Chaperone-Mediated Protein Disaggregation Triggers Proteolytic Clearance of Intra-nuclear Protein Inclusions

The formation of insoluble inclusions in the cytosol and nucleus is associated with impaired protein homeostasis and is a hallmark of several neurodegenerative diseases. Due to the absence of the autophagic machinery, nuclear protein aggregates require a solubilization step preceding degradation by the 26S proteasome. Using yeast, we identify a nuclear protein quality control pathway required for the clearance of protein aggregates. The nuclear J-domain protein Apj1 supports protein disaggregation together with Hsp70 but independent of the canonical disaggregase Hsp104. Disaggregation mediated by Apj1/Hsp70 promotes turnover rather than refolding. A loss of Apj1 activity uncouples disaggregation from proteasomal turnover, resulting in accumulation of toxic soluble protein species. Endogenous substrates of the Apj1/Hsp70 pathway include both nuclear and cytoplasmic proteins, which aggregate inside the nucleus upon proteotoxic stress. These findings demonstrate the coordinated activity of the Apj1/Hsp70 disaggregation system with the 26S proteasome in facilitating the clearance of toxic inclusions inside the nucleus

Treating patients as persons : a capabilities approach to support delivery of person-centered care

Peer reviewedPublisher PD

Experimental Apparatus for Production, Cooling, and Storing Multiply Charged Ions for Charge-Transfer Measurements

A novel method is described that combines the production of ions by laser ablation with an ion‐trap technique for the measurement of thermal‐energy charge‐transfer rates of multiply charged ions and neutrals. The charge‐transfer rate is determined by measuring the rate of loss of stored ions from the trap. Verification of the calibration of the apparatus is demonstrated through investigation of charge transfer of N2 and N2+, which has been studied by another group. We also have made the first measurement on the thermal‐energy charge‐transfer coefficient of Ar and W2+. The rate coefficient is 0.99(0.22)×10−11 cm3 s−1

Reproductive rights approach to reproductive health in developing countries

Research on reproductive health in developing countries focuses mostly on the role of economic development on various components of reproductive health. Cross-sectional and empirical research studies in particular on the effects of non-economic factors such as reproductive rights remain few and far between.This study investigates the influence of two components of an empowerment strategy, gender equality, and reproductive rights on women's reproductive health in developing countries. The empowerment strategy for improving reproductive health is theoretically situated on a number of background factors such as economic and social development.Cross-national socioeconomic and demographic data from a number of international organizations on 142 developing countries are used to test a model of reproductive rights and reproductive health.The findings suggest that both economic and democratic development have significant positive effects on levels of gender equality. The level of social development plays a prominent role in promoting reproductive rights. It is found that reproductive rights channel the influences of social structural factors and gender equality on reproductive health