Historical contingency affects signaling strategies and competitive abilities in evolving populations of simulated robots.

One of the key innovations during the evolution of life on earth has been the emergence of efficient communication systems, yet little is known about the causes and consequences of the great diversity within and between species. By conducting experimental evolution in 20 independently evolving populations of cooperatively foraging simulated robots, we found that historical contingency in the occurrence order of novel phenotypic traits resulted in the emergence of two distinct communication strategies. The more complex foraging strategy was less efficient than the simpler strategy. However, when the 20 populations were placed in competition with each other, the populations with the more complex strategy outperformed the populations with the less complex strategy. These results demonstrate a tradeoff between communication efficiency and robustness and suggest that stochastic events have important effects on signal evolution and the outcome of competition between distinct populations.

Species distribution models reveal apparent competitive and facilitative effects of a dominant species on the distribution of tundra plants

Abiotic factors are considered strong drivers of species distribution and assemblages. Yet these spatial patterns are also influenced by biotic interactions. Accounting for competitors or facilitators may improve both the fit and the predictive power of species distribution models (SDMs). We investigated the influence of a dominant species, Empetrum nigrum ssp. hermaphroditum, on the distribution of 34 subordinate species in the tundra of northern Norway. We related SDM parameters of those subordinate species to their functional traits and their co-occurrence patterns with E. hermaphroditum across three spatial scales. By combining both approaches, we sought to understand whether these species may be limited by competitive interactions and/or benefit from habitat conditions created by the dominant species. The model fit and predictive power increased for most species when the frequency of occurrence of E. hermaphroditum was included in the SDMs as a predictor. The largest increase was found for species that 1) co-occur most of the time with E. hermaphroditum, both at large (i.e. 750 m) and small spatial scale (i.e. 2 m) or co-occur with E. hermaphroditum at large scale but not at small scale and 2) have particularly low or high leaf dry matter content (LDMC). Species that do not co-occur with E. hermaphroditum at the smallest scale are generally palatable herbaceous species with low LDMC, thus showing a weak ability to tolerate resource depletion that is directly or indirectly induced by E. hermaphroditum. Species with high LDMC, showing a better aptitude to face resource depletion and grazing, are often found in the proximity of E. hermaphroditum. Our results are consistent with previous findings that both competition and facilitation structure plant distribution and assemblages in the Arctic tundra. The functional and co-occurrence approaches used were complementary and provided a deeper understanding of the observed patterns by refinement of the pool of potential direct and indirect ecological effects of E. hermaphroditum on the distribution of subordinate species. Our correlative study would benefit being complemented by experimental approaches.

Influence of seasons and sampling strategy on assessment of bioaerosols in sewage treatment plants in Switzerland

An assessment of sewage workers' exposure to airborne cultivable bacteria, fungi and inhaled endotoxins was performed at 11 sewage treatment plants. We sampled the enclosed and unenclosed treatment areas in each plant and evaluated the influence of seasons (summer and winter) on bioaerosol levels. We also measured personal exposure to endotoxins of workers during special operation where a higher risk of bioaerosol inhalation was assumed. Results show that only fungi are present in significantly higher concentrations in summer than in winter (2331 +/- 858 versus 329 +/- 95 CFU m(-3)). We also found that there are significantly more bacteria in the enclosed area, near the particle grids for incoming water, than in the unenclosed area near the aeration basins (9455 +/- 2661 versus 2435 +/- 985 CFU m(-3) in summer and 11 081 +/- 2299 versus 2002 +/- 839 CFU m(-3) in winter). All bioaerosols were frequently above the recommended values of occupational exposure. Workers carrying out special tasks such as cleaning tanks were exposed to very high levels of endotoxins (up to 500 EU m(-3)) compared to routine work. The species composition and concentration of airborne Gram-negative bacteria were also studied. A broad spectrum of different species within the Pseudomonadaceae and the Enterobacteriaceae families were predominant in nearly all plants investigated. [Authors]

