Melanin-based coloration in juvenile kestrels (Falco tinnunculus) covaries with anti-predatory personality traits

Recent studies have shown that melanin-based coloration is associated with the ability to cope with stressful environments, potentially explaining why coloration covaries with anti-predator behaviours, boldness and docility. To investigate whether these relationships are consistent across species, we performed a study in the European kestrel (Falco tinnunculus). Similar to our results found previously in the barn owl (Tyto alba), nestling kestrels displaying a larger sub-terminal black tail band stayed on their back longer (tonic immobility test) and breathed at a lower rate than individuals with a smaller black band when handled. However, in contrast to barn owls, nestling kestrels with a larger black tail band were more aggressive and more agitated. Our results strengthen the hypothesis that melanin coloration is related to stress response and in turn to the reaction to predators, a very important personality trait (i.e. boldness).

The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.

The caspase-3/p120 RasGAP module acts as a stress sensor that promotes pro-survival or pro-death signaling depending on the intensity and the duration of the stressful stimuli. Partial cleavage of p120 RasGAP generates a fragment, called fragment N, which protects stressed cells by activating Akt signaling. Akt family members regulate many cellular processes including proliferation, inhibition of apoptosis and metabolism. These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined. In this study, we investigated the individual contribution of each isoform in fragment N-mediated cell protection against Fas ligand induced cell death. To this end, DLD1 and HCT116 isogenic cell lines lacking specific Akt isoforms were used. It was found that fragment N could activate Akt1 and Akt2 but that only the former could mediate the protective activity of the RasGAP-derived fragment. Even overexpression of Akt2 or Akt3 could not rescue the inability of fragment N to protect cells lacking Akt1. These results demonstrate a strict Akt isoform requirement for the anti-apoptotic activity of fragment N.

Clinical uses of anti-Müllerian hormone assays : pitfalls and promises

Rapport de synthèse : OBJECTIF : étudier si les fluctuations sériques du taux d'hormone anti-müllérienne (AMH) sont liées à des différences méthodologiques entre les deux tests ELISA commercialement disponibles le kit de Beckman Coulter Immunotech (Fullerton, CA) et le kit de Diagnostic Systems Laboratories (Webster, TX). DESIGN : étude prospective au sein de deux services universitaires de médecine de la reproduction. POPULATION ETUDIEE : cent soixante-huit échantillons sanguins provenant de trois populations différentes ainsi que des dosages itératifs au cours du même cycle menstruel dans une population de dix volontaires. INTERVENTIONS : doubles mesures en aveugle des taux sériques d'AMH dans les 168 sera avec les deux kits commercialement disponibles. Sept dosages itératifs au cours du même cycle menstruel chez 10 volontaires normo-ovulantes. ANALYSE STATISTIQUE : régression linéaire pour l'étude de la corrélation entre les deux méthodes de dosage. Analyse des variances pour les dosages sériés en cours de cycle menstruel. RÉSULTATS : nous avons démontré une relation linéaire entre les deux méthodes, avec un coefficient de corrélation de 0,88 ainsi qu'une diminution faible mais statistiquement significative et concomitante avec l'ovulation du taux d'AMH sérique. CONCLUSION : les variations en cours de cycle menstruel rapportées par certains auteurs ne sont pas liées à des problèmes méthodologiques. La chute du taux d'AMH lors de l'ovulation est faible mais statistiquement significative. Les variations observées en cours de cycle restent toutefois inférieures aux variations intercycles et ne représentent de ce fait pas un obstacle au dosage de l'AMH à n'importe quel jour du cycle menstruel.

Bayesian-MCMC inversion of time-lapse geophysical data to characterize vadose zone hydraulic behaviour

Geophysical methods have the potential to provide valuable information on hydrological properties in the unsaturated zone. In particular, time-lapse geophysical data, when coupled with a hydrological model and inverted stochastically, may allow for the effective estimation of subsurface hydraulic parameters and their corresponding uncertainties. In this study, we use a Bayesian Markov-chain-Monte-Carlo (MCMC) inversion approach to investigate how much information regarding vadose zone hydraulic properties can be retrieved from time-lapse crosshole GPR data collected at the Arrenaes field site in Denmark during a forced infiltration experiment.

Inversion of multiple intersecting high-resolution crosshole GPR profiles for hydrological characterization at the Boise Hydrogeophysical Research Site

The integration of geophysical data into the subsurface characterization problem has been shown in many cases to significantly improve hydrological knowledge by providing information at spatial scales and locations that is unattainable using conventional hydrological measurement techniques. In particular, crosshole ground-penetrating radar (GPR) tomography has shown much promise in hydrology because of its ability to provide highly detailed images of subsurface radar wave velocity, which is strongly linked to soil water content. Here, we develop and demonstrate a procedure for inverting together multiple crosshole GPR data sets in order to characterize the spatial distribution of radar wave velocity below the water table at the Boise Hydrogeophysical Research Site (BHRS) near Boise, Idaho, USA. Specifically, we jointly invert 31 intersecting crosshole GPR profiles to obtain a highly resolved and consistent radar velocity model along the various profile directions. The model is found to be strongly correlated with complementary neutron porosity-log data and is further corroborated by larger-scale structural information at the BHRS. This work is an important prerequisite to using crosshole GPR data together with existing hydrological measurements for improved groundwater flow and contaminant transport modeling.

