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    ABSTRACT: Echinoderms are of special interest for studies in comparative endocrinology because of their phylogenetic position in the animal kingdom as deuterostomian invertebrates. Furthermore, their pentaradial symmetry as adult animals provides a unique context for analysis of the physiological and behavioural roles of peptide signalling systems. Here we report the first extensive survey of neuropeptide and peptide hormone precursors in a species belonging to the class Holothuroidea. Transcriptome sequence data obtained from the sea cucumber Apostichopus japonicus were analysed to identify homologs of precursor proteins that have recently been identified in the sea urchin Strongylocentrotus purpuratus (class Echinoidea). A total of seventeen precursor proteins have been identified in A. japonicus, including precursors of peptides related to thyrotropin-releasing hormone, pedal peptide / orcokinin-type peptides, AN peptides / tachykinins, luqins, corticotropin-releasing hormone (CRH), GPA2-type glycoprotein hormone subunits and bursicon. In addition, an unusual finding was an A. japonicus calcitonin-type precursor protein (AjCTLPP), the first to be discovered that comprises two calcitonin-like peptides; this contrasts with the products of the alternatively-spliced calcitonin/CGRP gene in vertebrates, which comprise either calcitonin or CGRP. Collectively, the data obtained provide new insights on the evolution and diversity of neuropeptides and polypeptide hormones. Furthermore, because A. japonicus is one of several sea cucumber species that are used for human consumption, our findings may have practical and economic impact by providing a basis for neuroendocrine-based strategies to improve methods of aquaculture.
    General and Comparative Endocrinology 12/2013;
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    ABSTRACT: The thylakoid membranes of cyanobacteria are the major site of respiratory electron transport as well as the photosynthetic light reactions. The photosynthetic and respiratory electron transport chains share some components, and their presence in the same membrane opens up the possibility for a variety of "unorthodox" electron transport routes. Many of the theoretically possible electron transport pathways have indeed been detected in particular species and circumstances. Electron transport has a crucial impact on the redox balance of the cell and therefore the pathways of electron flow in the cyanobacterial thylakoid membrane must be tightly regulated. This review summarises what is known of cyanobacterial electron transport components, their interactions and their sub-cellular location. The role of thylakoid membrane organisation in controlling electron transport pathways is discussed with respect to recent evidence that the larger-scale distribution of complexes in the membrane is important for controlling electron exchange between the photosynthetic and respiratory complexes. The distribution of complexes on scales of 100nm or more is under physiological control, showing that larger-scale thylakoid membrane re-arrangement is a key factor in controlling the crosstalk between photosynthetic and respiratory electron transport. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.
    Biochimica et Biophysica Acta 12/2013;
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    ABSTRACT: Variation in prey resources influences the diet and behaviour of predators. When prey become limiting, predators may travel farther to find preferred food or adjust to existing local resources. When predators are habitat limited, local resource abundance impacts foraging success. We analysed the diet of Myotis lucifugus (little brown bats) from Nova Scotia (eastern Canada) to the Northwest Territories (north-western Canada). This distribution includes extremes of season length and temperature and encompasses colonies on rural monoculture farms, and in urban and unmodified areas. We recognized nearly 600 distinct species of prey, of which ≈30% could be identified using reference sequence libraries. We found a higher than expected use of lepidopterans, which comprised a range of dietary richness from ≈35% early in the summer to ≈55% by late summer. Diptera were the second largest prey group consumed, representing ≈45% of dietary diversity early in the summer. We observed extreme local dietary variability and variation among seasons and years. Based on the species of insects that were consumed, we observed that two locations support prey species with extremely low pollution and acidification tolerances, suggesting that these are areas without environmental contamination. We conclude that there is significant local population variability in little brown bat diet that is likely driven by seasonal and geographical changes in insect diversity, and that this prey may be a good indicator of environment quality.
    Molecular Ecology 11/2013;
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    ABSTRACT: In the present study we address the following questions: 1) How is performance affected when patients with Parkinson's Disease (PD) perform a dynamic decision making task? 2) Does dopaminergic medication differentially affect dynamic decision making? Participants were trained with different goals during learning: either they made intervention-based decisions or prediction-based decisions during learning. The findings show that overall there is an advantage for those trained to intervene over those trained to predict. In addition, the results are the first demonstration that PD patients 'On' (N=20) compared to 'Off' L-Dopa (N=15) medication and also relative to Healthy age matched controls (N=16) showed lower levels of relative improvement in the accuracy of their decisions in a dynamic decision making task, and tended to use sub-optimal strategies. These findings provide support for the 'Dopamine Overdose' hypothesis using a novel decision making task, and suggest that executive functions such as decision making can be adversely affected by dopaminergic medication in PD.
    Neuropsychologia 11/2013;
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    ABSTRACT: The neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide), which share sequence similarity, were discovered in the starfish Asterias rubens and are prototypical members of the SALMFamide family of neuropeptides in echinoderms. SALMFamide neuropeptides act as muscle relaxants and both S1 and S2 cause relaxation of cardiac stomach and tube foot preparations in vitro but S2 is an order of magnitude more potent than S1. Here we investigated a structural basis for this difference in potency using spectroscopic techniques. Circular dichroism spectroscopy showed that S1 does not have a defined structure in aqueous solution and this was supported by 2D nuclear magnetic resonance experiments. In contrast, we found that S2 has a well-defined conformation in aqueous solution. However, the conformation of S2 was concentration dependent, with increasing concentration inducing a transition from an unstructured to a structured conformation. Interestingly, this property of S2 was not observed in an N-terminally truncated analog of S2 (short S2 or SS2; SFNSGLTFamide). Collectively, the data obtained indicate that the N-terminal region of S2 facilitates peptide self-association at high concentrations, which may have relevance to the biosynthesis and/or bioactivity of S2 in vivo.
    Biochimica et Biophysica Acta 11/2013;
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    ABSTRACT: Molecular phylogenetics has rapidly established the evolutionary positions of most major mammal groups [1, 2], yet analyses have repeatedly failed to agree on that of bats (order Chiroptera) [3-6]. Moreover, the relationship among the major bat lineages has proven equally contentious, with ongoing disagreements about whether echolocating bats are paraphyletic [7-9] or a true group [10] having profound implications for whether echolocation evolved once or possibly multiple times. By generating new bat genome data and applying model-based phylogenomic analyses designed to accommodate heterogeneous evolutionary processes [4, 11], we show that-contrary to recent suggestions-bats are not closely related to odd-toed ungulates but instead have a more ancient origin as sister group to a large clade of carnivores, ungulates, and cetaceans. Additionally, we provide the first genome-scale support showing that laryngeal echolocating bats are not a true group and that this paraphyly is robust to their position within mammals. We suggest that earlier disagreements in the literature may reflect model misspecification, long-branch artifacts, poor taxonomic coverage, and differences in the phylogenetic markers used. These findings are a timely reminder of the relevance of experimental design and careful statistical analysis as we move into the phylogenomic era.
    Current biology: CB 10/2013;
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    ABSTRACT: Many of the nitroaromatic agents used in medicine function as prodrugs and must undergo activation before exerting their toxic effects. In most cases this is catalysed by FMN-dependent type I nitroreductases (NTRs), a class of enzyme absent from higher eukaryotes but expressed by bacteria and several eukaryotic microbes including trypanosomes and Leishmania. Here, we utilize this difference to evaluate whether a library of aziridinyl nitrobenzamides have activity against Leishmania major. Biochemical screens using purified L. major NTR (LmNTR) revealed that compounds containing an aziridinyl-2,4-dinitrobenzyl core were effective substrates for the enzyme and showed that the 4-nitro group was important for this activity. To facilitate drug screening against intracellular amastigote parasites, we generated leishmanial cells that expressed the luciferase reporter gene and optimized a mammalian infection model in a 96-well plate format. A subset of aziridinyl-2,4-dinitrobenzyl compounds possessing a 5-amide substituent displayed significant growth inhibitory properties against the parasite, with the most potent agents generating 50 % inhibitory concentrations of <100 nM towards the intracellular form. This antimicrobial activity was shown to be LmNTR specific since L. major NTR(+/-) heterozygote parasites were slightly resistance to the most aziridinyl dinitrobenzyl agents tested. When the most potent leishmanicidal agents were screened against the mammalian cells in which the amastigote parasites were propagated, no growth inhibitory effect was observed at concentration up to 100 μM. We conclude that the aziridinyl nitrobenzamides represent a new lead structure that may have the potential to treat leishmanial infections.
    Antimicrobial Agents and Chemotherapy 10/2013;
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    ABSTRACT: Get on top of your chemistry! An "on water", palladium-catalyzed, phosphine-free direct CH arylation of indoles, with iodoarenes at 25-30 °C, is disclosed (see scheme; TBDMS=N-tert-butyldimethylsilyl ether). The generality and mildness of the reaction conditions is a significant advance in direct indole arylation, as it permits the tolerance of a variety of N1-protected indoles.
    Chemistry 10/2013;
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    ABSTRACT: There is enormous interest in molecular self-assembly and the development of biological systems to form smart nanostructures for biotechnology (so-called 'bottom-up fabrications'). Repeat proteins are ideal choices for development of such systems as they: (i) possess a relatively simple relationship between sequence, structure and function; (ii) are modular and non-globular in structure; (iii) act as diverse scaffolds for the mediation of a diverse range of protein-protein interactions; and (iv) have been extensively studied and successfully engineered and designed. In the present review, we summarize recent advances in the use of engineered repeat proteins in the self-assembly of novel materials, nanostructures and biosensors. In particular, we show that repeat proteins are excellent monomeric programmable building blocks that can be triggered to associate into a range of morphologies and can readily be engineered as stimuli-responsive biofunctional materials.
    Biochemical Society Transactions 10/2013; 41(5):1152-8.
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    ABSTRACT: Jeffery et al. suggest that three-dimensional environments are not represented according to their volumetric properties, but in a quasi-planar fashion. Here we take into consideration the role of visual experience and the use of technology for spatial learning to better understand the nature of the preference of horizontal over vertical spatial representation.
    Behavioral and Brain Sciences 10/2013; 36(5):559-560.
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