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Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington’s disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, we engineer the ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins to peroxisomes, to remove mHttex1 aggregates. Using yeast toxicity-based screening with a random mutant library, we identify two yeast PEX19 variants and engineer equivalent mutations into human PEX19 ( hs PEX19). These variants effectively delay mHttex1 aggregation in vitro and in cellular HD models. The mutated hydrophobic residue in the α4 helix of hs PEX19 variants binds to the N17 domain of mHttex1, thereby inhibiting the initial aggregation process. Overexpression of the hs PEX19-FV variant rescues HD-associated phenotypes in primary striatal neurons and in Drosophila . Overall, our data reveal that engineering ATP-independent membrane protein chaperones is a promising therapeutic approach for rational targeting of mHttex1 aggregation in HD. Toxic protein aggregation is a hallmark of various neurodegenerative diseases. Here, authors show that ATP-independent membrane protein chaperones can serve as a simple design platform for targeting proteotoxic aggregates linked to Huntington’s disease.

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

Background Ambient air pollution can contribute to the development and exacerbation of COPD. However, the influence of air pollution on objective COPD phenotypes, especially from imaging, is not well studied. We investigated the influence of long-term exposure to air pollution on lung function and quantitative imaging measurements in a Korean cohort of participants with and without COPD diagnosis. Methods Study participants ( N  = 457 including 296 COPD cases) were obtained from the COPD in Dusty Areas (CODA) cohort. Annual average concentrations of particulate matter less than or equal to 10 μm in diameter (PM 10 ) and nitrogen dioxide (NO 2 ) were estimated at the participants’ residential addresses using a spatial air pollution prediction model. All the participants underwent volumetric computerized tomography (CT) and spirometry measurements and completed survey questionnaires. We examined the associations of PM 10 and NO 2 with FVC, FEV 1 , emphysema index, and wall area percent, using linear regression models adjusting for age, gender, education, smoking, height, weight, and COPD medication. Results The age of study participants averaged 71.7 years. An interquartile range difference in annual PM 10 exposure of 4.4 μg/m 3 was associated with 0.13 L lower FVC (95% confidence interval (CI), − 0.22- -0.05, p  = 0.003). Emphysema index (mean = 6.36) was higher by 1.13 (95% CI, 0.25–2.02, p  = 0.012) and wall area percent (mean = 68.8) was higher by 1.04 (95% CI, 0.27–1.80, p  = 0.008). Associations with imaging phenotypes  were not observed with NO 2 . Conclusions Long-term exposure to PM 10 correlated with both lung function and COPD-relevant imaging phenotypes in a Korean cohort.

Ambient air pollution can contribute to the development and exacerbation of COPD. However, the influence of air pollution on objective COPD phenotypes, especially from imaging, is not well studied. We investigated the influence of long-term exposure to air pollution on lung function and quantitative imaging measurements in a Korean cohort of participants with and without COPD diagnosis. Study participants (N = 457 including 296 COPD cases) were obtained from the COPD in Dusty Areas (CODA) cohort. Annual average concentrations of particulate matter less than or equal to 10 μm in diameter (PM ) and nitrogen dioxide (NO ) were estimated at the participants' residential addresses using a spatial air pollution prediction model. All the participants underwent volumetric computerized tomography (CT) and spirometry measurements and completed survey questionnaires. We examined the associations of PM and NO with FVC, FEV , emphysema index, and wall area percent, using linear regression models adjusting for age, gender, education, smoking, height, weight, and COPD medication. The age of study participants averaged 71.7 years. An interquartile range difference in annual PM exposure of 4.4 μg/m was associated with 0.13 L lower FVC (95% confidence interval (CI), - 0.22- -0.05, p = 0.003). Emphysema index (mean = 6.36) was higher by 1.13 (95% CI, 0.25-2.02, p = 0.012) and wall area percent (mean = 68.8) was higher by 1.04 (95% CI, 0.27-1.80, p = 0.008). Associations with imaging phenotypes  were not observed with NO . Long-term exposure to PM correlated with both lung function and COPD-relevant imaging phenotypes in a Korean cohort.

The Korea Rare Isotope Accelerator, currently referred to as KoRIA, is briefly presented. The KoRIA facility is aimed to enable cutting-edge sciences in a wide range of fields. It consists of a 70 kW isotope separator on-line (ISOL) facility driven by a 70 MeV, 1 mA proton cyclotron and a 400 kW in-flight fragmentation (IFF) facility. The ISOL facility uses a superconducting (SC) linac for post-acceleration of rare isotopes up to about 18 MeV/u, while the SC linac of IFF facility is capable of accelerating uranium beams up to 200 MeV/u, 8 pμA and proton beams up to 600 MeV, 660 μA. Overall features of the KoRIA facility are presented with a focus on the accelerator design.

We present that a statistical method known as the Complexity-Entropy analysis is useful to characterize a state of plasma turbulence and flux in the resonant magnetic perturbation (RMP) edge localized mode (ELM) control experiment. The RMP ELM suppression phase with the stochastic pedestal top temperature fluctuation can be distinguished from the natural ELM free phase with the chaotic fluctuation. It is discussed that the stochastic temperature fluctuation localized near the pedestal top can be originated from the narrow layer of the field penetration near the pedestal top. The forced magnetic island can emit the resonant drift wave of comparable sizes (relatively low-k) in the RMP ELM suppression phase, and it can results in the generation of stochastic higher wavenumber fluctuations coupled to tangled fields around the island. The analysis of the ion saturation current measurement around the main outer striking point on the divertor shows that it also becomes more stochastic as the stronger plasma response to the RMP field is expected.