bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PPAR‐γ agonist rosiglitazone facilitates Akt rephosphorylation and inhibits apoptosis in cardiomyocytes during hypoxia/reoxygenation
Authors: Kilter H. , Werner M. , Roggia C. , Reil J.‐C. , Schäfers H.‐J. , Kintscher U. , Böhm M. 
Published: September 2009

Background and Aim: Results on the cardiovascular effects of PPAR‐γ agonists are conflicting. On one hand, it was suggested that the PPAR‐γ agonist rosiglitazone may increase the risk of cardiovascular events. On the other hand, PPAR‐γ agonists reduce myocardial infarct size and improve myocardial function during ischemia/reperfusion in animal studies in vivo. However, the mechanism of this effect is unclear, and it is open if PPAR‐γ agonists have a direct effect on cardiac myocyte survival in ischemia/reperfusion. The aim of this study was to determine the effect of the PPAR‐γ agonist rosiglitazone on hypoxia/reoxygenation‐induced apoptosis of isolated cardiomyocytes.Methods: Isolated rat cardiac myocytes were pretreated with rosiglitazone or vehicle for 30 min before they were subjected to hypoxia for 4 h followed by different times of reoxygenation (5 min to 12 h). Apoptosis was determined by in situ hybridization for DNA fragmentation (TUNEL) as well as detection of cytoplasmic accumulation of histone‐associated DNA fragments by enzyme‐linked immunosorbent assay (ELISA). Activation of apoptosis regulating intracellular signalling pathways was studied by immunoblotting using phosphospecific antibodies.Results: Rosiglitazone significantly reduced apoptosis of isolated cardiomyocytes subjected to hypoxia/reoxygenation, independently determined with two methods. After 4 h of hypoxia and 12 h of reoxygenation, 34 ± 3.6% of the vehicle treated cardiac myocytes stained positive for DNA fragmentation in the TUNEL staining. Rosiglitazone treatment reduced this effect by 23% (p < 0.01). Even more pronounced, cytoplasmic accumulation of histone‐associated DNA fragments detected by ELISA was reduced by 35% (p < 0.05) in the presence of rosiglitazone. This inhibition of hypoxia/reoxygenation‐induced apoptosis was associated with an increased reoxygenation‐induced rephosphorylation of the protein kinase Akt, a crucial mediator of cardiomyocyte survival in ischemia/reperfusion of the heart. This effect was reversed by GW‐9662, an irreversible PPAR‐γ antagonist. However, rosiglitazone did not alter phosphorylation of the MAP kinases ERK1/2 and c‐Jun N‐terminal kinase (JNK).Conclusion: It can be concluded that cardiac myocytes are direct targets of PPAR‐γ agonists promoting its survival in ischemia/reperfusion, at least in part by facilitating Akt rephosphorylation. This effect may be of clinical relevance inhibiting the reperfusion‐induced injury in patients suffering from myocardial infarction or undergoing cardiac surgery.
Prostate cancer grading: the effect of stratification of needle biopsy Gleason Score 4 + 3 as high or intermediate grade
Authors: Fanning Deirdre M. , Kay Elaine , Fan Yue , Fitzpatrick John M. , Watson R. William G. 
Published: September 2009

