Ovine serum biomarkers of early and late phase scrapie

<p>Abstract</p> <p>Background</p> <p>Transmissible spongiform encephalopathies are fatal neurodegenerative disease occurring in animals and humans for which no <it>ante-mortem </it>diagnostic test in biological fluids is available. In such pathologies, detection of the pathological form of the prion protein (i.e., the causative factor) in blood is difficult and therefore identification of new biomarkers implicated in the pathway of prion infection is relevant.</p> <p>Methods</p> <p>In this study we used the SELDI-TOF MS technology to analyze a large number of serum samples from control sheep and animals with early phase or late phase scrapie. A few potential low molecular weight biomarkers were selected by statistical methods and, after a training analysis, a protein signature pattern, which discriminates between early phase scrapie samples and control sera was identified.</p> <p>Results</p> <p>The combination of early phase biomarkers showed a sensitivity of 87% and specificity of 90% for all studied sheep in the early stage of the disease. One of these potential biomarkers was identified and validated in a SELDI-TOF MS kinetic study of sera from Syrian hamsters infected by scrapie, by western blot analysis and ELISA quantitation.</p> <p>Conclusions</p> <p>Differential protein expression profiling allows establishing a TSE diagnostic in scrapie sheep, in the early phase of the disease. Some proteic differences observed in scrapie sheep exist in infected hamsters. Further studies are being performed to identify all the discriminant biomarkers of interest and to test our potential markers in a new cohort of animals.</p

Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression

Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K+ currents, we compared their function by patch-clamp technique in wild-type Tmprss3WT and Tmprss3Y260X-mutant mice. Interestingly, only outward K+ currents were altered in Tmprss3Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3WT and Tmprss3Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3WT, Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs

A new method for 2D gel spot alignment: application to the analysis of large sample sets in clinical proteomics

<p>Abstract</p> <p>Background</p> <p>In current comparative proteomics studies, the large number of images generated by 2D gels is currently compared using spot matching algorithms. Unfortunately, differences in gel migration and sample variability make efficient spot alignment very difficult to obtain, and, as consequence most of the software alignments return noisy gel matching which needs to be manually adjusted by the user.</p> <p>Results</p> <p>We present Sili2DGel an algorithm for automatic spot alignment that uses data from recursive gel matching and returns meaningful Spot Alignment Positions (SAP) for a given set of gels. In the algorithm, the data are represented by a graph and SAP by specific subgraphs. The results are returned under various forms (clickable synthetic gel, text file, etc.). We have applied Sili2DGel to study the variability of the urinary proteome from 20 healthy subjects.</p> <p>Conclusion</p> <p>Sili2DGel performs noiseless automatic spot alignment for variability studies (as well as classical differential expression studies) of biological samples. It is very useful for typical clinical proteomic studies with large number of experiments.</p

Emerging RNA editing biomarkers will foster drug development

International audienc

Essais d’aptitude par comparaison inter-analystes pour l’évaluation des performances de l’indicateur Macrophytes en milieu lagunaire poly-euhalin

The spatial and temporal variability of macrophyte sampling in polyhaline lagoons (with an annual average salinity of >18 PSU) in the context of the EU's Water Framework Directive is well estimated. However, there is a need to better define the variability of in-situ observations (evaluating coverage) between and among team members. This Inter-Laboratory Comparison (ILC) is based on in situ observations and was conducted with service providers with whom we usually perform our diagnostics, while implementing the specific DCE macrophyte protocol for poly-euhaline lagoons.La variabilité spatiale et temporelle des prélèvements de macrophytes réalisés sur les lagunes poly-euhalines (salinité moyenne annuelle >18 PSU) dans le cadre de la DCE est bien estimée. En revanche, la variabilité, entre agent d'une même équipe et inter-équipe, liée aux observations réalisées in situ (évaluation du recouvrement) reste à préciser. Cette Comparaison Inter Laboratoire (CIL) s’appuie sur des observations in situ et a été réalisée avec les prestataires avec qui nous réalisons habituellement nos diagnostics en mettant en oeuvre le protocole DCE macrophyte spécifique aux lagunes poly-euhaline

Opening the Black Box of Decision Support Tools in Marine Spatial Planning: Shedding Light into Reserve Site Selection Algorithms for a Balanced Empowerment of Stakeholders

Marine spatial planning (MSP) is positioning itself as a rational decision-making process regulating uses of marine spaces and resources in order to reduce tensions between exploitation and conservation as well as between ocean stakeholders. As global political agendas identified marine protected areas as a key answer to biodiversity erosion, systematic reserve site selection became a critical component of MSP. Establishing an ocean zoning involves the analysis of large quantities of heterogeneous, multi-sources and spatially explicit data. This often leads to problems too complex to be solved by human intuition only, thus calling for optimisation tools to support the decisions. In that context, our work aims at informing practitioners about stakes, possibilities and limitations of MSP approach through reserve site selection tools. We first clarify the reserve site selection framework, especially the underlying mathematics - the problem formulation and the solving method. Then, we highlight potential pitfalls due to input data feeding the reserve-based planning approach. Finally, and more practically, we show to what extent parameters used in reserve selection tools shape the reserve outcome. These elements are explored and illustrated on a real case study, namely the Fernando de Noronha archipelago in the Brazilian tropical Atlantic. This work provides a brief overview of informational challenges brought by decision support tools in marine spatial planning negotiations

High Speed Atomic Force Microscope

International audienceAtomic Force Microscope (AFM) is now a common tool for material analysis in the academic and industrial areas because it enables non-destructive high-resolution images of nanometric objects. However, a main drawback is the slow scan rate that hinders many potential applications. Recently, breakthroughs have been achieved in AFM sensors based on MEMS technology, allowing to extend AFM operation in terms of measurement bandwidth and data acquisition. The present work focusses on developing an electronic controller for AFM featuring the wide bandwidth and the fast data processing rate required to enable the exploitation of the full potential of MEMS AFM sensors