Macroecological patterns and niche structure in a new marine food web

The integration of detailed information on feeding interactions with measures of abundance and body mass of individuals provides a powerful platform for understanding ecosystem organisation. Metabolism and, by proxy, body mass constrain the flux, turnover and storage of energy and biomass in food webs. Here, we present the first food web data for Lough Hyne, a species rich Irish Sea Lough. Through the application of individual-and size-based analysis of the abundance-body mass relationship, we tested predictions derived from the metabolic theory of ecology. We found that individual body mass constrained the flux of biomass and determined its distribution within the food web. Body mass was also an important determinant of diet width and niche overlap, and predator diets were nested hierarchically, such that diet width increased with body mass. We applied a novel measure of predator-prey biomass flux which revealed that most interactions in Lough Hyne were weak, whereas only a few were strong. Further, the patterning of interaction strength between prey sharing a common predator revealed that strong interactions were nearly always coupled with weak interactions. Our findings illustrate that important insights into the organisation, structure and stability of ecosystems can be achieved through the theoretical exploration of detailed empirical data.

Transport properties of protic ionic liquids, pure and in aqueous solutions: Effects of the anion and cation structure

Ionic conductivities of twelve protic ionic liquids (PILs) and their mixtures with water over the whole composition range are reported at 298.15 K and atmospheric pressure. The selected PILs are the pyrrolidinium-based PILs containing nitrate, acetate or formate anions; the formate-based PILs containing diisopropylethylammonium, amilaminium, quinolinium, lutidinium or collidinium cations; and the pyrrolidinium alkylcarboxylates, [Pyrr][CnH2n+1COO] with n = 5–8. This study was performed in order to investigate the influence of molecular structures of the ions on the ionic conductivities in aqueous solutions. The ionic conductivities of the aqueous solutions are 2–30 times higher than the conductivities of pure PILs. The maximum in conductivity varies from ww=0.41???to???0.74 and is related to the nature of cations and anions. The molar conductance and the molar conductance at infinite dilution for (PIL + water) solutions are then determined. Self-diffusion coefficients of the twelve protic ionic liquids in water at infinite dilution and at 298.15 K are calculated by using the Nernst–Haskell, the original and the modified Wilke–Chang equations. These calculations show that similar values are obtained using the modified Wilke–Chang and the Nernst–Haskell equations. Finally, the effective hydrodynamic (or Stokes) radius of the PILs was determined by using the Stokes–Einstein equation. A linear relationship was established in order to predict this radius as a function of the anion alkyl chain length in the case of the pyrrolidinium alkylcarboxylates PILs.

A phase I study of combined docetaxel and repeated high activity Re-186-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Purpose Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and Re-186-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity.

The synthesis and electronic structure of a novel [NiS4Fe2(CO)(6)] radical cluster: Implications for the active site of the [NiFe] hydrogenases

A novel [Ni'S-4'Fe-2(CO)(6)] cluster (1: 'S-4'=(CH3C6H3S2)(2)(CH2)(3)) has been synthesised, structurally characterised and has been shown to undergo a chemically reversible reduction process at -1.31 V versus Fc(+)/Fc to generate the EPR-active monoanion 1(-). Multifrequency Q-, X- and S-band EPR spectra of Ni-61-enriched 1(-) show a well-resolved quartet hyperfine splitting in the low-field region due to the interaction with a single Ni-61 (I = 3/2) nucleus. Simulations of the EPR spectra require the introduction of a single angle of non-coincidence between g, and A(1), and g(3) and A(3) to reproduce all of the features in the S- and X-band spectra. This behaviour provides a rare example of the detection and measurement of non-coincidence effects from frozen-solution EPR spectra without the need for single-crystal measurements, and in which the S-band experiment is sensitive to the non-coincidence. An analysis of the EPR spectra of 1(-) reveals a 24% Ni contribution to the SOMO in 1(-), supporting a delocalisation of the spin-density across the NiFe2 cluster. This observation is supported by IR spectroscopic results which show that the CO stretching frequencies, v(CO), shift to lower frequency by about 70 cm(-1) when 1 is reduced to 1(-). Density functional calculations provide a framework for the interpretation of the spectroscopic properties of 1(-) and suggest that the SOMO is delocalised over the whole cluster, but with little S-centre participation. This electronic structure contrasts with that of the Ni-A, -B, -C and -L forms of [NiFe] hydrogenase in which there is considerable S participation in the SOMO.

