Structurally-related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. While recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn is largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In the present study, we developed a method for the analysis of structurally-related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally-related (−)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (−)-epicatechin-3′-β-D-glucuronide, (−)-epicatechin-3′-sulfate, and a 3′-O-methyl(−)-epicatechin-5/7-sulfate are the predominant SREM in humans, and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting to a significant extent of inter-laboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic

Bottlenose dolphins (Tursiops truncatus) do also cast neutrophil extracellular traps against the apicomplexan parasite Neospora caninum

Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear DNA decorated with histones and cytoplasmic peptides which antiparasitic properties have not previously been investigated in cetaceans. Polymorphonuclear neutrophils (PMN) were isolated from healthy bottlenose dolphins (Tursiops truncatus), and stimulated with Neospora caninum tachyzoites and the NETs-agonist zymosan. In vitro interactions of PMN with the tachyzoites resulted in rapid extrusion of NETs. For the demonstration and quantification of cetacean NETs, extracellular DNA was stained by using either Sytox Orange® or Pico Green®. Scanning electron microscopy (SEM) and fluorescence analyses demonstrated PMN-derived release of NETs upon exposure to tachyzoites of N. caninum. Co-localization studies of N. caninum induced cetacean NETs proved the presence of DNA adorned with histones (H1, H2A/H2B, H3, H4), neutrophil elastase (NE), myeloperoxidase (MPO) and pentraxin (PTX) confirming the molecular properties of mammalian NETosis. Dolphin-derived N. caninum-NETosis were efficiently suppressed by DNase I and diphenyleneiodonium (DPI) treatments. Our results indicate that cetacean-derived NETs represent an ancient, conserved and relevant defense effector mechanism of the host innate immune system against N. caninum and probably other related neozoan parasites circulating in the marine environment

EXACT2: the semantics of biomedical protocols

© 2014 Soldatova et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: The reliability and reproducibility of experimental procedures is a cornerstone of scientific practice. There is a pressing technological need for the better representation of biomedical protocols to enable other agents (human or machine) to better reproduce results. A framework that ensures that all information required for the replication of experimental protocols is essential to achieve reproducibility. Methods: We have developed the ontology EXACT2 (EXperimental ACTions) that is designed to capture the full semantics of biomedical protocols required for their reproducibility. To construct EXACT2 we manually inspected hundreds of published and commercial biomedical protocols from several areas of biomedicine. After establishing a clear pattern for extracting the required information we utilized text-mining tools to translate the protocols into a machine amenable format. We have verified the utility of EXACT2 through the successful processing of previously ‘unseen’ (not used for the construction of EXACT2) protocols. Results: The paper reports on a fundamentally new version EXACT2 that supports the semantically-defined representation of biomedical protocols. The ability of EXACT2 to capture the semantics of biomedical procedures was verified through a text mining use case. In this EXACT2 is used as a reference model for text mining tools to identify terms pertinent to experimental actions, and their properties, in biomedical protocols expressed in natural language. An EXACT2-based framework for the translation of biomedical protocols to a machine amenable format is proposed. Conclusions: The EXACT2 ontology is sufficient to record, in a machine processable form, the essential information about biomedical protocols. EXACT2 defines explicit semantics of experimental actions, and can be used by various computer applications. It can serve as a reference model for for the translation of biomedical protocols in natural language into a semantically-defined format.This work has been partially funded by the Brunel University BRIEF award and a grant from Occams Resources

Partitioning of on-demand electron pairs

We demonstrate the high fidelity splitting of electron pairs emitted on demand from a dynamic quantum dot by an electronic beam splitter. The fidelity of pair splitting is inferred from the coincidence of arrival in two detector paths probed by a measurement of the partitioning noise. The emission characteristic of the on-demand electron source is tunable from electrons being partitioned equally and independently to electron pairs being split with a fidelity of 90%. For low beam splitter transmittance we further find evidence of pair bunching violating statistical expectations for independent fermions

Niche-breadth of freshwater macrophytes occurring in tropical southern African rivers predicts species global latitudinal range

