No abstract

Canines are able to differentiate between serum samples taken from cancer patients and samples taken from normal controls. This study further supports the use of dogs as biomedical research tools for detection of cancer biomarkers. In particular, this study was designed to determine the accuracy of canines' ability to detect, by scent alone, lung cancer biomarkers in blood serum. Operant conditioning was used in the form of clicker training to train four beagles to distinguish, by scent alone, blood serum from malignant lung cancer patients when presented along with healthy controls in a double‐blind format. Non‐small cell lung cancer and healthy control blood serum samples were presented to 2‐year‐old beagles. Three dogs were able to correctly identify the cancer samples with a sensitivity of 96.7%, specificity of 97.5%, positive predictive value (PPV) of 90.6% and negative predictive value (NPV) of 99.2%. One of the dogs, Snuggles, was unmotivated to perform during training and tested with 80% specificity and 60% sensitivity. This study paves the way for a larger scale research project designed to explore the use of canine scent detection as a tool for detecting cancer biomarkers, ultimately leading to their identification. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

In eukaryotes, the 26S proteasome degrades ubiquitinylated proteins in an ATP-dependent manner. Archaea mediate a form of post-translational modification of proteins termed sampylation that resembles ubiquitinylation. Sampylation was identified in Haloferax volcanii, a moderate halophilic archaeon that synthesizes homologs of 26S proteasome subunits including 20S core particles and regulatory particle triple-A ATPases (Rpt)-like proteasome-associated nucleotidases (PAN-A/1 and PAN-B/1). To determine whether sampylated proteins associate with the Rpt subunit homologs, PAN-A/1 was purified to homogeneity from Hfx. volcanii and analyzed for its subunit stoichiometry, nucleotide hydrolyzing activity and binding to sampylated protein targets. PAN-A/1 was found associated as a dodecamer (630-kDa) with a configuration in TEM suggesting a complex of two stacked hexameric rings. PAN-A/1 had high affinity for ATP (Km of ∼0.44 mM) and hydrolyzed this nucleotide with a specific activity of 0.33 ± 0.1 μmol Pi/h per mg protein and maximum at 42°C. PAN-A1 was stabilized by 2M salt with a decrease in activity at lower concentrations of salt that correlated with dissociation of the dodecamer into trimers to monomers. Binding of PAN-A/1 to a sampylated protein was demonstrated by modification of a far Western blotting technique (derived from the standard Western blot method to detect protein-protein interaction in vitro) for halophilic proteins. Overall, our results support a model in which sampylated proteins associate with the PAN-A/1 AAA+ ATPase in proteasome-mediated proteolysis and/or protein remodeling and provide a method for assay of halophilic protein-protein interactions.

Canines are able to differentiate between serum samples taken from cancer patients and samples taken from normal controls. This study further supports the use of dogs as biomedical research tools for detection of cancer biomarkers. In particular, this study was designed to determine the accuracy of canines' ability to detect, by scent alone, lung cancer biomarkers in blood serum.Operant conditioning was used in the form of clicker training to train four beagles to distinguish, by scent alone, blood serum from malignant lung cancer patients when presented along with healthy controls in a double‐blind format. Non‐small cell lung cancer and healthy control blood serum samples were presented to 2‐year‐old beagles.Three dogs were able to correctly identify the cancer samples with a sensitivity of 96.7%, specificity of 97.5%, positive predictive value (PPV) of 90.6% and negative predictive value (NPV) of 99.2%. One of the dogs, Snuggles, was unmotivated to perform during training and tested with 80% specificity and 60% sensitivity. This study paves the way for a larger scale research project designed to explore the use of canine scent detection as a tool for detecting cancer biomarkers, ultimately leading to their identification.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.