Use of Nuclear Magnetic Resonance Imaging Angiography to Follow-Up Arterial Remodeling in an Animal Model

Appropriately sized arteries in small animals may be possible models for studying the remodeling process as occurs after arterial balloon injury in humans. Magnetic resonance imaging (MRI) is able to noninvasively image tissue in vivo. To date, small animal angiog raphy models have mostly used research-dedicated instruments and resolution, which are not universally available.Experiments were carried out on a rat aorta model of remodeling in vivo (n=40). Arteries were injured by oversized balloon dilation; control arteries were uninjured. Angiography imaging was performed immediately before sacrifice with an unmodified clinical MRI unit, a 1.5 Tesla MR tomograph with a 20-cm-diameter coil. Longitudinal MRI pictures of the aorta and morphometry of tissue sections to measure luminal and arterial wall areas were analyzed with use of computer-assisted techniques.Comparison of dimensions demonstrated correlation between MRI and histology measurements of the lumen. MRI and morphometry showed a gradual increase in mean luminal area over 6 weeks following injury. The lumen increase correlated with total arterial area and thickness.In this rat aorta model, remodeling documented at histology was followed-up in vivo. The use of such clinical MRI scanners has potential to reduce animal numbers needed to follow-up the remodeling process after therapeutic intervention

Isolation and purification of Cu-free methanobactin from Methylosinus trichosporium OB3b

<p>Abstract</p> <p>Background</p> <p>The isolation of highly pure copper-free methanobactin is a prerequisite for the investigation of the biogeochemical functions of this chalkophore molecule produced by methane oxidizing bacteria. Here, we report a purification method for methanobactin from <it>Methylosinus trichosporium </it>OB3b cultures based on reversed-phase HPLC fractionation used in combination with a previously reported resin extraction. HPLC eluent fractions of the resin extracted product were collected and characterized with UV-vis, FT-IR, and C-1s NEXAFS spectroscopy, as well as with elemental analysis and ESI-MS.</p> <p>Results</p> <p>The results showed that numerous compounds other than methanobactin were present in the isolate obtained with resin extraction. Molar C/N ratios, mass spectrometry measurements, and UV-vis spectra indicated that methanobactin was only present in one of the HPLC fractions. On a mass basis, methanobactin carbon contributed only 32% to the total organic carbon isolated with resin extraction. Our spectroscopic results implied that besides methanobactin, the organic compounds in the resin extract comprised breakdown products of methanobactin as well as polysaccharide-like substances.</p> <p>Conclusion</p> <p>Our results demonstrate that a purification step is indispensable in addition to resin extraction in order to obtain pure methanobactin. The proposed HPLC purification procedure is suitable for semi-preparative work and provides copper-free methanobactin.</p

Strategies of a parasite of the ant–Acacia mutualism

Mutualisms can be exploited by parasites—species that obtain resources from a partner but provide no services. Though the stability of mutualisms in the presence of such parasites is under intensive investigation, we have little information on life history traits that allow a species to be a successful mutualist or rather a parasite, particularly in cases where both are closely related. We studied the exploitation of Acacia myrmecophytes by the ant, Pseudomyrmex gracilis, contrasting with the mutualistic ant Pseudomyrmex ferrugineus. P. gracilis showed no host-defending behavior and had a negative effect on plant growth. By preventing the mutualist from colonization, P. gracilis imposes opportunity costs on the host plant. P. gracilis produced smaller colonies with a higher proportion of alates than did the mutualist and thus showed an “r-like” strategy. This appears to be possible because P. gracilis relies less on host-derived food resources than does the mutualist, as shown by behavioral and stable isotope studies. We discuss how this system allows the identification of strategies that characterize parasites of mutualisms

Renal function during rofecoxib therapy in patients with metastatic cancer: retrospective analysis of a prospective phase II trial

