Chemical control through dissociative electron attachment - A study on pentafluorotoluene, pentafluoroaniline and pentafluorophenol

In a combined experimental and theoretical study on dissociative electron attachment (DEA) to pentafluorotoluene, pentafluoroaniline and pentafluorophenol in the energy range 0-3 eV we reveal the role of rearrangement and hydrogen bonded intermediates in the DEA process and show that HF formation can be used to enable otherwise inaccessible, efficient low energy DEA processes.

Dissociative electron attachment to C2F5 radicals

Dissociative electron attachment to the reactive C2F5 molecular radical has been investigated with two complimentary experimental methods; a single collision beam experiment and a new flowing afterglow Langmuir probe technique. The beam results show that F- is formed close to zero electron energy in dissociative electron attachment to C2F5. The afterglow measurements also show that F- is formed in collisions between electrons and C2F5 molecules with rate constants of 3.7 × 10-9 cm3 s-1 to 4.7 × 10-9 cm3 s-1 at temperatures of 300–600 K. The rate constant increases slowly with increasing temperature, but the rise observed is smaller than the experimental uncertainty of 35%.

A comparison of three bacterial phosphonoacetate hydrolases from different environmental sources

Cleavage of the carbon-phosphorus bond of the xenobiotic phosphonoacetate by phosphonoacetate hydrolase: represents a novel route for the microbial metabolism of organophosphonates, and is unique in that it: is substrate-inducible and its expression is independent of the phosphate status of the cell. The enzyme has previously only been demonstrated in cell extracts of Pseudomonas fluorescens 23F. Phosphonoacetate hydrolase activity is now reported in extracts of environmental Curtobacterium sp. and Pseudomonas sp. isolates capable of the phosphate-insensitive mineralization of phosphonoacetate as the sole source of carbon, energy and phosphorus at concentrations up to 40 mmol l(-1) and 100 mmol l(-1), respectively. The enzymes in both strains were similarly inducible by phosphonoacetate and had a unique specificity ibr this substrate. However, they differed significantly from each other, and from the previously described Ps. fluorescens 23F enzyme, in respect of their apparent molecular masses, temperature optima, thermostability, sensitivity to inhibition by chelating agents and by structural analogues of phosphonoacetate, and in their affinities for the substrate.

Ecotoxicological screening of Kenyan tannery dust using a luminescent-based bacterial biosensor

Ecotoxicological screening of dust sampled throughout a Kenyan tannery was conducted using a luminescence (lux)-based bacterial biosensor for both solid and liquid assays. This was complemented by chemical analysis in an attempt to identify possible causative toxic components. The biosensor results showed a highly significant (p <0.001) difference in both solid and liquid phase toxicity in samples collected from various identified sampling points in the tannery. A positive correlation was observed between results of the solid and liquid phase techniques, for most of the sampling points indicating that the toxic contaminants were bioavailable both in the solid and liquid state. However, the results generally indicated toxicity associated with liquid phase except certain areas in solid phase such as chemical handling, buffing area and weighing. The most toxic tannery area identified was the weighing area (p <0.001), showing the lowest bioluminescence for both the solid (0.38 +/- 2.21) and liquid phases (0.01 +/- 0.001). Chromium was the metal present in the highest concentration indicating levels higher than the stipulated regulatory requirement of 0.5 mg Cr/m3 for total Cr (highest Cr concentration was at chemical handling at 209.24 mg l(-1)) in all dust samples. The weighing area had the highest Ni concentration (1.87 mg l(-1)) and the chemical handling area showed the highest Zn concentration (31.9 mg l(-1)). These results raise environmental health concerns, as occupational exposure to dust samples from this site has been shown to give rise to elevated concentrations (above the stipulated levels) of chromium in blood, urine and some body tissues, with inhalation being the main route. Health and Safety Executive (HSE), UK, and American Conference of Governmental Industrial Hygienist (ACGIH) and National Institute for Occupational Safety and Health (NIOSH), USA stipulates an occupational exposure limit of 0.5 mg Cr/m3 (8 h TWA) for total chromium. However, schedule 1 of Controls of substances hazardous to health (COSHH) regulations developed by HSE, indicate 0.05 mg m3 (8 h TWA reference periods) to be the limit for Cr (VI) exposure. The exposure limit for individual (e.g., Cr, Zn, Ni etc.) contaminants (homogeneity) was not exceeded, but potential impact of heterogeneity (multi-element synergistic effect) on toxicity requires application of the precautionary principle.

Lung Microbiota and Bacterial Abundance in Patients with Bronchiectasis when Clinically Stable and during Exacerbation

RATIONALE: Characterization of bacterial populations in infectious respiratory diseases will provide improved understanding of the relationship between the lung microbiota, disease pathogenesis and treatment outcomes.

OBJECTIVES: To comprehensively define lung microbiota composition during stable disease and exacerbation in bronchiectasis patients.

METHODS: Sputum was collected from patients when clinically stable and before and after completion of antibiotic treatment of exacerbations. Bacterial abundance and community composition were analyzed using anaerobic culture and 16S rDNA pyrosequencing.

MEASUREMENTS AND MAIN RESULTS: In clinically stable patients, aerobic and anaerobic bacteria were detected in 40/40 (100%) and 33/40 (83%) sputum samples, respectively. The dominant organisms cultured were P. aeruginosa (n=10 patients), H. influenzae (n=12), Prevotella (n=18) and Veillonella (n=13). Pyrosequencing generated over 150,000 sequences, representing 113 distinct microbial taxa; the majority of observed community richness resulted from taxa present in low abundance with similar patterns of phyla distribution in clinically stable patients and patients at the onset of exacerbation. Following treatment of exacerbation, there was no change in total (p=0.925), aerobic (p=0.917) or anaerobic (p=0.683) load and only a limited shift in community composition. Agreement for detection of bacteria by culture and pyrosequencing was good for aerobic bacteria such as P. aeruginosa (kappa=0.84) but poorer for other genera including anaerobes. Lack of agreement was largely due to bacteria been detected by pyrosequencing but not by culture.

CONCLUSIONS: A complex microbiota is present in the lungs of bronchiectasis patients which remains stable through treatment of exacerbations suggesting that changes in microbiota composition do not account for exacerbations.

Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis

OBJECTIVES: The gastrointestinal microbiota is considered important in inflammatory bowel disease (IBD) pathogenesis. Discoveries from established disease cohorts report reduced bacterial diversity, changes in bacterial composition, and a protective role for Faecalibacterium prausnitzii in Crohn's disease (CD). The majority of studies to date are however potentially confounded by the effect of treatment and a reliance on established rather than de-novo disease.

METHODS: Microbial changes at diagnosis were examined by biopsying the colonic mucosa of 37 children: 25 with newly presenting, untreated IBD with active colitis (13 CD and 12 ulcerative colitis (UC)), and 12 pediatric controls with a macroscopically and microscopically normal colon. We utilized a dual-methodology approach with pyrosequencing (threshold >10,000 reads) and confirmatory real-time PCR (RT-PCR).

RESULTS: Threshold pyrosequencing output was obtained on 34 subjects (11 CD, 11 UC, 12 controls). No significant changes were noted at phylum level among the Bacteroidetes, Firmicutes, or Proteobacteria. A significant reduction in bacterial alpha-diversity was noted in CD vs. controls by three methods (Shannon, Simpson, and phylogenetic diversity) but not in UC vs. controls. An increase in Faecalibacterium was observed in CD compared with controls by pyrosequencing (mean 16.7% vs. 9.1% of reads, P = 0.02) and replicated by specific F. prausnitzii RT-PCR (36.0% vs. 19.0% of total bacteria, P = 0.02). No disease-specific clustering was evident on principal components analysis.

CONCLUSIONS: Our results offer a comprehensive examination of the IBD mucosal microbiota at diagnosis, unaffected by therapeutic confounders or changes over time. Our results challenge the current model of a protective role for F. prausnitzii in CD, suggesting a more dynamic role for this organism than previously described.

