Ontogeny has a phylogeny: background to adjunctive behaviors in pigeons and budgerigars

Animals coping with operant conditioning tasks often show behaviors that are not recorded by keys, levers and similar response transducers. Nevertheless, these adjunctive behaviors should not be disposed of by classifying them as incidental. Often they are found to be at least partially influenced by the experimentally programmed contingencies, and under certain conditions they can in turn influence conditioned behaviors. Here we describe the occurrence and characteristics of two such behaviors, stimulus grasping in operantly key-pecking pigeons and intra-delay stereotypies in a delayed matching-to-sample task with budgerigars. It is argued that for a proper account of these behaviors it is necessary to refer to a behavioral systems approach that appeals to longer ranging ontogenetic and phylogenetic histories than is usually considered in the psychological literature. The gaping towards on-key stimuli by pigeons is attributed to the hypothesis that operantly conditioned key-pecks probably relate to a grasp-pecking response that is normally executed towards non-edible items covering food. The intra-delay behaviors shown by the budgerigars are assumed to have originated from stress-induced displacement responses that adventitiously came under the influence of differential reinforcement contingencies. Finally, we discuss what kinds of evidence are needed to put these hypothetical explanations on a more certain footing.     

Mycobacterium leprae binds to a major human peripheral nerve glycoprotein myelin P zero (P0)

We have previously shown that a major phosphorylated 25-kDa glycoprotein of the human peripheral nerve binds to Mycobacterium leprae. In the present study, we confirm that the 25-kDa glycoprotein of the human peripheral nerve is myelin P zero (P₀) by immunoprecipitation and Western blot experiments using monoclonal antibodies to myelin P₀. Immunohistochemical studies on human nerve using these antibodies to myelin P₀ exhibited a strong immunoreactivity to the myelin and Schwann cells. Myelin P₀ is a peripheral nerve specific protein; therefore it could likely be one of the key target molecules for M. leprae binding/internalization or even contact-dependent demyelination. This finding of M. leprae binding to myelin P₀ adds to the present understanding on neural predilection of M. leprae.     

Fgf signaling controls the number of phalanges and tip formation in developing digits

Tetrapods have two pairs of limbs, each typically with five digits, each of which has a defined number of phalanges derived from an archetypal formula. Much progress has been made in understanding vertebrate limb initiation and the patterning processes that determine digit number in developing limb buds, but little is known about how phalange number is controlled. We and others previously showed that an additional phalange can be induced in a chick toe if sonic hedgehog protein is applied in between developing digit primordia. Here we show that formation of an additional phalange is associated with prolonged Fgf8 expression in the overlying apical ridge and that an Fgf Receptor inhibitor blocks its formation. The additional phalange is produced by elongation and segmentation of the penultimate phalange, suggesting that the digit tip forms when Fgf signaling ceases by a special mechanism, possibly involving Wnt signaling. Consistent with this, Fgfs inhibit tip formation whereas attenuation of Fgf signaling induces tip formation prematurely. We propose that duration of Fgf signaling from the ridge, responsible for elongation of digit primordia, coupled with a characteristic periodicity of joint formation, generates the appropriate number of phalanges in each digit. We also propose that the process that generates the digit tips is independent of that which generates more proximal phalanges. This has implications for understanding human limb congenital malformations and evolution of digit diversity.     

Amino acid sequence and homology modeling of obtustatin,a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa

Disintegrins represent a group of cysteine-rich peptides occurring in Crotalidae and Viperidae snake venoms, and are potent antagonists of several integrin receptors. A novel disintegrin, obtustatin, was isolated from the venom of the Vipera lebetina obtusa viper, and represents the first potent and selective inhibitor of the binding of integrin alpha(1)beta(1) to collagen IV. The primary structure of obtustatin contains 41 amino acids and is the shortest disintegrin described to date. Obtustatin shares the pattern of cysteines of other short disintegrins. However, in contrast to known short disintegrins, the integrin-binding loop of obtustatin is two residues shorter and does not express the classical RGD sequence. Using synthetic peptides, a KTS motif was identified as the integrin-binding sequence. A three-dimensional model of obtustatin, built by homology-modeling structure calculations using different templates and alignments, strongly indicates that the novel KTS motif may reside at the tip of a flexible loop.     

