From Osmolytes to Diabetes: the Impact of Sugars and Sugar Alcohols on the Cystic Fibrosis Pathogen, Burkholderia multivorans

The incidence of CF related diabetes is on the rise as patient life expectancy continues to improve. Sugars elevated in diabetics include glucose, fructose, and mannose. These sugars, in addition to mannitol (recently approved as an inhaled osmolyte) are the basis for this study, aimed at assessing the impact these clinically relevant sugars have on virulence in Burkholderia multivorans. B. multivorans is a member of the Burkholderia cepacia complex (Bcc), and is the most frequent cause of Bcc infection in CF patients. Using an exopolysaccharide-deficient knockout in macrophage and Galleria mellonella infection models, biofilm formation, and adhesion assays, this study has identified exopolysaccharide-dependent and -independent phenotypes. Sequencing of B. multivorans C1576, a CF outbreak isolate, identified three putative adhesins in clinical isolate C1576 but not present in the sequenced environmental strain ATCC17616. Mannitol promoted adhesion and enhanced expression of these adhesins. This study characterised these adhesins and assessed the distribution within other clinical and environmental isolates of B. multivorans and the Bcc. Additionally, transcriptomic profiling of B. multivorans assessed the sugar response and EPS regulation during growth on clinically relevant sugars. Where possible, links were made between phenotypic studies and transcriptome data. B. multivorans EPS derived from fructose and mannitol was subjected to composition analysis using mass spectrometry, and assessed for biological activity. Still relevant to CF related diabetes, the ability of some members of the Bcc to bind insulin was assessed. Results indicated that a minority of strains bound insulin. Furthermore, by using flow cytometry cell sorting and fluorescence microscopy, results also showed only a small number of cells within a given population that bound insulin. In all, this study has added to the knowledge base of B. multivorans but more work is needed to fully understand virulence strategies exploited by this CF pathogen

Flexstab on the IBM 360

FLEXSTAB, an array of computer programs developed on CDC equipment, has been converted to operate on the IBM 360 computation system. Instructions for installing, validating, and operating FLEXSTAB on the IBM 360 are included. Hardware requirements are itemized and supplemental materials describe JCL sequences, the CDC to IBM conversion, the input output subprograms, and the interprogram data flow

Oxygen and nitrogen cycling in the northeast Pacific – Simulations and observations at Station Papa in 2003/2004

A long-term air-sea exchange mooring has been maintained in the North Pacific near Ocean Station Papa (OSP, 145W, 50N) since September 2002 as part of the Canadian Surface Ocean Lower Atmosphere Study (C-SOLAS). The mooring provides a new long-term data set for gas measurements. In addition to Conductivity, Temperature and Depth (CTD) recorders at two depths, the mooring is equipped with ProOceanus Gas Tension Devices (GTDs) measuring the total gas pressure at four different depths, two oxygen sensors, two fluorometers for chlorophyll estimates, and an upward-looking 200 kHz echo-sounder for bubble measurements. Chlorophyll data have been added using SeaWiFS imagery and occasional bottle casts. Data collected from June 2003 to June 2004 are compared with simulations from a 1-D coupled atmosphere-ocean-biogeochemical model. The coupled model consists of an atmospheric Single Column Model (SCM), based on the CCCma AGCM (Canadian Centre for Climate Modelling and Analysis-Atmospheric General Circulation Model), the General Ocean Turbulence Model (GOTM) and a 7-component ecosystem model embedded in GOTM. The ecosystem model also includes oxygen, nitrogen, carbon, and silica cycling. The study focuses on simulated and observed N2 and O2 variability. The comparison of these gases allows for separation of physical and biological processes; which can then be evaluated in more detail with the aid of model simulations. The model also tests different parameterizations for saturation and gas exchange, including a formulation for gas injection via bubbles, which affects gas concentrations within the whole mixed layer. For most of the time the model shows good agreement with observations. However, in summer 2003 the observations reveal a strong oxygen and chlorophyll event, which is not reproduced in the standard model run. A weaker signal is seen in May 2004. OSP is a High Nutrient Low Chlorophyll (HNLC) region, limited by the micronutrient iron. Increases in usually low chlorophyll values occur occasionally due to natural iron enrichment (dust deposition, eddy transport, below surface layer transport). Although limitations of 1-D modeling become apparent here, an assumed input of iron in the model explains the differences between simulated and observed oxygen and chlorophyll maxima. The model provides information on the strength and duration of potential iron contribution. No obvious dust events or eddy traverses to supply iron were recorded during this time period. An alternative explanation is entrainment from deeper waters, where occasional iron enrichment is known to occur due to off-shelf transport via eddies or recirculation from the Alaskan shelf

