S100A10, a novel biomarker in pancreatic ductal adenocarcinoma.

Pancreatic cancer is arguably the deadliest cancer type. The efficacy of current therapies is often hindered by the inability to predict patient outcome. As such, the development of tools for early detection and risk prediction is key for improving outcome and quality of life. Here, we introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. We demonstrated that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to normal ducts and nonductal stroma. S100A10 mRNA and methylation status were predictive of overall survival and recurrence-free survival across multiple patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness, and in vivo growth of pancreatic cancer cell lines. These findings delineate the clinical and functional contribution of S100A10 as a biomarker in pancreatic cancer.

Small Ne of the Isolated and Unmanaged Horse Population on Sable Island.

For small, isolated populations 2 common conservation concerns relate to genetic threats: inbreeding and negative consequences associated with loss of genetic diversity due to drift. Mitigating these threats often involves conservation actions that can be controversial, such as translocations or captive breeding programs. Although such actions have been successful in some situations, in others they have had undesirable outcomes. Here, we estimated the effective population size (N e ) of the Sable Island horses to assess the risk to this population of these genetic threats. We found surprising consistency of N e estimates across the 5 different methods used, with a mean of 48 effective individuals. This estimate falls below the 50 criterion of the "50/500 rule," below which inbreeding depression is a concern for population viability. However, simulations and knowledge of population history indicate that this population is still in its early stages of approaching equilibrium between mutation, drift, and genetic diversity; and no negative consequences have been identified that could be associated with inbreeding depression. Therefore, we do not recommend taking management action (such as translocations) at this stage. Rather, we propose continued monitoring of genetic diversity and fitness over time so that trends and any substantial changes can be detected. This represents one of the few unmanaged horse populations in the world, and therefore these data will not only alert us to serious concerns regarding their conservation status, but will also provide a wealth of information about how natural processes drive patterns of reproduction, mortality, and population growth over time.