Study Type – Prognosis (case series) Level of Evidence 4OBJECTIVESTo assess the discrepancy between needle biopsy (NB) and radical prostatectomy (RP) Gleason score (GS) in Irish men, specifically the influence of the stratification of GS 4 + 3 on overall levels of agreement, levels of discrepancy and κ coefficients, as the GS assigned to prostate cancer NBs affects clinical decision‐making and influences future therapeutic strategies.PATIENTS AND METHODSWe reviewed retrospectively a database of the discrepancies between NB and RP Gleason grades (GG) from 2003 to 2008. All patients had clinically localized prostate cancer, and none had had neoadjuvant therapy. Grading of 206 NB specimens was compared with their corresponding RP specimens. The discrepancy rate between NB and RP GS was assessed for each combination of GG. Intermediate‐ (GS 7, defined as GS 3 + 4 alone vs GS 7) and high‐grade (GS 4 + 3 and GS 8–10 vs GS 8–10) classifications were compared. The level of agreement and the κ coefficient for each system was assessed.RESULTSIn NB, GS 6 was most frequently diagnosed (53%); after RP, GS 3 + 4 was most frequent (36%). In 42% of cases the exact GG remained unchanged after RP, increasing to 48% for GS 6 and GS 3 + 4. Overall 42% of cases showed an increase in their GG. In GS 6 NBs, the rate of increase in the primary GG or increase in the GS was 52%. Biopsy GS 6 and 3 + 4 showed the highest levels of agreement between NB and RP. Low‐grade prostate cancer on NB was upgraded in 52% of cases; high‐grade prostatic adenocarcinoma was downgraded in 27–77% of cases depending on the grading system used.CONCLUSIONSClassification of high‐grade prostate cancer as GS 4 + 3 and GS 8–10 results in higher levels of agreement between NB and RP GS. Reliable identification of well differentiated prostatic adenocarcinoma in NB specimens represents an ongoing diagnostic challenge, necessitating careful preoperative consideration of the definitive grade of a patient’s disease.
Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment
Authors: Roehrborn Claus G. , Kaminetsky Jed C. , Auerbach Stephen M. , Montelongo Rafael Martínez , Elion‐Mboussa Albert , Viktrup Lars 
Published: September 2009

Study Type – Therapy (RCT) Level of Evidence 1bOBJECTIVETo determine, by post hoc analysis, the effects of tadalafil (a long‐acting phosphodiesterase 5 inhibitor) on peak urinary flow (Qmax), bladder capacity, voiding efficiency and the obstructive symptoms of benign prostatic hyperplasia (BPH) in men with lower urinary tract symptoms secondary to BPH (BPH‐LUTS), compared with placebo.PATIENTS AND METHODSAfter a 4‐week placebo run‐in period, 1058 men with BPH‐LUTS were randomly allocated to receive once daily treatment with placebo or tadalafil (2.5, 5, 10, or 20 mg) for 12 weeks. Uroflowmetry, postvoid residual volume (PVR), and BPH symptom score measurements were assessed throughout the trial.RESULTSIncreases in Qmax were numerically greater for tadalafil (2.5, 5, 10, and 20 mg with percentage changes of 15%, 16%, 17%, 22%, respectively) vs placebo (12%), but did not reach statistical significance. Age, baseline Qmax, erectile dysfunction history, sexual activity, and previous α‐blocker therapy significantly influenced the Qmax response. Tadalafil was not associated with significant changes in PVR. Tadalafil had its greatest effects on bladder capacity and voiding efficiency in men with a Qmax of <10 mL/s at baseline, but these changes were not significantly different from placebo responses. Tadalafil treatment significantly improved the IPSS obstructive subscores (tadalafil 2.5, 5, 10, 20 mg with percentage changes of 24%, 31%, 33%, 33%, respectively) vs placebo (13%).CONCLUSIONSOnce daily tadalafil did not significantly change Qmax or voiding efficiency compared with placebo in men with BPH‐LUTS, although there were dose‐dependent improvements. No subgroups were identified where tadalafil or placebo treatment had a deleterious effect on Qmax. Despite these minimal changes in uroflowmetric measures, tadalafil was associated with clinically meaningful and statistically significant improvements in the obstructive symptoms of BPH.
Predicting invasions in Australia by a Neotropical shrub under climate change: the challenge of novel climates and parameter estimation
Authors: Van Klinken Rieks D. , Lawson Ben E. , Zalucki Myron P. 
Published: September 2009

