Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy

In synucleinopathies, including Parkinson's disease, partially ubiquitylated α-synuclein species phosphorylated on serine 129 (PS129-α-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against α-synuclein-mediated toxicity in various models

Human insulin gene expression in transgenic mice: mutational analysis of the regulatory region

International audienc

Conception and bicentric validation of the proSCANNED score, a simplified bedside prognostic score for Heart Failure patients

International audienceA simple and accurate prognostic tool for Heart Failure (HF) patients is critical to improve follow-up. Different risk scores are accurate but with limited clinical applicability. The current study aims to derive and validate a simple predictive tool for HF prognosis. French outpatients with stable HF of two university hospitals were included in the derivation (N = 134) or in the validation (N = 274) sample and followed up for a median of 23 months. Potential predictors were variables with known association with mortality and easily available. The proSCANNED risk score was derived using a parametric survival model on complete case data; it includes 8 binary variables and its values are 0-8. In the validation sample, the ability of the score to discriminate the 1-year vital status was moderate (AUC = 0.71, IC95% = [0.64-0.71]). However, the stratification of the score in three groups showed a good calibration for patients in the low- and medium-risk risk group. The proSCANNED score is an easy-to-use tool in clinical practice with a good discrimination, stability, and calibration sufficient to improve the medical care of patients. Other follow up studies are necessary to assess score applicability in larger populations, and its impact

Change in recharge of aquifers under several cropping systems due to climate change. Consequences on land use at territorial level

session 2 : Adapation au changement climatiqueClimate change will produce a decrease in rainfall over French territory, especially in western France. Cropping systems pattern is a key factor in water resources management at catchment basin level. In the frame of the ANR French project ―Climator‖, we have undertaken an analysis of the relationship between rainfall and the annual supply of water to the aquifers under several cropping systems and ecosystems. This was performed through crop modelling using agroclimatic data provided either by measurements at 12 experimental sites in France (1971-2000) or by using regionalised outputs of the French climatological model Arpege (2021-2050 and 2071-2100). The simulations highlight the important differences in aquifers recharge between cropping systems (rainfed vs irrigated but also winter vs spring crops and annual crops vs perennial vegetation). For the 12 sites, they also give an estimate of the decrease with time of the annual recharge under each cropping system (at least 2/3 of rain decrease). In the driest locations, that decrease may lead to a partial change in cropping systems pattern in order to match the total water demand at catchment level. Such change could be devoted either to increase annual recharge when irrigation water is pumped from large aquifers or to reduce summer water demand when irrigation water comes from rivers. Both cases are illustrated

Massive CA1/2 Neuronal Loss with Intraneuronal and N-Terminal Truncated Aβ(42) Accumulation in a Novel Alzheimer Transgenic Model

Alzheimer’s disease (AD) is characterized by a substantial degeneration of pyramidal neurons and the appearance of neuritic plaques and neurofibrillary tangles. Here we present a novel transgenic mouse model, APP(SL)PS1KI that closely mimics the development of AD-related neuropathological features including a significant hippocampal neuronal loss. This transgenic mouse model carries M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human β-amyloid (Aβ) precursor protein. Aβ(x-42) is the major form of Aβ species present in this model with progressive development of a complex pattern of N-truncated variants and dimers, similar to those observed in AD brain. At 10 months of age, an extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer that correlates with strong accumulation of intraneuronal Aβ and thioflavine-S-positive intracellular material but not with extracellular Aβ deposits. A strong reactive astrogliosis develops together with the neuronal loss. This loss is already detectable at 6 months of age and is PS1KI gene dosage-dependent. Thus, APP(SL)PS1KI mice further confirm the critical role of intraneuronal Aβ(42) in neuronal loss and provide an excellent tool to investigate therapeutic strategies designed to prevent AD neurodegeneration

Generating controlled image sets in cognitive neuroscience research.

The investigation of perceptual and cognitive functions with non-invasive brain imaging methods critically depends on the careful selection of stimuli for use in experiments. For example, it must be verified that any observed effects follow from the parameter of interest (e.g. semantic category) rather than other low-level physical features (e.g. luminance, or spectral properties). Otherwise, interpretation of results is confounded. Often, researchers circumvent this issue by including additional control conditions or tasks, both of which are flawed and also prolong experiments. Here, we present some new approaches for controlling classes of stimuli intended for use in cognitive neuroscience, however these methods can be readily extrapolated to other applications and stimulus modalities. Our approach is comprised of two levels. The first level aims at equalizing individual stimuli in terms of their mean luminance. Each data point in the stimulus is adjusted to a standardized value based on a standard value across the stimulus battery. The second level analyzes two populations of stimuli along their spectral properties (i.e. spatial frequency) using a dissimilarity metric that equals the root mean square of the distance between two populations of objects as a function of spatial frequency along x- and y-dimensions of the image. Randomized permutations are used to obtain a minimal value between the populations to minimize, in a completely data-driven manner, the spectral differences between image sets. While another paper in this issue applies these methods in the case of acoustic stimuli (Aeschlimann et al., Brain Topogr 2008), we illustrate this approach here in detail for complex visual stimuli