A Tropical Freshwater Wetland: I. Structure,Growth, and Regeneration

Forested wetlands dominated by Terminalia carolinensis are endemic to Micronesia but common only on the island of Kosrae, Federated States of Micronesia. On Kosrae, these forests occur on Nansepsep, Inkosr, and Sonahnpil soil types, which differ in degree of flooding and soil saturation. We compared forest structure, growth, nutrition, and regeneration on two sites each on Nansepsep and Inkosr soils and one site on the much less common Sonahnpil soil type. Terminalia tree sizes were similar on all three soil types, but forests differed in total basal area, species of smaller trees, and total plant species diversity. Terminalia regeneration was found only on the Inkosr soil type, which had the highest water table levels. Other Terminalia species are relatively light demanding, and T. carolinensis exhibited similar characteristics. It is therefore likely that Terminalia requires periodic, but perhaps naturally rare, stand-replacing disturbances (e.g., typhoons) in order to maintain its dominance, except on the wettest sites, where competition from other species is reduced. Terminalia swamps in the Nansepsep soil type appeared to be at the greatest risk of conversion to other uses, but swamps on all three types may face greater pressure as Kosrae's population increases and the island's infrastructure becomes more developed.     

Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an enethiolate intermediate with a mechanism-based inactivating agent

Phosphopantothenoylcysteine decarboxylase (PPC-DC) catalyzes the decarboxylation of the cysteine moiety of 4'-phosphopantothenoylcysteine (PPC) to form 4'-phosphopantetheine (PPantSH); this reaction forms part of the biosynthesis of coenzyme A. The enzyme is a member of the larger family of cysteine decarboxylases including the lantibiotic-biosynthesizing enzymes EpiD and MrsD, all of which use a tightly bound flavin cofactor to oxidize the thiol moiety of the substrate to a thioaldehyde. The thioaldehyde serves to delocalize the charge that develops in the subsequent decarboxylation reaction. In the case of PPC-DC enzymes the resulting enethiol is reduced to a thiol giving net decarboxylation of cysteine, while in EpiD and MrsD it is released as the final product of the reaction. In this paper, we describe the characterization of the novel cyclopropyl-substituted product analogue 4'-phospho-N-(1-mercaptomethyl-cyclopropyl)-pantothenamide (PPanDeltaSH) as a mechanism-based inhibitor of the human PPC-DC enzyme. This inhibitor alkylates the enzyme on Cys(173), resulting in the trapping of a covalently bound enethiolate intermediate. When Cys(173) is exchanged for the weaker acid serine by site-directed mutagenesis the enethiolate reaction intermediate also accumulates. This suggests that Cys(173) serves as an active site acid in the protonation of the enethiolate intermediate in PPC-DC enzymes. We propose that this protonation step is the key mechanistic difference between the oxidative decarboxylases EpiD and MrsD (which have either serine or threonine at the corresponding position in their active sites) and PPC-DC enzymes, which also reduce the intermediate in an overall simple decarboxylation reaction.     

Testing meter, rhythm, and tempo discriminations in pigeons

Rhythmic grouping and discrimination is fundamental to music. When compared to the perception of pitch, rhythmic abilities in animals have received scant attention until recently. In this experiment, four pigeons were tested with three types of auditory rhythmic discriminations to investigate their processing of this aspect of sound and music. Two experiments examined a meter discrimination in which successively presented idiophonic sounds were repeated in meters of different lengths in a go/no-go discrimination task. With difficulty, the birds eventually learned to discriminate between 8/4 and 3/4 meters constructed from cymbal and tom drum sounds at 180 beats per minute. This discrimination subsequently transferred to faster tempos, but not to different drum sounds or their combination. Experiment 3 tested rhythmic and arrhythmic patterns of sounds. After 40 sessions of training, these same pigeons showed no discrimination. Experiment 4 tested repetitions of a piano sound at fast and slow tempos. This discrimination was readily learned and showed transfer to novel tempos. The pattern of results suggests that pigeons can time periodic auditory events, but their capacity to understand generalized rhythmic groupings appears limited.     

Voltage clamp methods for the study of membrane currents and SR Ca(2+) release in adult skeletal muscle fibres

Skeletal muscle excitation-contraction (E-C)(1) coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)(2) Ca(2+) release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca(2+), due to depolarization-initiated SR Ca(2+) release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or 'high resistance gap' techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca(2+) signalling properties of mouse skeletal muscle membranes are being investigated.     

Gene flow at major transitional areas in sea bass (Dicentrarchus labrax) and the possible emergence of a hybrid swarm

The population genetic structure of sea bass (Dicentrarchus labrax) along a transect from the Atlantic Ocean (AO) to the Eastern Mediterranean (EM) Sea differs from that of most other marine taxa in this area. Three populations (AO, Western Mediterranean [WM], EM) are recognized today, which were originally two allopatric populations. How two ancestral genetic units have evolved into three distinct units has not been addressed yet. Therefore, to investigate mechanisms that lead to the emergence of the central WM population, its current status, and its connectivity with the two parental populations, we applied 20 nuclear loci that were either gene associated or gene independent. Results confirmed the existence of three distinct gene pools, with higher differentiation at two transitional areas, the Almeria‐Oran Front (AOF) and of the Siculo‐Tunisian Strait (STS), than within any population. Significant linkage disequilibrium and heterozygote excess indicated that the STS is probably another tension zone, as already described for the AOF. Neutrality tests fail to reveal marker loci that could be driven by selection within or among metapopulations, except for locus DLA0068. Collectively, results support that the central WM population arose by trapping two tensions zones at distinct geographic locations of limited connectivity. Population assignment further revealed that WM individuals were more introgressed than individuals from the other two metapopulations. This suggests that this population might result from hybrid swarming, and was or is still seeded by genes received through the filter of each tension zone.     

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database

Background

Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy.

Methods and Findings

FDA Drug Approval Packages for eight second-generation antipsychotics—aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone—were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant.

Conclusions

The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. Please see later in the article for the Editors'' Summary     

Microbial communities in contaminated sediments, associated with bioremediation of uranium to submicromolar levels

Microbial enumeration, 16S rRNA gene clone libraries, and chemical analysis were used to evaluate the in situ biological reduction and immobilization of uranium(VI) in a long-term experiment (more than 2 years) conducted at a highly uranium-contaminated site (up to 60 mg/liter and 800 mg/kg solids) of the U.S. Department of Energy in Oak Ridge, TN. Bioreduction was achieved by conditioning groundwater above ground and then stimulating growth of denitrifying, Fe(III)-reducing, and sulfate-reducing bacteria in situ through weekly injection of ethanol into the subsurface. After nearly 2 years of intermittent injection of ethanol, aqueous U levels fell below the U.S. Environmental Protection Agency maximum contaminant level for drinking water and groundwater (<30 microg/liter or 0.126 microM). Sediment microbial communities from the treatment zone were compared with those from a control well without biostimulation. Most-probable-number estimations indicated that microorganisms implicated in bioremediation accumulated in the sediments of the treatment zone but were either absent or in very low numbers in an untreated control area. Organisms belonging to genera known to include U(VI) reducers were detected, including Desulfovibrio, Geobacter, Anaeromyxobacter, Desulfosporosinus, and Acidovorax spp. The predominant sulfate-reducing bacterial species were Desulfovibrio spp., while the iron reducers were represented by Ferribacterium spp. and Geothrix spp. Diversity-based clustering revealed differences between treated and untreated zones and also within samples of the treated area. Spatial differences in community structure within the treatment zone were likely related to the hydraulic pathway and to electron donor metabolism during biostimulation.