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Francois, C.

Publications and source records attributed to Francois, C..

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" Idol with feet of clay ": reliable predictions of forest ecosystem functioning require flawless climate forcings.

Climate change affects various aspects of the functioning of ecosystem, especially photosynthesis, respiration and carbon storage. We need accurate modelling approaches (impact models) to simulate the functioning, vitality and provision of ecosystem services of forests in a warmer world. These impact models require climate data as forcings, which are often produced by climate models comparing more or less well with observational climate data. The bias percentage of the climate forcings propagates throughout the modeling chain from the climate model to the impact model. In this study, we aimed to quantify these bias percentage, addressing three questions: (1) Do the impact model predictions vary when forcing it with different climate models, and how do the predictions under climate model vs. observational climate forcing differ? (2) Does the variability in the impact climate simulations caused by climate forcings fade out at large spatial scale? (3) How the fact of using simulated climatic data affects the process-based model predictions in the case of stressful events? To answer these questions, we present results obtained over the historical period (e.g. 1970-2010) with the CASTANEA ecophysiological forest model and use the data from three climate models. Our analysis focuses on French forests, studying European beech (Fagus sylvatica), temperate deciduous oaks (Quercus robur and Q. petraea), Scots pine (Pinus sylvestris) and spruce (Picea abies) monospecific stands. We show that prediction of photosynthesis, respiration and wood growth highly depends on the climate model used, whether debiased or not, and also on species and region considered. Overall, we observed an improvement of prediction after a monthly mean bias or monthly quantile mapping correction for three model considered, but not with the same success. Then we highlighted a large variability in the processes simulated by the impact model under different climate forcings when considering the plot (i.e. scale of a few hectares) scale. This variability fades out at larger scale (e.g. the scale of an ecological region, i.e. 100 km2), owing to an aggregation effect. Moreover, process predictions obtained under different climate forcings are more variable during driest years. These results highlight the necessity to quantify bias and uncertainties in climate forcings before predicting fluxes dynamics with process-based model.

ecology

Characterization and validation of 15 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology: How specific are the conformation-specific α-synuclein antibodies?

Increasing evidence suggests that alpha-synuclein (-syn) oligomers are obligate intermediates in the pathway involved in -syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinsons disease (PD) and other synucleinopathies. Therefore, the development of tools and methods to detect and quantify -syn oligomers has become increasingly crucial for mechanistic studies to understand the role of these oligomers in PD, and to develop new diagnostic methods and therapies for PD and other synucleinopathies. The majority of these tools and methods rely primarily on the use of aggregation state-specific or conformation-specific antibodies. Given the impact of the data and knowledge generated using these antibodies on shaping the foundation and directions of -syn and PD research, it is crucial that these antibodies are thoroughly characterized, and their specificity or ability to capture diverse -syn species is tested and validated. Herein, we describe an antibody characterization and validation pipeline that allows a systematic investigation of the specificity of -syn antibodies using well-defined and well-characterized preparations of various -syn species, including monomers, fibrils, and different oligomer preparations that are characterized by distinct morphological, chemical and secondary structure properties. This pipeline was used to characterize 18 -syn antibodies, 16 of which have been reported as conformation- or oligomer-specific antibodies, using an array of techniques, including immunoblot analysis (slot blot and Western blot), a digital ELISA assay using single molecule array technology and surface plasmon resonance. Our results show that i) none of the antibodies tested are specific for one particular type of -syn species, including monomers, oligomers or fibrils; ii) all antibodies that were reported to be oligomer-specific also recognized fibrillar -syn; and iii) a few antibodies showed high specificity for oligomers and fibrils but did not bind to monomers. These findings suggest that the great majority of -syn aggregate-specific antibodies do not differentiate between oligomers and fibrils, thus highlighting the importance of exercising caution when interpreting results obtained using these antibodies. Our results also underscore the critical importance of the characterization and validation of antibodies before their use in mechanistic studies and as diagnostic and therapeutic agents. This will not only improve the quality and reproducibility of research and reduce costs but will also reduce the number of therapeutic antibody failures in the clinic.

neuroscience