Re-evaluation of Cryptosporiopsis eucalypti and Cryptosporiopsis-like species occurring on Eucalyptus

Cryptosporiopsis eucalypti is a common follicolous pathogen of Eucalyptus species in tropical and temperate regions where these trees are grown in plantations. The taxonomy of C. eucalypti is confused by the fact that it is phylogenetically unrelated to the type species of Cryptosporiopsis (Cryptosporiopsis nigra = C. scutellata, Helotiales). The aim of this study was to resolve the taxonomic position of C. eucalypti based on morphology and phylogenetic inference. Thirty-two Eucalyptus leaf samples with symptoms typical of C. eucalypti infection were collected from 10 tropical and temperate countries across four continents. Cultures were established from single conidia, as well as from ascospores of a previously unreported teleomorph state. DNA sequences were obtained for the 28 S nrDNA, the internal transcribed spacers of the nrDNA operon, and beta-tubulin regions to determine generic and species-level relationships. DNA-sequence analysis showed that conidial and ascospore isolates of C. eucalypti have low intraspecific variation, although two collections from Australia and one from Uruguay represented two novel taxa. Based on the newly collected teleomorph stage, as well as the phylogenetic data, C. eucalypti is shown to represent a new genus closely related to Plagiostoma (Gnomoniaceae, Diaporthales) for which the names Pseudoplagiostoma gen. nov. and Pseudoplagiostomaceae fam. nov. (Diaporthales) are introduced. Two new species of Cryptosporiopsis (Dermateaceae, Helotiales) on Eucalyptus from Australia and California (USA) are also described

Mannitol promotes adherence of an outbreak strain of Burkholderia multivorans via an exopolysaccharide-independent mechanism that is associated with upregulation of newly identified fimbrial and afimbrial adhesins

© Society for General Microbiology, 2013. Post-print version of article deposited in accordance with SHERPA RoMEO guidelinesBurkholderia multivorans, a member of the Burkholderia cepacia complex (Bcc), is an important pathogen of the cystic fibrosis (CF) lung. Mannitol, approved as an inhaled osmolyte therapy for use in CF patients, promotes exopolysaccharide (EPS) production by the Bcc. In the present study, we investigated the role of mannitol-induced EPS in the adherence of B. multivorans. We report that mannitol promoted adherence of two representative B. multivorans strains. However, whilst this enhanced adherence was largely EPS-dependent in an environmental isolate, it was EPS-independent within a CF outbreak strain, suggesting strain-to-strain variation in adhesins. Genome sequencing of the outbreak strain enabled the identification of two distinct loci encoding putative fimbrial and afimbrial adhesins. The putative fimbriae-encoding locus was found to be widely distributed amongst clinical and environmental B. multivorans. In contrast, the locus encoding the putative afimbrial adhesin (of the filamentous haemagglutinin family, FHA) was restricted to clinical isolates. Both loci contributed to biofilm formation and mucin adherence. Furthermore, we report that mannitol promoted expression of both loci, and that the locus encoding the putative FHA-family adhesin is a key determinant of the enhanced adherence observed following growth in mannitol. Our studies provide the first characterization, to our knowledge, of B. multivorans adhesins, and in so doing highlight the strain-dependent role of EPS in the Bcc and the difficulties in assigning phenotypic traits to Bcc EPS due to the wider response to mannitol. Our observations also highlight the need to monitor the microbiological effects of inhaled mannitol therapy in Bcc-infected CF patients