The study tested the hypothesis that measurement, using multivariate Principal Components Analy-sis (PCA), of the niche-breadth of river macrophyte species in southern tropical Africa, may predicttheir larger-scale biogeographical range. Two measures of niche-breadth were calculated for 44 riverinemacrophyte species, from 20 families commonly occurring in Zambia, using an approach based on PCAordination with 16 bio-physico-chemical input variables. These included altitude, stream order, streamflow, pH, conductivity and soluble reactive phosphate concentration (SRP). In the absence of additionalchemical water quality data for Zambian rivers, invertebrate-based measures of general water qualitywere also used. These were benthic macroinvertebrate Average Score per Taxon (ASPT), and individualabundance of nine macroinvertebrate families with differing water quality tolerance, indicated by theirSensitivity Weightings within the Zambian Invertebrate Scoring System (ZISS). Macrophyte large-scalelatitudinal range was derived from world geopositional records held by online databases, and additionalrecords held by the authors. The two niche-breadth metrics divided the species into narrow-niche andintermediate/broad-niche categories, showing significant variation (from one or both of correlation andANOVA test outcomes) in altitude, stream flow, conductivity, SRP, pH and ASPT, but not stream order.Macrophyte alpha-diversity (as a measure of number of individual niches co-existing per habitat) showedno significant relationship with individual species niche-breadth. Narrow-niche species included a higherproportion of Afrotropical endemics than did species with broader niche size. There were significant pre-dictive relationships between macrophyte niche-breadth and latitudinal range of the target species atglobal and Afrotropical scales, but not for the Neotropics.Fil: Kennedy, Michael. University Of Aberdeen; Reino UnidoFil: Lang, Pauline. University of Glasgow; Reino UnidoFil: Tapia Grimaldo, Julissa. University of Glasgow; Reino UnidoFil: Varandas Martins, Sara. University of Glasgow; Reino UnidoFil: Bruce, Alannah. University of Glasgow; Reino UnidoFil: Moore, Isabel. University of Glasgow; Reino UnidoFil: Taubert, Rebeca. University of Glasgow; Reino UnidoFil: Macleod-Nolan, Chantal. University of Glasgow; Reino UnidoFil: McWaters, Stephanie. University of Glasgow; Reino UnidoFil: Briggs, John. University of Glasgow; Reino UnidoFil: Lowe, Steve. University of Glasgow; Reino UnidoFil: Saili, Kochelani. University Of Zambia;Fil: SICHINGABULA, Henry. University Of Zambia;Fil: Dallas, Helen. Nelson Mandela Metropolitan University, Sudafrica; SudáfricaFil: Morrison, Sean. University of Glasgow; Reino UnidoFil: Franceschini, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; ArgentinaFil: Willems, Frank. The Kasanka Trust; ZambiaFil: Bottino, Flavia. Universidad Federal de San Carlos; BrasilFil: MURPHY Kevin. University of Glasgow; Reino Unid

Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division. It is strongly overexpressed in the vast majority of cancers. We were interested if survivin detected by immunohistochemistry has prognostic relevance especially for patients of the two soft tissue sarcoma entities leiomyosarcoma and synovial sarcoma.</p> <p>Methods</p> <p>Tumors of leiomyosarcoma (n = 24) and synovial sarcoma patients (n = 26) were investigated for their expression of survivin by immunohistochemistry. Survivin expression was assessed in the cytoplasm and the nucleus of tumor cells using an immunoreactive scoring system (IRS).</p> <p>Results</p> <p>We detected a survivin expression (IRS > 2) in the cytoplasm of 20 leiomyosarcomas and 22 synovial sarcomas and in the nucleus of 12 leiomyosarcomas and 9 synovial sarcomas, respectively. There was no significant difference between leiomyosarcoma and synovial sarcoma samples in their cytoplasmic or nuclear expression of survivin. Next, all sarcoma patients were separated in four groups according to their survivin expression in the cytoplasm and in the nucleus: group 1: negative (IRS 0 to 2); group 2: weak (IRS 3 to 4); group 3: moderate (IRS 6 to 8); group 4: strong (IRS 9 to 12). In a multivariate Cox's regression hazard analysis survivin expression detected in the cytoplasm or in the nucleus was significantly associated with overall survival of patients in group 3 (RR = 5.7; P = 0.004 and RR = 5.7; P = 0.022, respectively) compared to group 2 (reference). Patients whose tumors showed both a moderate/strong expression of survivin in the cytoplasm and a moderate expression of survivin in the nucleus (in both compartments IRS ≥ 6) possessed a 24.8-fold increased risk of tumor-related death (P = 0.003) compared to patients with a weak expression of survivin both in the cytoplasm and in the nucleus.</p> <p>Conclusion</p> <p>Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.</p