Recognition of greater diversity of Bacillus species and related bacteria in human faeces

In a study looking at the culturable, aerobic Actinobacteria associated with the human gastrointestinal tract, the vast majority of isolates obtained from dried human faeces belonged to the genus Bacillus and related bacteria. A total of 124 isolates were recovered from the faeces of 10 healthy adult donors. 16S rRNA gene sequence analyses showed the majority belonged to the families Bacillaceae (n = 81) and Paenibacillaceae (n = 3), with Bacillus species isolated from all donors. Isolates tentatively identified as Bacillus clausii (n = 32) and B. licheniformis (n = 28) were recovered most frequently, with the genera Lysinibacillus, Ureibacillus, Oceanobacillus, Ornithinibacillus and Virgibacillus represented in some donors. Phenotypic data confirmed the identities of isolates belonging to well-characterized species. Representatives of the phylum Actinobacteria were recovered in much lower numbers (n = 11). Many of the bacilli exhibited antimicrobial activity against one or more strains of Clostridium difficile, C. perfringens, Listeria monocytogenes and Staphylococcus aureus, with some (n = 12) found to have no detectable cytopathic effect on HEp-2 cells. This study has revealed greater diversity within gut-associated aerobic spore-formers than previous studies, and suggests that bacilli with potential as probiotics could be isolated from the human gut.

Rhodium cationic complexes using dithioethers as chiral ligands. Application in styrene hydroformylation

Addition of the dithioethers (−)-DIOSR2 (R=Me, iPr) (2,3-O-isopropylidene-1,4-dimethyl (and diisopropyl) thioether-L-threitol) to a dichloromethane solution of [Rh(COD)2]ClO4 (COD=1,5-cyclooctadiene) yielded the mononuclear complexes [Rh(COD)(DIOSR2)]ClO4. X-ray diffraction methods showed that the [Rh(COD)(DIOSiPr2)]ClO4 complex had an square-planar coordination geometry at the rhodium atom with the iPr groups in anti position. Cyclooctadiene complexes react with carbon monoxide to form dinuclear tetracarbonylated complexes [(CO)2Rh(μ-DIOSR2)2(CO)2](ClO4)2. [Rh(COD)(DIOSR2)]ClO4 are active catalyst precursors in styrene hydroformylation at 30 atm and 65°C which give conversions of up to 99% with a regioselectivity in 2-phenylpropanal as high as 74%. In all cases enantioselectivities are low.

An unexpected photoadduct of N-carbomethoxymethylpyrrolidine with a chiral butenolide and benzophenone: X-ray structure and synthetic utility

The regio- and stereoselective photoinduced addition of N-carbomethoxymethylpyrrolidine to 5(S)-tert-butyldimethylsiloxymethyl-furan-2(5H)-one in the presence of benzophenone yields 3(R)-[N-(diphenylhydroxymethyl)carbo methoxymethylpyrrolidin-2′-yl]-4(S)-tert-butyldimethylsiloxymethyl)-butan-4-olides (epimeric at C-2′), and we report the X-ray structure of the major adduct together with its conversion into the 1-azabicyclo[4.3.0]-nonane ring system.

Organocatalytic enantioselective construction of nitrocyclohexanes containing multiple chiral centres via a cascade reaction

The stereoselective construction of complex molecules with multiple stereogenicity in a single step represents an extremely useful, but challenging approach to complexity in chemical synthesis. The development of organocatalytic cascade processes has proven useful in these studies, but reports where four or more stereocentres are created in a single step from just two achiral reagents are rare. Herein we report the development of a novel asymmetric domino Michael-Michael reaction between nitrohex-4-enoates and nitro-olefins to generate cyclohexanes of high complexity, including one with a quaternary centre, and one with five contiguous stereocentres. This methodology provides access to a range of useful nitrocyclohexane derivatives, including a novel class of a-lycorane-like structures.

Conformational modulation of sequence recognition in synthetic macromolecules

The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue.

