Induced uniaxial magnetic anisotropy field in very thin NiFe and CoZrNb films

科研費報告書収録論文(課題番号:11305027・基盤研究(A)(2)・H11～H12/研究代表者:中村, 慶久/柔軟なスピンクラスター配列からなる超高密度磁気記録メディアの研究

Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans

The small ciliary G protein Arl13b is required for cilium biogenesis and sonic hedgehog signaling and is mutated in patients with Joubert syndrome (JS). In this study, using Caenorhabditis elegans and mammalian cell culture systems, we investigated the poorly understood ciliary and molecular basis of Arl13b function. First, we show that Arl13b/ARL-13 localization is frequently restricted to a proximal ciliary compartment, where it associates with ciliary membranes via palmitoylation modification motifs. Next, we find that loss-of-function C. elegans arl-13 mutants possess defects in cilium morphology and ultrastructure, as well as defects in ciliary protein localization and transport; ciliary transmembrane proteins abnormally accumulate, PKD-2 ciliary abundance is elevated, and anterograde intraflagellar transport (IFT) is destabilized. Finally, we show that arl-13 interacts genetically with other ciliogenic and ciliary transport-associated genes in maintaining cilium structure/morphology and anterograde IFT stability. Together, these data implicate a role for JS-associated Arl13b at ciliary membranes, where it regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

Model construction of medical endoscope service evaluation system-based on the analysis of Delphi method

Background: Medical endoscope is widely used in clinical practice for the purpose of diagnosis and treatment, occupying around 5% of the medical device market. Evaluating the true service level of medical endoscope is essential and necessary to improve overall performance of medical diagnosis and treatment, and to maintain competitiveness of endoscope manufacturers, however, such a tool is not available in the market. This study develops an Evaluation Index System (EIS) to assess service level of medical endoscope, and to provide suggestions for improving the service level through the Delphi method. Methods: Firstly, the possible factors influencing the service level were identified from literature review. In parallel, the Delphi expert method questionnaire was designed and 25 experts were invited to conduct three rounds of questionnaire, to evaluate and rate the possible factors. Finally, we determined the weights associated with the factors, using the analytic hierarchy process (AHP) and percentage method, and developed the service level EIS. Results: The EIS consists of 3 first-level indicators, 24 s-level indicators and 68 third-level indicators. According to the weights computed using AHP, first-level indicators are ranked as post-sale (0.62), in-sale (0.25) and pre-sale (0.13). Through case verification, the medical endoscope brand Olympus had a total score of 4.17, Shanghai Aohua had a total score of 3.71, and Shanghai Chengyun had a total score of 3.28, which matches its market popularity and ranking in terms of market share. The results obtained from the EIS are consistent with the reality. Conclusions: The EIS established in this study is comprehensive, reliable and reasonable with strong practicality. The EIS can act as a tool for the endoscope users to evaluate potential products and make informed choices. It also provides a measurable basis for endoscope manufacturers and service providers to improve service quality

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer

BACKGROUND: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker. METHODS: The 5-aza-2'-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. RESULTS: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P=0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P=0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P=0.561. CONCLUSIONS: These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker

A Framework for Exploring Functional Variability in Olfactory Receptor Genes

BACKGROUND: Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested. METHODOLOGY: Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region. CONCLUSIONS: Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability