| 1. |
- Andrys, Rudolf, et al.
(författare)
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Improved detection of beta-N-methylamino-L-alanine using N-hydroxysuccinimide ester of N-butylnicotinic acid for the localization of BMAA in blue mussels (Mytilus edulis)
- 2015
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 407:13, s. 3743-3750
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Tidskriftsartikel (refereegranskat)abstract
- beta-N-Methylamino-l-alanine (BMAA) is an important non-protein amino acid linked to neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). Because it can be transferred and bioaccumulated higher up the food chain, it poses significant public health concerns; thus, improved detection methods are of prime importance for the identification and management of these toxins. Here, we report the successful use of N-hydroxysuccinimide ester of N-butylnicotinic acid (C-4-NA-NHS) for the efficient separation of BMAA from its isomers and higher sensitivity in detecting BMAA compared to the current method of choice using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization. Implementation of this efficient method allowed localization of BMAA in the non-visceral tissues of blue mussels, suggesting that more efficient depuration may be required to remove this toxin prior to consumption. This is a crucial method in establishing the absence or presence of the neurotoxic amino acid BMAA in food, environmental or biomedical samples.
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| 2. |
- Downing, Simone, et al.
(författare)
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Human Scalp Hair as an Indicator of Exposure to the Environmental Toxin -N-Methylamino-l-alanine
- 2018
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Dietary or aerosol exposure to the environmental neurotoxin -N-methylamino-l-alanine (BMAA) is a putative risk factor for the development of sporadic neurodegenerative disease. There are many potential sources of BMAA in the environment, but BMAA presence and quantities are highly variable. It has been suggested that BMAA in human hair may serve as an indicator of exposure. We sought to evaluate the use of the BMAA content of human scalp hair as an indicator of exposure, as well as the correlation between specific lifestyle or dietary habits, reported as hypothesised exposure risk factors, and BMAA in hair. Scalp hair samples and questionnaires were collected from participants in a small residential village surrounding a freshwater impoundment renowned for toxic cyanobacterial blooms. Data suggested a positive correlation between hair BMAA content and consumption of shellfish, and possibly pork. No statistically significant correlations were observed between hair BMAA content and residential proximity to the water or any other variable. Hair BMAA content was highly variable, and in terms of exposure, probably reflects primarily dietary exposure. However, the BMAA content of human hair may be affected to a great extent by several other factors, and as such, should be used with caution when evaluating human BMAA exposure, or correlating exposure to neurodegenerative disease incidence.
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| 3. |
- Faassen, Elisabeth J., et al.
(författare)
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A Collaborative Evaluation of LC-MS/MS Based Methods for BMAA Analysis : Soluble Bound BMAA Found to Be an Important Fraction
- 2016
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to beta-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of various analytical methods currently employed is rarely compared. A CYANOCOST initiated workshop was organized aimed at training scientists in BMAA analysis, creating mutual understanding and paving the way towards interlaboratory comparison exercises. During this workshop, we tested different methods (extraction followed by derivatization and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis, or directly followed by LC-MS/MS analysis) for trueness and intermediate precision. We adapted three workup methods for the underivatized analysis of animal, brain and cyanobacterial samples. Based on recovery of the internal standard D(3)BMAA, the underivatized methods were accurate (mean recovery 80%) and precise (mean relative standard deviation 10%), except for the cyanobacterium Leptolyngbya. However, total BMAA concentrations in the positive controls (cycad seeds) showed higher variation (relative standard deviation 21%-32%), implying that D(3)BMAA was not a good indicator for the release of BMAA from bound forms. Significant losses occurred during workup for the derivatized method, resulting in low recovery (<10%). Most BMAA was found in a trichloroacetic acid soluble, bound form and we recommend including this fraction during analysis.
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| 4. |
- Sigurlásdóttir, Sara, et al.
(författare)
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Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal
- 2017
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- The development of meningococcal disease, caused by the human pathogen Neisseria meningitidis, is preceded by the colonization of the epithelial layer in the nasopharynx. After initial adhesion to host cells meningococci form aggregates, through pilus-pilus interactions, termed microcolonies from which the bacteria later detach. Dispersal from microcolonies enables access to new colonization sites and facilitates the crossing of the cell barrier; however, this process is poorly understood. In this study, we used live-cell imaging to investigate the process of N. meningitidis microcolony dispersal. We show that direct contact with host cells is not required for microcolony dispersal, instead accumulation of a host-derived effector molecule induces microcolony dispersal. By using a host-cell free approach, we demonstrated that lactate, secreted from host cells, initiate rapid dispersal of microcolonies. Interestingly, metabolic utilization of lactate by the bacteria was not required for induction of dispersal, suggesting that lactate plays a role as a signaling molecule. Furthermore, Neisseria gonorrhoeae microcolony dispersal could also be induced by lactate. These findings reveal a role of host-secreted lactate in microcolony dispersal and virulence of pathogenic Neisseria.
