Publications
104 results found
Thompson RB, Reffatto V, Bundy JG, et al., 2015, Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye, Proceedings of the National Academy of Sciences of the United States of America, Vol: 112, Pages: 1565-1570, ISSN: 1091-6490
Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5–20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch’s membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch’s membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.
Behrends V, Maharjan RP, Ryall B, et al., 2014, A metabolic trade-off between phosphate and glucose utilization in Escherichia coli, MOLECULAR BIOSYSTEMS, Vol: 10, Pages: 2820-2822, ISSN: 1742-206X
Liebeke M, Bruford MW, Donnelly RK, et al., 2014, Identifying biochemical phenotypic differences between cryptic species., Biology Letters, Vol: 10, ISSN: 1744-9561
Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status.
Hao J, Liebeke M, Astle W, et al., 2014, Bayesian deconvolution and quantification of metabolites in complex 1D NMR spectra using BATMAN, NATURE PROTOCOLS, Vol: 9, Pages: 1416-1427, ISSN: 1754-2189
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- Citations: 126
Bundy JG, Kille P, Liebeke M, et al., 2014, Metallothioneins May Not Be Enough-The Role of Phytochelatins in Invertebrate Metal Detoxification, ENVIRONMENTAL SCIENCE & TECHNOLOGY, Vol: 48, Pages: 885-886, ISSN: 0013-936X
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- Citations: 24
Fuchs S, Behrends V, Bundy JG, et al., 2014, Phenylalanine Metabolism Regulates Reproduction and Parasite Melanization in the Malaria Mosquito, Plos One, Vol: 9
Bundy JG, Kille P, 2014, Metabolites and metals in Metazoa - what role do phytochelatins play in animals?, METALLOMICS, Vol: 6, Pages: 1576-1582, ISSN: 1756-5901
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- Citations: 16
Behrends V, Williams HD, Bundy JG, 2014, Metabolic Footprinting: Extracellular Metabolomic Analysis, PSEUDOMONAS: METHODS AND PROTOCOLS, Vol: 1149, Pages: 281-292, ISSN: 1064-3745
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- Citations: 13
Geier FM, Fuchs SY, Valbuena G, et al., 2013, Profiling the metabolic signature of senescence, Methods in Molecular Biology, Vol: 965, Pages: 355-371, ISSN: 1064-3745
Aging is a complex process, which involves changes in different cellular functions that all can be integrated on the metabolite level. This means that different gene regulation pathways that affect aging might lead to similar changes in metabolism and result in a metabolic signature of senescence. In this chapter, we describe how to establish a metabolic signature of senescence by analyzing the metabolome of various longevity mutants of the model organism Caenorhabditis elegans using gas chromatography-mass spectrometry (GC-MS). Since longevity-associated genes exist for other model organisms and humans, this analysis could be universally applied to body fluids or whole tissue samples for studing the relationship between senescence and metabolism. © Springer Science+Business Media New York 2013.
Liebeke M, Garcia-Perez I, Anderson CJ, et al., 2013, Earthworms Produce phytochelatins in Response to Arsenic, PLOS One, Vol: 8, ISSN: 1932-6203
Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such ascadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are alsopresent in animal species from several different phyla, but there is still little known about whether these genes arefunctional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by directchemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenicclearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure thephytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase geneexpression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A furtheruntargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway,which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biologicaltransformation of arsenic (e.g. into methylated species) as a result of laboratory arsenic exposure. Finally, wecompared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated andcadmium-contaminated mine site worms had elevated phytochelatin concentrations.