German Clinical Trials Register DRKS: DRKS0000011

Generative Embedding for Model-Based Classification of fMRI Data

Decoding models, such as those underlying multivariate classification algorithms, have been increasingly used to infer cognitive or clinical brain states from measures of brain activity obtained by functional magnetic resonance imaging (fMRI). The practicality of current classifiers, however, is restricted by two major challenges. First, due to the high data dimensionality and low sample size, algorithms struggle to separate informative from uninformative features, resulting in poor generalization performance. Second, popular discriminative methods such as support vector machines (SVMs) rarely afford mechanistic interpretability. In this paper, we address these issues by proposing a novel generative-embedding approach that incorporates neurobiologically interpretable generative models into discriminative classifiers. Our approach extends previous work on trial-by-trial classification for electrophysiological recordings to subject-by-subject classification for fMRI and offers two key advantages over conventional methods: it may provide more accurate predictions by exploiting discriminative information encoded in ‘hidden’ physiological quantities such as synaptic connection strengths; and it affords mechanistic interpretability of clinical classifications. Here, we introduce generative embedding for fMRI using a combination of dynamic causal models (DCMs) and SVMs. We propose a general procedure of DCM-based generative embedding for subject-wise classification, provide a concrete implementation, and suggest good-practice guidelines for unbiased application of generative embedding in the context of fMRI. We illustrate the utility of our approach by a clinical example in which we classify moderately aphasic patients and healthy controls using a DCM of thalamo-temporal regions during speech processing. Generative embedding achieves a near-perfect balanced classification accuracy of 98% and significantly outperforms conventional activation-based and correlation-based methods. This example demonstrates how disease states can be detected with very high accuracy and, at the same time, be interpreted mechanistically in terms of abnormalities in connectivity. We envisage that future applications of generative embedding may provide crucial advances in dissecting spectrum disorders into physiologically more well-defined subgroups

No cold dust within the supernova remnant Cassiopeia A

A large amount (about three solar masses) of cold (18 K) dust in the prototypical type II supernova remnant Cassiopeia A was recently reported. It was concluded that dust production in type II supernovae can explain how the large quantities (10^8 solar masses) of dust observed in the most distant quasars could have been produced within only 700 million years after the Big Bang. Foreground clouds of interstellar material, however, complicate the interpretation of the earlier submillimetre observations of Cas A. Here we report far-infrared and molecular line observations that demonstrate that most of the detected submillimetre emission originates from interstellar dust in a molecular cloud complex located in the line of sight between the Earth and Cas A, and is therefore not associated with the remnant. The argument that type II supernovae produce copious amounts of dust is not supported by the case of Cas A, which previously appeared to provide the best evidence for this possibility.Comment: 13 pages, 3 figure

Graphenes in the absence of metals as carbocatalysts for selective acetylene hydrogenation and alkene hydrogenation