Renal transplantation following aorto-iliac reconstruction is a safe a strategy

Introduction: Renal transplantation is considered the treatment of choice for end-stage renal disease. However, the association of occlusive aorto-iliac disease and chronic renal failure is frequent and aorto-iliac reconstruction may be necessary prior to renal transplantation. This retrospective study reviews the results of this operative strategy.Material and Methods: Between January 2001 and June 2010, 309 patients underwent renal transplantation at our institution and 8 patients had prior aorto-iliac reconstruction using prosthetic material. There were 6 men and 2 women with a median age of 62 years (range 51-70). Five aorto-bifemoral and 2 aorto-bi-iliac bypasses were performed for stage II (n=5), stage IV (n=1) and aortic aneurysm (n=1). In one patient, iliac kissing stents and an ilio-femoral bypass were implanted. 4 cadaveric and 4 living donor renal transplantations were performed with an interval of 2 months to 10 years after revascularization.The results were analysed with respect of graft and patients survival. Differences between groups were tested by the log rank method.Results: No complications and no death occurred in the post-operative period. All bypasses remained patent during follow-up. The median time of post transplantation follow-up was 46 months for all patients and 27 months for patients with prior revascularization. In the revascularized group and control group, the graft and patient survival at 1 year were respectively 100%/96%, 100%/99% and at 5 years 86%/86%, 86%/94%, without significant differences between both groups.Discussion: Our results suggest that renal transplantation following prior aorto-iliac revascularisation with prosthetic material is safe and effective. Patients with end-stage renal disease and concomitant aorto-iliac disease should therefore be considered for renal transplantation. However, caution in the interpretation of the results is indicated due to the small sample size of our study.

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization.

AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

Competitive ability not kinship affects growth of Arabidopsis thaliana accessions.

In many organisms, individuals behave more altruistically towards relatives than towards unrelated individuals. Here, we conducted a study to determine if the performance of Arabidopsis thaliana is influenced by whether individuals are in competition with kin or non-kin. We selected seven pairs of genetically distinct accessions that originated from local populations throughout Europe. We measured the biomass of one focal plant surrounded by six kin or non-kin neighbours in in vitro growth experiments and counted the number of siliques produced per pot by one focal plant surrounded by four kin or non-kin neighbours. The biomass and number of siliques of a focal plant were not affected by the relatedness of the neighbour. Depending on the accession, a plant performed better or worse in a pure stand than when surrounded by non-kin plants. In addition, whole-genome microarray analyses revealed that there were no genes differentially expressed between kin and non-kin conditions. In conclusion, our study does not provide any evidence for a differential response to kin vs non-kin in A. thaliana. Rather, the outcome of the interaction between kin and non-kin seems to depend on the strength of the competitive abilities of the accessions.

Peroxisomal polyhydroxyalkanoate biosynthesis is a promising strategy for bioplastic production in high biomass crops.

Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers with diverse plastic-like properties. PHA biosynthesis in transgenic plants is being developed as a way to reduce the cost and increase the sustainability of industrial PHA production. The homopolymer polyhydroxybutyrate (PHB) is the simplest form of these biodegradable polyesters. Plant peroxisomes contain the substrate molecules and necessary reducing power for PHB biosynthesis, but peroxisomal PHB production has not been explored in whole soil-grown transgenic plants to date. We generated transgenic sugarcane (Saccharum sp.) with the three-enzyme Ralstonia eutropha PHA biosynthetic pathway targeted to peroxisomes. We also introduced the pathway into Arabidopsis thaliana, as a model system for studying and manipulating peroxisomal PHB production. PHB, at levels up to 1.6%-1.8% dry weight, accumulated in sugarcane leaves and A. thaliana seedlings, respectively. In sugarcane, PHB accumulated throughout most leaf cell types in both peroxisomes and vacuoles. A small percentage of total polymer was also identified as the copolymer poly (3-hydroxybutyrate-co-3-hydroxyvalerate) in both plant species. No obvious deleterious effect was observed on plant growth because of peroxisomal PHA biosynthesis at these levels. This study highlights how using peroxisomal metabolism for PHA biosynthesis could significantly contribute to reaching commercial production levels of PHAs in crop plants.

ATP-competitive inhibitors of mTOR: new perspectives in the treatment of renal cell carcinoma.