Microbial Abundance and Community Analysis in Devil’s Hole, Harrington Sound, Bermuda

Microbial activity within elevated CO2 and oxygen depleted environments changes with density driven stratification overturn in the seasonally anoxic region of Devil’s Hole, Bermuda. The temperature gradient developed during the summer months creates a natural laboratory to study bacterial and virus population density and microbial community dynamics in the anoxic layer during stratification and in response to naturally raised pCO2 levels. Chemical properties and microbial communities were measured and evaluated during stratification and after turnover. The study concludes that there are different bacterial communities present during pre and post turnover conditions, with two unknown bacterial populations accounting for a majority of bacterial diversity. Virus counts fluctuate with depth, while bacterial populations flourish near the sediment layer at the anoxic zone. Organic matter falling through the water column settles in the anoxic layer and sediment, creating a nutrient rich environment for bacteria to metabolize. These anaerobic and elevated pCO2 conditions give a glimpse into microorganism’s nutrient use and production under elevated pCO2 conditions which are similar or higher than future pCO2 levels projected according to Intergovernmental Panel for Climate Control

Intracellular replication of the well-armed pathogen Burkholderia pseudomallei.

The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to cause disease in animals, B. mallei primarily infects Equus spp. and B. pseudomallei (BPS), that is able to cause potentially life-threatening disease in humans. BPS is naturally resistant to many antibiotics and there is no vaccine available. Although not a specialised human pathogen, BPS possesses a large genome and many virulence traits that allow it to adapt and survive very successfully in the human host. Key to this survival is the ability of BPS to replicate intracellularly. In this review we highlight recent advances in our understanding of the intracellular survival of BPS, including how it overcomes host immune defenses and other challenges to establish its niche and then spread the infection. Knowledge of these mechanisms increases our capacity for therapeutic interventions against a well-armed foe

Embedding Recovery to Transform Inpatient Mental Health Care: The 333 Model

Objective: The 333 model is a radical redesign of acute mental health care. Time-limited inpatient pathways for assessment (≤3 days), treatment (≤3 weeks), and recovery (≤3 months) replaced traditional geographical-sector wards. By making beds available, 333 aspired to improve access, deliver early treatment, and shorten hospital stays—generating savings through reductions in beds and out-of-area placements (OAPs). This article compares the model’s performance against national benchmarking and internal targets. Methods: The complement of general adult beds (2011–2016) was mapped out. Patient flow data (April 2015–March 2017) were extracted from the National Health Service data warehouse and compared with 2016 NHS benchmarking and 333 targets. Results: Between 2012 and 2016, beds were reduced by 44% compared with 17% nationally. OAPs due to bed unavailability became extremely rare. More than 74% (N=2,679) of patients who were admitted to the assessment unit between 2015 and 2017 were discharged back to the community, minimizing fragmentation of care. Median length of stay was one-sixth as long as the national rate, but readmission rates were higher than the national mean because of the model’s innovative approach to managing treatment of patients with personality disorders. Bed occupancy was below the national average, with beds available every night for 2 years. Conclusions: With its recovery-focused approach, 333 has reduced length of stay and ensured that a stay on any ward is meaningful and adds value. The article demonstrates that bed and OAP reduction and the delivery of safe care can be achieved simultaneously

Chaotic advection of reacting substances: Plankton dynamics on a meandering jet

We study the spatial patterns formed by interacting populations or reacting chemicals under the influence of chaotic flows. In particular, we have considered a three-component model of plankton dynamics advected by a meandering jet. We report general results, stressing the existence of a smooth-filamental transition in the concentration patterns depending on the relative strength of the stirring by the chaotic flow and the relaxation properties of planktonic dynamical system. Patterns obtained in open and closed flows are compared.Comment: 5 pages, 3 figues, latex compiled with modegs.cl