C. Dejean

Opiate dependence induces network state shifts in the limbic system

Among current theories of addiction, hedonic homeostasis dysregulation predicts that the brain reward systems, particularly the mesolimbic dopamine system, switch from a physiological state to a new set point. In opiate addiction, evidence show that the dopamine system principal targets, prefrontal cortex (PFC), nucleus accumbens (NAC) and basolateral amygdala complex (BLA) also adapt to repeated drug stimulation. Here we investigated the impact of chronic morphine on the dynamics of the network of these three interconnected structures. For that purpose we performed simultaneous electrophysiological recordings in freely-moving rats subcutaneously implanted with continuous-release morphine pellets. Chronic morphine produced a shift in the network state underpinned by changes in Delta and Gamma oscillations in the LFP of PFC, NAC and BLA, in correlation to behavioral changes. However despite continuous stimulation by the drug, an apparent normalization of the network activity and state occurred after 2 days indicating large scale adaptations. Blockade of μ opioid receptors was nonetheless sufficient to disrupt this acquired new stability in morphine-dependent animals. In line with the homeostatic dysregulation theory of addiction, our study provides original direct evidence that the PFC-NAC-BLA network of the dependent brain is characterized by a de novo balance for which the drug of abuse becomes the main contributor.

Deterministic model for the transport of energetic particles: Application in the electron radiotherapy

A new deterministic method for calculating the dose distribution in the electron radiotherapy field is presented. The aim of this work was to validate our model by comparing it with the Monte Carlo simulation toolkit, GEANT4. A comparison of the longitudinal and transverse dose deposition profiles and electron distributions in homogeneous water phantoms showed a good accuracy of our model for electron transport, while reducing the calculation time by a factor of 50. Although the Bremsstrahlung effect is not yet implemented in our model, we propose here a method that solves the Boltzmann kinetic equation and provides a viable and efficient alternative to the expensive Monte Carlo modeling.

Pre-Hispanic Mortuary Practices in Quebrada de Humahuaca (North-Western Argentina): Genetic Relatedness among Individuals Buried in the Same Grave.

Almost all pre‐Hispanic societies from Quebrada de Humahuaca (north‐western Argentina) buried their defuncts in domestic areas, demonstrating the importance of death and its daily presence among the living. Presumably, the collective graves contained related individuals, a hypothesis that can be tested through the study of ancient DNA. This study analyzes autosomal and uniparental genetic markers in individuals from two archaeological sites in Quebrada de Humahuaca occupied during the Late Formative (1450–1050 BP) and Regional Developments I (1050–700 BP) periods. Mitochondrial and Y‐chromosome haplotypes were compared in order to establish possible maternal and paternal relatedness. Genotypes for 15 autosomal STRs were used to calculate pairwise relatedness coefficients and pedigree probabilities. High kinship levels among individuals buried in the same graves were found in both sites. Although only two particular cases were analyzed, these results represent an important contribution to the study of mortuary practices in the region by means of ancient DNA.

Les relations entre le bisphénol A et les troubles du spectre autistique se précisent : la sérotonine est-elle le lien manquant ?

The etiology of autism spectrum disorders (ASD) is believed to be multifactorial and to involve genetic and environmental components. Environmental chemical exposures are increasingly understood to be important in causing neurotoxicity in fetuses and newborns. Recent data from the Centers for Disease Control and Prevention in the United States suggest a substantial increase in ASD prevalence, only partly explicable by factors such as diagnostic substitution. Bisphenol A (BPA) is an ubiquitous xenoestrogen widely employed in a variety of consumer products including plastic and metal food and beverage containers, dental sealants and fillings, medical equipment and thermal receipts. Therefore, most people are exposed almost continuously to BPA in industrialized countries. Sources of BPA exposure are predominantly diet, but also through inhalation or dermal absorption. BPA can be measured in many human fluids and tissues including saliva, serum, urine, amniotic fluid, follicular fluid, placental tissue and breast milk. There is concern that BPA exposure may influence human brain development and may contribute to the increasing prevalence of neurodevelopmental and behavioural problems. Epigenetic mechanisms are suggested by a mouse study that demonstrated that BPA exposure during gestation had long lasting, transgenerational effects on social recognition. Previous epidemiological studies suggested a relationship between maternal BPA exposure and ASD. A recent study of 46xa0children with ASD and 52xa0controls found for the first time a direct association between children with ASD and BPA exposure and demonstrated that BPA is not metabolized well in children with ASD. The metabolomic analyses showed a correlation between ASD and essential amino acid metabolism pathways. Essential amino acids are precursors of neurotransmitters, for example tryptophan for serotonin. Fetal and prenatal BPA exposure was suggested to perturb the serotonergic system in rat and mice models. On the other hand, hyperserotonemia was reported in approximately one-third of autistic patients and also in relatives. Moreover, neuroimaging studies revealed two fundamentally different types of serotonin synthesis abnormality in children with autism compared to age-matched nonautistic children, a difference in whole-brain capacity and focal abnormalities. Finally, decreased serotonin transporter and serotonin receptor binding have been reported in both children and adults with autism. So, the link between BPA and autism could be a defect of the normal in utero or perinatal serotonergic system development. In France, BPA was banned in baby bottles in 2010 and in any food or beverage packaging since January 2015. Therefore, there is an urgent need to find safe alternatives in the use of BPA in the manufacture of industrial products.

Ancient DNA reveals temporal population structure within the South-Central Andes area

OBJECTIVESnThe main aim of this work was to contribute to the knowledge of pre-Hispanic genetic variation and population structure among the South-central Andes Area by studying individuals from Quebrada de Humahuaca, North-western (NW) Argentina.nnnMATERIALS AND METHODSnWe analyzed 15 autosomal STRs in 19 individuals from several archaeological sites in Quebrada de Humahuaca, belonging to the Regional Developments Period (900-1430 AD). Compiling autosomal, mitochondrial, and Y-chromosome data, we evaluated population structure and differentiation among eight South-central Andean groups from the current territories of NW Argentina and Peru.nnnRESULTSnAutosomal data revealed a structuring of the analyzed populations into two clusters which seemed to represent different temporalities in the Andean pre-Hispanic history: pre-Inca and Inca. All pre-Inca samples fell into the same cluster despite being from the two different territories of NW Argentina and Peru. Also, they were systematically differentiated from the Peruvian Inca group. These results were mostly confirmed by mitochondrial and Y-chromosome analyses. We mainly found a clearly different haplotype composition between clusters.nnnDISCUSSIONnPopulation structure in South America has been mostly studied on current native groups, mainly showing a west-to-east differentiation between the Andean and lowland regions. Here we demonstrated that genetic population differentiation preceded the European contact and might have been more complex than thought, being found within the South-central Andes Area. Moreover, divergence among temporally different populations might be reflecting socio-political changes occurred in the evermore complex pre-Hispanic Andean societies.

Mitochondrial lineage A2ah found in a pre-Hispanic individual from the Andean region

The aim of this study was to contribute to the knowledge of pre‐Hispanic Andean mitochondrial diversity by analyzing an individual from the archaeological site Pukara de La Cueva (North‐western Argentina). The date of the discovery context (540u2009±u200960 BP) corresponds to the Regional Developments II period.