Latitudinal patterns in plant defense: evolution of cardenolides, their toxicity and induction following herbivory.

Attempts over the past 50 years to explain variation in the abundance, distribution and diversity of plant secondary compounds gave rise to theories of plant defense. Remarkably, few phylogenetically robust tests of these long-standing theories have been conducted. Using >50 species of milkweed (Asclepias spp.), we show that variation among plant species in the induction of toxic cardenolides is explained by latitude, with higher inducibility evolving more frequently at lower latitudes. We also found that: (1) the production of cardenolides showed positive-correlated evolution with the diversity of cardenolides, (2) greater cardenolide investment by a species is accompanied by an increase in an estimate of toxicity (measured as chemical polarity) and (3) instead of trading off, constitutive and induced cardenolides were positively correlated. Analyses of root and shoot cardenolides showed concordant patterns. Thus, milkweed species from lower latitudes are better defended with higher inducibility, greater diversity and added toxicity of cardenolides.

The ghost of social environments past: dominance relationships include current interactions and experience carried over from previous groups.

Dominance hierarchies pervade animal societies. Within a static social environment, in which group size and composition are unchanged, an individual's hierarchy rank results from intrinsic (e.g. body size) and extrinsic (e.g. previous experiences) factors. Little is known, however, about how dominance relationships are formed and maintained when group size and composition are dynamic. Using a fusion-fission protocol, we fused groups of previously isolated shore crabs (Carcinus maenas) into larger groups, and then restored groups to their original size and composition. Pre-fusion hierarchies formed independently of individuals' sizes, and were maintained within a static group via winner/loser effects. Post-fusion hierarchies differed from pre-fusion ones; losing fights during fusion led to a decline in an individual's rank between pre- and post-fusion conditions, while spending time being aggressive during fusion led to an improvement in rank. In post-fusion tanks, larger individuals achieved better ranks than smaller individuals. In conclusion, dominance hierarchies in crabs represent a complex combination of intrinsic and extrinsic factors, in which experiences from previous groups can carry over to affect current competitive interactions.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients.

The transcription factor PHR1 plays a key role in the regulation of sulfate shoot-to-root flux upon phosphate starvation in Arabidopsis.

Background: Sulfate and phosphate are both vital macronutrients required for plant growth and development. Despite evidence for interaction between sulfate and phosphate homeostasis, no transcriptional factor has yet been identified in higher plants that affects, at the gene expression and physiological levels, the response to both elements. This work was aimed at examining whether PHR1, a transcription factor previously shown to participate in the regulation of genes involved in phosphate homeostasis, also contributed to the regulation and activity of genes involved in sulfate inter-organ transport. Results: Among the genes implicated in sulfate transport in Arabidopsis thaliana, SULTR1;3 and SULTR3;4 showed up-regulation of transcripts in plants grown under phosphate-deficient conditions. The promoter of SULTR1;3 contains a motif that is potentially recognizable by PHR1. Using the phr1 mutant, we showed that SULTR1;3 up regulation following phosphate deficiency was dependent on PHR1. Furthermore, transcript up regulation was found in phosphate-deficient shoots of the phr1 mutant for SULTR2;1 and SULTR3;4, indicating that PHR1 played both a positive and negative role on the expression of genes encoding sulfate transporters. Importantly, both phr1 and sultr1;3 mutants displayed a reduction in their sulfate shoot-to-root transfer capacity compared to wild-type plants under phosphate-deficient conditions. Conclusions: This study reveals that PHR1 plays an important role in sulfate inter-organ transport, in particular on the regulation of the SULTR1;3 gene and its impact on shoot-to-root sulfate transport in phosphate-deficient plants. PHR1 thus contributes to the homeostasis of both sulfate and phosphate in plants under phosphate deficiency. Such a function is also conserved in Chlamydomonas reinhardtii via the PHR1 ortholog PSR1.