Catalysis makes possible a chemical reaction by increasing the transformation rate. Hydrogenation of carbon-carbon multiple bonds is one of the most important examples of catalytic reactions. Currently, this type of reaction is carried out in petrochemistry at very large scale, using noble metals such as platinum and palladium or first row transition metals such as nickel. Catalysis is dominated by metals and in many cases by precious ones. Here we report that graphene (a single layer of one-atom-thick carbon atoms) can replace metals for hydrogenation of carbon-carbon multiple bonds. Besides alkene hydrogenation, we have shown that graphenes also exhibit high selectivity for the hydrogenation of acetylene in the presence of a large excess of ethylene.This study was financially supported by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa and CTQ2012-32315); and Generalidad Valenciana (Prometeo 21/013) is gratefully acknowledged.Primo Arnau, AM.; Neatu, F.; Florea, M.; Parvulescu, V.; García Gómez, H. (2014). Graphenes in the absence of metals as carbocatalysts for selective acetylene hydrogenation and alkene hydrogenation. Nature Communications. 5:1-9. https://doi.org/10.1038/ncomms6291S195Dreyer, D. R. & Bielawski, C. W. Carbocatalysis: heterogeneous carbons finding utility in synthetic chemistry. Chem. Sci. 2, 1233–1240 (2011).Machado, B. F. & Serp, P. Graphene-based materials for catalysis. Catal. Sci. Technol. 2, 54–75 (2012).Schaetz, A., Zeltner, M. & Stark, W. J. Carbon modifications and surfaces for catalytic organic transformations. 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Reduced graphene oxide for catalytic oxidation of aqueous organic pollutants. ACS Appl. Mater. Interf. 4, 5466–5471 (2012).Dreyer, D. R., Jia, H. P. & Bielawski, C. W. Graphene oxide: a convenient carbocatalyst for facilitating oxidation and hydration reactions. Angew. Chem. Int. Ed. 49, 6813–6816 (2010).Dreyer, D. R., Jia, H. P., Todd, A. D., Geng, J. X. & Bielawski, C. W. Graphite oxide: a selective and highly efficient oxidant of thiols and sulfides. Org. Biomol. Chem. 9, 7292–7295 (2011).Hayashi, M. Oxidation using activated carbon and molecular oxygen system. Chem. Rec. 8, 252–267 (2008).Jia, H. P., Dreyer, D. R. & Bielawski, C. W. C-H oxidation using graphite oxide. Tetrahedron 67, 4431–4434 (2011).Kumar, A. V. & Rao, K. R. Recyclable graphite oxide catalyzed Friedel-Crafts addition of indoles to alpha, beta-unsaturated ketones. Tetrahedron Lett. 52, 5188–5191 (2011).Soria-Sanchez, M. et al. Carbon nanostructure materials as direct catalysts for phenol oxidation in aqueous phase. Appl. Catal. B Environ. 104, 101–109 (2011).Verma, S. et al. Graphene oxide: an efficient and reusable carbocatalyst for aza-Michael addition of amines to activated alkenes. Chem. Commun. 47, 12673–12675 (2011).Yu, H. et al. Solvent-free catalytic dehydrative etherification of benzyl alcohol over graphene oxide. Chem. Phys. Lett. 583, 146–150 (2013).Holschumacher, D., Bannenberg, T., Hrib, C. G., Jones, P. G. & Tamm, M. Heterolytic dihydrogen activation by a frustrated carbene-borane Lewis pair. Angew. Chem. Int. Ed. 47, 7428–7432 (2008).Staubitz, A., Robertson, A. P. M., Sloan, M. E. & Manners, I. Amine- and phosphine-borane adducts: new interest in old molecules. Chem. Rev. 110, 4023–4078 (2010).Stephan, D. W. & Erker, G. Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More. Angew. Chem. Int. Ed. 49, 46–76 (2010).Poh, H. L., Sanek, F., Sofer, Z. & Pumera, M. 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Engineering Genetically Encoded Nanosensors for Real-Time In Vivo Measurements of Citrate Concentrations

Citrate is an intermediate in catabolic as well as biosynthetic pathways and is an important regulatory molecule in the control of glycolysis and lipid metabolism. Mass spectrometric and NMR based metabolomics allow measuring citrate concentrations, but only with limited spatial and temporal resolution. Methods are so far lacking to monitor citrate levels in real-time in-vivo. Here, we present a series of genetically encoded citrate sensors based on Förster resonance energy transfer (FRET). We screened databases for citrate-binding proteins and tested three candidates in vitro. The citrate binding domain of the Klebsiella pneumoniae histidine sensor kinase CitA, inserted between the FRET pair Venus/CFP, yielded a sensor highly specific for citrate. We optimized the peptide linkers to achieve maximal FRET change upon citrate binding. By modifying residues in the citrate binding pocket, we were able to construct seven sensors with different affinities spanning a concentration range of three orders of magnitude without losing specificity. In a first in vivo application we show that E. coli maintains the capacity to take up glucose or acetate within seconds even after long-term starvation