ABSTRACTAim  To test how well species distributions and abundance can be predicted following invasion and climate change when using only species distribution and abundance data to estimate parameters.Location  Models were developed for the species' native range in the Americas and applied to Australia.Methods  We developed a predictive model for an invasive neotropical shrub (Parkinsonia aculeata) using a popular ecophysiological bioclimatic modelling technique (CLIMEX) fitted against distribution and abundance data in the Americas. The effect of uncertainty in model parameter estimates on predictions in Australia was tested. Alternative data sources were used when model predictions were sensitive to uncertainty in parameter estimates. The resulting best‐fit model was run under two climate change scenarios.Results  Of the 19 parameters used, 9 could not be fitted using data from the native range. However, only parameters that lowered temperature or increased moisture requirements for growth noticeably altered the model prediction in Australia. Differences in predictions were dramatic, and reflect climates in Australia that were not represented in the Americas (novel climates). However, these poorly fitted parameters could be fitted post hoc using alternative data sources prior to predicting responses to climate change.Conclusions  Novel climates prevented the development of a predictive model which relied only on native‐range distribution and abundance data because certain parameters could not be fitted. In fact, predictions were more sensitive to parameter uncertainty than to climate change scenarios. Where uncertainty in parameter estimates affected predictions, it could be addressed through the inclusion of alternative data sources. However, this may not always be possible, for example in the absence of post‐invasion data.
Ensemble models predict Important Bird Areas in southern Africa will become less effective for conserving endemic birds under climate change
Authors: Coetzee Bernard W. T. , Robertson Mark P. , Erasmus Barend F. N. , Van Rensburg Berndt J. , Thuiller Wilfried 
Published: September 2009

ABSTRACTAim  To examine the impacts of climate change on endemic birds, which are of global significance for conservation, on a continent with few such assessments. We specifically assess projected range changes in relation to the Important Bird Areas (IBAs) network and assess the possible consequences for conservation.Location  South Africa, Lesotho and Swaziland.Methods  The newly emerging ensemble modelling approach is used with 50 species, four climate change models for the period 2070–2100 and eight bioclimatic niche models in the statistical package biomod. Model evaluation is done using the receiver operating characteristic and the recently introduced true skill statistic. Future projections are made considering two extreme assumptions: species have full dispersal ability and species have no dispersal ability. A consensus forecast is identified using principal components analysis. This forecast is interpreted in terms of the IBA network. An irreplaceability analysis is used to highlight priority IBAs for conservation attention in terms of climate change.Results  The majority of species (62%) are predicted to lose climatically suitable space. Five species lose at least 85% of their climatically suitable space. Many IBAs lose species (41%; 47 IBAs) and show high rates of species turnover of more than 50% (77%; 95 IBAs). Highly irreplaceable regions for endemic species become highly localized under climate change, meaning that the endemic species analysed here experience similar range contractions to maintain climate niches.Main conclusions  The South African IBAs network is likely to become less effective for conserving endemic birds under climate change. The irreplaceability analysis identified key refugia for endemic species under climate change, but many of these areas are not currently IBAs. In addition, many of these high‐priority areas that are IBAs fall outside the current formal protected areas network.
Molecular analysis of menadione‐induced resistance against biotic stress in Arabidopsis
Authors: Borges Andrés A. , Dobon Albor , Expósito‐Rodríguez Marino , Jiménez‐Arias David , Borges‐Pérez Andrés , Casañas‐Sánchez Verónica , Pérez Jose A. , Luis Juan C. , Tornero Pablo 
Published: September 2009

SummaryMenadione sodium bisulphite (MSB) is a water‐soluble derivative of vitamin K3, or menadione, and has been previously demonstrated to function as a plant defence activator against several pathogens in several plant species. However, there are no reports of the role of this vitamin in the induction of resistance in the plant model Arabidopsis thaliana. In the current study, we demonstrate that MSB induces resistance by priming in Arabidopsis against the virulent strain Pseudomonas syringae pv. tomato DC3000 (Pto) without inducing necrosis or visible damage. Changes in gene expression in response to 0.2 mm MSB were analysed in Arabidopsis at 3, 6 and 24 h post‐treatment using microarray technology. In general, the treatment with MSB does not correlate with other publicly available data, thus MSB produces a unique molecular footprint. We observed 158 differentially regulated genes among all the possible trends. More up‐regulated genes are included in categories such as ‘response to stress’ than the background, and the behaviour of these genes in different treatments confirms their role in response to biotic and abiotic stress. In addition, there is an over‐representation of the G‐box in their promoters. Some interesting functions are represented among the individual up‐regulated genes, such as glutathione S‐transferases, transcription factors (including putative regulators of the G‐box) and cytochrome P450s. This work provides a wide insight into the molecular cues underlying the effect of MSB as a plant resistance inducer.
Changes in Poverty Rates during the Howard Era
Authors: Rodgers Joan R. , Siminski Peter , Bishop James 
Published: September 2009

Abstract This article considers changes in poverty rates under the Howard government. We also make three methodological contributions. We consider the statistical significance of the estimated changes in poverty. We propose a decomposition technique that reconciles the trends in absolute and relative poverty. We also use ‘poverty profiles’, which illustrate sensitivity to alternative poverty lines. We find decreases in absolute poverty and increases in relative poverty, both of which are statistically significant over a range of poverty lines. At a poverty line equal to half of the median income, the increase in relative poverty is statistically significant for all people and borders on significance for children.
What Happened to Australia's Productivity Surge?
Authors: Dolman Ben 
Published: September 2009

Abstract Australia's productivity has grown 1 percentage point per year slower in the current decade than in the 1990s. This article shows that almost one‐half of the slowdown is related to unusual developments in the mining industry, the effects of drought and the overstatement of productivity growth in the 1990s. Part of the remainder might be as a result of a combination of slower technological change, unmeasured declines in labour quality, the diminishing effects of past reforms and the increasing profitability of Australian firms.
A Bayesian Hierarchical Mixture Model for Platelet-Derived Growth Factor Receptor Phosphorylation to Improve Estimation of Progression-Free Survival in Prostate Cancer
Authors: Morita Satoshi , Thall Peter F. , Bekele B. Nebiyou , Mathew Paul 
Published: September 2009

SummaryAdvances in understanding the biological underpinnings of many cancers have led increasingly to the use of molecularly targeted anticancer therapies. Because the platelet-derived growth factor receptor (PDGFR) has been implicated in the progression of prostate cancer bone metastases, it is of great interest to examine possible relationships between PDGFR inhibition and therapeutic outcomes. We analyse the association between change in activated PDGFR (phosphorylated PDGFR) and progression-free survival time based on large within-patient samples of cell-specific phosphorylated PDGFR values taken before and after treatment from each of 88 prostate cancer patients. To utilize these paired samples as covariate data in a regression model for progression-free survival time, and be cause the phosphorylated PDGFR distributions are bimodal, we first employ a Bayesian hierarchical mixture model to obtain a deconvolution of the pretreatment and post-treatment within-patient phosphorylated PDGFR distributions. We evaluate fits of the mixture model and a non-mixture model that ignores the bimodality by using a supnorm metric to compare the empirical distribution of each phosphorylated PDGFR data set with the corresponding fitted distribution under each model. Our results show that first using the mixture model to account for the bimodality of the within-patient phosphorylated PDGFR distributions, and then using the posterior within-patient component mean changes in phosphorylated PDGFR so obtained as covariates in the regression model for progression-free survival time, provides an improved estimation.
Topiramate modulates excitability of the occipital cortex when measured by transcranial magnetic stimulation
Authors: Aurora SK , Barrodale PM , Vermaas AR , Rudra CB 
Published: September 2009

