Opportunities for improvements in flocking models

Flocking is the capacity of coherent movement between multiple animals, including birds. Prominent research into flocking is presented. Particle Swarm Optimisation (PSO) has been the prominent result from research into flocking. It is considered that opportunities for further research in flocking exist. With the potential for automated traffic systems, it is concluded that flocking should be reinvestigated for this purpose.

Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the anti-epileptiform and anti-seizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of status epilepticus-like epileptiform activity in hippocampal brain slices via multi-electrode array (MEA) recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude (in CA1 and dentate gyrus (DG) regions) and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1, only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10 and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole (PTZ) model of generalised seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality in comparison to vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in [(35)S]GTPgammaS assays in cortical membranes. These findings suggest that CBD acts to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel anti-epileptic drug (AED) in the unmet clinical need associated with generalised seizures.

How global is the global biodiversity information facility?

There is a concerted global effort to digitize biodiversity occurrence data from herbarium and museum collections that together offer an unparalleled archive of life on Earth over the past few centuries. The Global Biodiversity Information Facility provides the largest single gateway to these data. Since 2004 it has provided a single point of access to specimen data from databases of biological surveys and collections. Biologists now have rapid access to more than 120 million observations, for use in many biological analyses. We investigate the quality and coverage of data digitally available, from the perspective of a biologist seeking distribution data for spatial analysis on a global scale. We present an example of automatic verification of geographic data using distributions from the International Legume Database and Information Service to test empirically, issues of geographic coverage and accuracy. There are over 1/2 million records covering 31% of all Legume species, and 84% of these records pass geographic validation. These data are not yet a global biodiversity resource for all species, or all countries. A user will encounter many biases and gaps in these data which should be understood before data are used or analyzed. The data are notably deficient in many of the world's biodiversity hotspots. The deficiencies in data coverage can be resolved by an increased application of resources to digitize and publish data throughout these most diverse regions. But in the push to provide ever more data online, we should not forget that consistent data quality is of paramount importance if the data are to be useful in capturing a meaningful picture of life on Earth.

Eukaryotic expression: developments for structural proteomics

The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe ( SPINE) consortium have developed and implemented high- throughput ( HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast ( Pichia pastoris and Saccharomyces cerevisiae), baculovirusinfected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for coexpression, selenomethionine labelling ( in all three eukaryotic systems) and control of glycosylation ( for secreted proteins in mammalian cells) are assessed.

Investigation of cooperativity in the binding of ligands to the D-2 dopamine receptor

The D 2 dopamine receptor exists as dimers or as higher-order oligomers, as determined from data from physical experiments. In this study, we sought evidence that this oligomerization leads to cooperativity by examining the binding of three radioligands ([H-3] nemonapride, [H-3] raclopride, and [H-3] spiperone) to D 2 dopamine receptors expressed in membranes of Sf9 cells. In saturation binding experiments, the three radioligands exhibited different B-max values, and the B-max values could be altered by the addition of sodium ions to assays. Despite labeling different numbers of sites, the different ligands were able to achieve full inhibition in competition experiments. Some ligand pairs also exhibited complex inhibition curves in these experiments. In radioligand dissociation experiments, the rate of dissociation of [H-3] nemonapride or [H-3] spiperone depended on the sodium ion concentration but was independent of the competing ligand. Although some of the data in this study are consistent with the behavior of a cooperative oligomeric receptor, not all of the data are in agreement with this model. It may, therefore, be necessary to consider more complex models for the behavior of this receptor.

Glycosaminoglycans and protein disulfide isomerase-mediated reduction of HIV Env

Conformational changes within the human immunodeficiency virus-1 (HIV-1) surface glycoprotein gp120 result from binding to the lymphocyte surface receptors and trigger gp41-mediated virus/cell membrane fusion. The triggering of fusion requires cleavage of two of the nine disulfide bonds of gp120 by a cell-surface protein disulfide-isomerase (PDI). Soluble glycosaminoglycans such as heparin and heparan sulfate bind gp120 via V3 and, possibly, a CD4-induced domain. They exert anti-HIV activity by interfering with the HIV envelope glycoprotein ( Env)/cell-surface interaction. Env also binds cell-surface glycosaminoglycans. Here, using surface plasmon resonance, we observed an inverse relationship between heparin binding by gp120 and its thiol content. In vitro, and in conditions in which gp120 could bind CD4, heparin and heparan sulfate reduced PDI-mediated gp120 reduction by approximately 80%. Interaction of Env with the surface of lymphocytes treated using sodium chlorate, an inhibitor of glycosaminoglycan synthesis, led to gp120 reduction. We conclude that besides their capacity to block Env/cell interaction, soluble glycosaminoglycans can effect anti-HIV activity via interference with PDI- mediated gp120 reduction. In contrast, their presence at the cell surface is dispensable for Env reduction during the course of interaction with the lymphocyte surface. This work suggests that the reduction of exofacial proteins in various diseases can be inhibited by compounds targeting the substrates ( not by targeting PDI, as is usually done), and that glycosaminoglycans that primarily protect proteins by preserving them from proteolysis also have a role in preventing reduction.

