Mutational analysis of the tyrosine phosphatome in colorectal cancers

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.     

Observation learning in cats

In two experiments cats acquired a stimulus-controlled approach or avoidance response by observational or conventional shaping procedures. Observer cats acquired the avoidance response (hurdle jumping in response to a buzzer stimulus) significantly faster and made fewer errors than cats that were conventionally trained. Observer cats acquired the approach response (lever pressing for food in response to a light stimulus) with significantly fewer errors than cats that were conventionally trained. In some cases, observer cats committed one or no errors while reaching criterion.     

Bias in Peer Review of Organic Farming Grant Applications

Peer reviews of 84 organic farming grant applications from Sweden were analyzed to determine whether the reviewers’ affiliation to one of two types of agriculture (i.e., organic and conventional) influenced their reviews. Fifteen reviewers were divided into three groups: (1) scientists with experience in organic farming research; (2) scientists with no experience in organic farming research; and (3) users of organic farming research. The two groups of scientists assessed the societal relevance and scientific quality of the grant applications based on three criteria (i.e., presentation, methodology, qualifications), whereas the user group only assessed societal relevance. The analysis showed that the two groups of scientists provided very different reviews. Scientist reviewers with experience in organic farming research agreed more with the user group on research relevance than did scientist reviewers without such experience, and the assessment of relevance was closely correlated to the assessment of scientific quality within both scientific groups. As both scientific groups did not clearly distinguish between societal relevance and scientific quality, the idea of an objective science is challenged. The contextual values associated with the norms of good agriculture were not clearly distinguished from the constitutive values of science associated with the traditional norms of good science. This raises the question of whether organic and conventional grant applications should be mixed for review regardless of the reviewers.     

Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.