Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington’s Disease PSC-Derived Striatal Neurons

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene (HTT). Disease progression is characterized by the loss of vulnerable neuronal populations within the striatum. A consistent phenotype across HD models is disruption of nucleocytoplasmic transport and nuclear pore complex (NPC) function. Here we demonstrate that high content imaging is a suitable method for detecting mislocalization of lamin-B1, RAN and RANGAP1 in striatal neuronal cultures thus allowing a robust, unbiased, highly powered approach to assay nuclear pore deficits. Furthermore, nuclear pore deficits extended to the selectively vulnerable DARPP32 + subpopulation neurons, but not to astrocytes. Striatal neuron cultures are further affected by changes in gene and protein expression of RAN, RANGAP1 and lamin-B1. Lowering total HTT using HTT-targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein

T4肺癌に対する一時バイパス法による大動脈合併切除術

金沢大学医薬保健研究域医学系Radical operation for T4 lung cancer is technically difficult. We report here 3 cases of T4N0M0 lung cancer involving aorta or left subclavian artery which was successfully operated on. We could carry out combined aortic resection more safely and speedy under the assistant devices, such as Anthrontube and Biomedicus Centrifugal Pump. Even T4 lung cancer having aortic invasion with N0 disease can be operated on and be expected long-term survival using these assistant devices.1

播磨灘および大阪湾のイガイ中のノニルフェノール

Nonylphenol (NP) having an endocrine disrupter effect is used in the form of a poly(oxy ethylene)nonylphenyl ether (NPnEO) as a non-ion surfactant, ethoxy straight chain is decomposed by the microbial degradation in environment, then NPnEO is converted to NP through the action. Consequently it is concerned about the effect of NP on wildlife. Blue Mussel has the tolerance, which is strong in pollution. In this study, seawater and Blue Mussel were collected in Harimanada and Osaka Bay enclosed coastal seas. We investigated the distribution and seasonal movement of NP concentration. The result of the study showed that the concentrations of NP in seawater were gradually increasing from August. Moreover, the concentrations in Blue Mussel were the highest in almost all points in August. These results indicate that the water environment where Blue Mussel lives influenced them. The water temperature of 25℃ demonstrated most efficient filtration capability in August and dissolved oxygen (DO) concentration was low in August and September, so the Blue Mussel took in sea water so much. NP concentration in Blue Mussel was varied in the short term. This was suggested that Blue Mussel could become the important indicator of NP concentration in seawater