White-handed gibbons discriminate context-specific songs compositions

This research project has been funded by the Leverhulme Trust (Research Leadership Award F/00268/AP), the European Research Council (grant number FP7; PRILANG GA283871) and the Swiss National Science Foundation (310030_185324).White-handed gibbons produce loud and acoustically complex songs when interacting with their neighbours or when encountering predators. In both contexts, songs are assembled from a small number of units although their composition differs in context-specific ways. Here, we investigated whether wild gibbons could infer the ‘meaning’ when hearing exemplars recorded in both contexts (i.e. ‘duet songs’ vs. ‘predator songs’). We carried out a playback experiment by which we simulated the presence of a neighbouring group producing either its duet or a predator song in order to compare subjects’ vocal and locomotor responses. When hearing a recording of a duet song, subjects reliably responded with their own duet song, which sometimes elicited further duet songs in adjacent groups. When hearing a recording of a predator song, however, subjects typically remained silent, apart from one of six groups which replied with its own predator song. Moreover, in two of six trials, playbacks of predator songs elicited predator song replies in non-adjacent groups. Finally, all groups showed strong anti-predator behaviour to predator songs but never to duet songs. We concluded that white-handed gibbons discriminated between the two song types and were able to infer meaning from them. We discuss the implications of these findings in light of the current debate on the evolutionary origins of syntax.Publisher PDFPeer reviewe

Influence of the transient conditions on release of corrosion products and oxidation of alloy 690 tubes during pressurized water reactor restart after steam generators replacement

The radioactivity of the Reactor Coolant System (RCS) of Pressurized Water Reactors (PWRs) mainly comes from the release of corrosion products of Steam Generator (SG) tubes made of Ni-base alloys. In order to reduce this activity and thus the radiation exposure of PWR operators during maintenance operations, it is necessary to minimize the release. That requires prior understanding of the various mechanisms involved. EDF R&D constructed a loop, BOREAL, to specifically measure rates of release of SG tubes in various conditions of primary environment. Tubes were usually tested at high temperature, under con- stant conditions of primary chemistry. So, it is necessary to carefully investigate the impact of transient conditions during a PWR restart after SG replacement. Tests were performed on the industrial material with curvature, roughness, defects and heterogeneities, regularly observed on this type of component. Characterisations of the inner surface were done on as-received and corroded specimens of SG tubes and were correlated with the obtained release kinetics. The native oxide layer is formed of a very thin layer (1-2 nm) of oxidised matrix, without specific en- richment. During the restart, the most critical step for the release phenomenon is revealed from 170 °C to 297 °C. The majority of the metal is indeed released into the fluid during this step. The characterisa- tions after release tests have made it possible to propose oxidation and release mechanism during a PWR restart after SG replacement. Up to 170 °C, a thin layer of amorphous chromium oxide is formed by selec- tive dissolution of iron and nickel. When the temperature rises, this chromium oxide layer is not stable enough to be protective and the diffusion phenomena are activated. At 325 °C, the oxide does not exhibit any particular enrichment and corresponds to an oxidised metal layer; an equilibrium is established and the rate of release reaches a pseudo-stationary regime

Río Bec. Des grandes maisons et des récoltes

Dans la région de Río Bec, les données archéologiques, iconographiques et épigraphiques indiquent que la royauté n’a pas vraiment eu cours de 550 à 950 apr. J.-C. Des élites nobles, en revanche, furent d’importants acteurs, construisant des résidences à forte visibilité et contrôlant des domaines agricoles, ce qui servit leurs stratégies de factions et, tardivement, la diffusion d’idées architecturales sur une large zone. L’image que l’on reconstitue est celle d’une société fortement fragmentée entre de nombreux acteurs économiquement indépendants : chacun poursuivait ses intérêts de groupe lesquels combinaient une production vivrière intensive et l’auto-édification de résidences stables sur chaque domaine, mais, à l’inverse, peu d’investissement dans la production artisanale et dans les échanges commerciaux.In the Río Bec region, archaeological, iconographic and epigraphic data indicate that kingship has been weakly articulated from AD 550 to 950. Sub-royal elites were active, creating highly visible houses with land domains that served factional strategies and, late in time, diffused architectural ideas over a wide area. The picture is one of a highly fragmented society consisting of many economically autonomous agents, each pursuing corporate interests that combined intensive staple production and auto-construction of stable residences on their land, with minimal insertion in craft production and regional exchanges.En la región de Río Bec, los datos arqueológicos, iconográficos y epigráficos indican que la realeza no existió verdaderamente entre 550 y 950 d.C. En cambio, elites nobles fueron actores importantes, edificando residencias de alta visibilidad y controlando dominios agrícolas. Estas realizaciones servían sus estrategias como facciones y propiciaron a la vez, pero más tarde, la difusión de ideas arquitectónicas en una amplia zona. La imagen que se logra reconstruir es la de una sociedad muy fragmentada entre numerosos actores económicamente independientes: cada uno perseguía sus intereses de grupo, los cuales combinaban una producción agrícola intensiva y la auto-construcción de residencias estables en su dominio. En cambio, invirtieron poco en las actividades artesanales y los intercambios comerciales

Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation

Background: Breast cancer risk increases drastically in individuals carrying a germline BRCA1 mutation. The exposure to ionizing radiation for diagnostic or therapeutic purposes of BRCA1 mutation carriers is counterintuitive, since BRCA1 is active in the DNA damage response pathway. The aim of this study was to investigate whether healthy BRCA1 mutations carriers demonstrate an increased radiosensitivity compared with healthy individuals. Methods: We defined a novel radiosensitivity indicator (RIND) based on two endpoints measured by the G2 micronucleus assay, reflecting defects in DNA repair and G2 arrest capacity after exposure to doses of 2 or 4 Gy. We investigated if a correlation between the RIND score and nonsense-mediated decay (NMD) could be established. Results: We found significantly increased radiosensitivity in the cohort of healthy BRCA1 mutation carriers compared with healthy controls. In addition, our analysis showed a significantly different distribution over the RIND scores (p = 0.034, Fisher’s exact test) for healthy BRCA1 mutation carriers compared with non-carriers: 72 % of mutation carriers showed a radiosensitive phenotype (RIND score 1–4), whereas 72 % of the healthy volunteers showed no radiosensitivity (RIND score 0). Furthermore, 28 % of BRCA1 mutation carriers had a RIND score of 3 or 4 (not observed in control subjects). The radiosensitive phenotype was similar for relatives within several families, but not for unrelated individuals carrying the same mutation. The median RIND score was higher in patients with a mutation leading to a premature termination codon (PTC) located in the central part of the gene than in patients with a germline mutation in the 5′ end of the gene. Conclusions: We show that BRCA1 mutations are associated with a radiosensitive phenotype related to a compromised DNA repair and G2 arrest capacity after exposure to either 2 or 4 Gy. Our study confirms that haploinsufficiency is the mechanism involved in radiosensitivity in patients with a PTC allele, but it suggests that further research is needed to evaluate alternative mechanisms for mutations not subjected to NMD

Recommendations for the use of Serious Games in people with Alzheimer's Disease, related disorders and frailty.

International audienceAlzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority

Immunoregulatory molecule expression on extracellular microvesicles in people living with HIV

IntroductionPeople living with HIV (PLWH) now benefit from combined antiviral treatments that durably control viral replication. These antiretroviral treatments decrease mortality and improve quality of life in PLWH, but do not completely control the excessive non-specific activation of the immune system in PLWH. This chronic immune activation is a key element of HIV immunopathology that contributes to the pathophysiology of inflammatory comorbid conditions, such as cardiovascular disorders, cancer and autoimmune diseases. Circulating non-exosomal extracellular vesicles, also known as microparticles (MPs) are detected in these diseases and have been linked to immune activation. The objective of this study was to characterize the MPs present in PLWH and to assess their association with chronic immune activation.MethodsWe performed flow cytometry for the complete phenotypic characterization of MPs from fresh plasma from PLWH and from people without HIV as the control group. The absolute number, size and cellular origin of MPs were evaluated. The immunoregulatory profile was determined by cell origin, for MPs derived from platelets (PMPs), monocytes (MMPs) and T lymphocytes (LMPs).ResultsPLWH had significantly more circulating MPs than controls, for MPs of all sizes originating from T lymphocytes, red blood cells, neutrophils, dendritic cells, B lymphocytes and endothelial cells. PMPs and MMPs were not more numerous in PLWH, but the immunoregulatory phenotypes of these MPs differed between PLWH and controls. These differences in immunoregulatory molecule expression profile were also observed for LMPs. PDL1, ICOSL, CCR5, TGFβ1, MHC classes I and II, TRAIL, CXCR4, OX40, DC-SIGN, CTLA4 and PDL2 were more strongly expressed on the surface of MPs from PLWH than on those from controls.ConclusionMPs are an important element in intercellular communication, making it possible to transfer phenotypes and functions to immune cells. The significantly higher numbers of MPs expressing diverse immunomodulatory molecules in PLWH may make a major contribution to the maintenance and/or the development of immune-cell activation in these individuals

Necdin, a p53-Target Gene, Is an Inhibitor of p53-Mediated Growth Arrest

In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT), a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT) cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP) where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers