Influence of sex and age on T3 receptors and T3 concentration in the pituitary gland of the rat: consequences on TSH secretion.

A reduced secretion of thyroid hormones with age has been documented in humans and animals with no substantial increase in TSH secretion, which may be indicative of an age-related impairment of the pituitary sensitivity to the negative control exerted by thyroid hormones. We have evaluated in rats the influence of sex and age on pituitary T3 nuclear receptors--known to be determinant in the regulation of TSH secretion--as well as on T3 concentration in the pituitary gland. As regards sex, the density of T3 receptors and the concentration of T3 in pituitary gland and plasma were greater in females than in males whereas pituitary and plasma TSH concentrations were less. As for age, the density of T3 receptors was greater in old male rats than in young ones with no changes in pituitary T3 and plasma TSH concentrations. In old female rats in contrast, there was no significant increase in T3 receptors but pituitary T3 was less and plasma TSH greater than in young female rats. In both sexes plasma thyroid hormones and pituitary TSH were reduced with age whereas TSH response to TRH was not altered. These results illustrate sex and age differences in pituitary T3 receptors and pituitary T3 concentration as well as in TSH secretion. In young animals of both sexes an inverse correlation is observed between the density of pituitary T3 receptors and plasma TSH. In contrast, in old animals the absence of this correlation is suggestive of an age-related impairment of T3 action on the thyrotrophs or of changes pertaining to other factors modulating TSH secretion.

The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing

Removal of introns during pre-mRNA splicing is a critical process in gene expression, and understanding its control at both single-gene and genomic levels is one of the great challenges in Biology. Splicing takes place in a dynamic, large ribonucleoprotein complex known as the spliceosome. Combining Genetics and Biochemistry, Saccharomyces cerevisiae provides insights into its mechanisms, including its regulation by RNA-protein interactions. Recent genome-wide analyses indicate that regulated splicing is broad and biologically relevant even in organisms with a relatively simple intronic structure, such as yeast. Furthermore, the possibility of coordination in splicing regulation at genomic level is becoming clear in this model organism. This should provide a valuable system to approach the complex problem of the role of regulated splicing in genomic expression.

Pre-Treatment for Reduction of Asphalt Absorption in Porous Aggregate, April 2005

The objective of this research was to evaluate the performance of the product Ultracote® (a polymer based additive produced by Ultrapave, a division of Goodyear) as an aggregate pre-treatment for the reduction of asphalt binder absorption in hot mix asphalt (HMA). The product was tested with a paving project in Louisa county, Iowa with aggregate that had historically shown very high asphalt binder absorption. Results of the testing did not provide any evidence of reduction in binder absorption.

Amniotic fluid insulin-like growth factor binding-protein 3 concentration as early indicator of fetal growth restriction

Rapport de synthèse : Introduction : La croissance foetale infra-utérine dépend d'un grand nombre de facteurs maternels, placentaires et foetaux. Une inadéquation d'un ou plusieurs de ces facteurs peut induire un retard de croissance infra-utérin (RCIU) ou au contraire une macrosomie. Les principales causes de RCIU comprennent les infections maternelles, l'éclampsie, les cardiovasculopathies maternelles, la toxicomanie, les malformations foetales et les insuffisances placentaires. Les facteurs endocriniens constituent un petit pourcentage des causes de RCIU, mais méritent que l'on s'y intéresse de plus près. Les facteurs hormonaux les plus importants pour la croissance fatale sont l'insuline et les insuline-like growth factors (IGFs) et non l'hormone de croissance (GH) qui joue un rôle majeur dans la croissance postnatale. Notre attention s'est portée sur IGF-1 qui joue un rôle important dans la croissance intrautérine. Sa biodisponibilité dépend de plusieurs protéines plasmatiques, les IGF-binding proteins (IGFBP 1 à 9). IGFBP-3 est la principale de ces IGFBPs, autant d'un point de vue quantitatif que fonctionnel. Nous avons cherché à déterminer si les concentrations d'IGF-1 et d'IGFBP-3 dans le liquide amniotique au début du deuxième trimestre étaient prédictives de la croissance infra-utérine. Les gènes codant pour IGF-1 et IGFBP-3 contenant certaines séquences polymorphiques, nous avons également étudié leur influence sur la croissance foetale. L'analyse du liquide amniotique présente l'avantage de pouvoir être effectuée dès la 14ème semaine d'aménorrhée alors que la biométrie foetale échographique ne permet pas à ce stade de déceler des anomalies de la croissance infra-utérine. Méthode : Nous avons analysé des échantillons de liquide amniotique prélevés entre la 14ème et la 18ème semaine de grossesse chez 196 patientes. Les concentrations d'IGF-1 et d'IGFBP-3 ont été dosées par ELISA, les polymorphismes analysés par PCR. Ces résultats ont été ensuite analysés en fonction du poids de naissance des nouveaux-nés, répartis en trois groupes normal pour l'âge gestationnel (AGA), petit pour l'âge gestationnel (SGA) et grand pour l'âge gestationnel (LGA). Résultats : Les concentrations d'IGFBP3 dans le liquide amniotique sont significativement plus élevées (p = 0.030) dans le groupe SGA par rapport au groupe AGA, d'autant plus quand les taux sont ajustés en fonction de paramètres tels que l'âge gestationnel lors de l'amniocentèse (ANCOVA analysis : p = 0.009). La distribution du polymorphisme VNTR (variable number of tandem repeat) dans la région promotrice d'IGF-1 au sein du groupe SGA est significativement différente de celle du groupe AGA (p = 0.029). En effet, la fréquence de l'association allélique 19CA/20CA est diminuée dans le groupe SGA. Nous n'avons pas identifié de différence de distribution des séquences polymorphiques d'IGFBP-3 entre les différents groupes. Conclusion : Une concentration élevée d'IGFBP-3 dans le liquide amniotique au début du deuxième trimestre est associée à un risque plus élevé de retard de croissance alors que l'association allélique 19CA/20CA dans la région polymorphique IGF-1 VNTR est un facteur protecteur.