Domain swapping in the human histamine H-1 receptor

G-protein-coupled receptors (GPCRs) represent the largest family of receptors involved in transmembrane signaling. Although these receptors were generally believed to be monomeric entities, accumulating evidence supports the presence of GPCRs in multimeric forms. Here, using immunoprecipitation as well as time-resolved fluorescence resonance energy transfer to assess protein-protein interactions in living cells, we unambiguously demonstrate the occurrence of dimerization of the human histamine H-1 receptor. We also show the presence of domain-swapped H-1 receptor dimers in which there is the reciprocal exchange of transmembrane domain TM domains 6 and 7 between the receptors present in the dimer. Mutation of aspartate(107) in transmembrane (TM) 3 or phenylalanine(432) in TM6 to alanine results in two radioligand-binding-deficient mutant H-1 receptors. Coexpression of H-1 D(107)A and H-1 F(432)A, however, results in a reconstituted radioligand binding site that exhibits a pharmacological profile that corresponds to the wildtype H-1 receptor. Interestingly, the H-1 receptor radioligands [H-3] mepyramine and [H-3]-(-)- trans-1-phenyl-3-N, N-dimethylamino-1,2,3,4-tetrahydronaphthalene show differential saturation binding values (B-max) for wild-type H-1 receptors but not for the radioligand binding site that is formed upon coexpression of H-1 D(107)A and H-1 F(432)A receptors, suggesting the presence of different H-1 receptor populations.

Mechanisms of agonist action at D-2 dopamine receptors

In this study, we investigated the biochemical mechanisms of agonist action at the G protein-coupled D-2 dopamine receptor expressed in Chinese hamster ovary cells. Stimulation of guanosine 5'-O-(3-[S-35]thio) triphosphate ([S-35]GTPgammaS) binding by full and partial agonists was determined at different concentrations of [S-35]GTPgammaS (0.1 and 10 nM) and in the presence of different concentrations of GDP. At both concentrations of [S-35]GTPgammaS, increasing GDP decreased the [S-35]GTPgammaS binding observed with maximally stimulating concentrations of agonist, with partial agonists exhibiting greater sensitivity to the effects of GDP than full agonists. The relative efficacy of partial agonists was greater at the lower GDP concentrations. Concentration-response experiments were performed for a range of agonists at the two [S-35]GTPgammaS concentrations and with different concentrations of GDP. At 0.1 nM [S-35]GTPgammaS, the potency of both full and partial agonists was dependent on the GDP concentration in the assays. At 10 nM [S-35]GTPgammaS, the potency of full agonists exhibited a greater dependence on the GDP concentration, whereas the potency of partial agonists was virtually independent of GDP. We concluded that at the lower [S-35]GTPgammaS concentration, the rate-determining step in G protein activation is the binding of [S-35]GTPgammaS to the G protein. At the higher [S-35]GTPgammaS concentration, for full agonists, [S-35]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining.

Solid-state interconversions of coordination networks and hydrogen-bonded salts

Thermal or chemical treatment of crystalline 4,4-bipyridinium salts of [MCl4]2- (M=Co, Zn, Fe, or Pt) leads to HCl loss and formation of coordination network solids [{MCl2(4,4-bipy)}n]. For M=Co, Zn, and Fe, these solids can also be prepared by mechanochemical means. Their exposure to HCl vapor or the mechanochemical reaction of metal dichlorides with [4,4-H2bipy]Cl2 gives [4,4-H2bipy]2+ salts of [CoCl4]2-, [ZnCl4]2-, and, for the first time, [FeCl4]2-.

