WAVECLOCK: wavelet analysis of circadian oscillation

Oscillations in mRNA and protein of circadian clock components can be continuously monitored in vitro using synchronized cell lines. These rhythms can be highly variable due to culture conditions and are non-stationary due to baseline trends, damping and drift in period length. We present a technique for characterizing the modal frequencies of oscillation using continuous wavelet decomposition to non-parametrically model changes in amplitude and period while removing baseline effects and noise. AVAILABILITY: The method has been implemented as the package waveclock for the free statistical software program R and is available for download from http://cran.r-project.org/     

Invited review: gender issues related to spaceflight: a NASA perspective.

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.     

Restoration of the Sieperda Tidal Marsh in the Scheldt Estuary, The Netherlands

Because of land reclamation, reinforcement of dikes, and the deepening of shipping channels, large areas of tidal marshes have been removed or eroded from the Scheldt estuary during the last two centuries. Tidal wetland restoration contributes toward compensating this loss of habitat. Not all restoration projects are meticulously planned, however; some are forced by nature. During a severe storm in 1990, a dike was breached in the brackish part of the Scheldt estuary and returned tidal influence to the Sieperda polder. In the 10 years since the dike breach, the former polder has changed into a brackish tidal marsh. Here we report on the geomorphologic and ecological developments that have taken place in the marsh. Tidal intrusion into the former polder turned crop fields into mudflats and changed pastures into salty marsh vegetation. The digging of a new creek improved marsh hydrology and enhanced tidal intrusion further into the marsh. Macrofauna typical of estuarine mudflats established rapidly in the developing marsh. Vegetation succession took place rapidly. Within 5 years, large areas of mudflats became covered with marsh vegetation. Birds characteristic of salt marshes were observed breeding or seen foraging in the marsh. The number of wading birds declined as areas of mudflat became overgrown. It is demonstrated that tidal flow is the engine to tidal marsh restoration. Tidal influence caused geomorphologic changes, which directed ecological developments in the former polder.     

Nitrogen and phosphorus limitation in a coastal barrier salt marsh: the implications for vegetation succession

1 A factorial fertilizer experiment was conducted in a 15-year-old coastal barrier salt marsh with a low soil nitrogen content, and in an older 100-year-old marsh with a higher nitrogen content. Plots were fertilized at high and low marsh elevations in both marshes. Nitrogen and phosphorus were applied at low and high concentrations both separately and in combination in each of 3 successive years.
2 Nitrogen limited above-ground plant growth in both young and old salt marshes in all years. Phosphorus limitation of plant growth was apparent in the first year in the young marsh and in the last year in both marshes. In young marshes with low soil organic matter, phosphorus limitation may occur. In addition, phosphorus limitation occurs at both successional stages when a marsh is saturated with nitrogen.
3 Plant species that are typical of nitrogen-rich habitats and late successional stages significantly increased in biomass after fertilization. Limonium vulgare , a low stature species of early and intermediate successional stages, decreased in biomass, whereas the taller Elymus pycnanthus and Artemisia maritima increased. After 3 years of fertilization, plant species composition in a young marsh was similar to the species composition in an unfertilized older marsh. Fertilization of a 100-year-old marsh, however, still resulted in a change in plant species composition, suggesting that succession was still occurring and that, overall, plants in marshes of different age are similar in their response to fertilization.     

Interaction of the Molecular Chaperone DNAJB6 with Growing Amyloid-beta 42 (Aβ42) Aggregates Leads to Sub-stoichiometric Inhibition of Amyloid Formation

The human molecular chaperone protein DNAJB6 was recently found to inhibit the formation of amyloid fibrils from polyglutamine peptides associated with neurodegenerative disorders such as Huntington disease. We show in the present study that DNAJB6 also inhibits amyloid formation by an even more aggregation-prone peptide (the amyloid-beta peptide, Aβ42, implicated in Alzheimer disease) in a highly efficient manner. By monitoring fibril formation using Thioflavin T fluorescence and far-UV CD spectroscopy, we have found that the aggregation of Aβ42 is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide. Quantitative kinetic analysis and immunochemistry studies suggest that the high inhibitory efficiency is due to the interactions of the chaperone with aggregated forms of Aβ42 rather than the monomeric form of the peptide. This interaction prevents the growth of such species to longer fibrils and inhibits the formation of new amyloid fibrils through both primary and secondary nucleation. A low dissociation rate of DNAJB6 from Aβ42 aggregates leads to its incorporation into growing fibrils and hence to its gradual depletion from solution with time. When DNAJB6 is eventually depleted, fibril proliferation takes place, but the inhibitory activity can be prolonged by introducing DNAJB6 at regular intervals during the aggregation reaction. These results reveal the highly efficacious mode of action of this molecular chaperone against protein aggregation, and demonstrate that the role of molecular chaperones can involve interactions with multiple aggregated species leading to the inhibition of both principal nucleation pathways through which aggregates are able to form.     

Mineralocorticoid Receptors Guide Spatial and Stimulus-Response Learning in Mice

Adrenal corticosteroid hormones act via mineralocorticoid (MR) and glucocorticoid receptors (GR) in the brain, influencing learning and memory. MRs have been implicated in the initial behavioral response in novel situations, which includes behavioral strategies in learning tasks. Different strategies can be used to solve navigational tasks, for example hippocampus-dependent spatial or striatum-dependent stimulus-response strategies. Previous studies suggested that MRs are involved in spatial learning and induce a shift between learning strategies when animals are allowed a choice between both strategies. In the present study, we further explored the role of MRs in spatial and stimulus-response learning in two separate circular holeboard tasks using female mice with forebrain-specific MR deficiency and MR overexpression and their wildtype control littermates. In addition, we studied sex-specific effects using male and female MR-deficient mice. First, we found that MR-deficient compared to control littermates and MR-overexpressing mice display altered exploratory and searching behavior indicative of impaired acquisition of novel information. Second, female (but not male) MR-deficient mice were impaired in the spatial task, while MR-overexpressing female mice showed improved performance in the spatial task. Third, MR-deficient mice were also impaired in the stimulus-response task compared to controls and (in the case of females) MR-overexpressing mice. We conclude that MRs are important for coordinating the processing of information relevant for spatial as well as stimulus-response learning.