The study of chiral adsorption systems using synchrotron- based structural and spectroscopic techniques: stereospecific adsorption of serine on Au-modified chiral Cu{531} surfaces

We apply modern synchrotron-based structural techniques to the study of serine adsorbed on the pure andAumodified intrinsically chiral Cu{531} surface. XPS and NEXAFS data in combination with DFT show that on the pure surface both enantiomers adsorb in l4 geometries (with de-protonated b-OH groups) at low coverage and in l3 geometries at saturation coverage. Significantly larger enantiomeric differences are seen for the l4 geometries, which involve substrate bonds of three side groups of the chiral center, i.e. a three-point interaction. The l3 adsorption geometry, where only the carboxylate and amino groups form substrate bonds, leads to smaller but still significant enantiomeric differences, both in geometry and the decomposition behavior. When Cu{531} is modified by the deposition of 1 and 2ML Au the orientations of serine at saturation coverage are significantly different from those on the clean surface. In all cases, however, a l3 bond coordination is found at saturation involving different numbers of Au atoms, which leads to relatively small enantiomeric differences.

Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment

Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI.

Improving sequence-based fold recognition by using 3D model quality assessment

Motivation: The ability of a simple method (MODCHECK) to determine the sequence–structure compatibility of a set of structural models generated by fold recognition is tested in a thorough benchmark analysis. Four Model Quality Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench-9 automated structure evaluation experiment. We systematically test and evaluate whether the MQAP methods can successfully detect native-likemodels. Results: We show that compared with the other three methods tested MODCHECK is the most reliable method for consistently performing the best top model selection and for ranking the models. In addition, we show that the choice of model similarity score used to assess a model's similarity to the experimental structure can influence the overall performance of these tools. Although these MQAP methods fail to improve the model selection performance for methods that already incorporate protein three dimension (3D) structural information, an improvement is observed for methods that are purely sequence-based, including the best profile–profile methods. This suggests that even the best sequence-based fold recognition methods can still be improved by taking into account the 3D structural information.

Prediction of novel and analogous folds using fragment assembly and fold recognition

A number of new and newly improved methods for predicting protein structure developed by the Jones–University College London group were used to make predictions for the CASP6 experiment. Structures were predicted with a combination of fold recognition methods (mGenTHREADER, nFOLD, and THREADER) and a substantially enhanced version of FRAGFOLD, our fragment assembly method. Attempts at automatic domain parsing were made using DomPred and DomSSEA, which are based on a secondary structure parsing algorithm and additionally for DomPred, a simple local sequence alignment scoring function. Disorder prediction was carried out using a new SVM-based version of DISOPRED. Attempts were also made at domain docking and “microdomain” folding in order to build complete chain models for some targets.

Improvement of the GenTHREADER method for genomic fold recognition

Motivation: In order to enhance genome annotation, the fully automatic fold recognition method GenTHREADER has been improved and benchmarked. The previous version of GenTHREADER consisted of a simple neural network which was trained to combine sequence alignment score, length information and energy potentials derived from threading into a single score representing the relationship between two proteins, as designated by CATH. The improved version incorporates PSI-BLAST searches, which have been jumpstarted with structural alignment profiles from FSSP, and now also makes use of PSIPRED predicted secondary structure and bi-directional scoring in order to calculate the final alignment score. Pairwise potentials and solvation potentials are calculated from the given sequence alignment which are then used as inputs to a multi-layer, feed-forward neural network, along with the alignment score, alignment length and sequence length. The neural network has also been expanded to accommodate the secondary structure element alignment (SSEA) score as an extra input and it is now trained to learn the FSSP Z-score as a measurement of similarity between two proteins. Results: The improvements made to GenTHREADER increase the number of remote homologues that can be detected with a low error rate, implying higher reliability of score, whilst also increasing the quality of the models produced. We find that up to five times as many true positives can be detected with low error rate per query. Total MaxSub score is doubled at low false positive rates using the improved method.