Evaluation of a Commercial Enzyme Linked Immunosorbent Assay (ELISA) for the Determination of the Neurotoxin BMAA in Surface Waters

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is suspected to play a role in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Because BMAA seems to be produced by cyanobacteria, surface waters are screened for BMAA. However, reliable analysis of BMAA requires specialized and expensive equipment. In 2012, a commercial enzyme-linked immunosorbent assay (ELISA) for determination of BMAA in surface waters was released. This kit could enable fast and relatively cheap screening of surface waters for BMAA. The objective of this study was to determine whether the BMAA ELISA kit was suitable for the determination of BMAA concentrations in surface waters. We hypothesised that the recovery of spiked samples was close to 100% and that the results of unspiked sample analysis were comparable between ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. However, we found that recovery was higher than 100% in most spiked samples, highest determined recovery was over 400%. Furthermore, the ELISA gave a positive signal for nearly each tested sample while no BMAA could be detected by LC-MS/MS. We therefore conclude that in its current state, the kit is not suitable for screening surface waters for BMAA

Limit on suppression of ionization in metastable neon traps due to long-range anisotropy

This paper investigates the possibility of suppressing the ionization rate in a magnetostatic trap of metastable neon atoms by spin-polarizing the atoms. Suppression of the ionization is critical for the possibility of reaching Bose-Einstein condensation with such atoms. We estimate the relevant long-range interactions for the system, consisting of electric quadrupole-quadrupole and dipole-induced dipole terms, and develop short-range potentials based on the Na_2 singlet and triplet potentials. The auto-ionization widths of the system are also calculated. With these ingredients we calculate the ionization rate for spin-polarized and for spin-isotropic samples, caused by anisotropy of the long-range interactions. We find that spin-polarization may allow for four orders of magnitude suppression of the ionization rate for Ne. The results depend sensitively on a precise knowledge of the interaction potentials, however, pointing out the need for experimental input. The same model gives a suppression ratio close to unity for metastable xenon in accordance with experimental results, due to a much increased anisotropy in this case.Comment: 15 pages including figures, LaTex/RevTex, uses epsfig.st

Synthesis of methylphosphonic acid by marine microbes: a source for methane in the aerobic ocean

Relative to the atmosphere, much of the aerobic ocean is supersaturated with methane; however, the source of this important greenhouse gas remains enigmatic. Catabolism of methylphosphonic acid by phosphorus-starved marine microbes, with concomitant release of methane, has been suggested to explain this phenomenon, yet methylphosphonate is not a known natural product, nor has it been detected in natural systems. Further, its synthesis from known natural products would require unknown biochemistry. Here we show that the marine archaeon Nitrosopumilus maritimus encodes a pathway for methylphosphonate biosynthesis and that it produces cell-associated methylphosphonate esters. The abundance of a key gene in this pathway in metagenomic data sets suggests that methylphosphonate biosynthesis is relatively common in marine microbes, providing a plausible explanation for the methane paradox

Coherent matter wave inertial sensors for precision measurements in space

We analyze the advantages of using ultra-cold coherent sources of atoms for matter-wave interferometry in space. We present a proof-of-principle experiment that is based on an analysis of the results previously published in [Richard et al., Phys. Rev. Lett., 91, 010405 (2003)] from which we extract the ratio h/m for 87Rb. This measurement shows that a limitation in accuracy arises due to atomic interactions within the Bose-Einstein condensate

A Comparative Study on Three Analytical Methods for the Determination of the Neurotoxin BMAA in Cyanobacteria