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| 5. |
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| 6. |
- Zguna, Nadezda, et al.
(författare)
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Insufficient evidence for BMAA transfer in the pelagic and benthic food webs in the Baltic Sea
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The evidence regarding BMAA occurrence in the Baltic Sea is contradictory, with benthic sources appearing to be more important than pelagic ones. The latter is counterintuitive considering that the identified sources of this compound in the food webs are pelagic primary producers, such as diatoms, dinoflagellates, and cyanobacteria. To elucidate BMAA distribution, we analyzed BMAA in the pelagic and benthic food webs in the Northern Baltic Proper. As potential sources, phytoplankton communities were used. Pelagic food chain was represented by zooplankton, mysids and zooplanktivorous fish, whereas benthic invertebrates and benthivorous fish comprised the benthic chain. The trophic structure of the system was confirmed by stable isotope analysis. Contrary to the reported ubiquitous occurrence of BMAA in the Baltic food webs, only phytoplankton, zooplankton and mysids tested positive, whereas no measurable levels of this compound occurred in the benthic invertebrates and any of the tested fish species. These findings do not support the widely assumed occurrence and transfer of BMAA to the top consumers in the Baltic food webs. More controlled experiments and field observations are needed to understand the transfer and possible transformation of BMAA in the food web under various environmental settings.
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| 7. |
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| 8. |
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| 9. |
- Zguna, Nadezda, 1989-
(författare)
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Mass-spectrometry based survey of BMAA sources, distribution and transfer
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- β-methylaminoalanine (BMAA) is a neurotoxic non-protein amino acid first isolated from cycad seeds in 1967. It is believed to be connected to neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS) and is a ubiquitous compound produced by cyanobacteria, diatoms and dinoflagellates. Consequently, elucidating natural production, distribution and routes for human exposure of BMAA are of particular importance. However, the natural function of BMAA and its mechanisms of toxicity have not been fully established yet. The contradictory results about BMAA presence in cyanobacterial cultures and food webs have been reported by different scientific groups, which required the development of more sensitive and reliable analytical methods. This thesis is focused on the analytical chemistry dimension of BMAA research: covering both new method development and novel applications. New analytical methods for BMAA detection and quantification were developed, focusing on improving sensitivity, since BMAA is normally found in natural samples at low concentrations. In Paper I, a new derivatization technique was implemented, which increased sensitivity and selectivity in the analysis of BMAA and its isomers. Subsequently, this developed method was applied to determine the presence of BMAA in fat and oil matrices in Paper II, which is a step towards discovering BMAA forms other than the documented free and protein-bound BMAA species. In Paper III, a method for separation and quantification of L- and D-BMAA stereoisomers in complex biological matrix was developed and applied to determine the enantiomeric composition of BMAA in cycad seed. Studying environmental distribution of BMAA is important to evaluate potential exposure routes and health risks for humans. Part of the work was devoted to broaden assessment on environmental occurrence of BMAA by applying existing robust methodology to new samples, such as commercial seafood in Paper IV and Baltic Sea biota in Paper V. Some of the “overlooked” aspects in the existing BMAA literature (i.e., BMAA chiral analysis, possible BMAA presence in dietary oil supplements and defined food webs) were successfully addressed. Overall, the thesis presents important analytical developments, which can help to further elucidate sources, distribution and transfer of BMAA.
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| 10. |
- Zurita, Javier, et al.
(författare)
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Chiral separation of beta-Methylamino-alanine (BMAA) enantiomers after (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) derivatization and LC-MS/MS
- 2019
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Ingår i: Analytical Methods. - 1759-9660 .- 1759-9679. ; 11, s. 432-442
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Tidskriftsartikel (refereegranskat)abstract
- β-Methylamino-L-alanine, a neurotoxin first isolated from the seeds of cycad tree Cycas circinalis, is widely spread in a variety of environments. New sensitive techniques and robust methodologies are needed to detect its presence in complex biological samples and to further understand its biochemical properties. In this context, the determination of the enantiomeric composition of natural BMAA is of great importance. In this study, a simple and easily implemented LC-ESI-MS/MS method was developed to determine the presence of both D- and L-BMAA enantiomers in samples of cycad seed (Cycas micronesica). The samples were subjected to enzymatic hydrolysis to avoid racemization that occurs during strong acid hydrolysis. Derivatization with (+)-1-(9-fluorenyl)-ethyl chloroformate (FLEC) was performed prior to LC-ESI-MS/MS to produce chromatographically separable derivatives of D- and L-BMAA. Together with the retention time, two MRM transitions and their peak area ratios were used to identify the compounds. The LOQ obtained was 0.3 μg BMAA per g wet weight for each enantiomer. Method repeatability was within 3 RSD% both intraday and interday and accuracy was 98–108%. An accurate enantiomeric composition was obtained from the samples of cycad seed, where L- and D-BMAA were detected at 50.13 ± 0.05 and 4.08 ± 0.04 μg BMAA per g wet weight respectively (n = 3).
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