Personalized modeling for drug concentration prediction using Support Vector Machine

Building a personalized model to describe the drug concentration inside the human body for each patient is highly important to the clinical practice and demanding to the modeling tools. Instead of using traditional explicit methods, in this paper we propose a machine learning approach to describe the relation between the drug concentration and patients' features. Machine learning has been largely applied to analyze data in various domains, but it is still new to personalized medicine, especially dose individualization. We focus mainly on the prediction of the drug concentrations as well as the analysis of different features' influence. Models are built based on Support Vector Machine and the prediction results are compared with the traditional analytical models.

The role of antibody concentration and avidity in antiviral protection.

Neutralizing antibodies are necessary and sufficient for protection against infection with vesicular stomatitis virus (VSV). The in vitro neutralization capacities and in vivo protective capacities of a panel of immunoglobulin G monoclonal antibodies to the glycoprotein of VSV were evaluated. In vitro, neutralizing activity correlated with avidity and with neutralization rate constant, a measure of on-rate. However, in vivo, protection was independent of immunoglobulin subclass, avidity, neutralization rate constant, and in vitro neutralizing activity; above a minimal avidity threshold, protection depended simply on a minimum serum concentration. These two biologically defined thresholds of antibody specificity offer hope for the development of adoptive therapy with neutralizing antibodies.

Teaching motivational interviewing to medical students : a pre-post test pilot study

Objective: To test the efficacy of teaching motivational interviewing (MI) to medical students. Methods: Thirteen 4th year medical students volunteered to participate. Seven days before and 7 days after an 8-hour interactive training MI workshop, each student performed a videorecorded interview with two standardized patients: a 60 year old alcohol dependent woman and a 50 year old cigarette smoking man. Students' counseling skills were coded by two blinded clinicians using the Motivational Interviewing Treatment Integrity 3.0 (MITI). Inter-rater reliability was calculated for all interviews and a test-retest was completed in a sub-sample of 10 consecutive interviews three days apart. Difference between MITI scores before and after training were calculated and tested using non-parametric tests. Effect size was approximated by calculating the probability that posttest scores are greater than pretest scores (P*=P(Pre<Post)+1/2P(Pre=Post)), P*>1/2 indicating greater scores in posttest, P*=1/2 no effect, and P*<1/2 smaller scores in posttest. Results: Median differences between MITI scores before and after MI training indicated a general progression in MI skills: MI spirit global score (median difference=1.5, Inter quartile range=1.5, p<0.001, P*=0.90); Empathy global score (med diff=1, IQR=0.5, p<0.001, P*=0.85); Percentage of MI adherent skills (med diff=36.6, IQR=50.5, p<0.001, P*=0.85); Percentage of open questions (med diff=18.6, IQR=21.6, p<0.001, P*=0.96); reflections/ questions ratio (med diff=0.2, IQR=0.4, p<0.001, P*=0.81). Only Direction global score and the percentage of complex reflections were not significantly improved (med diff=0, IQR=1, p=0.53, P*=0.44, and med diff=4.3, IQR=24.8, p=0.48, P*=0.62, respectively). Inter-rater reliability indicated weighted kappa ranged between 0.14 for Direction to 0.51 for Collaboration and ICC ranged between 0.28 for Simple reflection to 0.95 for Closed question. Test-retests indicated weighted kappa ranged between 0.27 for Direction to 0.80 for Empathy and ICC ranged between 0.87 for Complex reflection to 0.98 for Closed question. Conclusion: This pilot study indicated that an 8-hour training in MI for voluntary 4th year medical students resulted in significant improvement of MI skills. Larger sample of unselected medical students should be studied to generalize the benefit of MI training to medical students. Interrater reliability and test-retests suggested that coders' training should be intensified.

The concentration of foreigners in French schools: interaction effects in place?

