Chronic treatment with an erythropoietin receptor ligand prevents chronic kidney disease–induced enlargement of myocardial infarct size

慢性腎臓病による心筋梗塞の拡大には，心筋リンゴ酸アスパラギン酸シャトル抑制を介したAkt活性化障害が関与し，慢性的なエリスロポエチン受容体刺激はこれらの障害を修復して心筋梗塞の拡大を予防する

An In Vitro Model for Lewy Body-Like Hyaline Inclusion/Astrocytic Hyaline Inclusion: Induction by ER Stress with an ALS-Linked SOD1 Mutation

Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast-HI) containing mutant Cu/Zn superoxide dismutase 1 (SOD1) are morphological hallmarks of familial amyotrophic lateral sclerosis (FALS) associated with mutant SOD1. However, the mechanisms by which mutant SOD1 contributes to formation of LBHI/Ast-HI in FALS remain poorly defined. Here, we report induction of LBHI/Ast-HI-like hyaline inclusions (LHIs) in vitro by ER stress in neuroblastoma cells. These LHI closely resemble LBHI/Ast-HI in patients with SOD1-linked FALS. LHI and LBHI/Ast-HI share the following features: 1) eosinophilic staining with a pale core, 2) SOD1, ubiquitin and ER resident protein (KDEL) positivity and 3) the presence of approximately 15–25 nm granule-coated fibrils, which are morphological hallmark of mutant SOD1-linked FALS. Moreover, in spinal cord neurons of L84V SOD1 transgenic mice at presymptomatic stage, we observed aberrant aggregation of ER and numerous free ribosomes associated with abnormal inclusion-like structures, presumably early stage neuronal LBHI. We conclude that the LBHI/Ast-HI seen in human patients with mutant SOD1-linked FALS may arise from ER dysfunction

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS

Sources of Contamination in GaAs Crystal Growth

ABSTRACT Current evidence indicates that the purity of GaAs is now limited by contamination during crystal growth, rather than by the purity of the starting materials. A careful study has been carried out to identify sources of such contamination in the preparation of GaAs. Vacuum baking of gallium at 650~ for several hours in a quartz boat to remove oxides was found to increase the copper content, but not the silicon or other spectrographically detectable impurities. Back diffusion of impurities from a contaminated high vacuum pump was observed to affect properties of GaAs even when pressures of 10 -~ torr were maintained. Sealing under vacuum of large (20 ram) diameter quartz ampoules introduces significant quantities of silicon and copper onto the inner ampoule walls, which subsequently contaminate arsenic vapor when heated to above 1000~ During growth, it was found that there is no appreciable diffusion of atmospheric gases through quartz at 1200~ However, nearly 10 TM molecules of gas are released due to outgassing of the walls. The most serious contamination, especially with silicon, occurs from the reaction between t.he GaAs melt and the quartz boat, and the reaction increases rapidly with increasing melt temperature