Roles of Metacognitive Suggestions in Hypothesis Revision

We investigated whether metacognitive suggestions alone can function as a means of encouraging recipients’ reflec-tion and facilitate hypothesis revision. We also examined whether it is necessary to ground the suggestions on the recipients’thinking processes for the facilitative effects. 108 participants were assigned to one of the four conditions: metacognitivesuggestion collaboration with/without grounding support; free collaboration; and sole. They were asked to engage in a rulediscovery task. The task was designed so that hypothesis revision was necessary for the participants to find the correct rule.The results showed that performance both in the free collaboration and in the metacognitive suggestion collaboration withgrounding support conditions was higher than that in the solo condition. We concluded that metacognitive suggestions alonecan facilitate hypothesis revision as well as free collaboration and that grounding support is necessary for the facilitative effectto be obtained

Zinc transport via ZNT5-6 and ZNT7 is critical for cell surface glycosylphosphatidylinositol-anchored protein expression

Glycosylphosphatidylinositol (GPI)-anchored proteins play crucial roles in various enzyme activities, cell signaling and adhesion, and immune responses. While the molecular mechanism underlying GPI-anchored protein biosynthesis has been well studied, the role of zinc transport in this process has not yet been elucidated. Zn transporter (ZNT) proteins mobilize cytosolic zinc to the extracellular space and to intracellular compartments. Here, we report that the early secretory pathway ZNTs [ZNT5-ZNT6 heterodimers (ZNT5-6) and ZNT7-ZNT7 homodimers (ZNT7)], which supply zinc to the lumen of the early secretory pathway compartments are essential for GPI-anchored protein expression on the cell surface. We show, using overexpression and gene disruption/re-expression strategies in cultured human cells, that loss of ZNT5-6 and ZNT7 zinc transport functions results in significant reduction in GPI-anchored protein levels similar to that in mutant cells lacking phosphatidylinositol glycan anchor biosynthesis (PIG) genes. Furthermore, medaka fish with disrupted Znt5 and Znt7 genes show touch-insensitive phenotypes similar to zebrafish Pig mutants. These findings provide a previously unappreciated insight into the regulation of GPI-anchored protein expression and protein quality control in the early secretory pathway

Effect of Ethylene Diurea on Oxygen-induced Ischemic Retinopathy in the Neonatal Rat

This study investigated the effect of N-[2- (2-oxo-1-imidazolidinyl) ethyl]-N-phenylurea (ethylene diurea, EDU) on oxygen-induced ischemic retinopathy (OIR) in a neonatal rat model. OIR was induced by maintaining daily cycles of 80% oxygen (20.5h), ambient air (0.5h), and a progressive return to 80% oxygen (3h) for 12 days (postnatal day: P12). The rats were treated intraperitoneally with EDU (30mg/kg body weight) or distilled water (DW) from P6 to P17. At P18, the percentage of avascular areas in the total retinal area (%AVA) was measured, and retinal neovascularization (NV) was scored in ADPase-stained retinas. Retinal superoxide dismutase (SOD) activity in the retina was also determined by a chemiluminescence method. The mean %AVA in the EDU-treated group (9.3 ± 1.7%, n = 16) was lower than in the DW group (18.2 ± 4.7%, n = 17). EDU did not significantly affect NV, but significantly increased SOD activity (1.36 ± 0.13 units/mg protein, n = 4) compared to DW treatment (1.04 ± 0.01 units/mg protein, n = 4, P = 0.032) at P18. These results suggest that EDU treatment decreased the %AVA, accompanied by an increase in normal retinal vascular growth and/or a decrease in vessel proliferation. The increased SOD activity observed in the present study is likely to involve the EDU-mediated effects

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44(High) cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44(High) cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway

高齢者のライフコースおよび幸福感に関する研究の動向

社会学領域において,人生の振り返りに関するライフコース研究や,生きがいや幸福感について主観的幸福感という尺度を用いて調査を行う研究が,1980年前後より発展してきている。本稿では,ライフコース,主観的幸福感の研究における知見の看護学領域,特に高齢者理解,高齢者ケアへの実践的応用を目的として,それらの研究の動向を概観した

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

成人看護学慢性期実習における透析センター見学実習の意義

平成9年度カリキュラム改正において,実質的に慢性期実習の期間が短縮される中で,慢性期実習に位置づけられている透析センター見学実習を継続するかどうか,見直しの時期である。そこで,学生の透析センター見学実習終了後の記録の中から,実習目標に沿った内容を抽出し,その内容の目標達成度と学習内容から透析センター見学実習の学習効果を考察し,見学実習の意義と問題点を明確にした。その結果,透析センター見学実習の意義として,(1)患者個々の生活の多様性を理解し,成人看護学実習のねらいである『対象理解』を充たしている。(2)透析治療を一生涯受けて生活する人間を理解しようとする学生の意識は,慢性期にある患者の看護を学ぶことにつながる。(3)退院後の継続看護を医療・保健・福祉の面から直接学べる実習であることがわかった。また,今後の課題として,学習の機会を有効に活用するため実習前のオリエンテーション,実習後の学内カンファレンスにおいて,学生への動機づけや振り返り等を行い,記録用紙の工夫も行うことが必要であることなども示唆された

A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins

A major challenge of the post-genomic era is the functional characterization of anonymous open reading frames (ORFs) identified by the Human Genome Project. In this context, there is a strong requirement for the development of technologies that enhance our ability to analyze gene functions at the level of the whole organism. Here, we describe a rapid and efficient procedure to generate transgenic chimaeric mice that continuously secrete a foreign protein into the systemic circulation. The transgene units were inserted into the genomic site adjacent to the endogenous immunoglobulin (Ig) κ locus by homologous recombination, using a modified mouse embryonic stem (ES) cell line that exhibits a high frequency of homologous recombination at the Igκ region. The resultant ES clones were injected into embryos derived from a B-cell-deficient host strain, thus producing chimaerism-independent, B-cell-specific transgene expression. This feature of the system eliminates the time-consuming breeding typically implemented in standard transgenic strategies and allows for evaluating the effect of ectopic transgene expression directly in the resulting chimaeric mice. To demonstrate the utility of this system we showed high-level protein expression in the sera and severe phenotypes in human EPO (hEPO) and murine thrombopoietin (mTPO) transgenic chimaeras