Recent advances and fundamentals of microalgae cultivation technology.

Microalgae are considered to be a promising group of organisms for fuel production, waste processing, pharmaceutical applications, and as a source of food components. Unicellular algae are worth being considered because of their capacity to produce comparatively large amounts of lipids, proteins, and vitamins while requiring little room for growth. They can also grow on waste and fix CO2 and nitrogen compounds. However, production costs limit the industrial use of microalgae to the most profitable applications including micronutrient production and fish farming. Therefore, novel microalgae based technologies require an increase of the production efficiencies or values. Here we review the recent studies focused on getting strains with novel characteristics or cultivating techniques that improve production's robustness or efficiency and categorize these findings according to the fundamental factors that determine microalgae growth. Improvements of light and nutrient delivery, as well as other aspects of photobioreactor design, have shown the highest average increase in productivity. Other methods, such as an improvement of phosphorus or CO2 fixation and temperature adaptation have been found to be less effective. Furthermore, interactions with particular bacteria may promote the growth of microalgae, although bacterial and grazer contaminations must be managed to avoid culture failure. The competitiveness of the algal products will increase if these discoveries are applied to industrial settings.

Atomic-resolution three-dimensional structure of amyloid ß fibrils bearing the Osaka mutation.

Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high-resolution structural information on amyloid ß-peptide (Aß) fibrils, which are intimately linked with AD, is scarce. We report an atomic-resolution fibril structure of the Aß1-40 peptide with the Osaka mutation (E22Δ), associated with early-onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra- and intermolecular solid-state NMR distance restraints.

Solid-state NMR sequential assignment of Osaka-mutant amyloid-beta (Aß1-40 E22Δ) fibrils.

Alzheimer's disease (AD) is the most common form of dementia. Aggregation of amyloid ß (Aß), a peptide of 39-43 residues length, into insoluble fibrils is considered to initiate the disease. Determination of the molecular structure of Aß fibrils is technically challenging and is a significant goal in AD research that may lead to design of effective therapeutical inhibitors of Aß aggregation. Here, we present chemical-shift assignments for fibrils formed by highly pure recombinant Aß1-40 with the Osaka E22Δ mutation that is found in familial AD. We show that that all regions of the peptide are rigid, including the N-terminal part often believed to be flexible in Aß wt.

Direct evidence for self-propagation of different amyloid-ß fibril conformations.

BACKGROUND: Amyloid fibrils formed by amyloid-ß (Aß) peptides are associated with Alzheimer's disease and can occur in a range of distinct morphologies that are not uniquely determined by the Aß sequence. Whether distinct conformations of Aß fibrils can be stably propagated over multiple cycles of seeding and fibril growth has not been established experimentally. OBJECTIVE: The ability of the 40-residue peptide Aß1-40 to assemble into fibrils with the conformation of the mutant Aß1-40 peptide containing the 'Osaka' mutation E22Δ was investigated. METHODS: Fibril formation of highly pure, recombinant Aß1-40 in the presence of distinct, preformed seeds in vitro was recorded with thioflavin T fluorescence, and distinct fibrillar structures were identified and distinguished by fluorescence spectroscopy and electron microscopy. RESULTS: We propagated the specific quaternary structure of Aß1-40 E22Δ fibrils with wild-type Aß1-40 over up to seven cycles of seeding and fibril elongation. As a result of a 10(7)-fold dilution of the initially present Aß1-40 E22Δ seeds, the vast majority of fibrils formed after the seventh propagation cycle with Aß1-40 did not contain a single molecule of Aß1-40 E22Δ, but still retained the conformation of the initial Aß1-40 E22Δ seeds. Increased critical concentrations of Aß1-40 fibrils formed in the presence of Aß1-40 E22Δ nuclei suggest that these fibrils are less stable than homologously seeded Aß1-40 fibrils, consistent with a kinetically controlled mechanism of fibril formation. CONCLUSION: The propagation of a distinct Aß fibril conformation over multiple cycles of seeded fibril growth demonstrates the basic ability of the Aß peptide to form amyloid strains that in turn may cause phenotypes in Alzheimer's disease.

The Osaka FAD mutation E22Δ leads to the formation of a previously unknown type of amyloid ß fibrils and modulates Aß neurotoxicity.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cerebral deposition of amyloid fibrils formed by the amyloid ß (Aß) peptide. Aß has a length of 39-43 amino acid residues; the predominant Aß isoforms are Aß1-40 and Aß1-42. While the majority of AD cases occur spontaneously, a subset of early-onset familial AD cases is caused by mutations in the genes encoding the Aß precursor protein or presenilin 1/presenilin 2. Recently, a deletion of glutamic acid at position 22 within the Aß sequence (E22Δ) was identified in Japanese patients with familial dementia, but the aggregation properties of the deletion variant of Aß are not well understood. We investigated the aggregation characteristics and neurotoxicity of recombinantly expressed Aß isoforms 1-40 and 1-42 with and without the E22Δ mutation. We show that the E22Δ mutation strongly accelerates the fibril formation of Aß1-42 E22Δ compared to Aß1-42 wild type (wt). In addition, we demonstrate that fibrils of Aß1-40 E22Δ form a unique quaternary structure characterized by a strong tendency to form fibrillar bundles and a strongly increased thioflavin T binding capacity. Aß1-40 E22Δ was neurotoxic in rat primary neuron cultures as compared to nontoxic Aß1-40 wt. Aß1-42 E22Δ was less toxic than Aß1-42 wt, but it significantly decreased neurite outgrowth per cell in neuronal primary cultures. Because Aß1-40 is the major Aß form in vivo, the gain of toxic function caused by the E22 deletion may explain the development of familial AD in mutation carriers.