Circulating miRNAs: a new generation of anti-doping biomarkers

MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of biological processes. Cell-free miRNAs detected in blood plasma are used as specific and sensitive markers of physiological processes and some diseases. Circulating miRNAs are highly stable in body fluids, for example plasma. Therefore, profiles of circulating miRNAs have been investigated for potential use as novel, non-invasive anti-doping biomarkers. This review describes the biological mechanisms underlying the variation of circulating miRNAs, revealing that they have great potential as a new class of biomarker for detection of doping substances. The latest developments in extraction and profiling technology, and the technical design of experiments useful for anti-doping, are also discussed. Longitudinal measurements of circulating miRNAs in the context of the athlete biological passport are proposed as an efficient strategy for the use of these new markers. The review also emphasizes potential challenges for the translation of circulating miRNAs from research into practical anti-doping applications.

Report of the ECCO workshop on anti-TNF therapy failures in inflammatory bowel diseases: biological roles and effects of TNF and TNF antagonists.

This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.

Short- and long-term changes in chromosomal inversion polymorphism and global warming: Drosophila subobscura from the Balkans

The chromosomal inversion polymorphism of Drosophila subobscura is adaptive to environmental changes. The population of Petnica, Serbia, was chosen to analyze short- and long-term changes in this polymorphism. Short-term changes were studied in the samples collected in May, June, and August of 1995. The inversion polymorphism varied over these months, although various interpretations are possible. To analyze long-term changes, samples obtained in May 1995 and May 2010 were compared. The frequency of the 'cold' adapted inversions (Ast, Jst, Ust, Est, and Ost) decreased and that of the 'warm' adapted inversions (A2, J1, U1+2, and O3+4) increased, from 1995 to 2010. These changes are consistent with the general increase in temperature recorded in Petnica for the same period. Finally, the possible response of chromosomal polymorphism to global warming was analyzed at the regional level (Balkan peninsula). This polymorphism depends on the ecological conditions of the populations, and the changes observed appear to be consistent with global warming expectations. Natural selection seems to be the main mechanism responsible for the evolution of this chromosomal polymorphism.

Short- and long-term changes in chromosomal inversion polymorphism and global warming: Drosophila subobscura from the Balkans

The chromosomal inversion polymorphism of Drosophila subobscura is adaptive to environmental changes. The population of Petnica, Serbia, was chosen to analyze short- and long-term changes in this polymorphism. Short-term changes were studied in the samples collected in May, June, and August of 1995. The inversion polymorphism varied over these months, although various interpretations are possible. To analyze long-term changes, samples obtained in May 1995 and May 2010 were compared. The frequency of the 'cold' adapted inversions (Ast, Jst, Ust, Est, and Ost) decreased and that of the 'warm' adapted inversions (A2, J1, U1+2, and O3+4) increased, from 1995 to 2010. These changes are consistent with the general increase in temperature recorded in Petnica for the same period. Finally, the possible response of chromosomal polymorphism to global warming was analyzed at the regional level (Balkan peninsula). This polymorphism depends on the ecological conditions of the populations, and the changes observed appear to be consistent with global warming expectations. Natural selection seems to be the main mechanism responsible for the evolution of this chromosomal polymorphism.

Efficacy Of Canakinumab (Acz885), A Fully Human Anti-Interleukin (Il)-1beta Monoclonal Antibody, In The Prevention Of Flares In Gout Patients Initiating Allopurinol Therapy

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by IL-1b. Canakinumab targets and inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 week double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150 mg divided in doses every 4 weeks (50+50+25+25 mg [q4wk]) or colchicine 0.5 mg p.o. daily for 16 weeks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to the number of gout flares occurring during first 16 weeks. Secondary outcomes included number of patients with gout flares and C-reactive protein (CRP) levels during the first 16 weeks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine could not be determined. Based on a negative binomial model, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25 mg 0.60, 50 mg 0.34, 100 mg 0.28, 200 mg 0.37, 300 mg 0.29, q4wk 0.38; p<=0.05). The percentage of patients with flares was lower for all canakinumab groups (25 mg 27.3%, 50 mg 16.7%, 100 mg 14.8%, 200 mg 18.5%, 300 mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p<=0.05 for all). The median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN=3 mg/L) throughout the 16 week period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), and 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg) and 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. One fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusion: In this large randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine (standard of care), and was well tolerated.

3D coronary vessel wall imaging utilizing a local inversion technique with spiral image acquisition.

Current 2D black blood coronary vessel wall imaging suffers from a relatively limited coverage of the coronary artery tree. Hence, a 3D approach facilitating more extensive coverage would be desirable. The straightforward combination of a 3D-acquisition technique together with a dual inversion prepulse can decrease the effectiveness of the black blood preparation. To minimize artifacts from insufficiently suppressed blood signal of the nearby blood pools, and to reduce residual respiratory motion artifacts from the chest wall, a novel local inversion technique was implemented. The combination of a nonselective inversion prepulse with a 2D selective local inversion prepulse allowed for suppression of unwanted signal outside a user-defined region of interest. Among 10 subjects evaluated using a 3D-spiral readout, the local inversion pulse effectively suppressed signal from ventricular blood, myocardium, and chest wall tissue in all cases. The coronary vessel wall could be visualized within the entire imaging volume.