Schumacher J, Behrends V, Pan Z, et al., 2013, Nitrogen and Carbon Status Are Integrated at the Transcriptional Level by the Nitrogen Regulator NtrC <i>In Vivo</i>, MBIO, Vol: 4, ISSN: 2150-7511
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- Citations: 45
Behrends V, Bell TJ, Liebeke M, et al., 2013, Metabolite Profiling to Characterize Disease-related Bacteria <i>GLUCONATE EXCRETION BY PSEUDOMONAS AERUGINOSA MUTANTS AND CLINICAL ISOLATES FROM CYSTIC FIBROSIS PATIENTS</i>, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 288, Pages: 15098-15109, ISSN: 0021-9258
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- Citations: 31
Liebeke M, Hao J, Ebbels TMD, et al., 2013, Combining Spectral Ordering with Peak Fitting for One-Dimensional NMR Quantitative Metabolomics, ANALYTICAL CHEMISTRY, Vol: 85, Pages: 4605-4612, ISSN: 0003-2700
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- Citations: 16
Behrends V, Geier B, Williams HD, et al., 2013, Direct Assessment of Metabolite Utilization by <i>Pseudomonas aeruginosa</i> during Growth on Artificial Sputum Medium, APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Vol: 79, Pages: 2467-2470, ISSN: 0099-2240
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- Citations: 13
Behrends V, Ryall B, Zlosnik JEA, et al., 2013, Metabolic adaptations of Pseudomonas aeruginosa during cystic fibrosis chronic lung infections, ENVIRONMENTAL MICROBIOLOGY, Vol: 15, Pages: 398-408, ISSN: 1462-2912
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- Citations: 57
Kille P, Andre J, Anderson C, et al., 2013, DNA sequence variation and methylation in an arsenic tolerant earthworm population, SOIL BIOLOGY & BIOCHEMISTRY, Vol: 57, Pages: 524-532, ISSN: 0038-0717
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- Citations: 65
Liebeke M, Bundy JG, 2013, Biochemical diversity of betaines in earthworms, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 430, Pages: 1306-1311, ISSN: 0006-291X
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- Citations: 20
Geier FM, Fuchs S, Valbuena G, et al., 2013, Profiling the metabolic signature of senescence., Methods Mol Biol, Vol: 965, Pages: 355-371
Aging is a complex process, which involves changes in different cellular functions that all can be integrated on the metabolite level. This means that different gene regulation pathways that affect aging might lead to similar changes in metabolism and result in a metabolic signature of senescence. In this chapter, we describe how to establish a metabolic signature of senescence by analyzing the metabolome of various longevity mutants of the model organism Caenorhabditis elegans using gas chromatography-mass spectrometry (GC-MS). Since longevity-associated genes exist for other model organisms and humans, this analysis could be universally applied to body fluids or whole tissue samples for studing the relationship between senescence and metabolism.
Strittmatter N, Jones EA, Veselkov KA, et al., 2013, Analysis of intact bacteria using rapid evaporative ionisation mass spectrometry, CHEMICAL COMMUNICATIONS, Vol: 49, Pages: 6188-6190, ISSN: 1359-7345
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- Citations: 52
Burgess SJ, Tredwell G, Molnar A, et al., 2012, Artificial microRNA-mediated knockdown of pyruvate formate lyase (PFL1) provides evidence for an active 3-hydroxybutyrate production pathway in the green alga <i>Chlamydomonas reinhardtii</i>, JOURNAL OF BIOTECHNOLOGY, Vol: 162, Pages: 57-66, ISSN: 0168-1656
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- Citations: 18
Behrends V, Ryall B, Zlosnik JEA, et al., 2012, Metabolic adaptations of Pseudomonas aeruginosa during cystic fibrosis lung infections, INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, Vol: 302, Pages: 109-109, ISSN: 1438-4221
Geier FM, Fearn S, Bundy JG, et al., 2012, ToF-SIMS analysis of biomolecules in the modelorganism Caenorhabditis elegans, Surface and Interface Analysis, Vol: 45, Pages: 234-236
C.elegans is a biomedical key model organism as it is a simple, easy to maintain eukaryote, which shares many gene homologueswith higher mammals. As each of its cells has been traced during development and characterized by light microscopy, massspectrometry-based time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging seems to promise exciting new insights.In this study, we have investigated simple but basic factors for ToF-SIMS-based imaging of C.elegans. By comparing chemicalstandards and two authentic C. elegans mutant extracts (N2 and Daf-2), we found that for our purposes, Bi3+ is better suiteddue to its higher mass and spatial resolution. We also investigated the use of light microscopy slides as imaging substrates andgold coating as standard for mass calibration in higher mass ranges. Our findings and preliminary imaging results show thatToF-SIMS is a well-suited platform for mass spectrometry imaging.
