Synthesis and X-ray crystal structure of a bridging trispiran ligand

The document attached has been archived with permission from the publisher.Spiro[3,3]heptane-2,6-dispiro-4,5-diazafluorene (4) has been synthesized in three steps from 1,10-phenanthroline. It crystallizes in the orthorhombic space group P212121 and has the two 4,5-diazafluorene metal binding domains mutually orthogonal.Peter J. Steel and Christopher J. Sumb

Proteomic analysis at the sites of clinical infection with invasive Streptococcus pyogenes

Invasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive S. pyogenes infection (empyema, septic arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were found in a single pleural fluid sample including streptococcal inhibitor of complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human proteins were detected in patient fluids, 177 (38%) of which could be identified as neutrophil proteins, including alpha enolase and lactotransferrin which, together, were found in all 17 samples. Our data suggest that streptococcal proteins are difficult to detect in infected fluid samples. A vast array of human proteins associated with leukocyte activity are, however, present in samples that deserve further evaluation as potential biomarkers of infection

The effect of carboxylate position on the structure of a metal organic framework derived from cyclotriveratrylene

Two cyclotriveratrylene-based ligands H3L1 and H3L2 have been synthesised using microwave heating and used in the formation of 1 [Zn2(L1)(DMA)2(CH3COO)] and 2 [Zn6(L2)4(DMA)6(H2O)5] (DMA = N,N-dimethylacetamide). 1 displays an unusual trigonal paddlewheel node geometry, while Zn(II) paddlewheels are observed in 2. However the stacking of CTV molecules in 1 is replaced by an uncommon molecular capsule structure in 2

Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines

Bdellovibrio bacteriovorus Inhibits Staphylococcus aureus Biofilm Formation and Invasion into Human Epithelial Cells

Bdellovibrio bacteriovorus HD100 is a predatory bacterium that attacks many Gram-negative human pathogens. A serious drawback of this strain, however, is its ineffectiveness against Gram-positive strains, such as the human pathogen Staphylococcus aureus. Here we demonstrate that the extracellular proteases produced by a host-independent B. bacteriovorus (HIB) effectively degrade/inhibit the formation of S. aureus biofilms and reduce its virulence. A 10% addition of HIB supernatant caused a 75% or greater reduction in S. aureus biofilm formation as well as 75% dispersal of pre-formed biofilms. LC-MS-MS analyses identified various B. bacteriovorus proteases within the supernatant, including the serine proteases Bd2269 and Bd2321. Tests with AEBSF confirmed that serine proteases were active in the supernatant and that they impacted S. aureus biofilm formation. The supernatant also possessed a slight DNAse activity. Furthermore, treatment of planktonic S. aureus with the supernatant diminished its ability to invade MCF-10a epithelial cells by 5-fold but did not affect the MCF-10a viability. In conclusion, this study illustrates the hitherto unknown ability of B. bacteriovorus to disperse Gram-positive pathogenic biofilms and mitigate their virulence.open6

Activity in perceptual classification networks as a basis for human subjective time perception

Despite being a fundamental dimension of experience, how the human brain generates the perception of time remains unknown. Here, we provide a novel explanation for how human time perception might be accomplished, based on non-temporal perceptual classification processes. To demonstrate this proposal, we build an artificial neural system centred on a feed-forward image classification network, functionally similar to human visual processing. In this system, input videos of natural scenes drive changes in network activation, and accumulation of salient changes in activation are used to estimate duration. Estimates produced by this system match human reports made about the same videos, replicating key qualitative biases, including differentiating between scenes of walking around a busy city or sitting in a cafe or office. Our approach provides a working model of duration perception from stimulus to estimation and presents a new direction for examining the foundations of this central aspect of human experience

Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis

Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (≥4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (≥4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence

No rapid audiovisual recalibration in adults on the autism spectrum

Autism spectrum disorders (ASD) are characterized by difficulties in social cognition, but are also associated with atypicalities in sensory and perceptual processing. Several groups have reported that autistic individuals show reduced integration of socially relevant audiovisual signals, which may contribute to the higher-order social and cognitive difficulties observed in autism. Here we use a newly devised technique to study instantaneous adaptation to audiovisual asynchrony in autism. Autistic and typical participants were presented with sequences of brief visual and auditory stimuli, varying in asynchrony over a wide range, from 512 ms auditory-lead to 512 ms auditory-lag, and judged whether they seemed to be synchronous. Typical adults showed strong adaptation effects, with trials proceeded by an auditory-lead needing more auditory-lead to seem simultaneous, and vice versa. However, autistic observers showed little or no adaptation, although their simultaneity curves were as narrow as the typical adults. This result supports recent Bayesian models that predict reduced adaptation effects in autism. As rapid audiovisual recalibration may be fundamental for the optimisation of speech comprehension, recalibration problems could render language processing more difficult in autistic individuals, hindering social communication

Protein surface functionalisation as a general strategy for facilitating biomimetic mineralisation of ZIF-8

The durability of enzymes in harsh conditions can be enhanced by encapsulation within metal-organic frameworks (MOFs) via a process called biomimetic mineralisation. Herein we show that the surface charge and chemistry of a protein determines its ability to seed MOF growth. We demonstrate that chemical modification of amino acids on the protein surface is an effective method for systematically controlling biomimetic mineralisation by zeolitic imidazolate framework-8 (ZIF-8). Reaction of surface lysine residues with succinic (or acetic) anhydride facilitates biomimetic mineralisation by increasing the surface negative charge, whereas reaction of surface carboxylate moieties with ethylenediamine affords a more positively charged protein and hinders the process. Moreover, computational studies confirm that the surface electrostatic potential of a protein is a good indicator of its ability to induce biomimetic mineralisation. This study highlights the important role played by protein surface chemistry in encapsulation and outlines a general method for facilitating the biomimetic mineralisation of proteins

Selected Schizosaccharomyces pombe Strains Have Characteristics That Are Beneficial for Winemaking

At present, wine is generally produced using Saccharomyces yeast followed by Oenococus bacteria to complete malolactic fermentation. This method has some unsolved problems, such as the management of highly acidic musts and the production of potentially toxic products including biogenic amines and ethyl carbamate. Here we explore the potential of the fission yeast Schizosaccharomyces pombe to solve these problems. We characterise an extensive worldwide collection of S. pombe strains according to classic biochemical parameters of oenological interest. We identify three genetically different S. pombe strains that appear suitable for winemaking. These strains compare favourably to standard Saccharomyces cerevisiae winemaking strains, in that they perform effective malic acid deacidification and significantly reduce levels of biogenic amines and ethyl carbamate precursors without the need for any secondary bacterial malolactic fermentation. These findings indicate that the use of certain S. pombe strains could be advantageous for winemaking in regions where malic acid is problematic, and these strains also show superior performance with respect to food safety