WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Climatic drivers of hemispheric asymmetry in global patterns of ant species richness

Although many taxa show a latitudinal gradient in richness, the relationship between latitude and species richness is often asymmetrical between the northern and southern hemispheres. Here we examine the latitudinal pattern of species richness across 1003 local ant assemblages. We find latitudinal asymmetry, with southern hemisphere sites being more diverse than northern hemisphere sites. Most of this asymmetry could be explained statistically by differences in contemporary climate. Local ant species richness was positively associated with temperature, but negatively (although weakly) associated with temperature range and precipitation. After contemporary climate was accounted for, a modest difference in diversity between hemispheres persisted, suggesting that factors other than contemporary climate contributed to the hemispherical asymmetry. The most parsimonious explanation for this remaining asymmetry is that greater climate change since the Eocene in the northern than in the southern hemisphere has led to more extinctions in the northern hemisphere with consequent effects on local ant species richness. © 2009 Blackwell Publishing Ltd/CNRS.Peer Reviewe

Early-Warning Signals of Individual Tree Mortality Based on Annual Radial Growth

Tree mortality is a key driver of forest dynamics and its occurrence is projected to increase in the future due to climate change. Despite recent advances in our understanding of the physiological mechanisms leading to death, we still lack robust indicators of mortality risk that could be applied at the individual tree scale. Here, we build on a previous contribution exploring the differences in growth level between trees that died and survived a given mortality event to assess whether changes in temporal autocorrelation, variance, and synchrony in time-series of annual radial growth data can be used as early warning signals of mortality risk. Taking advantage of a unique global ring-width database of 3065 dead trees and 4389 living trees growing together at 198 sites (belonging to 36 gymnosperm and angiosperm species), we analyzed temporal changes in autocorrelation, variance, and synchrony before tree death (diachronic analysis), and also compared these metrics between trees that died and trees that survived a given mortality event (synchronic analysis). Changes in autocorrelation were a poor indicator of mortality risk. However, we found a gradual increase in inter- annual growth variability and a decrease in growth synchrony in the last similar to 20 years before mortality of gymnosperms, irrespective of the cause of mortality. These changes could be associated with drought-induced alterations in carbon economy and allocation patterns. In angiosperms, we did not find any consistent changes in any metric. Such lack of any signal might be explained by the relatively high capacity of angiosperms to recover after a stress-induced growth decline. Our analysis provides a robust method for estimating early-warning signals of tree mortality based on annual growth data. In addition to the frequently reported decrease in growth rates, an increase in inter-annual growth variability and a decrease in growth synchrony may be powerful predictors of gymnosperm mortality risk, but not necessarily so for angiosperms.Peer reviewe

Synthetic Toll Like Receptor-4 (TLR-4) Agonist Peptides as a Novel Class of Adjuvants

Background: Adjuvants serve as catalysts of the innate immune response by initiating a localized site of inflammation that is mitigated by the interactions between antigens and toll like receptor (TLR) proteins. Currently, the majority of vaccines are formulated with aluminum based adjuvants, which are associated with various side effects. In an effort to develop a new class of adjuvants, agonists of TLR proteins, such as bacterial products, would be natural candidates. Lipopolysaccharide (LPS), a major structural component of gram negative bacteria cell walls, induces the systemic inflammation observed in septic shock by interacting with TLR-4. The use of synthetic peptides of LPS or TLR-4 agonists, which mimic the interaction between TLR-4 and LPS, can potentially regulate cellular signal transduction pathways such that a localized inflammatory response is achieved similar to that generated by adjuvants. Methodology/Principal Findings: We report the identification and activity of several peptides isolated using phage display combinatorial peptide technology, which functionally mimicked LPS. The activity of the LPS-TLR-4 interaction was assessed by NF-kB nuclear translocation analyses in HEK-BLUE TM-4 cells, a cell culture model that expresses only TLR-4, and the murine macrophage cell line, RAW264.7. Furthermore, the LPS peptide mimics were capable of inducing inflammatory cytokine secretion from RAW264.7 cells. Lastly, ELISA analysis of serum from vaccinated BALB/c mice revealed that the LPS peptide mimics act as a functional adjuvant

Phenotypic Signatures Arising from Unbalanced Bacterial Growth

Fluctuations in the growth rate of a bacterial culture during unbalanced growth are generally considered undesirable in quantitative studies of bacterial physiology. Under well-controlled experimental conditions, however, these fluctuations are not random but instead reflect the interplay between intra-cellular networks underlying bacterial growth and the growth environment. Therefore, these fluctuations could be considered quantitative phenotypes of the bacteria under a specific growth condition. Here, we present a method to identify “phenotypic signatures” by time-frequency analysis of unbalanced growth curves measured with high temporal resolution. The signatures are then applied to differentiate amongst different bacterial strains or the same strain under different growth conditions, and to identify the essential architecture of the gene network underlying the observed growth dynamics. Our method has implications for both basic understanding of bacterial physiology and for the classification of bacterial strains

Estimating Correlated Jumps and Stochastic Volatilities

We formulate a bivariate stochastic volatility jump-diffusion model with correlated jumps and volatilities. An MCMC Metropolis-Hastings sampling algorithm is proposed to estimate the model's parameters and latent state variables (jumps and stochastic volatilities) given observed returns. The methodology is successfully tested on several artificially generated bivariate time series and then on the two most important Czech domestic financial market time series of the FX (CZK/EUR) and stock (PX index) returns. Four bivariate models with and without jumps and/or stochastic volatility are compared using the deviance information criterion (DIC) confirming importance of incorporation of jumps and stochastic volatility into the model

Pre-Admission Statin Use and In-Hospital Severity of 2009 Pandemic Influenza A(H1N1) Disease

In this group of patients hospitalized with pandemic influenza, a significant beneficial effect of pre-admission statin use on the in-hospital course of illness was not identified. Although the database from which these observations are derived represents the largest available suitable UK hospital cohort, a larger study would be needed to confirm whether there is any benefit in this setting

Individual differences in reproductive strategy are related to views about recreational drug use in Belgium, the Netherlands and Japan

Individual differences in moral views are often explained as the downstream effect of ideological commitments, such as political orientation and religiosity. Recent studies in the U.S. suggest that moral views about recreational drug use are also influenced by attitudes towards sex and that this relationship cannot be explained by ideological commitments. In this study, we investigate student samples from Belgium, the Netherlands, and Japan. We find that, in all samples, sexual attitudes are strongly related to views about recreational drug use, even after controlling for various ideological variables. We discuss our results in the light of reproductive strategies as determinants of moral views

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

Legacy of pre-disturbance spatial pattern determines early structural diversity following severe disturbance in mountain spruce forests in Czech Republic

Background Severe canopy-removing disturbances are native to many temperate forests and radically alter stand structure, but biotic legacies (surviving elements or patterns) can lend continuity to ecosystem function after such events. Poorly understood is the degree to which the structural complexity of an old-growth forest carries over to the next stand. We asked how predisturbance spatial pattern acts as a legacy to influence post-disturbance stand structure, and how this legacy influences the structural diversity within the early-seral stand. Methods Two stem-mapped one-hectare forest plots in the Czech Republic experienced a severe bark beetle outbreak, thus providing before-and-after data on spatial patterns in live and dead trees, crown projections, down logs, and herb cover. Results Post-disturbance stands were dominated by an advanced regeneration layer present before the disturbance. Both major species, Norway spruce (Picea abies) and rowan (Sorbus aucuparia), were strongly self-aggregated and also clustered to former canopy trees, predisturbance snags, stumps and logs, suggesting positive overstory to understory neighbourhood effects. Thus, although the disturbance dramatically reduced the stand’s height profile with ~100% mortality of the canopy layer, the spatial structure of post-disturbance stands still closely reflected the pre-disturbance structure. The former upper tree layer influenced advanced regeneration through microsite and light limitation. Under formerly dense canopies, regeneration density was high but relatively homogeneous in height; while in former small gaps with greater herb cover, regeneration density was lower but with greater heterogeneity in heights