Behrends V, Williams KJ, Jenkins VA, et al., 2012, Free glucosylglycerate is a marker of nitrogen stress in Mycobacterium smegmatis., Journal of Proteome Research
Davies SK, Leroi AM, Bundy JG, 2012, Fluorodeoxyuridine affects the identification of metabolic responses to <i>daf</i>-2 status in <i>Caenorhabditis elegans</i>, MECHANISMS OF AGEING AND DEVELOPMENT, Vol: 133, Pages: 46-49, ISSN: 0047-6374
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- Citations: 36
Ellis JK, Athersuch TJ, Thomas LD, et al., 2012, Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population., BMC medicine, Vol: 10, Pages: 61-61
Lawrence D, Fiegna F, Behrends V, et al., 2012, Species interactions alter evolutionary responses to a novel environment., PLoS Biol, Vol: 10
Studies of evolutionary responses to novel environments typically consider single species or perhaps pairs of interacting species. However, all organisms co-occur with many other species, resulting in evolutionary dynamics that might not match those predicted using single species approaches. Recent theories predict that species interactions in diverse systems can influence how component species evolve in response to environmental change. In turn, evolution might have consequences for ecosystem functioning. We used experimental communities of five bacterial species to show that species interactions have a major impact on adaptation to a novel environment in the laboratory. Species in communities diverged in their use of resources compared with the same species in monocultures and evolved to use waste products generated by other species. This generally led to a trade-off between adaptation to the abiotic and biotic components of the environment, such that species evolving in communities had lower growth rates when assayed in the absence of other species. Based on growth assays and on nuclear magnetic resonance (NMR) spectroscopy of resource use, all species evolved more in communities than they did in monocultures. The evolutionary changes had significant repercussions for the functioning of these experimental ecosystems: communities reassembled from isolates that had evolved in polyculture were more productive than those reassembled from isolates that had evolved in monoculture. Our results show that the way in which species adapt to new environments depends critically on the biotic environment of co-occurring species. Moreover, predicting how functioning of complex ecosystems will respond to an environmental change requires knowing how species interactions will evolve.
Spurgeon DJ, Lawlor A, Hooper HL, et al., 2011, Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure, ENVIRONMENTAL POLLUTION, Vol: 159, Pages: 3425-3432, ISSN: 0269-7491
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- Citations: 12
Tredwell GD, Behrends V, Geier FM, et al., 2011, Between-Person Comparison of Metabolite Fitting for NMR-Based Quantitative Metabolomics, ANALYTICAL CHEMISTRY, Vol: 83, Pages: 8683-8687, ISSN: 0003-2700
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- Citations: 44
Liebeke M, Bundy JG, 2011, Tissue disruption and extraction methods for metabolic profiling of an invertebrate sentinel species, Metabolomics
Metabolic profiling of tissues needs special attention, because the compartmentalization of cellular constituents will be abolished by sample homogenization. This loss of partitioning leads to protein and metabolite instability in extracts, and therefore metabolite extraction protocols need to ensure very rapid inactivation of mac- romolecules as well as solubilization of metabolites. There are many published methods for tissue metabolome anal- ysis, but no universally accepted standard, and a lack of measurable quality benchmarks. We developed a protocol for efficient tissue disruption and metabolite extraction of the earthworm Lumbricus rubellus guided by prior biological knowledge as well as metrics based on the data. In particular, we identified an unusual degree of instability of L. rubellus tissue extracts, and evaluated different approaches such as heating and filtration to counteract this. Finally, we evaluated four different solvent systems for comprehensive metabolite extraction using three analytical platforms (1H NMR spectroscopy, GC–MS, and direct- infusion FT-ICR-MS), and also compared bead-beating and cryogenic milling for tissue disruption. Initially we ranked methods by common analytical criteria (e.g. num- bers and total intensity of detected peaks) in order to compare protocols. These approaches to assess protocol suitability proved to be inadequate to judge earthworm tissue extraction methods because of sample instability.Existing tissue extraction protocols should not be assumed to be automatically applicable to novel species.
Behrends V, Tredwell GD, Bundy JG, 2011, A software complement to AMDIS for processing GC-MS metabolomic data, ANALYTICAL BIOCHEMISTRY, Vol: 415, Pages: 206-208, ISSN: 0003-2697
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- Citations: 104
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