Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects.

RAS mutations prevalent in high-risk leukemia have been linked to relapse and chemotherapy resistance. Efforts to directly target RAS proteins have been largely unsuccessful. However, since RAS-mediated transformation is dependent on signaling through the RAS-related C3 botulinum toxin substrate (RAC) small GTPase, we hypothesized that targeting RAC may be an effective therapeutic approach in RAS mutated tumors.

Interobserver Reliability of the Animal Welfare Indicators Welfare Assessment Protocol for Horses.

Objective tools for the assessment of animal welfare are needed. The present study analyzed the interobserver reliability of the Animal Welfare Indicators (AWIN) welfare assessment protocol for horses to further enhance knowledge concerning reliability. Therefore, two trained observers conducted 18 assessments on farm at the same time and on the same animals.

An Indication of Reliability of the Two-Level Approach of the AWIN Welfare Assessment Protocol for Horses.

To enhance feasibility, the Animal Welfare Indicators (AWIN) assessment protocol for horses consists of two levels: the first is a visual inspection of a sample of horses performed from a distance, the second a close-up inspection of all horses. The aim was to analyse whether information would be lost if only the first level were performed. In this study, 112 first and 112 second level assessments carried out on a subsequent day by one observer were compared by calculating the Spearman's Rank Correlation Coefficient (RS), Intraclass Correlation Coefficients (ICC), Smallest Detectable Changes (SDC) and Limits of Agreements (LoA).

Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness.

Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion.

Allelic heterogeneity of Crooked Tail Syndrome: result of balancing selection?

We report the identification of a second loss-of-function mutation (c.1906T>C) in the bovine MRC2 gene causing the Crooked Tail Syndrome in Belgian Blue Cattle. We demonstrate that the ensuing substitution of the highly conserved Cysteine 636 with Arginine causes illegitimate receptor oligomerization, which is predicted to impair function of the MRC2 encoded protein, Endo180.