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A primitive fish provides key characters bearing on deep osteichthyan phylogeny.

Osteichthyans, or bony vertebrates, include actinopterygians (teleosts and their relatives) and sarcopterygians (coelacanths, lungfishes and tetrapods). Despite features found in basal actinopterygians (for example, Dialipina and Ligulalepis) and basal sarcopterygians (for example, Psarolepis and Achoania), the morphological gap between the two lineages remains wide and how sarcopterygians developed a dermal surface covering known as cosmine (composed of a pore-canal network and a single layer of odontodes and enamel) is still poorly known. Here we describe a primitive fossil fish, Meemannia eos gen. et sp. nov., that possesses an actinopterygian-like skull roof and a cosmine-like dermal surface combining a pore-canal network (found in various fossil sarcopterygians) with superimposed layers of odontodes and enamel (previously known in actinopterygians and some acanthodians). This 405-million-year-old fish from the Lower Devonian of Yunnan (China) demonstrates that cosmine in many fossil sarcopterygians arose step by step through the acquisition of a pore-canal network followed by the subsequently developed ability to resorb previous generations of odontodes and enamel. Meemannia provides key characters for studying deep osteichthyan phylogeny and indicates a possible morphotype for the common ancestor of actinopterygians and sarcopterygians.

Animals↗

Progressive induction of caudal neural character by graded Wnt signaling.

Early in differentiation, all neural cells have a rostral character. Only later do posteriorly positioned neural cells acquire characteristics of caudal forebrain, midbrain and hindbrain cells. Caudalization of neural tissue in the chick embryo apparently involves the convergent actions of (i) fibroblast growth factor (FGF) signaling and (ii) signaling from the caudal paraxial mesoderm, or 'PMC activity', which has not yet been defined molecularly. Here we report evidence that Wnt signaling underlies PMC activity, and show that Wnt signals act directly and in a graded manner on anterior neural cells to induce their progressive differentiation into caudal forebrain, midbrain and hindbrain cells.

Animals↗

Perceptions of moral character modulate the neural systems of reward during the trust game.

Studies of reward learning have implicated the striatum as part of a neural circuit that guides and adjusts future behavior on the basis of reward feedback. Here we investigate whether prior social and moral information about potential trading partners affects this neural circuitry. Participants made risky choices about whether to trust hypothetical trading partners after having read vivid descriptions of life events indicating praiseworthy, neutral or suspect moral character. Despite equivalent reinforcement rates for all partners, participants were persistently more likely to make risky choices with the 'good' partner. As expected from previous studies, activation of the caudate nucleus differentiated between positive and negative feedback, but only for the 'neutral' partner. Notably, it did not do so for the 'good' partner and did so only weakly for the 'bad' partner, suggesting that prior social and moral perceptions can diminish reliance on feedback mechanisms in the neural circuitry of trial-and-error reward learning.

Adult↗

Iconographic dental typography. A dental character font for computer graphics.

The recent massive increase in available memory for microcomputers now allows multiple font faces to be stored in computer RAM memory for instant access to the screen and for printed output. Fonts can be constructed in which the characters are not just letters or numbers, but are miniature graphic icons--in this instance pictures of teeth. When printed on an appropriate laser printer, this produces printed graphics of publishing quality.

Computer Graphics↗

Structure-reactivity relationships in the photoreduction of n,pi*-excited ketones and azoalkanes: the effect of reaction thermodynamics, excited-state electrophilicity, and antibonding character in the transition state.

The reaction enthalpies for the photoreduction of n,pi*-excited states (acetone, benzophenone, 2.3-diazabicyclo[2.2.2]oct-2-ene, and a 2,3-diazabicyclo[2.2.1]hept-2-ene derivative) by model hydrogen donors (methanol and dimethylamine) were calculated on the basis of a critically evaluated data set of bond dissociation energies for donors and reduced acceptors. These were compared with the observed photoreactivity, which can be assessed through quenching rate constants of the excited states by hydrogen donors. The intriguing observation of a preferential attack at electrophilic hydrogen atoms, i.e., N-H or O-H, by n,pi*-excited azoalkanes is rationalised on the basis of the calculated thermochemical data, differences in electrophilicity, and varying contributions of antibonding character in the transition state. Singlet-excited azoalkanes act as nucleophilic species, while excited ketones display an electrophilic reactivity. This is in line with the pictorial description of the electron distribution in these excited states.

Journal Article↗

Dinuclear ruthenium bipyridine complexes with a bis(iminodioxolene)-meta-phenylene ligand: magnetic coupling and mixed valence character of the semiquinonato species.

