オンガク エンソウ ニオケル ヒョウゲン ツイキュウ プロセス ニツイテ ノ ケンキュウ : エンソウカ エノ インタビュー エンソウ シミュレーション チョウサ カラ

This study involved an investigation of the process for pursuing expressions for playing a musical piece. Two musicians were interviewed about how they pursued expressions of a musical piece ; additionally, they simulated this process for the researcher. Accordingly, the findings of the study are revealed. Pursuing the expression for playing a musical piece occurs in two phases. In the first phase, musicians examine the outline of a musical piece and acquire bodily wisdom and insight for playing it. The goal of this phase is to play the piece fluently without notes, although the aim is not only to develop solutions to technical problems. In this phase, musicians comprehend the structure of the piece and develop tastes and fascinations for it by repeatedly playing the piece. These foundations prepare musicians for the next phase. In the second phase, musicians pursue satisfactory expressions of the piece using various sound images and technical skills. Leads for the pursuit are the results of analyzing the piece, taste preferences and fascinations associated with the piece, the message of the composer, performances of others(CDs)，reflections on their own recorded performances, and observations from repetitions of the music. These elements are intertwined in a complicated manner and synthesized in the minds of the musicians until they are finally satisfied with their expressions. It is not a logical process ; rather, it is based on musicians’ aesthetic senses or feelings. In addition, a satisfactory expression is not a fixed goal. It changes constantly. The process of pursuing an expression for playing a musical piece differs from the process employed in intellectual thinking based on knowledge of the written word. Musical expression reflects bodily wisdom, judgements based on aesthetic senses or feelings, complexity, synthesis, and variability. The findings of this investigation have led to two suggestions for music education in primary and secondary schools. First, the importance of bodily wisdom should be emphasized ; in other words, playing fluently without notes and having sound images and techniques for achieving them are important skills. It is true that acquiring bodily wisdom takes a long time, and music education in schools does not provide enough time for that. However, underrating the importance of such wisdom may make the pursuit of musical expression difficult, as it is the foundation for this pursuit. Second, the complexity, synthesis, and variability of the process of this pursuit should be acknowledged. The process of finding satisfactory expressions cannot be explained by a single causal relationship. Musicians’ satisfactory expressions come from the synthesis of their many experiences, sound images, senses, and feelings. An idea regarding an expression typically flashes into a musician’s mind in the process of the pursuit. Therefore, students should not be instructed to explain their expressions logically, an approach that differs from what is mostly observed in music education in many primary and secondary schools

A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bond formation

The esterification of fragment C1-C8 (2) with fragment C16-C23 (3) to give iodo derivative 4, followed by a Pd-catalysed coupling with a C9-C15 fragment (7 or 8), may provide a common precursor of most palmerolides. Ligands and reaction conditions were exhaustively examined to perform the C15-C16 bond formation via Negishi reaction. With simple models, pre-activated Pd-Xantphos and Pd-DPEphos complexes were the most efficient catalysts at RT. Zincation of the C9-C15 fragment (8) and cross coupling with 4 required 3 equiv of t-BuLi, 10 mol % of Pd-Xantphos and 60 °C

The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer

MAb 4C5 is a cell impermeable, anti-HSP90 murine monoclonal antibody, originally produced using hybridoma technology. We have previously shown that mAb 4C5 specifically recognizes both the α- and to a lesser extent the β-isoform of HSP90. Additionally, in vitro and in vivo studies revealed that by selectively inhibiting the function of cell-surface HSP90, mAb 4C5 significantly impairs cancer cell invasion and metastasis. Here we describe the reconstitution of mAb 4C5 into a mouse-human chimera. More importantly we report that mAb 4C5 and consequently its chimeric counterpart are completely devoid of heavy chain and consist only of a functional kappa light chain dimer. The chimeric antibody is shown to retain the original antibody's specificity and functional properties. Thus it is capable of inhibiting the function of surface HSP90, leading to reduced cancer cell invasion in vitro. Finally, we present in vivo evidence showing that the chimeric 4C5 significantly inhibits the metastatic deposit formation of MDA-MB-453 cells into the lungs of SCID mice. These data suggest that a chimeric kappa light chain antibody could be potentially used as an anti-cancer agent, thereby introducing a novel type of antibody fragment, with reduced possible adverse immunogenic effects, into cancer therapeutics

