Taxonomic versus allometric constraints on non‐linear interaction strengths

Recently, the importance of body mass and allometric scaling for the structure and dynamics of ecological networks has been highlighted in several ground‐breaking studies. However, advances in the understanding of generalities across ecosystem types are impeded to a considerable extent by a methodological dichotomy contrasting a considerable portion of marine ecology on the one hand opposite to traditional community ecology on the other hand. Many marine ecologists are bound to the taxonomy‐neglecting size spectrum approach when describing and analysing community patterns. In contrast, the mindset of the other school is focused on taxonomies according to the Linnean system at the cost of obscuring information due to applying species or population averages of body masses and other traits. Following other pioneering studies, we addressed this lingering gap, and studied non‐linear interaction strengths (i.e. functional responses) between two taxonomically‐distinct terrestrial arthropod predators (centipedes and spiders) of varying individual body masses and their prey. We fitted three non‐linear functional response models to the data: (1) a taxonomic model not accounting for variance in body masses amongst predator individuals, (2) an allometric model ignoring taxonomic differences between predator individuals, and (3) a combined model including body mass and taxonomic effects. Ranked according to their AICs, the combined model performs better than the allometric model, which provides a superior fit to the data than the taxonomic model. These results strongly indicate that the body masses of predator and prey individuals were responsible for most of the variation in non‐linear interaction strengths. Taxonomy explained some specific patterns in allometric exponents between groups and revealed mechanistic insights in predation efficiencies. Reconciling quantitative allometric models as employed by the marine size‐spectrum approach with taxonomic information may thus yield quantitative results that are generalized across ecosystem types and taxonomic groups. Using these quantitative models as novel null models should also strengthen subsequent taxonomic analyses.     

Definition of the M-conotoxin superfamily: characterization of novel peptides from molluscivorous Conus venoms

Most of the >50,000 different pharmacologically active peptides in Conus venoms belong to a small number of gene superfamilies. In this work, the M-conotoxin superfamily is defined using both biochemical and molecular criteria. Novel excitatory peptides purified from the venoms of the molluscivorous species Conus textile and Conus marmoreus all have a characteristic pattern of Cys residues previously found in the mu-, kappaM-, and psi-conotoxins (CC-C-C-CC). The new peptides are smaller (12-19 amino acids) than the mu-, kappaM-, and psi-conotoxins (22-24 amino acids). One peptide, mr3a, was chemically synthesized in a biologically active form. Analysis of the disulfide bridges of a natural peptide tx3c from C. textile and synthetic peptide mr3a from C. marmoreus showed a novel pattern of disulfide connectivity, different from that previously established for the mu- and psi-conotoxins. Thus, these peptides belong to a new group of structurally and pharmacologically distinct conotoxins that are particularly prominent in the venoms of mollusc-hunting Conus species. Analysis of cDNA clones encoding the novel peptides as well as those encoding mu-, kappaM-, and psi-conotoxins revealed highly conserved amino acid residues in the precursor sequences; this conservation in both amino acid sequence and in the Cys pattern defines a gene superfamily, designated the M-conotoxin superfamily. The peptides characterized can be provisionally assigned to four distinct groups within the M-superfamily based on sequence similarity within and divergence between each group. A notable feature of the superfamily is that two distinct structural frameworks have been generated by changing the disulfide connectivity on an otherwise conserved Cys pattern.     

Definition and characterization of the short alphaA-conotoxins: a single residue determines dissociation kinetics from the fetal muscle nicotinic acetylcholine receptor

We report the definition and characterization of a conotoxin subfamily, designated the short alphaA-conotoxins (alphaA(S)) and demonstrate that all of these share the unique property of selectively antagonizing the fetal subtype of the mammalian neuromuscular nicotinic acetylcholine receptor (nAChR). We have characterized newly identified alphaA(S)-conotoxins from Conus pergrandis and have conducted a more detailed characterization of alphaA-conotoxins previously reported from additional Conus species. Among the results, the characterization of the short alphaA-conotoxins revealed diverse kinetics of a block of the fetal muscle nAChR, particularly in dissociation rates. The structure-function relationships of native alphaA(S)-conotoxins and some analogues revealed a single amino acid locus (alternatively either His or Pro in native peptides) that is a critical determinant of the dissociation kinetics. The unprecedented binding selectivity for the fetal muscle nAChR, coupled with the kinetic diversity, should make alphaA(S)-conotoxins useful ligands for a diverse set of studies. The rapidly reversible peptides may be most suitable for electrophysiological studies, while the relatively irreversible peptides should be most useful for binding and localization studies.     