The dinuclear bis-iminosemiquinonato [Ru(bpy)(2)(L)(2)Ru(bpy)(2)](PF(6))(2) complex where L is the deprotonated form of N,N'-bis(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-phenylenediamine (H(4)L), has been synthesised. For comparison purposes, the mononuclear iminosemiquinonato [Ru(bpy)(2)L']PF(6) formed by the N-phenyl-o-aminophenol (H(2)L') was also investigated. Magnetic investigation evidences that the bis-semiquinonato species is characterised by a moderately strong ferromagnetic interaction (H=JS(1) x S(2), J=-85(5) cm(-1)). This result is the theoretically expected one and it is contrasting with the antiferromagnetic interaction observed in previously investigated complexes containing the same ligand. It is suggested that the different behaviour is determined by the different coordination requirements occurring in these complexes. The spectroelectrochemical analysis provides a clear evidence of the valence trapped character of the mono-semiquinonato forms of the ligand. The two mixed valence semiquinonato species containing the quinonato-semiquinonato and semiquinonato-catecholato bridging ligand can be described as class II, but show a significantly different electronic coupling. The electronic factors determining this behaviour are discussed.

Aminophenols↗

Ligand dependence of pi-complex character in disilene-palladium complexes.

The synthesis and structures of new 16-electron disilene palladium complexes with 2,6-dimethylphenyl isocyanide and phenyldimethylphosphine ligands [L(1)L(2)Pd{(t-BuMe(2)Si)(2)Si=Si(SiMe(2)Bu-t)(2)}, where L(1) = L(2) = PhMe(2)P; L(1) = (cyclohexyl)(3)P, L(2) = 2,6-dimethylphenyl isocyanide; L(1) = L(2) = 2,6-dimethylphenyl isocyanide] are described. Comparison of the X-ray structural parameters around the disilene moiety among these complexes and related bis(trimethylphosphine)(disilene)palladium and 14-electron (tricyclohexylphosphine)(disilene)palladium revealed that the pi-complex character is sensitive to the residual ligands and increases with decreasing the strength of sigma-donation from the ligands.

Journal Article↗

The highly electrophilic character of 4-chloro-7-nitrobenzofurazan and possible consequences for its application as a protein-labelling reagent.

4-Chloro-7-nitrobenzofurazan possesses at least one highly electrophilic centre (C-6) that is much more reactive towards nucleophiles than position C-4, the irreversible alkylating site of this reagent. Possible consequences of the electrophilic character of 4-chloro-7-nitrobenzofurazan for its application as a protein-labelling reagent are discussed.

4-Chloro-7-nitrobenzofurazan↗

Evidence that the lack of high catalytic activity of thiolsubtilisin towards specific substrates may be due to an inappropriately located proton-distribution system. Demonstration of highly nucleophilic character of the thiol group of thiolsubtilisin in the catalytically relevant ionization state of the active centre by use of a two-protonic-state reactivity probe.

The active centre of the semi-synthetic enzyme thiolsubtilisin was investigated by studying the kinetics of the reaction of the thiol group of cysteine-221 with the thiol-specific two-protonic-state reactivity probe 2,2'-dipyridyl disulphide. The three-states criterion [Brocklehurst (1974) Tetrahedron 30, 2397-2407] was used to provide definitive evidence of the existence of a thiol--imidazole interactive system in acidic media in which the sulphur atom possesses highly nucleophilic character. The lack of catalytic competence of thiolsubtilisin despite its possession of the requisite nucleophilic capability is discussed. The exceedingly high rate of reaction of thiolsubtilisin with 2,2'-dipyridyl disulphide at pH 4--5 is shown to constitute a rapid and convenient active-site titration in which intact thiol--imidazole interaction is detected even in the presence of other thiols.

2,2'-Dipyridyl↗

The N-terminal 26-residue fragment of human programmed cell death 5 protein can form a stable alpha-helix having unique electrostatic potential character.

PDCD5-(1-26) is a N-terminal 26-residue fragment of human PDCD5 (programmed cell death 5) protein. PDCD5 is an important novel protein that regulates both apoptotic and non-apoptotic programmed cell death. The conformation of PDCD5 protein is a stable helical core consisting of a triple-helix bundle and two dissociated terminal regions. The N-terminal region is ordered and contains abundant secondary structure. Overexpression and purification of the N-terminal 26-residure fragment, PDCD5-(1-26), was performed in this study to better understand its tertiary structure. The spectroscopic studies using CD and hetero- and homo-nuclear NMR methods determine a stable alpha-helix formed by Asp3-Ala19 of PDCD5-(1-26). The N-terminal residues Asp3-Ala19 of PDCD5 were then affirmed to have the capacity to form a stable alpha-helix independently of the core of the protein. Analysis of the helical peptide of PDCD5-(1-26) indicates that the surface of this well-formed alpha-helix has a unique electrostatic potential character. This may provide an environment for the N-terminal alpha-helix of PDCD5 to serve as an independent functional entity of the protein. The apoptosis activity assay shows that the deletion of the N-terminal alpha-helix of PDCD5 significantly attenuates the apoptosis-promoting effects on HL-60 cells induced by serum withdrawal.

