Mutation of PTPN11 (Encoding SHP-2) Promotes MEK Activation and Malignant Progression in Neurofibromin-Deficient Cells in a Manner Sensitive to BRAP Mutation

Germline mutations of NF1 cause neurofibromatosis type 1 (NF1) through the activation of the RAS signaling pathway, and some NF1 patients develop malignant peripheral nerve sheath tumors (MPNSTs). Here, we established subclones of the human NF1-MPNST cell line sNF96.2 that manifest increased tumorigenic activity and increased phosphorylation of the protein kinases MEK and Akt relative to the parental cells. Genomic DNA sequencing identified 14 additional heterozygous mutations within the coding regions of 13 cancer- and other disease-related genes in these subclones. One of these genes, PTPN11, encodes SHP-2, and the forced expression of the identified G503V mutant of SHP-2 increased both tumorigenic activity and MEK phosphorylation in parental sNF96.2 cells, suggesting that the combination of PTPN11 and NF1 mutations induces the pathological activation of the RAS pathway. These effects of SHP-2 (G503V) were inhibited by the coexpression of the G370A mutant of BRAP, which was also detected in the highly malignant subclones, and this inhibition was accompanied by the calpain-dependent cleavage of SHP-2 (G503V). The cleavage of SHP-2 (G503V) and suppression of MEK phosphorylation mediated by BRAP (G370A) were not detected in NF1-intact (HeLa) cells. Tumor promotion by SHP-2 (G503V) and its suppression by BRAP (G370A) may serve as a basis for the development of new treatment strategies for NF1

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>

インクルーシブ保育における子どもの「参加」 : 国際生活機能分類(ICF)を活用し保育実践を考える

本研究では，さまざまな子を含めた保育の方向性を検討するため，いわゆる「気になる」子の遊び場面や生活場面について，ICFを活用して評価を行い「活動と参加」の実際およびその環境因子について分析を行った。その結果，子どもの発達や状況に応じた「参加」の姿があること，ICFを用いることでインクルーシブ社会を目指す側面から保育実践の意味づけが可能となることを明らかにした。また，子どもの「参加」を支える促進要因に関しては，異年齢保育の持つ多様性がたぶんに関与していること，保育者の考え方と実践場面での関わりが影響を及ぼすことが示唆された。In the study, we observed a young child with difficulty in communication from a standpoint of International Classification of Functioning, Disability and Health (ICF), in order to clarify the future direction of inclusive childcare and the role of people around children with developmental disorders. By using the concepts of activity and participation in ICF, we searched both the characteristic of relation between the child and people around him and promoting factors for his participation in his class. As a result, we found that there can be the suitable form of participation which is fitted to the levels of children’s development and the situation in which children live and play. We also found that we can evaluate our childcare activity from the viewpoint of inclusive society. We suggest that promoting factors of participation are diversities of children in multiage class and the attitude of childcare workers.8KJ0000931693

Solvent-Induced Reversed Stereoselectivity in Reciprocal Resolutions of Mandelic Acid and <i>erythro</i>-2-Amino-1,2-diphenylethanol

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (<b>1</b>) and <i>erythro</i>-2-amino-1,2-diphenylethanol (<b>2</b>) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from ¹H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic <b>2</b>, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of <b>1</b> and <b>2</b>