Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-Lhomoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3- hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones. Originally published Proc. Natl. Acad. Sci, Vol. 96, No. 20, Sep. 199

On lions, impala, and bigraphs: modelling interactions in physical/virtual spaces

While HCI has a long tradition of formally modelling task-based interactions with graphical user interfaces, there has been less progress in modelling emerging ubiquitous computing systems due in large part to their highly contextual nature and dependence on unreliable sensing systems. We present an exploration of modelling an example ubiquitous system, the Savannah game, using the mathematical formalism of bigraphs, which are based on a universal process algebra that encapsulates both dynamic and spatial behaviour of autonomous agents that interact and move among each other, or within each other. We establish a modelling approach based on four perspectives on ubiquitous systems—Computational, Physical, Human, and Technology—and explore how these interact with one another. We show how our model explains observed inconsistencies in user trials of Savannah, and then, how formal analysis reveals an incompleteness in design and guides extensions of the model and/or possible system re-design to resolve this

Biological Responses of Lumbriculus variegatus Exposed to Fluoranthene-Spiked Sediment

Lumbriculus variegatus was used as a bioassay organism to examine the impact of the sediment-associated polycyclic aromatic hydrocarbon (PAH) fluoranthene on behavior, reproduction, and toxicokinetics. The number of worms increased between the beginning and end of the experiment at 59 μg g −1 fluoranthene, but at the next higher treatment (108 μg g −1 ) the number of worms found was lower and not different from the control. Worms exposed to 95 μg g −1 also exhibited increased reproduction when fed a yeast-cerophyl-trout chow mixture. On a total biomass basis, only the 95 μg g −1 exposure with food exhibited a statistically significant increase over the nonfed control. Evaluation of reproduction at the two highest treatments was compromised by a brief aeration failure 2 days before the end of the experiment. The behavioral responses were followed as changes in biological burial rate (sediment reworking rate) of a 137 Cs-labeled marker layer. The biological burial rate increased toward a plateau as the concentration increased from the control (3.9 μg g −1 dry weight total PAH) to 355 μg g −1 dry weight fluoranthene in sediment. The aeration failure had minimal impact on the determination of reworking rate because all the data for the rate determination were collected prior to the aeration failure. Uptake and elimination rates declined with increasing treatment concentration across the range of fluoranthene concentrations, 59–355 μg g −1 dry weight sediment. The disconnect between the increasing biological burial rates and the decreasing toxicokinetics rates with increasing exposure concentration demonstrates that the toxicokinetic processes are dominated by uptake and elimination to interstitial water. The bioaccumulation factor (concentration in the organisms on a wet weight basis divided by the concentration in sediment on a dry weight basis) ranged from 0.92 to 1.88 on day 10 and declined to a range of 0.52 to 0.99 on day 28 with the lowest value at the highest dose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42373/1/244-42-3-292_20420292.pd

Chapter nine: Understanding Declines in Rusty Blackbirds

The Rusty Blackbird (Euphagus carolinus), a formerly common breeding species of boreal wetlands, has exhibited the most marked decline of any North American landbird. North American Breeding Bird Survey (BBS) trends in abundance are estimated to be ‒12.5%/yr. over the last 40 years, which is tantamount to a \u3e95% cumulative decline. Trends in abundance calculated from Christmas Bird Counts (CBC) for a similar period indicate a range-wide decline of ‒5.6%/yr. Qualitative analyses of ornithological accounts suggest the species has been declining for over a century. Several studies document range retraction in the southern boreal forest, whereas limited data suggest that abundance may be more stable in more northerly areas. The major hypotheses for the decline include degradation of boreal habitats from logging and agricultural development, mercury contamination, and wetland desiccation resulting from global warming. Other likely reasons for decline include loss or degradation of wooded wetlands of the southeastern U.S and mortality associated with abatement efforts targeting nuisance blackbirds. In addition, the patchy breeding distribution of this species may inhibit population consolidation, causing local populations to crash when reduced to low levels. Progress in understanding the causes and mechanisms for observed declines has remained limited until recently. Here we present initial attempts to understand the habitat requirements of Rusty Blackbirds and offer specific predictions associated with each of the hypotheses for decline as a way of guiding future research

Cytopenia levels for aiding establishment of the diagnosis of Myelodysplastic Syndromes

We recommend that standard hematologic values be used to define cytopenias in MDS and believe a modification of the WHO definition of cytopenias as 1 of the criteria (in addition to definitive morphologic and/or cytogenetic findings) to diagnose MDS would be valuable and most accurate

Cause of Death in Patients With Acute Heart Failure: Insights From RELAX-AHF-2

OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. METHODS: Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. RESULTS: By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. CONCLUSIONS: Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)

Cause of Death in Patients With Acute Heart Failure Insights From RELAX-AHF-2

OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. METHODS: Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. RESULTS: By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. CONCLUSIONS: Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes:Analysis from the International Working Group for Prognosis of MDS

Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS were significantly younger with more severe cytopenias, and cytogenetic differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q), del(16q), and del(20q). Although differences in time to acute myeloid leukemia transformation did not occur, a significantly better survival in JPN was demonstrated, even after the adjustment for age and FAB subtypes, especially in lower, but not in higher prognostic risk categories. Certain clinical factors (cytopenias, blast percentage, cytogenetic risk) had different impact on survival and time to transformation to leukemia between the two groups. Although possible confounding events (e.g., environment, diet, and access to care) could not be excluded, our results indicated the existence of clinically relevant ethnic differences regarding survival in MDS between JPN and CAUC patients. The good performance of the IPSS-R in both CAUC and JP patients underlines that its common risk model is adequate for CAUC and JP