A critical review of the postulated role of the non-essential amino acid, ß-N-methylamino-L-alanine, in neurodegenerative disease in humans.

The compound BMAA (ß-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer's disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

A bioengineering system for in situ bioremediation of contaminated groundwater.

Much of the past and current focus of bioremediation has been on laboratory studies of microbial processes. By necessity, early studies have ignored important field properties, parameters, and processes that control the ultimate success of in situ bioremediation of contaminated groundwater. This paper presents a bioengineering systems approach that examines the impact of some of these field variables on common bioremediation practices. Using simple systems, the niche of biostimulation is shown to be aquifers with high contaminant sorption. A novel gas-phase biostimulation filter and a novel resting-state bioaugmentation/biofilter approach which show promise for effective field implementation are discussed.

Biosorption of uranium by Pseudomonas aeruginosa strain CSU: characterization and comparison studies.

Pseudomonas aeruginosa strain CSU, a nongenetically engineered bacterial strain known to bind dissolved hexavalent uranium (as UO(2) (2+) and/or its cationic hydroxo complexes), was characterized with respect to its sorptive activity (equilibrium and dynamics). Living, heat-killed, permeabilized, and unreconstituted lyophilized cells were all capable of binding uranium. The uranium biosorption equilibrium could be described by the Langmuir isotherm. The rate of uranium adsorption increased following permeabilization of the outer and/or cytoplasmic membrane by organic solvents such as acetone. P. aeruginosa CSU biomass was significantly more sorptive toward uranium than certain novel, patented biosorbents derived from algal or fungal biomass sources. P. aeruginosa CSU biomass was also competitive with commercial cation-exchange resins, particularly in the presence of dissolved transition metals. Uranium binding by P. aeruginosa CSU was clearly pH dependent. Uranium loading capacity increased with increasing pH under acidic conditions, presumably as a function of uranium speciation and due to the H(+) competition at some binding sites. Nevertheless, preliminary evidence suggests that this microorganism is also capable of binding anionic hexavalent uranium complexes. Ferric iron was a strong inhibitor of uranium binding to P. aeruginosa CSU biomass, and the presence of uranium also decreased the Fe(3+) loading when the biomass was not saturated with Fe(3+), suggesting that Fe(3+) and uranium may share the same binding sites on biomass. Although the equilibrium loading capacity of uranium was greater than that of Fe(3+), this biomass showed preference of binding Fe(3+) over uranium. Thus, a two-stage process in which iron and uranium are removed in consecutive steps was proposed for efficient use of the biomass as a biosorbent in uranium removal from mine wastewater, especially acidic leachates.

Degradation of organic sulfur compounds by a coal-solubilizing fungus.

Paecilomyces sp. TLi, a coal-solubilizing fungus, was shown to degrade organic sulfur-containing coal substructure compounds. Dibenzothiophene was degraded via a sulfur-oxidizing pathway to 2,2'-dihydroxybiphenyl. No further metabolism of that compound was observed. Ethyl phenyl sulfide and diphenyl sulfide were degraded to the corresponding sulfones. A variety of products were formed from dibenzyl sulfide, presumably via free radical intermediates. Diphenyl disulfide and dibenzyl disulfide were cleaved to the corresponding thiols and other single-ring products. It was concluded that degradation of organic sulfur compounds by Paecilomyces involves an oxidative attack localized at the sulfur atom.

Binding of Dissolved Strontium by Micrococcus luteus.

Resting cells of Micrococcus luteus have been shown to remove strontium (Sr) from dilute aqueous solutions of SrCl(2) at pH 7. Loadings of 25 mg of Sr per g of cell dry weight were achieved by cells exposed to a solution containing 50 ppm (mg/liter) of Sr. Sr binding occurred in the absence of nutrients and did not require metabolic activity. Initial binding was quite rapid (<0.5 h), although a slow, spontaneous release of Sr was observed over time. Sr binding was inhibited in the presence of polyvalent cations but not monovalent cations. Ca and Sr were bound preferentially over all other cations tested. Sr-binding activity was localized on the cell envelope and was sensitive to various chemical and physical pretreatments. Bound Sr was displaced by divalent ions or by H. Other monovalent ions were less effective. Bound Sr was also removed by various chelating agents. It was concluded that Sr binding by M. luteus is a reversible equilibrium process. Both ion exchange mediated by acidic cell surface components and intracellular uptake may be involved in this activity.