Summary The aim of this study was to measure differences in occipital cortex excitability in migraineurs before and after administration of topiramate. We have previously demonstrated occipital cortex hyperexcitability in migraine using an objective technique of magnetic suppression of perceptual accuracy (MSPA). We hypothesized that a neuromodulator such as topiramate would demonstrate differences in MSPA in migraine compared with baseline. Ten migraine patients were recruited. To assess inhibitory function MSPA was measured using the following protocol. Timed transcranial magnetic stimulation were delivered at interstimulus intervals (ISI) varying from 40 to 190 ms (eight stimulations at each ISI) at 60% stimulus intensity. Subjects were asked to report letters projected at a fixed luminance on the screen. Visual suppression was calculated based on the number of errors the subjects made using automated analysis. This procedure was repeated at a minimum of two different dosages of topiramate when it was titrated for optimal migraine control. The interim dose was that at which an improvement in headache frequency was first observed, and the optimal dose was that at which the patient had a ≥ 50% reduction in headache frequency, or had reached a 100-mg dose. The mean [standard error (s.e.)] level of letters reported correct at baseline at 100-ms ISI was 91.6 (3.4) compared with 48.5 (6.0) ( P = 0.001) at an optimal dose of topiramate. Dose ranged from 50 to 100 mg; the average dose was 75 mg. The interim dose for most patients was 50 mg; the mean (s.e.) percentage of letters reported correct at interim was 75.9 (6.2) compared with baseline ( P = 0.01). Mean number of headaches at baseline was 27 per month, compared with eight headaches per month at interim dose and four headaches per month at optimal dose. There was no significant correlation between mean change in frequency of headache and mean change in inhibition from baseline to optimal dose (0.04, P = 0.89). Topiramate modulates occipital cortex excitability in chronic migraine possibly via mechanisms of cortical inhibition. Since there was not a strong correlation between the degree of inhibition and reduction of migraine frequency, it would appear that topiramate did have an independent effect on cortical excitability that was not dependent on reduction in migraine frequency.
Landscape features and crustacean prey as predictors of the Southern river otter distribution in Chile.
Authors: Sepúlveda M. A. , Bartheld J. L. , Meynard C. , Benavides M. , Astorga C. , Parra D. , Medina‐Vogel G. 
Published: September 2009

AbstractUnderstanding the processes that affect freshwater ecosystems at the watershed level is fundamental for the conservation and management of river otters. During 2 consecutive years, we surveyed the occurrence of the Southern river otter Lontra provocax and its main prey (crustaceans) in a watershed of 9900 km2 in the Chilean temperate forest. We modeled predator and prey distributions with a variety of statistical techniques by relating a set of environmental predictors to species occurrence records. Otter and crustaceans were associated with areas of intermediate to low human disturbance with a mosaic of riparian vegetation densities, mainly at low altitudes. The singularity of the Andean Range, with a very marked elevation gradient and oligotrophic watercourses in the higher areas, created more vulnerable conditions for otter presence because prey abundances were limited in those areas. Human impacts affected otter populations at a landscape scale through the presence of main roads, as these were mostly located in lower parts of the watershed where otters have their primary habitat. These results point to the importance of land management and protection of low‐elevation areas where otters still occur to ensure the long‐term viability of its freshwater populations.
Dating the divergence between Southern and European water voles using molecular coalescent‐based methods
Authors: Centeno‐Cuadros A. , Delibes M. , Godoy J. A. 
Published: September 2009

AbstractInvestigating the evolutionary history of the species is critical for understanding the evolution of biodiversity and for its conservation. Towards this goal, molecular approaches are becoming increasingly powerful with the incorporation of recent theoretical and analytical advances. Here, we apply an isolation‐with‐migration coalescent‐based model to control region and cytochrome b mitochondrial sequences to investigate the evolutionary history of European (Arvicola terrestris) and Southern (Arvicola sapidus) water voles throughout Eurasia. We date the time of the split of the common ancestor of European and Southern water voles around the fourth Mindel glacial (c. 252 000 bp), a date similar to that estimated by classical phylogenetic methods (c. 241 000 bp). Although postglacial expansions brought these species into secondary contact in Iberia and France, our results do not contain evidence of subsequent mitochondrial gene flow between descendant groups or current hybridization. We also estimate the effective population sizes of A. sapidus and Arvicola terrestris scherman on c. 199 000 and 52 000 individuals, respectively. This study illustrates the utility of modern coalescent‐based genetic tools to investigate recent species and population divergences and sheds some light on the evolution of the genus Arvicola in Eurasia.