The role of motion and intensity in deaf children’s recognition of real human facial expressions of emotion

© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.There is substantial evidence to suggest that deafness is associated with delays in emotion understanding, which has been attributed to delays in language acquisition and opportunities to converse. However, studies addressing the ability to recognise facial expressions of emotion have produced equivocal findings. The two experiments presented here attempt to clarify emotion recognition in deaf children by considering two aspects: the role of motion and the role of intensity in deaf children’s emotion recognition. In Study 1, 26 deaf children were compared to 26 age-matched hearing controls on a computerised facial emotion recognition task involving static and dynamic expressions of 6 emotions. Eighteen of the deaf and 18 age-matched hearing controls additionally took part in Study 2, involving the presentation of the same 6 emotions at varying intensities. Study 1 showed that deaf children’s emotion recognition was better in the dynamic rather than static condition, whereas the hearing children showed no difference in performance between the two conditions. In Study 2, the deaf children performed no differently from the hearing controls, showing improved recognition rates with increasing rates of intensity. With the exception of disgust, no differences in individual emotions were found. These findings highlight the importance of using ecologically valid stimuli to assess emotion recognition.Peer reviewedFinal Published versio

Structure and neurotoxicity of novel amyloids derived from the BRI gene

Abstract A number of human neurodegenerative diseases involve aggregated amyloid proteins in the brain, e.g. Alzheimer's disease (β-amyloid) and Parkinson's disease (α-synuclein). Other examples are rare familial dementias which involve the BRI gene. In a British family, mutation of the termination codon extends the reading frame of BRI to yield a furin-processed 34-residue peptide (Abri; British dementia peptide), 11 residues longer than the wild-type (WT). In a Danish family, a ten-base insertion also yields a 34-residue peptide (Adan; Danish dementia peptide). To explore the roles of Abri and Adan in neurodegeneration, we synthesized Abri and Adan in oxidized and reduced forms and generated transgenic mice colonies expressing the WT and mutated forms of BRI. We have generated transgenic mice colonies bearing the genes coding for WT-BRI, Adan and Abri under the control of the Thy1 promoter. Whereas WT-BRI transgenic mice express full-length WT-BRI protein in their brains, Adan protein is fully processed to small peptides. FBD (familial British dementia) and FDD (familial Danish dementia) are rare autosomal dominant neurodegenerative disorders that share features of AD (Alzheimer's disease), including amyloid plaques surrounded by astrocytes and microglia, neurofibrillary tangles, neuronal loss and progressive dementi

Elaboració d'una guia sobre aprenentatge cooperatiu a la Universitat de Girona

L’any 2009, l’Institut de Ciències de l’Educació Josep Pallach de la Universitat de Girona va impulsar la creació de diverses Xarxes d’Innovació Docent (XID). Aquestes xarxes agrupen professors de disciplines diverses que volen compartir experiències relatives a la millora docent. Una d’aquestes xarxes és la relativa a l’Aprenentatge Cooperatiu (XIDAC). Es compon de vuit professors que utilitzen aquest mètode d’aprenentatge a la seva docència. Un dels seus objectius és produir una guia o petit manual sobre aprenentatge cooperatiu (AC) a la UdG. Es tracta d’orientar els professors que vulguin posar- lo en pràctica, o que ja ho estiguin fent i necessitin un material de suport. A la present comunicació es descriu el procés d’elaboració d’aquesta guia. En primer lloc, s’exposen característiques de la UdG que poden determinarne en algun sentit el perfil i continguts. Després, es resumeixen els resultats d’entrevistes amb professors que apliquen l’AC tot i no pertànyer a la Xarxa. A continuació, es resumeixen els resultats d’una enquesta elaborada al professorat de la UdG (actualment està en fase de resposta). Amb posterioritat, es fa una presentació general de la futura guia i es descriu breument un exemple de fitxa d’activitat d’AC. Finalment, es fa referència al procés de debat obert de part d’aquests continguts a través d’una pàgina web, per tal de recollir punts de vista externs i millorar la proposta.Peer Reviewe

Extracellular Heat Shock Protein (Hsp)70 and Hsp90α Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion

Breast cancer is second only to lung cancer in cancer-related deaths in women, and the majority of these deaths are caused by metastases. Obtaining a better understanding of migration and invasion, two early steps in metastasis, is critical for the development of treatments that inhibit breast cancer metastasis. In a functional proteomic screen for proteins required for invasion, extracellular heat shock protein 90 alpha (Hsp90α) was identified and shown to activate matrix metalloproteinase 2 (MMP-2). The mechanism of MMP-2 activation by Hsp90α is unknown. Intracellular Hsp90α commonly functions with a complex of co-chaperones, leading to our hypothesis that Hsp90α functions similarly outside of the cell. In this study, we show that a complex of co-chaperones outside of breast cancer cells assists Hsp90α mediated activation of MMP-2. We demonstrate that the co-chaperones Hsp70, Hop, Hsp40, and p23 are present outside of breast cancer cells and co-immunoprecipitate with Hsp90α in vitro and in breast cancer conditioned media. These co-chaperones also increase the association of Hsp90α and MMP-2 in vitro. This co-chaperone complex enhances Hsp90α-mediated activation of MMP-2 in vitro, while inhibition of Hsp70 in conditioned media reduces this activation and decreases cancer cell migration and invasion. Together, these findings support a model in which MMP-2 activation by an extracellular co-chaperone complex mediated by Hsp90α increases breast cancer cell migration and invasion. Our studies provide insight into a novel pathway for MMP-2 activation and suggest Hsp70 as an additional extracellular target for anti-metastatic drug development

A Novel Extracellular Hsp90 Mediated Co-Receptor Function for LRP1 Regulates EphA2 Dependent Glioblastoma Cell Invasion

Extracellular Hsp90 protein (eHsp90) potentiates cancer cell motility and invasion through a poorly understood mechanism involving ligand mediated function with its cognate receptor LRP1. Glioblastoma multiforme (GBM) represents one of the most aggressive and lethal brain cancers. The receptor tyrosine kinase EphA2 is overexpressed in the majority of GBM specimens and is a critical mediator of GBM invasiveness through its AKT dependent activation of EphA2 at S897 (P-EphA2(S897)). We explored whether eHsp90 may confer invasive properties to GBM via regulation of EphA2 mediated signaling.We find that eHsp90 signaling is essential for sustaining AKT activation, P-EphA2(S897), lamellipodia formation, and concomitant GBM cell motility and invasion. Furthermore, eHsp90 promotes the recruitment of LRP1 to EphA2 in an AKT dependent manner. A finding supported by biochemical methodology and the dual expression of LRP1 and P-EphA2(S897) in primary and recurrent GBM tumor specimens. Moreover, hypoxia mediated facilitation of GBM motility and invasion is dependent upon eHsp90-LRP1 signaling. Hypoxia dramatically elevated surface expression of both eHsp90 and LRP1, concomitant with eHsp90 dependent activation of src, AKT, and EphA2.We herein demonstrate a novel crosstalk mechanism involving eHsp90-LRP1 dependent regulation of EphA2 function. We highlight a dual role for eHsp90 in transducing signaling via LRP1, and in facilitating LRP1 co-receptor function for EphA2. Taken together, our results demonstrate activation of the eHsp90-LRP1 signaling axis as an obligate step in the initiation and maintenance of AKT signaling and EphA2 activation, thereby implicating this pathway as an integral component contributing to the aggressive nature of GBM

Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice

Huntingtin Interacting Protein 14 (HIP14) is a palmitoyl acyl transferase (PAT) that was first identified due to altered interaction with mutant huntingtin, the protein responsible for Huntington Disease (HD). HIP14 palmitoylates a specific set of neuronal substrates critical at the synapse, and downregulation of HIP14 by siRNA in vitro results in increased cell death in neurons. We previously reported that mice lacking murine Hip14 (Hip14−/−) share features of HD. In the current study, we have generated human HIP14 BAC transgenic mice and crossed them to the Hip14−/− model in order to confirm that the defects seen in Hip14−/− mice are in fact due to loss of Hip14. In addition, we sought to determine whether human HIP14 can provide functional compensation for loss of murine Hip14. We demonstrate that despite a relative low level of expression, as assessed via Western blot, BAC-derived human HIP14 compensates for deficits in neuropathology, behavior, and PAT enzyme function seen in the Hip14−/− model. Our findings yield important insights into HIP14 function in vivo