Role of Veratryl Alcohol in Regulating Ligninase Activity in Phanerochaete chrysosporium.

Ligninase activity in Phanerochaete chrysosporium is stimulated by incubating cultures with various substrates for the enzyme, including veratryl (3,4-dimethoxybenzyl) alcohol, which is a secondary metabolite of this fungus. This study was designed to provide insight into the mechanism involved in this stimulation. Ligninase activity increased 2 to 4 h after the addition of exogenous veratryl alcohol to ligninolytic cultures. This increase was prevented by inhibitors of protein synthesis. Analysis of the extracellular proteins by high-performance anion-exchange liquid chromatography revealed increases in the amounts of some, but not all, ligninase species. The normal rapid decrease in ligninase activity in aging cultures was not prevented or retarded by veratryl alcohol, indicating that veratryl alcohol does not increase ligninase activity by protecting extant enzyme. We conclude that veratryl alcohol probably functions via an induction type of mechanism, affecting only certain ligninase species. Results with an isolated lignin indicate that lignin (or its biodegradation products) functions in the same way that veratryl alcohol does.

Factors Involved in the Regulation of a Ligninase Activity in Phanerochaete chrysosporium.

The regulation of an H(2)O(2)-dependent ligninolytic activity was examined in the wood decay fungus Phanerochaete chrysosporium. The ligninase appears in cultures upon limitation for nitrogen or carbohydrate and is suppressed by excess nutrients, by cycloheximide, or by culture agitation. Activity is increased by idiophasic exposure of cultures to 100% O(2). Elevated levels of ligninase and, in some cases, of extracellular H(2)O(2) production are detected after brief incubation of cultures with lignins or lignin substructure models, with the secondary metabolite veratryl alcohol, or with other related compounds. It is concluded that lignin degradation (lignin --> CO(2)) by this organism is regulated in part at the level of the ligninase, which is apparently inducible by its substrates or their degradation products.

Biochemistry of the oxidation of lignin by Phanerochaete chrysosporium.

The objective of this research was to identify the biochemical agents responsible for the oxidative degradation of lignin by the white-rot fungus Phanerochaete chrysosporium. We examined the hypothesis that activated oxygen species are involved, and we also sought the agent in ligninolytic cultures responsible for a specific oxidative degradative reaction in substructure model compounds. Results of studies of the production of activated oxygen species by cultures, of the effect of their removal on ligninolytic activity, and of their action on substructure model compounds support a role for hydrogen peroxide (H(2)O(2)) and possibly superoxide (O(2)(*)(-)) in lignin degradation. Involvement of hydroxyl radical (*OH) or singlet oxygen (1O(2)) is not supported by our data. The actual biochemical agent responsible for one important oxidative C-C bond cleavage reaction in non-phenolic lignin substructure model compounds, and in lignin itself, was found to be an enzyme. The enzyme is extracellular, has a molecular weight of 42,000 daltons, is azide-sensitive, and requires H(2)O(2) for activity.

Relationship Between Lignin Degradation and Production of Reduced Oxygen Species by Phanerochaete chrysosporium.

The relationship between the production of reduced oxygen species, hydrogen peroxide (H(2)O(2)), superoxide (O(2)), and hydroxyl radical (.OH), and the oxidation of synthetic lignin to CO(2) was studied in whole cultures of the white-rot fungus Phanerochaete chrysosporium Burds. The kinetics of the synthesis of H(2)O(2) coincided with the appearance of the ligninolytic system; also, H(2)O(2) production was markedly enhanced by growth under 100% O(2), mimicking the increase in ligninolytic activity characteristic of cultures grown under elevated oxygen tension. Lignin degradation by whole cultures was inhibited by a specific H(2)O(2) scavenger, catalase, implying a role for H(2)O(2) in the degradative process. Superoxide dismutase also inhibited lignin degradation, suggesting that O(2) is also involved in the breakdown of lignin. The production of .OH was assayed in whole cultures by a benzoate decarboxylation assay. Neither the kinetics of .OH synthesis nor the final activity of its producing system obtained under 100% O(2) correlated with that of the lignin-degrading system. However, lignin degradation was inhibited by compounds which react with .OH. It is concluded that H(2)O(2), and perhaps O(2), are involved in lignin degradation; because these species are relatively unreactive per se, their role must be indirect. Conclusions about a role for .OH in ligninolysis could not be reached.