Zoo to obtain primary polyps.
• 3. Larval settlement (A. tenuis) was observed to be 3.00 ± 2.57% (mean ± SD; n=1480) in 2002 and 17.36 ± 6.01% (mean ± SD; n=1480) in 2003, significantly lower compared to settlement at Rotterdam Zoo (57.84 ± 11.01% in 2003; mean ± SD, n=1480). High post‐transport survival rates of 95.18 ± 4.86% (mean ± SD; n=501) were observed in primary polyps of all species.
• 4. Juvenile survival (t=10 months; A. tenuis: 18.4–86.2%; A. humilis: 0–19.7%; F. fragum: 13.3–72.7%) differed significantly between institutions. Mean colony sizes (measured 10 months after transportation) were, in all cases, similar or higher to those reported from literature.
• 5. The results demonstrate the potential of this method to serve as an economical and sustainable alternative to existing mostly exploitative techniques for aquarium stocking. The use of sexual recruits provides an effective and low cost alternative, which is, in principle, applicable to all coral species.
• 6. The project was extended from 9 to 28 institutions across Europe, the USA and Japan in 2004.

Copyright © 2006 John Wiley & Sons, Ltd.     

Crystal structure of a lipid G protein-coupled receptor

The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.     

Bactericidal properties of pradofloxacin against veterinary pathogens

Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius, Staphylococcus aureus, Escherichia coli, Pasteurella multocida, Streptococcus canis, Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by pradofloxacin was determined. For 27 of the 30 tested aerobic strains the pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤ 0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone.