71 research outputs found
A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions
The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanismin the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events
Targeted Pten deletion plus p53-R270H mutation in mouse mammary epithelium induces aggressive claudin-low and basal-like breast cancer
Public service motivation and prosocial rule-breaking : an international vignettes study in Belgium, Germany, and the Netherlands
Public service motivation and prosocial rule-breaking: An international vignettes study in Belgium, Germany, and the Netherlands
We theorize that people with high Public Service Motivation (PSM) are especially prone to engage in prosocial rule-breaking (PSRB) behavior, which ultimately leads to discriminatory practices, particularly for clients associated with positive affect. We conduct an original vignette study in three countries (Belgium, Germany, and the Netherlands) with 928 observations in total. Our findings provide tentative behavioral evidence on a linear relationship between PSM and the likelihood of PSRB and a strong positive association with client likeability, which is an asymmetric relationship: Negative affect cues have a larger negative effect than positive affect cues have a positive effect on PSRB. Although our results vary across the three country studies regarding the effects of PSM, overall, the results imply that high-PSM individuals have a tendency to being more likely to engage in PSRB and that clients who are perceived as more favorable will receive a less strict application of bureaucratic rules compared to less favorable clients
Bribery and the role and social value orientation: A multi-site experimental study in Belgium, Germany, and the Netherlands
Bribery is a complex phenomenon rooted in both individual motives and the greater institutional context. Experimental research into causal mechanisms that drive bribing behavior is still scarce. To date, there is no empirical evidence on how the society-regarding motivational survey measure of Public Service Motivation (PSM) and the other-oriented motivational measure of Social Value Orientation (SVO) can help explain why some people are more susceptible to engage in the act of bribing than others. Based on a multi-site triple-replication, and a vignette-based research design, quasi-experimental evidence from Belgium, Germany, and the Netherlands shows that both measures interact and that-paradoxically-people with higher SVO are more likely to be willing to engage in bribery
- …