Effects of the organophosphorous pesticide, dimethoate, on cardiac and acetylcholinesterase (AChE) activity in the shore crab Carcinus maenas

The potential use of biochemical and physiological responses as biomarkers of organophosphate exposure and/or effect were assessed in the shore crab (Carcinus maenas). Male crabs were assigned to one of four dimethoate treatments (0, 0.5, 1.0 or 2.0 mg 1(-1)). Cardiac activity was measured non-invasively before and during dimethoate exposure using automated interpulse duration assessment. Heart rates decreased significantly in a concentration-dependent manner (p

Screening and Quantitative Confirmatory Method for the Analysis of Glucocorticoids in Bovine Milk Using Liquid Chromatography-Tandem Mass Spectrometry

An LC/MS/MS method was developed and validated for the simultaneous identification, confirmation, and quantification of 12 glucocorticoids in bovine milk. The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC. The developed method can detect and confirm the presence of dexamethasone, betamethasone, prednisolone, flumethasone, 6 alpha-methylprednisolone, fluorometholone, triamcinolone acetonide, prednisone, cortisone, hydrocortisone, clobetasol propionate, and clobetasol butyrate in bovine milk. Milk samples are extracted with acetonitrile; sodium chloride is subsequently added to aid partition of the milk and acetonitrile mixture. The acetonitrile extract is then subjected to liquid-liquid purification by the addition of hexane. The purified extract is evaporated to dryness and reconstituted in a water acetonitrile mixture, and determination is carried out by LC/MS/MS. The method permits analysis of up to 30 samples in 1 day.

Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity

Modulators of metabotropic glutamate receptor subtype 5 (mGluR5) may provide novel treatments for multiple central nervous system (CNS) disorders, including anxiety and schizophrenia. Although compounds have been developed to better understand the physiological roles of mGluR5 and potential usefulness for the treatment of these disorders, there are limitations in the tools available, including poor selectivity, low potency, and limited solubility. To address these issues, we developed an innovative assay that allows simultaneous screening for mGluR5 agonists, antagonists, and potentiators. We identified multiple scaffolds that possess diverse modes of activity at mGluR5, including both positive and negative allosteric modulators (PAMs and NAMs, respectively). 3-Fluoro-5-(3-(pyridine-2-yl)-1,2,4-oxadiazol-5-yl) benzonitrile (VU0285683) was developed as a novel selective mGluR5 NAM with high affinity for the 2-methyl-6-(phenyl-ethynyl)-pyridine (MPEP) binding site. VU0285683 had anxiolytic-like activity in two rodent models for anxiety but did not potentiate phen-cyclidine-induced hyperlocomotor activity. (4-Hydroxypiperidin-1-yl)(4-phenylethynyl) phenyl) methanone (VU0092273) was identified as a novel mGluR5 PAM that also binds to the MPEP site. VU0092273 was chemically optimized to an orally active analog, N-cyclobutyl-6-((3-fluorophenyl) ethynyl) nicotinamide hydrochloride (VU0360172), which is selective for mGluR5. This novel mGluR5 PAM produced a dose-dependent reversal of amphetamine-induced hyperlocomotion, a rodent model predictive of antipsychotic activity. Discovery of structurally and functionally diverse allosteric modulators of mGluR5 that demonstrate in vivo efficacy in rodent models of anxiety and antipsychotic activity provide further support for the tremendous diversity of chemical scaffolds and modes of efficacy of mGluR5 ligands. In addition, these studies provide strong support for the hypothesis that multiple structurally distinct mGluR5 modulators have robust activity in animal models that predict efficacy in the treatment of CNS disorders.

Tetrahexahedral Pt Nanocrystal Catalysts Decorated with Ru Adatoms and Their Enhanced Activity in Methanol Electrooxidation

Tetrahexahedral Pt nanocrystals (THH Pt NCs) bound by well-defined high index crystal planes offer exceptional electrocatalytic activity, owing to a high density of low-coordination surface Pt sites. We report, herein, on methanol electrooxidation at THH Pt NC electrodes studied by a combination of electrochemical techniques and in situ FTIR spectroscopy. Pure THH Pt NC surfaces readily facilitate the dissociative chemisorption of methanol leading to poisoning by strongly adsorbed CO. Decoration of the stepped surfaces by Ru adatoms increases the tolerance to poisoning and thereby reduces the onset potential for methanol oxidation by over 100 mV. The Ru modified THH Pt NCs exhibit greatly superior catalytic currents and CO2 yields in the low potential range, when compared with a commercial PtRu alloy nanoparticle catalyst. These results are of fundamental importance in terms of model nanoparticle electrocatalytic systems of stepped surfaces and also have practical significance in the development of surface tailored, direct methanol fuel cell catalysts.

Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric Modulator

Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molecular mechanisms mediating the activity of 4-chloro-alpha-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu(173) or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB.