A multi-subunit autophagic capture complex facilitates degradation of ER stalled MHC-I in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) evades immune detection partly via autophagic capture and lysosomal degradation of major histocompatibility complex class I (MHC-I). Why MHC-I is susceptible to capture via autophagy remains unclear. By synchronizing exit of proteins from the endoplasmic reticulum (ER), we show that PDAC cells display prolonged retention of MHC-I in the ER and fail to efficiently route it to the plasma membrane.

No Socioeconomic Inequalities in Mortality among Catholic Monks: A Quasi-Experiment Providing Evidence for the Fundamental Cause Theory.

We propose a novel approach to test the fundamental cause theory (FCT) by analyzing the association between socioeconomic status (SES), as measured by the order titles "brothers" and "padres," and mortality in 2,421 German Catholic monks born between 1840 and 1959. This quasi-experiment allows us to study the effect of SES on mortality in a population with largely standardized living conditions. Mortality analyses based on Kaplan-Meier product limit estimation show that there were no statistically significant survival differences between the high and lower SES monks.

Metabolic modulation of melanoma enhances the therapeutic potential of immune checkpoint inhibitors.

Introduction: Lactate is a pivotal molecule with diverse functions in the metabolic reprogramming of cancer cells. Beyond its role in metabolism, lactate exerts a modulatory effect within the tumor microenvironment; it is utilized by stromal cells and has been implicated in the suppression of the immune response against the tumor.

Methods: Using assays (including flow cytometry, live-cell imaging and metabolic analyses), the impact of lactate dehydrogenase inhibitors (LDHIs) on melanoma cells were assessed.

[The gender paradox in health-impaired lifetime-end of a myth?].

Background: Women live longer than men, but they spend more life years with health-impairment. This article examines the extent to which this gender paradox can be explained by two factors: the "mortality effect," which results from the higher life expectancy of women, and "differential item functioning" (DIF), which refers to gender differences in reporting behavior.

Methods: Impaired life expectancy at age 50 is calculated for the health indicators general health, limitations, and chronic morbidity using the Sullivan method.

[Healthy life expectancy: a critical look at the benefits and potential of the demographic health indicator].

Demographic ageing yields many societal consequences that depend strongly on the health status of the population. Special indicators have been developed for tracking and assessing population health, which are referred to with the overarching term healthy life expectancy (HLE). The derivation of HLE is intuitive and easily comprehensible.