Farnesyl Pyrophosphate Inhibits Epithelialization and Wound Healing through the Glucocorticoid Receptor

Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor. We used functional studies to evaluate the effects of FPP on wound healing. Both FPP and ZGA inhibited keratinocyte migration and epithelialization in vitro and ex vivo. These effects were independent of farnesylation and indicate that modulation of FPP levels in skin may be beneficial for wound healing. FPP inhibition of keratinocyte migration and wound healing proceeds, in part, by repression of the keratin 6 gene. Furthermore, we show that the 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitor mevastatin, which blocks FPP formation, not only promotes epithelialization in acute wounds but also reverses the effect of ZGA on activation of the GR and inhibition of epithelialization. We conclude that FPP inhibits wound healing by acting as a GR agonist. Of special interest is that FPP is naturally present in cells prior to glucocorticoid synthesis and that FPP levels can be further altered by the statins. Therefore, our findings may provide a better understanding of the pleiotropic effects of statins as well as molecular mechanisms by which they may accelerate wound healing.     

Cutting edge: transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer

Epithelial cell MUC1 is aberrantly expressed on human epithelial adenocarcinomas where it functions as a regulator of immune responses and an oncogene. Normally expressed at low levels in healthy colonic epithelium, MUC1 was reported to be overexpressed in human inflammatory bowel disease (IBD) and thus may be expected to play an important role in regulating chronic inflammation and its progression to colitis-associated colon cancer. Studies in the immunobiology and pathology of IBD and colitis-associated colon cancer have been done in various mouse models but none could properly address the role of MUC1 due to low homology between the mouse and the human molecule. We report that IL-10(-/-) mice, a widely accepted mouse model of IBD, crossed to human MUC1-transgenic mice, develop MUC1(+) IBD characterized by an earlier age of onset, higher inflammation scores, and a much higher incidence and number of colon cancers compared with IL-10(-/-) mice.     

Novel conantokins from Conus parius venom are specific antagonists of N-methyl-D-aspartate receptors

We report the discovery and characterization of three conantokin peptides from the venom of Conus parius. Each peptide (conantokin-Pr1, -Pr2, and -Pr3) contains 19 amino acids with three gamma-carboxyglutamate (Gla) residues, a post-translationally modified amino acid characteristic of conantokins. The new peptides contain several amino acid residues that differ from previous conantokin consensus sequences. Notably, the new conantokins lack Gla at the 3rd position from the N terminus, where the Gla residue is replaced by either aspartate or by another post-translationally modified residue, 4-trans-hydroxyproline. Conantokin-Pr3 is the first conantokin peptide to have three different post-translational modifications. Conantokins-Pr1 and -Pr2 adopt alpha-helical conformations in the presence of divalent cations (Mg2+ and Ca2+) but are generally unstructured in the absence of divalent cations. Conantokin-Pr3 adopts an alpha-helical conformation even in the absence of divalent cations. Like other conantokins, the new peptides induced sleep in young mice and hyperactivity in older mice upon intracranial injection. Electrophysiological assays confirmed that conantokins-Pr1, -Pr2, and -Pr3 are N-methyl-d-aspartate (NMDA) receptor antagonists, with highest potency for NR2B-containing NMDA receptors. Conantokin-Pr3 demonstrated approximately 10-fold selectivity for NR2B-containing NMDA receptors. However, conantokin-Pr2 showed minimal differences in potency between NR2B and NR2D. Conantokins-Pr1, -Pr2, and -Pr3 all demonstrated high specificity of block for NMDA receptors, when tested against various ligand-gated ion channels. Conus parius conantokins allow for a better definition of structural and functional features of conantokins as ligands targeting NMDA receptors.     

The effect of agitation intensity on alkali-catalyzed methanolysis of sunflower oil

The sunflower oil methanolysis was studied in a stirred reactor at different agitation speeds. The measurements of drop size, drop size distribution and the conversion degree demonstrate the effects of the agitation speed in both non-reaction (methanol/sunflower oil) and reaction (methanol/KOH/sunflower oil) systems. Drop size distributions were found to become narrower and shift to smaller sizes with increasing agitation speed as well as with the progress of the methanolysis reaction at a constant agitation speed. During the methanolysis reaction, the Sauter-mean drop diameter stays constant in the initial slow reaction region, rapidly decreases during the fast reaction period and finally reaches the equilibrium level. Due to the fact that the interfacial area increases, one can conclude that the rate of reaction occurring at the interface will also be enhanced progressively. The "autocatalytic" behavior of the methanolysis reaction is explained by this "self-enhancement" of the interfacial area, due to intensive drop breakage process.     

Expression and functional analysis of an Entamoeba histolytica truncated adhesin in tomato plants

Several antigens from Entamoeba histolytica the agent causing human amoebiasis have been identified as potential vaccine candidates. One of them is the EhADH112 adhesin, which plays an important role during trophozoite adherence to and phagocytosis of target cells. We report here the expression of the EhADH112 carboxy-terminus of the gene (Adh240) in tomato plants. A 28 kDa band is recognized by specific antibodies in total proteins from transformed tomatoes. The plant-based adhesin conserves the ability to inhibit trophozoite adherence and phagocytosis of target cells by an average of 32.8 and 44.75% respectively.