This paper explores the existence of negative peer-group pressures derived from the concentration of foreigners in French lower secondary schools. Using different dependent variables (number of years spent in lower secondary education, grades in 4th ‘and 3rd year and track election in upper secondary schooling) the analyses indicate that the much disputed existence of significant and negative effects of the concentration of foreign students in schools depends on the method used for the estimation. If we assume that the concentration of foreigners is a random and exogenous process, then the multivariate analyses confirm negative interactions. If, on the contrary, we question the assumption that this contextual information is not end the result of prior sorting mechanisms of individuals across social spaces, the concentration of foreigners has no statistical impact on attainment.

Profile order and time-dependent artifacts in contrast-enhanced coronary MR angiography at 3T: origin and prevention.

To enhance the clinical value of coronary magnetic resonance angiography (MRA), high-relaxivity contrast agents have recently been used at 3T. Here we examine a uniform bilateral shadowing artifact observed along the coronary arteries in MRA images collected using such a contrast agent. Simulations were performed to characterize this artifact, including its origin, to determine how best to mitigate this effect, and to optimize a data acquisition/injection scheme. An intraluminal contrast agent concentration model was used to simulate various acquisition strategies with two profile orders for a slow-infusion of a high-relaxivity contrast agent. Filtering effects from temporally variable weighting in k-space are prominent when a centric, radial (CR) profile order is applied during contrast infusion, resulting in decreased signal enhancement and underestimation of vessel width, while both pre- and postinfusion steady-state acquisitions result in overestimation of the vessel width. Acquisition during the brief postinfusion steady-state produces the greatest signal enhancement and minimizes k-space filtering artifacts.

Organization of pre-Variscan basement areas at the north-Gondwanan margin

Pre-Variscan basement elements of Central Europe appear in polymetamorphic domains juxtaposed through Variscan and/or Alpine tectonic events. Consequently, nomenclatures and zonations applied to Variscan and Alpine structures, respectively, cannot be valid for pre-Variscan structures. Comparing pre-Variscan relics hidden in the Variscan basement areas of Central Europe, the Alps included, large parallels between the evolution of basement areas of future Avalonia and its former peri-Gondwanan eastern prolongations (e.g. Cadomia, Intra-Alpine Terrane) become evident. Their plate-tectonic evolution from the Late Proterozoic to the Late Ordovician is interpreted as a continuous Gondwana-directed evolution. Cadomian basement, late Cadomian granitoids, late Proterozoic detrital sediments and active margin settings characterize the pre-Cambrian evolution of most of the Gondwana-derived microcontinental pieces. Also the Rheic ocean, separating Avalonia from Gondwana, should have had, at its early stages, a lateral continuation in the former eastern prolongation of peri-Gondwanan microcontinents (e.g. Cadomia, Intra-Alpine Terrane). Subduction of oceanic ridge (Proto-Tethys) triggered the break-off of Avalonia, whereas in the eastern prolongation, the presence of the ridge may have triggered the amalgamation of volcanic arcs and continental ribbons with Gondwana (Ordovician orogenic event). Renewed Gondwana-directed subduction led to the opening of Palaeo-Tethys.

The impact of pre- and post-natal contexts on immunity, glucocorticoids and oxidative stress resistance in wild and domesticated grey partridges

Genetic background, prenatal and post-natal early-life conditions influence the development of interconnected physiological systems and thereby shape the phenotype. Certain combinations of genotypes and pre- and post-natal conditions may provide higher fitness in a specific environmental context. Here, we investigated how grey partridges Perdix perdix of two strains (wild and domesticated) cope physiologically with pre- and post-natal predictable vs. unpredictable food supply. Food unpredictability occurs frequently in wild environments and requires physiological and behavioural adjustments. Well-orchestrated and efficient physiological systems are presumably more vital in a wild environment as compared to captivity. We thus predicted that wild-strain grey partridges have a stronger immunity, glucocorticoid (GC) stress response and oxidative stress resistance (OSR) than domesticated birds, which have undergone adaptations to captivity. We also predicted that wild-strain birds react more strongly to environmental stimuli and, when faced with harsh prenatal conditions, are better able to prepare their offspring for similarly poor post-natal conditions than birds of domesticated origin. We found that wild-strain offspring were physiologically better prepared for stressful situations as compared to the domesticated strain. They had a high GC stress response and a high OSR when kept under predictable food supply. Wild-strain parents reacted to prenatal unpredictable food supply by lowering their offspring's GC stress response, which potentially lowered GC-induced oxidative pressure. No such pattern was evident in the domesticated birds. Irrespective of strain and prenatal feeding scheme, post-natal unpredictable food supply boosted immune indices, and GC stress response was negatively related to antibody response in females and to mitochondrial superoxide production. Wild-strain grey partridge showed fitness-relevant physiological advantages and appeared to prepare their offspring for the prospective environment. Negative relationships between GC stress response, immunity and oxidative indices imply a pivotal role of an organism's oxidative balance and support the importance of considering multiple physiological systems simultaneously.