Diverging patterns of mitochondrial and nuclear DNA diversity in subarctic black spruce: imprint of a founder effect associated with postglacial colonization

High-latitude ecotonal populations at the species margins may exhibit altered patterns of genetic diversity, resulting from more or less recent founder events and from bottleneck effects in response to climate oscillations. Patterns of genetic diversity were investigated in nine populations of the conifer black spruce (Picea mariana [Mill.] BSP.) in northwestern Québec, Canada, using seed-dispersed mitochondrial (mt) DNA and nuclear (nc) DNA. mtDNA diversity (mitotypes) was assessed at three loci, and ncDNA diversity was estimated for nine expressed sequence tag polymorphism (ESTP) loci. Sampling included populations from the boreal forest and the southern and northern subzones of the subarctic forest-tundra, a fire-born ecotone. For ncDNA, populations from all three vegetation zones were highly diverse with little population differentiation (thetaN = 0.014); even the northernmost populations showed no loss of rare alleles. Patterns of mitotype diversity were strikingly different: within-population diversity and population differentiation were high for boreal forest populations [expected heterozygosity per locus (HE) = 0.58 and thetaM = 0.529], but all subarctic populations were fixed for a single mitotype (HE = 0). This lack of variation suggests a founder event caused by long-distance seed establishment during postglacial colonization, consistent with palaeoecological data. The estimated movement of seeds alone (effective number of migrants per generation, NmM < 2) was much restricted compared to that estimated from nuclear variants, which including pollen movement (NmN > 17). This could account for the conservation of a founder imprint in the mtDNA of subarctic black spruce. After reduction, presumably in the early Holocene, the diversity in ncDNA would have been replenished rapidly by pollen-mediated gene flow, and maintained subsequently through vegetative layering during the current cooler period covering the last 3000 years.     

Patterns of morphological integration in marine modular organisms: supra-module organization in branching octocoral colonies

Despite the relative simplicity of their modular growth, marine invertebrates such as arborescent gorgonian octocorals (Octocorallia: Cnidaria) generate complex colonial forms. Colony form in these taxa is a consequence of modular (polyp) replication, and if there is a tight integration among modular and supramodular traits (e.g. polyp aperture, inter-polyp spacing, branch thickness, internode and branch length), then changes at the module level may lead to changes in colony architecture. Alternatively, different groups of traits may evolve semi-independently (or conditionally independent). To examine the patterns of integration among morphological traits in Caribbean octocorals, we compared five morphological traits across 21 species, correcting for the effects of phylogenetic relationships among the taxa. Graphical modelling and phylogenetic independence contrasts among the five morphological characters indicate two groups of integrated traits based on whether they were polyp- or colony-level traits. Although all characters exhibited bivariate associations, multivariate analyses (partial correlation coefficients) showed the strongest integration among the colony-level characters (internode distance and branch length). It is a quantitative demonstration that branching characters within the octocorals studied are independent of characters of the polyps. Despite the universally recognized modularity of octocorals at the level of polyps, branching during colony development may represent an emergent level of integration and modularity.     

Synthesis and in vitro trypanocide activity of several polycyclic drimane-quinone derivatives

The Diels-Alder reaction between two polygodial-derived dienes and simple quinones to yield substituted naphtho- and anthraquinones, is described. The in vitro trypanocide activity for the series was determined. Two of the new compounds showed an activity ten and two times higher, respectively, than nifurtimox and benznidazole, the medicines of choice for the treatment of the acute Chagas' disease.     

Hepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion

We examined in vivo a role for sterol carrier protein-2 (SCP-2) in the regulation of lipid secretion across the hepatic sinusoidal and canalicular membranes. Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice. We determined plasma, hepatic, and biliary lipid concentrations; hepatic fatty acid (FA) and cholesterol synthesis; hepatic and biliary phosphatidylcholine (PC) molecular species; and VLDL triglyceride production. In Ad.rSCP2 mice, there was marked inhibition of hepatic fatty acids and cholesterol synthesis to <62% of control mice. Hepatic triglyceride contents were decreased, while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. As expected, biliary cholesterol, phospholipids, bile acids outputs, and biliary PC hydrophobic index were significantly increased in Ad.rSCP2 mice. These studies indicate that SCP-2 overexpression in the liver markedly inhibits lipid synthesis as well as VLDL production, and alters hepatic lipid contents. In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile. These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes.     

The 1.15A crystal structure of the Staphylococcus aureus methionyl-aminopeptidase and complexes with triazole based inhibitors

Methionyl aminopeptidases (MetAPs) represent a unique class of protease that are responsible for removing the N-terminal methionine residue from proteins and peptides. There are two major classes of MetAPs (type I and type II) described and each class can be subdivided into two subclasses. Eukaryotes contain both the type I and type II MetAPs, whereas prokaryotes possess only the type I enzyme. Due to the physiological importance of these enzymes there is considerable interest in inhibitors to be used as antiangiogenic and antimicrobial agents. Here, we describe the 1.15A crystal structure of the Staphylococcus aureus MetAP-I as an apo-enzyme and its complexes with various 1,2,4-triazole-based derivatives at high-resolution. The protein has a typical "pita-bread" fold as observed for the other MetAP structures. The inhibitors bind in the active site with the N1 and N2 atoms of the triazole moiety complexing two divalent ions. The 1,2,4-triazols represent a novel class of potent non-peptidic inhibitors for the MetAP-Is.