The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been considered a serious health threat because of its putative role in multiple neurodegenerative diseases. First reports on BMAA concentrations in cyanobacteria were alarming: nearly all cyanobacteria were assumed to contain high BMAA concentrations, implying ubiquitous exposure. Recent studies however question this presence of high BMAA concentrations in cyanobacteria. To assess the real risk of BMAA to human health, this discrepancy must be resolved. We therefore tested whether the differences found could be caused by the analytical methods used in different studies. Eight cyanobacterial samples and two control samples were analyzed by three commonly used methods: HPLC-FLD analysis and LC-MS/MS analysis of both derivatized and underivatized samples. In line with published results, HPLC-FLD detected relatively high BMAA concentrations in some cyanobacterial samples, while both LC-MS/MS methods only detected BMAA in the positive control (cycad seed sarcotesta). Because we could eliminate the use of different samples and treatments as causal factors, we demonstrate that the observed differences were caused by the analytical methods. We conclude that HPLC-FLD overestimated BMAA concentrations in some cyanobacterial samples due to its low selectivity and propose that BMAA might be present in (some) cyanobacteria, but in the low µg/g or ng/g range instead of the high µg/g range as sometimes reported before. We therefore recommend to use only selective and sensitive analytical methods like LC-MS/MS for BMAA analysis. Although possibly present in low concentrations in cyanobacteria, BMAA can still form a health risk. Recent evidence on BMAA accumulation in aquatic food chains suggests human exposure through consumption of fish and shellfish which expectedly exceeds exposure through cyanobacteria

Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?

The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential

Whole genome sequencing-based detection of antimicrobial resistance and virulence in non-typhoidal Salmonella enterica isolated from wildlife

The aim of this study was to generate a reference set of Salmonella enterica genomes isolated from wildlife from the United States and to determine the antimicrobial resistance and virulence gene profile of the isolates from the genome sequence data. We sequenced the whole genomes of 103 Salmonella isolates sampled between 1988 and 2003 from wildlife and exotic pet cases that were submitted to the Oklahoma Animal Disease Diagnostic Laboratory, Stillwater, Oklahoma. Among 103 isolates, 50.48% were from wild birds, 0.9% was from fish, 24.27% each were from reptiles and mammals. 50.48% isolates showed resistance to at least one antibiotic. Resistance against the aminoglycoside streptomycin was most common while 9 isolates were found to be multi-drug resistant having resistance against more than three antibiotics. Determination of virulence gene profile revealed that the genes belonging to csg operons, the fim genes that encode for type 1 fimbriae and the genes belonging to type III secretion system were predominant among the isolates. The universal presence of fimbrial genes and the genes encoded by pathogenicity islands 1-2 among the isolates we report here indicates that these isolates could potentially cause disease in humans. Therefore, the genomes we report here could be a valuable reference point for future traceback investigations when wildlife is considered to be the potential source of human Salmonellosis.Peer reviewedOklahoma Animal Disease Diagnostic Laborator

Application of geographic information systems and simulation modelling to dental public health: Where next?

Public health research in dentistry has used geographic information systems since the 1960s. Since then, the methods used in the field have matured, moving beyond simple spatial associations to the use of complex spatial statistics and, on occasions, simulation modelling. Many analyses are often descriptive in nature; however, and the use of more advanced spatial simulation methods within dental public health remains rare, despite the potential they offer the field. This review introduces a new approach to geographical analysis of oral health outcomes in neighbourhoods and small area geographies through two novel simulation methods-spatial microsimulation and agent-based modelling. Spatial microsimulation is a population synthesis technique, used to combine survey data with Census population totals to create representative individual-level population datasets, allowing for the use of individual-level data previously unavailable at small spatial scales. Agent-based models are computer simulations capable of capturing interactions and feedback mechanisms, both of which are key to understanding health outcomes. Due to these dynamic and interactive processes, the method has an advantage over traditional statistical techniques such as regression analysis, which often isolate elements from each other when testing for statistical significance. This article discusses the current state of spatial analysis within the dental public health field, before reviewing each of the methods, their applications, as well as their advantages and limitations. Directions and topics for future research are also discussed, before addressing the potential to combine the two methods in order to further utilize their advantages. Overall, this review highlights the promise these methods offer, not just for making methodological advances, but also for adding to our ability to test and better understand theoretical concepts and pathways

Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd