Resveratrol inhibits the activity of equine neutrophil myeloperoxidase by a direct interaction with the enzyme

Resveratrol is a polyphenolic antioxidant present in beverage and food known for its multiple protective effects. We report the inhibitory effects of resveratrol on equine myeloperoxidase (MPO), a hemic peroxidase present in the granules of the neutrophils involved in the inflammatory response. Resveratrol inhibited the production of reactive oxygen species (ROS) by stimulated equine neutrophils by acting as a direct scavenger of the ROS released by the cells but did not modify the degranulation of the stimulated neutrophils as the amounts of released MPO were unchanged. Resveratrol strongly inhibited the chlorination, oxidation, and nitration activities of MPO in a dose-dependent manner. By an original technique of specific immunological extraction followed by enzymatic detection (SIEFED), we demonstrated that resveratrol inhibited the peroxidasic activity of the MPO measured by a direct interaction such as the fixation of resveratrol on the enzyme. The observation of a decrease of the accumulation of compound II suggested that resveratrol acts as an electron donor for MPO reduction.     

Common Kibra alleles are associated with human memory performance

Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.     

Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host

Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.     

Effect of orally administered probiotic E. coli strain Nissle 1917 on intestinal mucosal immune cells of healthy young pigs

Several beneficial effects of probiotics have been described in studies using rodent disease models and in human patients; however, the underlying mechanisms remained mostly unclear. Only a few studies focused on the effects of probiotics on the intestinal mucosal immune system. Here, we studied the effect of the probiotic strain E. coli Nissle 1917 (EcN) administered orally to young pigs at two concentrations (10(9) and 10(11)CFU/d for 21 days) on the gut-associated lymphatic tissue. This probiotic strain was shown recently to reduce recurrence of inflammation in ulcerative colitis patients. We quantified the number and distribution of intestinal immune cells (granulocytes, mast cells, CD4+, CD8+, CD25+, IgA+ lymphocytes) and the mucosal mRNA expression of cytokines (IFN-gamma, TNF-alpha, TGF-beta, IL-10) and antimicrobial peptides (PR-39, NK-lysin, prepro-defensin-beta 1, protegrins). The number and distribution of cells were highly different between small intestinal and colon segments in all groups, but were not influenced by EcN, except high dose EcN fed pigs (10(11) CFU/d) showing an increase in mucosal CD8+ cells in the ascending colon. The mRNA analysis revealed no changes associated with EcN feeding. In conclusion, according to our analyses EcN has only minor effects on the distribution of mucosal immune cells in the gut of healthy individuals. The well-established preventive effects of EcN might therefore be relate to other mechanisms than simple modulation of immune cell distribution.     

Vesta's shape and morphology

Vesta's surface is characterized by abundant impact craters, some with preserved ejecta blankets, large troughs extending around the equatorial region, enigmatic dark material, and widespread mass wasting, but as yet an absence of volcanic features. Abundant steep slopes indicate that impact-generated surface regolith is underlain by bedrock. Dawn observations confirm the large impact basin (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying large basin (Veneneia). Vesta's geology displays morphological features characteristic of the Moon and terrestrial planets as well as those of other asteroids, underscoring Vesta's unique role as a transitional solar system body.     

High-resolution protein structure determination by serial femtosecond crystallography

Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.     

dSarm/Sarm1 is required for activation of an injury-induced axon death pathway

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.     

Physionomics and metabolomics-two key approaches in herbicidal mode of action discovery

BACKGROUND: For novel herbicides identified in greenhouse screens, efficient research is important to discover and chemically optimise new leads with new modes of action (MoAs). RESULTS: The metabolic and physiological response pattern to a herbicide can be viewed as the result of changes elicited in the molecular and biochemical process chain. These response patterns are diagnostic of a herbicide's MoA. At the starting point of MoA characterisation, an array of bioassays is used for comprehensive physiological profiling of herbicide effects. This physionomics approach enables discrimination between known, novel or multiple MoAs of a compound and provides a first clue to a new MoA. Metabolic profiling is performed with the use of treated Lemna paucicostata plants. After plant extraction and chromatography and mass spectrometry, changes in levels of approximately 200 identified and 300 unknown analytes are quantified. Check for known MoA assignment is performed by multivariate statistical data analyses. Distinct metabolite changes, which can direct to an affected enzymatic step, are visualised in a biochemical pathway view. Subsequent target identification includes metabolite feeding and molecular, biochemical and microscopic methods. CONCLUSION: The value of this cascade strategy is exemplified by new herbicides with MoAs in plastoquinone, auxin or very‐long‐chain fatty acid synthesis. Copyright © 2011 Society of Chemical Industry     

Efficacy of dinotefuran, permethrin and pyriproxyfen combination spot-on against Aedes aegypti mosquitoes on dogs

A spot-on formulation combining permethrin, dinotefuran and pyriproxyfen (Vectra 3D? spot-on solution for dogs - one 10-25kg pipette contains 196mg dinotefuran, 1429mg permethrin and 17mg pyriproxyfen) was evaluated in adult Beagle dogs in a study designed to measure its efficacy to control Aedes aegypti (anti-feeding effect and mortality effect). The trial was performed according to Animal Welfare and Good Clinical Practice. Twelve dogs (five males and seven female, >3 years old, weighing 8.8-13.0kg) were randomly allocated to treatment groups on pre-treatment mosquito counts: six dogs served as untreated controls, and six dogs were treated with the test formulation. Treatment consisted of applying a combination formulation to deliver at least 46.6mgkg(-1) permethrin, 6.40mgkg(-1) dinotefuran and 0.57mgkg(-1) pyriproxyfen. The combination is designed to control fleas, ticks, sand flies and mosquitoes. Each dog was infested with approximately 100 adult unfed A. aegypti once before treatment (day 6) then at 1, 7, 14, 21 and 28 days post-treatment. Counts and engorgement determination of dead and live mosquitoes were performed after 1h exposure period. In the treated group (group A), the repellency effect of the product based on engorgement status (anti-feeding effect), was 91.5%, 94%, 94.7%, 94% and 87% at 1, 7, 14, 21 and 28 days post-treatment. Mortality effect or insecticidal efficacy calculated at the end of the 1-h exposure was almost identical when calculated 24h after the 1-h exposure and remained above 93% until the end of the in-life phase. No adverse events were observed following treatment, including observations conducted 2, 4 and 24h after the last dog was treated.