Targeting mTOR (mammalian target of rapamycin) is an effective approach in the treatment of advanced RCC (renal cell carcinoma). Rapamycin-like drugs (rapalogues) have shown clinical activities and have been approved for the treatment of RCC. Recently, with the development of ATP-competitive inhibitors of mTOR, therapies targeting mTOR have entered a new era. Here, we discuss the biological relevance of blocking mTOR in RCC and review the mechanisms of action of rapalogues in RCC. We also advance some perspectives on the use of ATP-competitive inhibitors of mTOR in RCC.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Targeting mitochondria in the infection strategy of the hepatitis C virus.

Hepatitis C virus (HCV) infection induces a state of oxidative stress more pronounced than that observed in many other inflammatory diseases. Here, we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists of a release of Ca(2+) from the endoplasmic reticulum, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen species and a progressive metabolic adaptive response. Evidence is provided for a positive feed-back mechanism between alterations of calcium and redox homeostasis. This likely involves deregulation of the mitochondrial permeability transition and induces progressive dysfunction of cellular bioenergetics. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Strategy selection during exploratory behavior: sex differences

This study was designed to assess sex-related differences in the selection of an appropriate strategy when facing novelty. A simple visuo-spatial task was used to investigate exploratory behavior as a specific response to novelty. The exploration task was followed by a visual discrimination task, and the responses were analyzed using signal detection theory. During exploration women selected a local searching strategy in which the metric distance between what is already known and what is unknown was reduced, whereas men adopted a global strategy based on an approximately uniform distribution of choices. Women's exploratory behavior gives rise to a notion of a secure base warranting a sense of safety while men's behavior does not appear to be influenced by risk. This sex-related difference was interpreted as a difference in beliefs concerning the likelihood of uncertain events influencing risk evaluation. Keywords: exploration, spontaneous strategies, sex differences, decision-making.

A novel role for proline- and acid-rich basic region leucine zipper (PAR bZIP) proteins in the transcriptional regulation of a BH3-only proapoptotic gene.

Proline- and acid-rich (PAR) basic region leucine zipper (bZIP) proteins thyrotroph embryonic factor (TEF), D-site-binding protein (DBP), and hepatic leukemia factor have been involved in neurotransmitter homeostasis and amino acid metabolism. Here we demonstrate a novel role for these proteins in the transcriptional control of a BH3-only gene. PAR bZIP proteins are able to transactivate the promoter of bcl-gS. This promoter is particularly responsive to TEF activation and is silenced by NFIL3, a repressor that shares the consensus binding site with PAR bZIP proteins. Consistently, transfection of TEF induces the expression of endogenous bcl-gS in cancer cells, and this induction is independent of p53. A naturally occurring variant of DBP (tDBP), lacking the transactivation domain, has been identified and shown to impede the formation of active TEF dimers in a competitive manner and to reduce the TEF-dependent induction of bcl-gS. Of note, treatment of cancer cells with etoposide induces TEF activation and promotes the expression of bcl-gS. Furthermore, blockade of bcl-gS or TEF expression by a small interfering RNA strategy or transfection with tDBP significantly reduces the etoposide-mediated apoptotic cell death. These findings represent the first described role for PAR bZIP proteins in the regulation of a gene involved in the execution of apoptosis.

Multiple imputations applied to the DREAM3 phosphoproteomics challenge: a winning strategy.

DREAM is an initiative that allows researchers to assess how well their methods or approaches can describe and predict networks of interacting molecules [1]. Each year, recently acquired datasets are released to predictors ahead of publication. Researchers typically have about three months to predict the masked data or network of interactions, using any predictive method. Predictions are assessed prior to an annual conference where the best predictions are unveiled and discussed. Here we present the strategy we used to make a winning prediction for the DREAM3 phosphoproteomics challenge. We used Amelia II, a multiple imputation software method developed by Gary King, James Honaker and Matthew Blackwell[2] in the context of social sciences to predict the 476 out of 4624 measurements that had been masked for the challenge. To chose the best possible multiple imputation parameters to apply for the challenge, we evaluated how transforming the data and varying the imputation parameters affected the ability to predict additionally masked data. We discuss the accuracy of our findings and show that multiple imputations applied to this dataset is a powerful method to accurately estimate the missing data. We postulate that multiple imputations methods might become an integral part of experimental design as a mean to achieve cost savings in experimental design or to increase the quantity of samples that could be handled for a given cost.