A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models

In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes

Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. Objectives: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. Results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: –2.6, –0.5; p = 0.003). Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months. Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.130747

The GenTree Platform: growth traits and tree-level environmental data in 12 European forest tree species

Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information. Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species’ geographic ranges and reflecting local environmental gradients. Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available

Between but not within species variation in the distribution of fitness effects

New mutations provide the raw material for evolution and adaptation. The distribution of fitness effects (DFE) describes the spectrum of effects of new mutations that can occur along a genome, and is therefore of vital interest in evolutionary biology. Recent work has uncovered striking similarities in the DFE between closely related species, prompting us to ask whether there is variation in the DFE among populations of the same species, or among species with different degrees of divergence, i.e., whether there is variation in the DFE at different levels of evolution. Using exome capture data from six tree species sampled across Europe we characterised the DFE for multiple species, and for each species, multiple populations, and investigated the factors potentially influencing the DFE, such as demography, population divergence and genetic background. We find statistical support for there being variation in the DFE at the species level, even among relatively closely related species. However, we find very little difference at the population level, suggesting that differences in the DFE are primarily driven by deep features of species biology, and that evolutionarily recent events, such as demographic changes and local adaptation, have little impact

Effect of aging on hedonic appreciation of pleasant and unpleasant odors.

Does hedonic appreciation evolve differently for pleasant odors and unpleasant odors during normal aging? To answer this question we combined psychophysics and electro-encephalographic recordings in young and old adults. A first study showed that pleasant odorants (but not unpleasant ones) were rated as less pleasant by old adults. A second study validated this decrease in hedonic appreciation for agreeable odors and further showed that smelling these odorants decreased beta event-related synchronization in aged participants. In conclusion, the study offers new insights into the evolution of odor hedonic perception during normal aging, highlighting for the first time a change in processing pleasant odors

Olfactory hedonic coding in the brain

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Identification of new behavioral parameters to assess odorant hedonic value in humans: A naturalistic approach

International audienceBackground: When you smell an odorant, your first reaction will certainly be either I like it or I dislike it. This primary reaction is a reflection of what is called the "hedonic value" of the odor. Very often, this hedonic value dominates the olfactory percept, more than olfactory identification or intensity. This component of olfactory perception is of primary importance for guiding behavior: avoiding danger (the smell of smoke, gas, etc.), consuming food, or seduction. Olfactory hedonics can be assessed using a large number of methods in humans, including psychophysical measures, autonomic responses, measurement of facial expressions or peripheral nervous activity. All of these techniques have their limitations: subjectivity, invasiveness, need for expertise, etc. A new method: The olfactory system is closely linked to the reward system, the role of which is to mediate motivated behavior. In this context, we propose that the capacity odorants have of recruiting the reward system and thus inducing motivated behavior can be used to identify new behavioral parameters to assess odor hedonic value in humans. Results: We recorded freely moving human participants exploring odors emanating from flasks, and showed that five parameters linked to motivated behavior were closely linked to odor hedonics: speed of approach to the nose and withdrawal of the flask containing the odorant, distance between flask and nose, number of samplings, and withdrawal distance (maximal distance between nose and flask after odor sampling). Conclusions: We highlighted new non-verbal and non-invasive parameters to evaluate olfactory hedonics in humans based on the assessment of odor-motivated behavior

Modelisation de l'activite electrique cerebrale par la methode des elements finis

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 82607 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

In vivo beta and gamma subthreshold oscillations in rat mitral cells: origin and gating by respiratory dynamics

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"What-Where-Which" Episodic Retrieval Requires Conscious Recollection and Is Promoted by Semantic Knowledge

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