Le taux de détresse respiratoire du nouveau-né augmente, celui des césariennes aussi: et si ce n'était pas un hasard? [Respiratory distress of the neonate and the rate of caesarean section have increased over the last 30 years. Is there a link?]

Ces trente dernières années, on note en Suisse une augmentation significative de l'incidence du syndrome de détresse respiratoire (SDR) chez le nouveau-né (NN), touchant particulièrement les enfants avec un poids de naissance >2500 g. En même temps, le taux des césariennes (CS) s'est aussi accru. Une explication pour une éventuelle corrélation entre les deux évolutions est une augmentation en particulier des CS électives qui ont tendance à être planifiées à un terme précoce pour éviter la mise en travail spontanée. Suite à cela, le foetus est privé de différents mécanismes qui favorisent l'adaptation pulmonaire périnatale. Les bénéfices réels de la CS sur la morbidité tant foetale que maternelle ne doivent pas faire oublier que la CS est un facteur de risque pour le SDR du NN. Ce risque peut être diminué efficacement en planifiant une CS élective après 39 semaines révolues. In Switzerland, the rate of respiratory distress in neonates needing hospitalization has doubled over the last thirty years, concerning in particular babies weighing more than 2500 g. In the same time, the rate of Caesarean section (CS) has also multiplied. We suppose that a link between the two evolutions might be the increase of elective CS. They tend to be planned early at term to avoid the onset of spontaneous labour As a consequence, the foetus is deprived of different mechanisms helping pulmonary transition around birth. The potential benefits of CS regarding morbidity of foetus and mother should not overshadow that CS is a significant risk factor for respiratory problems of the neonate. This risk could be dramatically decreased by planning elective CS only after completed 39 weeks of gestation

Evaluation of a mixed approach combining stationary and wearable systems to monitor gait over long distance.

Thanks to decades of research, gait analysis has become an efficient tool. However, mainly due to the price of the motion capture systems, standard gait laboratories have the capability to measure only a few consecutive steps of ground walking. Recently, wearable systems were proposed to measure human motion without volume limitation. Although accurate, these systems are incompatible with most of existing calibration procedures and several years of research will be necessary for their validation. A new approach consisting of using a stationary system with a small capture volume for the calibration procedure and then to measure gait using a wearable system could be very advantageous. It could benefit from the knowledge related to stationary systems, allow long distance monitoring and provide new descriptive parameters. The aim of this study was to demonstrate the potential of this approach. Thus, a combined system was proposed to measure the 3D lower body joints angles and segmental angular velocities. It was then assessed in terms of reliability towards the calibration procedure, repeatability and concurrent validity. The dispersion of the joint angles across calibrations was comparable to those of stationary systems and good reliability was obtained for the angular velocities. The repeatability results confirmed that mean cycle kinematics of long distance walks could be used for subjects' comparison and pointed out an interest for the variability between cycles. Finally, kinematics differences were observed between participants with different ankle conditions. In conclusion, this study demonstrated the potential of a mixed approach for human movement analysis.

Accès sans prescription aux statines: bénéfique ou délétère. [Over-the-counter statins: benefit or harmful?]

Making statin available over the counter is one of the measures proposed to correct its underuse. Since May 2004, simvastatin 10 mg is sold over the counter in Great Britain. But uncertainties persist concerning the efficacy of statin in primary prevention and at a 10 mg dose. Finally, there is a risk of side effects and drug interactions. Beyond the correction of statin underuse and the hope of coronary heart disease mortality reduction, the British decision highlighted the will to give individuals a sense of responsibility concerning their health and its financial cost. Anyway, the benefit of switching statin from prescription to over the counter should be experimentally evaluated before its introduction.

Do socioeconomic factors shape weight and obesity trajectories over the transition from midlife to old age? Results from the French GAZEL cohort study

BACKGROUND: Obesity is a contemporary epidemic that does not affect all age groups and sections of society equally. OBJECTIVE: The objective was to examine socioeconomic differences in trajectories of body mass index (BMI; in kg/m(2)) and obesity between the ages of 45 and 65 y. DESIGN: A total of 13,297 men and 4532 women from the French GAZEL (Gaz de France Electricité de France) cohort study reported their height in 1990 and their weight annually over the subsequent 18 y. Changes in BMI and obesity between ages 45 and 49 y, 50 and 54 y, 55 and 59 y, and 60 and 65 y as a function of education and occupational position (at age 35 y) were modeled by using linear mixed models and generalized estimating equations. RESULTS: BMI and obesity rates increased between the ages of 45 and 65 y. In men, BMI was higher in unskilled workers than in managers at age 45 y; this difference in BMI increased from 0.82 (95% CI: 0.66, 0.99) at 45 y to 1.06 (95% CI: 0.85, 1.27) at 65 y. Men with a primary school education compared with those with a high school degree at age 45 y had a 0.75 (95% CI: 0.51, 1.00) higher BMI, and this difference increased to 1.32 (95% CI: 1.03,1.62) at age 65 y. Obesity rates were 3.35% and 7.68% at age 45 y and 9.52% and 18.10% at age 65 y in managers and unskilled workers, respectively; the difference in obesity increased by 4.25% (95% CI: 1.87, 6.52). A similar trend was observed in women. Conclusions: Weight continues to increase in the transition between midlife and old age; this increase is greater in lower socioeconomic groups.

Chromosomal rearrangements and gene flow over time in an inter-specific hybrid zone of the Sorex araneus group.

Most hybrid zones have existed for hundreds or thousands of years but have generally been observed for only a short time period. Studies extending over periods long enough to track evolutionary changes in the zones or assess the ultimate outcome of hybridization are scarce. Here, we describe the evolution over time of the level of genetic isolation between two karyotypically different species of shrews (Sorex araneus and Sorex antinorii) at a hybrid zone located in the Swiss Alps. We first evaluated hybrid zone movement by contrasting patterns of gene flow and changes in cline parameters (centre and width) using 24 microsatellite loci, between two periods separated by 10 years apart. Additionally, we tested the role of chromosomal rearrangements on gene flow by analysing microsatellite loci located on both rearranged and common chromosomes to both species. We did not detect any movement of the hybrid zone during the period analysed, suggesting that the zone is a typical tension zone. However, the gene flow was significantly lower among the rearranged than the common chromosomes for the second period, whereas the difference was only marginally significant for the first period. This further supports the role of chromosomal rearrangements on gene flow between these taxa.

Significant genetic and phenotypic changes arising from clonal growth of a single spore of an arbuscular mycorrhizal fungus over multiple generations.

Arbuscular mycorrhizal fungi (AMF) are highly successful plant symbionts. They reproduce clonally producing multinucleate spores. It has been suggested that some AMF harbor genetically different nuclei. However, recent advances in sequencing the Glomus irregulare genome have indicated very low within-fungus polymorphism. We tested the null hypothesis that, with no genetic differences among nuclei, no significant genetic or phenotypic variation would occur among clonal single spore lines generated from one initial AMF spore. Furthermore, no additional variation would be expected in the following generations of single spore lines. Genetic diversity contained in one initial spore repeatedly gave rise to genetically different variants of the fungus with novel phenotypes. The genetic changes represented quantitative changes in allele frequencies, most probably as a result of changes in the frequency of genetic variation partitioned on different nuclei. The genetic and phenotypic variation is remarkable, given that it arose repeatedly from one clonal individual. Our results highlight the dynamic nature of AMF genetics. Even though within-fungus genetic variation is low, some is probably partitioned among nuclei and potentially causes changes in the phenotype. Our results are important for understanding AMF genetics, as well as for researchers and biotechnologists hoping to use AMF genetic diversity for the improvement of AMF inoculum.

Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia--an fMRI-TMS study.

Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data.

BACKGROUND: Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges.METHODS: Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities.RESULTS: For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven.CONCLUSIONS: Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.