Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit

The self-assembly of a peptide based on a sequence from the amyloid beta peptide but incorporating the non-natural amino acid beta-2-thienylalanine (2-Thi) has been investigated in aqueous and methanol solutions. The peptide AAKLVFF was used as a design motif, replacing the phenylalanine residues (F) with 2-Thi units to yield (2-Thi)(2-Thi)VLKAA. The 2-Thi residues are expected to confer interesting electronic properties due to charge delocalization and pi-stacking. The peptide is shown to form beta-sheet-rich amyloid fibrils with a twisted morphology, in both water and methanol solutions at sufficiently high concentration. The formation of a self-assembling hydrogel is observed at high concentration. Detailed molecular modeling using molecular dynamics methods was performed using NOE constraints provided by 2D-NMR experiments. The conformational and charge properties of 2-Thi were modeled using quantum mechanical methods, and found to be similar to those previously reported for the beta-3-thienylalanine analogue. The molecular dynamics simulations reveal well-defined folded structures (turn-like) in dilute aqueous solution, driven by self-assembly of the hydrophobic aromatic units, with charged lysine groups exposed to water.

Influence of the solvent on the self-assembly of a modified amyloid beta peptide fragment. II. NMR and computer simulation investigation

The conformation of a model peptide AAKLVFF based on a fragment of the amyloid beta peptide A beta 16-20, KLVFF, is investigated in methanol and water via solution NMR experiments and Molecular dynamics computer simulations. In previous work, we have shown that AAKLVFF forms peptide nanotubes in methanol and twisted fibrils in water. Chemical shift measurements were used to investigate the solubility of the peptide as a function of concentration in methanol and water. This enabled the determination of critical aggregation concentrations, The Solubility was lower in water. In dilute solution, diffusion coefficients revealed the presence of intermediate aggregates in concentrated solution, coexisting with NMR-silent larger aggregates, presumed to be beta-sheets. In water, diffusion coefficients did not change appreciably with concentration, indicating the presence mainly of monomers, coexisting with larger aggregates in more concentrated solution. Concentration-dependent chemical shift measurements indicated a folded conformation for the monomers/intermediate aggregates in dilute methanol, with unfolding at higher concentration. In water, an antiparallel arrangement of strands was indicated by certain ROESY peak correlations. The temperature-dependent solubility of AAKLVFF in methanol was well described by a van't Hoff analysis, providing a solubilization enthalpy and entropy. This pointed to the importance of solvophobic interactions in the self-assembly process. Molecular dynamics Simulations constrained by NOE values from NMR suggested disordered reverse turn structures for the monomer, with an antiparallel twisted conformation for dimers. To model the beta-sheet structures formed at higher concentration, possible model arrangements of strands into beta-sheets with parallel and antiparallel configurations and different stacking sequences were used as the basis for MD simulations; two particular arrangements of antiparallel beta-sheets were found to be stable, one being linear and twisted and the other twisted in two directions. These structures Were used to simulate Circular dichroism spectra. The roles of aromatic stacking interactions and charge transfer effects were also examined. Simulated spectra were found to be similar to those observed experimentally.(in water or methanol) which show a maximum at 215 or 218 nm due to pi-pi* interactions, when allowance is made for a 15-18 nm red-shift that may be due to light scattering effects.

The structure of the mixed OH+H2O overlayer on Pt{111}

The structure of the mixed p(3x3)-(3OH+3H(2)O) phase on Pt{111} has been investigated by low-energy electron diffraction-IV structure analysis. The OH+H2O overlayer consists of hexagonal rings of coplanar oxygen atoms interlinked by hydrogen bonds. Lateral shifts of the O atoms away from atop sites result in different O-O separations and hexagons with only large separations (2.81 and 3.02 angstrom) linked by hexagons with alternating separations of 2.49 and 2.81/3.02 A. This unusual pattern is consistent with a hydrogen-bonded network in which water is adsorbed in cyclic rings separated by OH in a p(3x3) structure. The topmost two layers of the Pt atoms relax inwards with respect to the clean surface and both show vertical buckling of up to 0.06 angstrom. In addition, significant shifts away from the lateral bulk positions have been found for the second layer of Pt atoms. (C) 2005 American Institute of Physics.

Actinomyces coleocanis sp. nov., from the vagina of a dog

A hitherto undescribed Actinomyces-like bacterium was isolated from the vagina of a dog. Biochemical testing and PAGE analysis of whole-cell proteins indicated that the isolate was phenotypically different from previously described Actinomyces species and related taxa. Sequencing of 165 rRNA showed that the unknown bacterium was distinct from all currently known Actinomyces species. Phylogenetically, the unidentified organism displayed a specific association with Actinomyces europaeus, but a sequence divergence of > 5% demonstrated that it represents a distinct species. Based on both phenotypic and 165 rRNA sequence considerations, it is proposed that the unknown strain from a dog be classified as a novel species, Actinomyces coleocanis sp. nov. The type strain is CCUG 41708T (= CIP 106873T).

