Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity

It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS‐induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras‐induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation‐induced inactivation. Along those lines, Prdx1 tumour suppression of Ras‐ or ErbB‐2‐induced transformation was mediated mainly via PTEN.     

Should doctors be more proactive as advocates for victims of violence?

Currently the management of adult victims of violence by general practitioners and accident and emergency departments is reactive, concerned almost exclusively with the management of physical injuries. Professor Jonathan Shepherd outlines some ideas for a more proactive approach on the part of doctors to improve the protection and support of vulnerable people; to deal with psychological sequelae; to take the responsibility of making an official complaint to the police away from seriously injured people, who are unable to give or withhold consent to disclosure; and to prevent assailants inflicting further injuries. We asked a sociologist, a psychiatrist, a moral philosopher, and a police surgeon for their comments.     

Low apparent affinity for low-density lipoprotein of receptors expressed by human macrophages maintained with whole serum

Normal human monocyte-derived macrophages maintained in medium containing whole serum exhibited saturable degradation of low-density lipoprotein (LDL) that was mediated by LDL receptors. This degradation required a higher concentration of LDL to achieve one-half saturation than that in cells preincubated with lipoprotein-deficient serum (LPDS). Studies of short-term uptake and of heparin-releasable binding of LDL showed that binding to the surface receptors was the limiting factor for degradation under both conditions and that the LDL receptors expressed by cells in whole serum had a significantly lower affinity for LDL than those in cells pre-incubated in LPDS. LDL receptors in monocyte-macrophages could mediate the uptake and degradation of complexes between apolipoprotein E (apoE) and phospholipid. The receptors in cells pre-incubated in LPDS bound the complexes and LDL with apparently the same affinity and in approximately the same molar ratio. Receptors in cells maintained with whole serum did not have a lower affinity for the complexes than cells pre-incubated in LPDS, although the molar ratio of maximum degradation of LDL to that of complexes was greater.     

Co-culture with Synechococcus facilitates growth of Prochlorococcus under ocean acidification conditions

Anthropogenic CO₂ emissions are projected to lower the pH of the ocean 0.3 units by 2100. Previous studies suggested that Prochlorococcus and Synechococcus, the numerically dominant phytoplankton in the oceans, have different responses to elevated CO₂ that may result in a dramatic shift in their relative abundances in future oceans. Here we showed that the exponential growth rates of these two genera respond to future CO₂ conditions in a manner similar to other cyanobacteria, but Prochlorococcus strains had significantly lower realized growth rates under elevated CO₂ regimes due to poor survival after exposure to fresh culture media. Despite this, a Synechococcus strain was unable to outcompete a Prochlorococcus strain in co-culture at elevated CO₂. Under these conditions, Prochlorococcus' poor response to elevated CO₂ disappeared, and Prochlorococcus' relative fitness showed negative frequency dependence, with both competitors having significant fitness advantages when initially rare. These experiments suggested that the two strains should be able to coexist indefinitely in co-culture despite sharing nearly identical nutritional requirements. We speculate that negative frequency dependence exists due to reductive Black Queen evolution that has resulted in a passively mutualistic relationship analogous to that connecting Prochlorococcus with the ‘helper’ heterotrophic microbes in its environment.