Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response

We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations.

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.

Functional and molecular evolutionary analysis of the "Brevix Radix" gene family in mono-and dicotyledonous plants

ABSTRACTIn contrast to animals, plants cannot move from their place of birth and, therefore, need to adapt to their particular habitat in order to survive. Thus, plant development is remarkably plastic, making plants an ideal system for the isolation of genes that account for intraspecific natural variation and possibly environmental adaptation. However, to date, this approach mostly identified null alleles and missed mutations with subtle effects. For instance, BREVIS RADIX (BRX) has been isolated as a key regulator of root growth through a naturally occurring loss-of-function allele in the Arabidopsis thaliana accession Uk-1 and is the founding member of a highly-conserved plant-specific gene family.In this work, we show that a strong selective pressure is acting on the BRX gene family and dates back before the monocot-dicot divergence. However, functional diversification is observed mainly in dicotyledon BRX family genes and is correlated with acceleration in the evolutionary rates in the N-terminal regions. Population genetic data revealed that BRX is highly conserved across Arabidopsis accessions and presents signatures of adaptation. Interestingly, a seven amino acid deletion polymorphism in BRX sequence was found in a few accessions, which seems to be responsible for their enhanced primary root growth. Nevertheless, BRX might not only be active in the root, as suggested by its expression in the shoot. Indeed, leaves and cotyledons of brx mutants are significantly smaller than wild- type. This phenotype is a direct consequence of the absence of BRX function in the shoot rather than an indirect effect of an altered root system growth. Interestingly, cotyledons of brx plants reflect the same physiological defects as the root. Moreover, phenotypes in BRX gain-of-function plants, such as epinastic leaves and increased epidermal cell size, could be associated with an increase in leaf brassinosteroid content.Collectively, these results indicate that BRX contributes to local adaptation by ubiquitously regulating plant growth, probably through the modulation of brassinosteroid biosynthesis.RÉSUMÉContrairement à la plupart des animaux, les plantes ne peuvent se mouvoir et doivent ainsi s'adapter à leur environnement pour survivre. Pour cette raison, elles représentent un système idéal pour l'identification de gènes contribuant à la variation naturelle intra- spécifique, ainsi qu'à l'adaptation. Cependant, cette approche a, jusqu'à présent, surtout permis d'isoler des allèles nuls et non des mutations conférant des effets plus subtiles. C'est le cas du gène Β REVIS RADIX (BRX), un régulateur clé de la croissance racinaire, qui a été identifié grâce à un allèle non-fonctionnel présent dans l'accession naturelle d'Arabidopsis thaliana Uk-1. BRX et ses homologues des plantes mono- et dicotylédones forment une famille très conservée et spécifique aux plantes.Dans ce travail, nous démontrons que la famille de gènes BRX est soumise à une forte pression de sélection qui remonte avant la divergence entre mono- et dicotylédones. Cependant, une diversification fonctionnelle a été observée chez les gènes des dicotylédones et corrèle avec une accélération de la vitesse d'évolution dans leur région N- terminale. Une analyse génétique de différentes accessions naturelles d'Arabidopsis a révélé que BRX est hautement conservé et présente des signatures d'adaptation. Remarquablement, un polymorphisme de délétion de sept acides aminés a été détecté dans quelques accessions et a pour conséquence une plus forte croissance de la racine primaire. Néanmoins, il semble que le rôle de BRX ne se limite pas qu'à la racine, comme indiqué par son expression dans les parties aériennes de la plante. En effet, les mutants brx présentent des cotylédons et des feuilles significativement plus petits que le type sauvage, une conséquence directe de l'absence d'activité de BRX dans ces organes. Nous avons aussi noté que les cotylédons des mutants brx, à l'instar des racines, ont une perception altérée de l'auxine et peuvent être complémentés par l'application exogène de brassinostéroïdes. De plus, dans des plantes présentant un gain de fonction BRX, les feuilles sont épinastiques et les cellules de leur épiderme plus grandes. Ces phénotypes sont accompagnés d'une augmentation de la concentration de brassinostéroïdes dans les feuilles. Conjointement, ces résultats démontrent que BRX contribue à une adaptation locale de la plante par la régulation générale de sa croissance, probablement en modulant la biosynthèse des brassinostéroïdes.

A Label space reduction algorithm for P2MP LSPs using asymmetric tunnels

The aim of traffic engineering is to optimise network resource utilization. Although several works on minimizing network resource utilization have been published, few works have focused on LSR label space. This paper proposes an algorithm that uses MPLS label stack features in order to reduce the number of labels used in LSPs forwarding. Some tunnelling methods and their MPLS implementation drawbacks are also discussed. The algorithm described sets up the NHLFE tables in each LSR, creating asymmetric tunnels when possible. Experimental results show that the algorithm achieves a large reduction factor in the label space. The work presented here applies for both types of connections: P2MP and P2P

¿Son aplicables los criterios analíticos generales para definir el hipotiroidismo en personas con síndrome de down?

Title: Are suitable general clinic criteria for defining hypothyroidism in people with Down syndrome? Studies on the prevalence of thyroid disorders in people with Down syndrome (DS) show a wide dispersion of results. However, most of these studies agree in indicating a greater frequency than in the general population. The cause of these differences may depend on the method of sample selection. In this work we studied a healthy population of adolescents with DS of the Association of Málaga, selected randomly and regardless of the medical care. Mean TSH distribution, used here as a tool to define the biochemical thyroid function of the studied DS population, was two standard deviation higher than the mean for the general population. These data show that in terms of TSH the DS population is a distinct population with respect to the general population. This clearly indicates that it would be necessary to identify and define new criteria to establish what is normal, subclinical hypothyroidism, borderline or pathological, and to propose new treatment guide.

Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.