Strategies to Improve the Surface Plasmon Resonance-Based Immmunodetection of Bacterial Cells

We have made a comparison of (a) different surface chemistries of surface plasmon resonance (SPR) sensor chips (such as carboxymethylated dextran and carboxymethylated C1) and (b) of different assay formats (direct, sandwich and subtractive immunoassay) in order to improve the sensitivity of the determination of the model bacteria Acidovorax avenae subsp. citrulli (Aac). The use of the carboxymethylated sensor chip C1 resulted in a better sensitivity than that of carboxymethylated dextran CM5 in all the assay formats. The direct assay format, in turn, exhibits the best sensitivity. Thus, the combination of a carboxymethylated sensor chip C1 with the direct assay format resulted in the highest sensitivity for Aac, with a limit of detection of 1.6x106 CFU mL-1. This SPR immunosensor was applied to the detection of Aac in watermelon leaf extracts spiked with the bacteria, and the lower LOD is 2.2x107 CFU mL-1.

Maternal Religiosity, Family Resources and Stressors, and Parent-Child Attachment Security in Northern Ireland

This study explores the associations between mothers' religiosity, and families' and children's functioning in a stratified random sample of 695 Catholic and Protestant motherchild dyads in socially deprived areas in Belfast, Northern Ireland, a region which has experienced centuries of sectarian conflict between Protestant Unionists and Catholics Nationalists. Findings based on mother and child surveys indicated that even in this context of historical political violence associated with religious affiliation, mothers' religiosity played a consistently positive role, including associations with multiple indicators of better family functioning (i.e., more cohesion and behavioral control and less conflict, psychological distress, and adjustment problems) and greater parentchild attachment security. Mothers' religiosity also moderated the association between parentchild attachment security and family resources and family stressors, enhancing positive effects of cohesion and mother behavioral control on motherchild attachment security, and providing protection against risks associated with mothers' psychological distress. Findings are discussed in terms of implications for understanding the role of religiosity in serving as a protective or risk factor for children and families.

Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia

Rationale: Bacterial pneumonia is the most common infectious cause of death worldwide and treatment is increasingly hampered by antibiotic resistance. Mesenchymal stem cells (MSCs) have been demonstrated to provide protection against acute inflammatory lung injury; however, their potential therapeutic role in the setting of bacterial pneumonia has not been well studied.

Objective: This study focused on testing the therapeutic and mechanistic effects of MSCs in a mouse model of Gram-negative pneumonia.

Methods and results: Syngeneic MSCs from wild-type mice were isolated and administered via the intratracheal route to mice 4 h after the mice were infected with Escherichia coli. 3T3 fibroblasts and phosphate-buffered saline (PBS) were used as controls for all in vivo experiments. Survival, lung injury, bacterial counts and indices of inflammation were measured in each treatment group. Treatment with wild-type MSCs improved 48 h survival (MSC, 55%; 3T3, 8%; PBS, 0%; p<0.05 for MSC vs 3T3 and PBS groups) and lung injury compared with control mice. In addition, wild-type MSCs enhanced bacterial clearance from the alveolar space as early as 4 h after administration, an effect that was not observed with the other treatment groups. The antibacterial effect with MSCs was due, in part, to their upregulation of the antibacterial protein lipocalin 2.

Conclusions: Treatment with MSCs enhanced survival and bacterial clearance in a mouse model of Gram-negative pneumonia. The bacterial clearance effect was due, in part, to the upregulation of lipocalin 2 production by MSCs

Impact of cigarette smoke exposure on host-bacterial pathogen interactions

The human respiratory tract of individuals with normal lung function maintains a fine-tuned balance, being asymptomatically colonised by the normal microbiota in the upper airways and sterile in the lower tract. This equilibrium may be disrupted by the exposure to insults such as cigarette smoke. In the respiratory tract, the complex and noxious nature of inhaled cigarette smoke alters host-microorganisminteraction dynamics at all anatomical levels, causing infections in many cases. Moreover, continuous exposure to cigarette smoke itself causes deleterious effects on the host that can trigger the development of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. COPD is an irreversible airflow obstruction associated with emphysema, fibrosis, mucus hypersecretion and persistent colonisation of the lower airways by opportunistic pathogens. COPD patients keep a stable (without exacerbation) but progressively worsening condition and suffer periodic exacerbations caused, in most cases, by infections. Although smoking and smoking-associated diseases are associated with a high risk of infection, most therapies aim to reduce inflammatory parameters, but do not necessarily take into account the presence of persistent colonisers. The effect of cigarette smoke on host-pathogen interaction dynamics in the respiratory tract, together with current and novel therapies, is discussed. Copyright©ERS 2012.