Observation of a maternal transmission of scrapie in sheep

A pregnant ewe with suspected scrapie was referred to the Regional Veterinary Laboratory in Limoges on 11 January 2002, in compliance with the French scrapie eradication program. Western Blot confirmed the diagnosis of scrapie. Ten days later, the ewe gave birth. As we had to help the ewe, we were able to isolate the ewe lamb before she had any contact with her mother, and especially no colostrum. The ewe lamb was fed with milk replacers and isolated to prevent all possibility of horizontal transmission of scrapie. In August 2002, the first symptoms of scrapie appeared in the ewe lamb. Euthanasia was decided on 18 December 2002, as the animal was no longer able to stand. Western Blot and immunohistochemistry tests confirmed natural scrapie in the ewe lamb. PrP genotyping of this lamb was ARQ/VRQ. This first confirmed case of maternal transmission of scrapie in sheep is associated with a particularly short incubation time (6 months) in natural conditions.Dans le cadre du programme d'éradication de la tremblante en France, nous avons reçu une brebis gestante suspecte de tremblante le 11 janvier 2002, au laboratoire vétérinaire départemental de Limoges (confirmée ultérieurement par un Western Blot). Dix jours plus tard, la brebis agnela avec difficulté et nous avons dû intervenir pour l'aider. Cette assistance à l'agnelage nous permit d'isoler immédiatement le nouveau-né, en évitant tout contact ultérieur avec sa mère, en particulier sans la possibilité d'absorber le colostrum. L'agnelle fut placée dans un endroit isolé sans qu'il n'y ait de possibilité de transmission horizontale de la tremblante et fut nourrie avec des lactoremplaceurs. En août 2002, les premiers symptômes de la tremblante sont apparus chez l'agnelle née de cette brebis. Du fait d'une évolution vers le décubitus, l'euthanasie de l'agnelle fut décidée le 18 décembre 2002. La confirmation d'une tremblante naturelle chez l'agnelle a été obtenue par le Western-Blot et les examens immunohistochimiques. Le génotype de l'agnelle était ARQ/VRQ. Cette première confirmation d'une transmission maternelle de la tremblante chez le mouton s'accompagne aussi d'un temps d'incubation particulièrement court (6 mois) dans les conditions naturelles

Misty Mountain clustering: application to fast unsupervised flow cytometry gating

<p>Abstract</p> <p>Background</p> <p>There are many important clustering questions in computational biology for which no satisfactory method exists. Automated clustering algorithms, when applied to large, multidimensional datasets, such as flow cytometry data, prove unsatisfactory in terms of speed, problems with local minima or cluster shape bias. Model-based approaches are restricted by the assumptions of the fitting functions. Furthermore, model based clustering requires serial clustering for all cluster numbers within a user defined interval. The final cluster number is then selected by various criteria. These supervised serial clustering methods are time consuming and frequently different criteria result in different optimal cluster numbers. Various unsupervised heuristic approaches that have been developed such as affinity propagation are too expensive to be applied to datasets on the order of 10⁶points that are often generated by high throughput experiments.</p> <p>Results</p> <p>To circumvent these limitations, we developed a new, unsupervised density contour clustering algorithm, called Misty Mountain, that is based on percolation theory and that efficiently analyzes large data sets. The approach can be envisioned as a progressive top-down removal of clouds covering a data histogram relief map to identify clusters by the appearance of statistically distinct peaks and ridges. This is a parallel clustering method that finds every cluster after analyzing only once the cross sections of the histogram. The overall run time for the composite steps of the algorithm increases linearly by the number of data points. The clustering of 10⁶data points in 2D data space takes place within about 15 seconds on a standard laptop PC. Comparison of the performance of this algorithm with other state of the art automated flow cytometry gating methods indicate that Misty Mountain provides substantial improvements in both run time and in the accuracy of cluster assignment.</p> <p>Conclusions</p> <p>Misty Mountain is fast, unbiased for cluster shape, identifies stable clusters and is robust to noise. It provides a useful, general solution for multidimensional clustering problems. We demonstrate its suitability for automated gating of flow cytometry data.</p