Histodenz Separation of Lysosomal Subpopulations for Analysis of Chaperone-mediated Autophagy.

Chaperone-mediated autophagy (CMA) is the most selective form of lysosomal proteolysis, in which proteins are individually selected for lysosomal degradation. CMA degradation targets bear a pentapeptide consensus motif that is recognized by the cytosolic chaperone HSPA8 (Hsc70), which participates in the trafficking of the target to the lysosomal surface. From there, it is translocated into the lysosomal lumen, independent of vesicle fusion, in a process dependent upon the lysosomal transmembrane protein LAMP2A.

Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice.

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs.

PTEN is both an activator and a substrate of chaperone-mediated autophagy.

PTEN is a crucial negative regulator of the INS/PI3K/AKT pathway and is one of the most commonly mutated tumor suppressors in cancer. Global overexpression (OE) of PTEN in mice shifts metabolism to favor oxidative phosphorylation over glycolysis, reduces fat mass, and extends the lifespan of both sexes. We demonstrate that PTEN regulates chaperone-mediated autophagy (CMA).

LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice.

Chaperone-mediated autophagy (CMA) selectively degrades proteins that are crucial for glycolysis, fatty acid metabolism, and the progression of several age-associated diseases. Several previous studies, each of which evaluated males of a single inbred mouse or rat strain, have reported that CMA declines with age in many tissues, attributed to an age-related loss of LAMP2A, the primary and indispensable component of the CMA translocation complex. This has led to a paradigm in the field of CMA research, stating that the age-associated decline in LAMP2A in turn decreases CMA, contributing to the pathogenesis of late-life disease.

A last resort? A scoping review of patient and healthcare worker attitudes toward strike action.

While strike action has been common since the industrial revolution, it often invokes a passionate and polarising response, from the strikers themselves, from employers, governments and the general public. Support or lack thereof from health workers and the general public is an important consideration in the justification of strike action. This systematic review sought to examine the impact of strike action on patient and clinician attitudes, specifically to explore (1) patient and health worker support for strike action and (2) the predictors for supporting strike action and the reasons given for engaging in strike action.

Trust and risk communication in high-risk organizations: a test of principles from social risk research.

This study explored the effects of open communication about occupational risks on workers' trust beliefs and trust intentions toward risk management, and the resilience of these beliefs and intentions to further risk information. An experimental survey of 393 student nurses showed the importance of open communication in the development of worker trust in risk management. Consistent with the trust asymmetry principle, we found that the increase in trust beliefs following open communication was weaker than the reduction in trust following a lack of communication.

Explicit and implicit trust within safety culture.

Safety culture is an important topic for managers in high-hazard industries because a deficient safety culture has been linked to organizational accidents. Many researchers have argued that trust plays a central role in models of safety culture but trust has rarely been measured in safety culture/climate studies. This article used explicit (direct) and implicit (indirect) measures to assess trust at a UK gas plant.