Amino Acid Sequence↗

The hydrophobic character of thiol-activated cytolysins.

Hydrophobic chromatography on phenyl-Sepharose has revealed the decidedly hydrophobic character of several members of the group of cytolytic proteins termed ;thiol-activated'. Pneumolysin, alveolysin, cereolysin, and streptolysin O were found to be equally hydrophobic, as were the oxidized and reduced forms of alveolysin. Hydrophobic chromatography has been utilized in the development of an improved procedure for the purification of pneumolysin.

Bacterial Proteins↗

Tilorone-induced lysosomal lesions: the bisbasic character of the drug is essential for its high potency to cause storage of sulphated glycosaminoglycans.

The immunomodulatory agent tilorone -2,7-bis-[2-(diethyl-amino)ethoxy]fluoren-9-one- and congeners are potent inducers of lysosomal storage of sulphated glycosaminoglycans (GAGs) in animals and cultured fibroblasts of animals and man. All potent inducers of GAG storage hitherto described are bisbasic polycyclic aromatic compounds. They are accumulated in lysosomes and disturb the degradation of GAGs, mainly dermatan sulphate. It has been proposed that the drugs cross-link the polyanionic GAG chains giving rise to undergradable drug-GAG complexes. This hypothesis implies that the bisbasic character of the drug molecules is essential for the side effect in question. In the present study, this was tested by comparing tilorone and its monobasic derivative (MT) with respect to (i) induction of GAG storage in cultured bovine corneal fibroblasts and (ii) physicochemical interactions with GAGs in vitro. The intralysosomal concentration of MT achieved after 1-3 days was of the same order of magnitude as previously shown for tilorone. Nevertheless, under conditions that did not enhance the secretion of a lysosomal enzyme (beta-hexosaminidase, EC 3.2.1.52), the ability of MT to cause storage of [35S]GAGs was significantly lower than that of tilorone. Morphological observations showed that MT was much more potent in causing lysosomal storage of polar lipids than of GAGs. CD spectroscopy with tilorone revealed that the presence of GAGs caused the primarily achiral drug molecules to display CD. This suggested a helical orientation of the tilorone molecules within GAG-drug complexes, and short intermolecular distances which allowed electronic coupling of the aromatic ring systems of adjacent drug molecules. In contrast, MT failed to display any induced optical activity, indicating the absence of highly ordered GAG-drug complexes. In conclusion, the present results show that the substitution of the planar aromatic ring system with two basic side chains is essential for the high potency of tilorone in inducing lysosomal GAG storage. This is paralleled by, and presumably causally related to, strong physicochemical interactions with GAGs.

Adjuvants, Immunologic↗

Characterization of peripheral blood progenitor cells (PBPC) mobilized by filgrastim (rHuG-CSF) in normal volunteers: dose-effect relationship for filgrastim with the character of mobilized PBPC.

Filgrastim (rHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) in healthy Japanese volunteers were characterized in detail using two clonal cell culture systems and double-colour flow cytometry to detect multilineage colony-forming cells and subsets of CD34+ cells. The kinetics of PBPC during the administration of filgrastim was studied, and possible differences in the character of progenitor cells relative to given doses of filgrastim were investigated. Filgrastim was administered subcutaneously to normal volunteers for 7 d at doses of 100, 200 or 400 microgram/m2 (10 per cohort). Treatment with 100 or 200 microgram/m2 filgrastim was well tolerated; however, the 400 microgram/m2 dose level was not completed because of bone pain and myalgia. The treatment strikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells. The number of progenitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated with 200 microgram/m2 filgrastim was more pronounced than in those treated with 100 microgram/m2. Treatment with 200 microgram/m2 also released the less mature progenitor cells (i.e. mixed colony-forming cells CD34+/33- cells, and CD34+/HLA-DR-cells) into circulation better than the 100 microgram/m2 dose. These results suggest that daily subcutaneous injection with 200 microgram/m/2 filgrastim for 5 d will effectively mobilize, both qualitatively and quantitatively, PBPC in healthy donors.