Chemical, physical and electrical properties of aged dodecylbenzene: thermal ageing of mixed isomers in air

A commercial dodecylbenzene (DDB) cable oil was aged at temperatures between 90 and 135 degrees C in air and was analyzed using various analytical techniques including optical and infra-red spectroscopy and dielectric analysis. On ageing, the oil darkened, significant oxidation features were found by infra-red spectroscopy and the acid number, water content and dielectric loss all increased. Ageing in the presence of paper or aluminum did not affect the ageing process, whereas ageing was significantly modified by the presence of copper. An absorption at 680 nm ("red absorbers") was detected by ultra-violet/visible spectroscopy followed by the production of an opaque precipitate. A reaction between copper and the acid generated on ageing is thought to produce copper carboxylates, and X-ray fluorescence confirmed that copper was indeed present in both the aged oil and the precipitate. Significantly, once red absorbers were detected, the dielectric loss increased to catastrophically high values and, therefore, the appearance of these compounds may serve as a useful diagnostic indicator. The development of acidity on ageing appears to be key in initiating the destructive copper conversion reaction and hence the control of oil acidity may be key to prolonging the life of DDB cable oils.

Investigation of cooperativity in the binding of ligands to the D-2 dopamine receptor

The D 2 dopamine receptor exists as dimers or as higher-order oligomers, as determined from data from physical experiments. In this study, we sought evidence that this oligomerization leads to cooperativity by examining the binding of three radioligands ([H-3] nemonapride, [H-3] raclopride, and [H-3] spiperone) to D 2 dopamine receptors expressed in membranes of Sf9 cells. In saturation binding experiments, the three radioligands exhibited different B-max values, and the B-max values could be altered by the addition of sodium ions to assays. Despite labeling different numbers of sites, the different ligands were able to achieve full inhibition in competition experiments. Some ligand pairs also exhibited complex inhibition curves in these experiments. In radioligand dissociation experiments, the rate of dissociation of [H-3] nemonapride or [H-3] spiperone depended on the sodium ion concentration but was independent of the competing ligand. Although some of the data in this study are consistent with the behavior of a cooperative oligomeric receptor, not all of the data are in agreement with this model. It may, therefore, be necessary to consider more complex models for the behavior of this receptor.

The interpretation of symptoms of starvation/severe dietary restraint in eating disorder patients

The aims of the study were to test the hypotheses that some symptoms of starvation/severe dietary restraint are interpreted by patients with eating disorders in terms or control. Sixty-nine women satisfying the Diagnostic and Statistical Manual of Mental Disorders - IV edition (DSM-IV) criteria for a clinical eating disorder and 107 controls participated in the Study. All the participants completed an ambiguous scenarios paradigm, the Eating Disorder Lamination Questionnaire (EDE-Q) and the Beck Depression Inventory (BDI). Significantly more eating disorder patients than non clinical participants interpreted the starvation/dietary restraint symptoms of hunger, heightened satiety, and dizziness in terms of control. The data give further Support to the recent cognitive-behavioural theory of eating disorders suggesting that eating disorder patients interpret some starvation/dietary restraint symptoms in terms of control.

Effects of the Allosteric Antagonist 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 Receptor Modulation in the Cerebellum

PSNCBAM-1 has recently been described as a cannabinoid CB1 receptor allosteric antagonist associated with hypophagic effects in vivo; however, PSNCBAM-1 effects on CB1 ligand-mediated modulation of neuronal excitability remain unknown. Here, we investigate PSNCBAM-1 actions on CB1 receptor-stimulated [35S]GTPγS binding in cerebellar membranes and on CB1 ligand modulation of presynaptic CB1 receptors at inhibitory interneurone-Purkinje cell (IN-PC) synapses in the cerebellum using whole-cell electrophysiology. PSNCBAM-1 caused non-competitive antagonism in [35S]GTPγS binding studies, with higher potency against the CB receptor agonist CP55940 than for WIN55,212-2 (WIN55). In electrophysiological studies, WIN55 and CP55940 reduced miniature inhibitory postsynaptic currents (mIPSCs) frequency, but not amplitude. PSNCBAM-1 application alone had no effect on mIPSCs; however, PSNCBAM-1 pre-treatment revealed agonist-dependent functional antagonism, abolishing CP55940-induced reductions in mIPSC frequency, but having no clear effect on WIN55 actions. The CB1 antagonist/inverse agonist AM251 increased mIPSC frequency beyond control, this effect was reversed by PSNCBAM-1. PSNCBAM-1 pre-treatment also attenuated AM251 effects. Thus, PSNCBAM-1 reduced CB1 receptor ligand functional efficacy in the cerebellum. The differential effect of PSNCBAM-1 on CP55940 versus WIN55 actions in [35S]GTPγS binding and electrophysiological studies and the attenuation of AM251 effects are consistent with the ligand-dependency associated with allosteric modulation. These data provide the first description of functional PSNCBAM-1 allosteric antagonist effects on neuronal excitability in the mammalian CNS. PSNCBAM-1 allosteric antagonism may provide viable therapeutic alternatives to orthosteric CB1 antagonists/inverse agonists in the treatment of CNS disease.