Arcanobacterium hippocoleae sp. nov., from the vagina of a horse

A polyphasic taxonomic study was performed on a previously unidentified gram-positive, facultatively anaerobic, diphtheroid-shaped organism isolated from a vaginal discharge of a horse. Comparative 16S rRNA gene sequencing demonstrated that the strain was a member of the genus Arcanobacterium, but sequence divergence values of >4% with described species of this genus (viz: Arcanobacterium haemolyticum, Arcanobacterium bernardiae, Arcanobacterium phocae, Arcanobacterium pluranimalium and Arcanobacterium pyogenes) demonstrated that the isolate represented a novel species. The unknown bacterium was readily distinguished from other Arcanobacterium species by biochemical tests. Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Arcanobacterium hippocoleae sp. nov. The type strain of A. hippocoleae is CCUG 44697T (= CIP 106850T).

Arthrobacter nasiphocae sp. nov., from the common seal (Phoca vitulina)

An unknown gram-positive, catalase-positive, strictly aerobic, rod-shaped bacterium was isolated from the nasal cavities of two common seals. Chemical analysis revealed the presence in the bacterium of a hitherto unknown cell-wall murein [type: L-Lys-L-Ala2-Gly(2-3)-L-Ala (Gly)]. Comparative 16S rRNA gene sequencing showed that the unidentified rod was related to the Arthrobacter group of organisms, although sequence divergence values of >3% from established members of this genus indicated that it represents a novel species. On the basis of phenotypic and phylogenetic considerations, it is proposed that the unknown bacterium from seals (Phoca vitulina) be classified as a novel species, Arthrobacter nasiphocae sp. nov. The type strain of Arthrobacter nasiphocae is CCUG 42953T.

Characterization of a Gemella-like organism isolated from an abscess of a rabbit: description of Gemella cunicula sp. nov.

An unknown Gram-positive, catalase-negative, ovoid-shaped bacterium isolated from the submandibular abscess of a rabbit was subjected to a polyphasic taxonomic analysis. Comparative 16S rRNA gene sequencing demonstrated the unknown coccus represents a new subline within the genus Gemella. The unknown isolate was readily distinguished from other recognized members of the genus Gemella, namely Gemella haemolysans, Gemella bergeri, Gemella morbillorum, Gemella palaticanis and Gemella sanguinis, by biochemical tests and electrophoretic analysis of whole-cell proteins. Based on both phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium is classified in the genus Gemella as Gemella cuniculi sp. nov. The type strain is CCUG 42726T.

Actinomyces canis sp. nov., isolated from dogs

Three strains of a previously undescribed catalase-positive Actinomyces-like bacterium were isolated from dogs. Biochemical testing and PAGE analysis of whole-cell proteins indicated that the strains were phenotypically highly related to each other but different from previously described Actinomyces and Arcanobacterium species. Sequencing of 16S rRNA showed that the unknown bacterium represents a new subline within a cluster of species which includes Actinomyces hyovaginalis, Actinomyces georgiae, Actinomyces meyeri, Actinomyces odontolyticus, Actinomyces radingae and Actinomyces turicensis. On the basis of phenotypic evidence and 16S rRNA sequence divergence levels (greater than 5% with recognized Actinomyces species) it is proposed that the unknown strains from canine sources be classified as a new species with the name Actinomyces canis sp. nov. The type strain of Actinomyces canis is CCUG 41706T (= CIP 106351T).

Vagococcus fessus sp. nov., isolated from a seal and a harbour porpoise

A polyphasic taxonomic study was performed on two strains of an unknown Gram-positive, catalase-negative, coccus-shaped bacterium isolated from a dead seal and a harbour porpoise. Comparative 16S rRNA gene sequencing demonstrated that the unknown bacterium represents a new subline within the genus Vagococcus close to, but distinct from, Vagococcus fluvialis, Vagococcus lutrae and Vagococcus salmoninarum. The unknown bacterium was readily distinguished from the three currently recognized Vagococcus species by biochemical tests and electrophoretic analysis of whole-cell proteins. Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as a new species, Vagococcus fessus. The type strain of Vagococcus fessus is CCUG 41755T.

Mathematical notation: help or hindrance?

In this article Geoff Tennant puts forward a range of reasons for using mathematical notation, emphasising the need to allow children learning it time and space to come to terms with it. Examples are given in furthering the argument that the time to introduce notation is after the concept is already fully understood.

Euler's theorem under the microscope

In this article Geoff Tennant summarises the first half of Imre Lakatos's seminal 1976 book, "Proofs and refutations: the logic of mathematical discovery". Implications are drawn for the classroom treatment of proof.