Adult↗

Patterns of mitochondrial versus nuclear DNA sequence divergence among nymphalid butterflies: the utility of wingless as a source of characters for phylogenetic inference.

To investigate the utility of a region of wingless (wg) as a marker for molecular systematics, we compared wg sequences to mitochondrial COII sequences from twenty-two nymphalid butterfly taxa and one outgroup. Compositional characteristics of the two gene regions are compared, and their contributions to a cladogram inferred from the combined data set are assessed. Primarily due to its uniform base composition, wg appears to become saturated more slowly than mtDNA, although the two genes appear to be evolving at quite similar rates. We suggest that wg will be a useful source of characters for phylogenetic studies of butterflies, and perhaps other insect taxa, with divergence times up to 60 million years ago.

Animals↗

Intron insertion as a phylogenetic character: the engrailed homeobox of Strepsiptera does not indicate affinity with Diptera.

The phylogenetic relationships of the order Strepsiptera are unclear. Affiliation to Coleoptera has been proposed, however this implies that dipteran halteres and strep-sipteran haltere-like organs evolved convergently. An alternative is a sister group relationship with Diptera. In this case, halteres could be homologous but a radical homeotic mutation may have switched their position to the Strepsipteran mesothorax. Ribosomal DNA sequence analysis has been used to support Dipteran affiliation, although this is controversial. Here we investigate the potential of an intron insertion site as a phylogenetic character. We find that the en homeobox gene of the strepsipteran Stichotrema dallatorreanum lacks a derived intron insertion shared by representatives of Diptera and Lepidoptera. We argue against a close affiliation between Strepsiptera and Diptera.

Amino Acid Sequence↗

Dynamics of indigenous and inoculated yeast populations and their effect on the sensory character of Riesling and Chardonnay wines.

To study the impact of yeast populations on wine flavour and to better understand yeast growth dynamics, wines were produced by the (i) indigenous microflora, (ii) vigorous yeast starter EC1118 and (iii) slowly fermenting yeast Assmannshausen. Sensory analysis revealed that wines differed depending on the fermentation type. However, these yeast-related differences did not exceed the varietal character. Both added starter cultures clearly dominated the Saccharomyces population from the middle of fermentation onwards. The starter cultures differed in their repression of indigenous non-Saccharomyces yeast. EC1118 limited growth of non-Saccharomyces yeasts more strongly than Assmannshausen. Sulphite addition further repressed growth of non-Saccharomyces yeasts. On completion, more than one Saccharomyces strain was present in each fermentation, with the largest variety in the non-inoculated and the smallest in the EC1118-inoculated fermentation. Results from the two genetic assays, karyotyping, and PCR using delta-primers were not fully equivalent, limiting the usefulness of delta-PCR in studies of native Saccharomyces yeasts.

Antibiosis↗

The catalytic mechanism of adenosylhomocysteine/methylthioadenosine nucleosidase from Escherichia coli--chemical evidence for a transition state with a substantial oxocarbenium character.

The substrate and inhibitory specificity of Escherichia coli adenosylhomocysteine (AdoHcy)/methylthioadenosine (MeSAdo) nucleosidase has been explored with several MeSAdo analogues modified on the sugar moiety at the 2', 3' and 5' positions. Alteration at C3' or at C2' and C3' positions in MeSAdo abolished substrate activity. However, the 2'-deoxy analogue of MeSAdo is effective as a substrate; this result provides evidence against a possible general-base catalysis involving the anchimeric assistance of the 2'-alpha-hydroxy group and the formation of a 1,2-epoxide as an intermediate in the catalytic process. The results of a study of the interaction of an 8,5'-cyclo analogue of MeSAdo with the enzyme indicate the importance of the glycosidic conformation of the substrate for binding to the active site. The enzyme discriminates against methanol attack from the solvent during catalysis. This implies the participation of an enzyme-directed water nucleophile. A poor solvent kinetic deuterium-isotope effect was measured (0.93) on the Vmax. Plots of log Vmax and log (Vmax/Km) for MeSAdo as a function of pH values from 5.0 to 8.5 are similar, with two presumably essential ionisable groups for catalysis with apparent pKa values of 5.6 and 8.2, whereas Km is independent of pH. When the 2'-alpha-hydroxy group of MeSAdo is substituted by fluorine, a significant decrease (28 500-fold) in the Vmax for enzyme-catalysed hydrolysis of the modified substrate is observed. This result indicates a transition state with a substantial oxocarbenium character. From these data, the reaction mechanism for AdoHcy/MeSAdo nucleosidase is discussed.

Catalysis↗