Search

電気通信大学では，人間・社会・自然・システムなどに関する全てのデータと機能をネットワークアクセス可能とし，それらをAIと人間が連携し分析することにより，リアルタイムに進化し続ける社会を「共創進化スマート社会」と名付け，その実現を目指し研究・教育・実現を進めている．本論文では，このアプローチによる認知症高齢者問題（BPSD）の解決の試みについて説明する．The University of Electro-Communications has named a society in which all data and functions related to humans, society, nature, and systems are network-accessible, and AI and humans collaborate and analyze them to continue evolving in real time as a "self-evolving smart society." We are conducting research, education, and implementation with the aim of realizing this approach. This paper describes an attempt to solve the problem of dementia in the elderly (BPSD) using this approach.

介護施設や家庭において，認知症の方が発症する行動・心理症状（BPSD）は，家族・介護者に大きな負担を課しているだけでなく本人にも負の影響を与えている．本研究では，IOTの技術を用い複数の介護施設で環境センサ・バイタルセンサの情報を収集し，そのデータに基づき，機械学習の手法である勾配ブースティング木とDNNの一種CNNを利用してBPSDの予測を行う．約5か月間のデータを用いて評価実験を行った結果，勾配ブースティングを使った手法において，BPSD発症推定の可能性を示すことができた．In nursing homes and homes, Behavioral and Psychological Symptoms of Dementia (BPSD) that developed by people with dementia not only impose a heavy burden on family members and caregivers but also give the individuals themselves negative impacts. In this study, we used IOT technology to collect data from environmental and vital sensors at multiple nursing homes, and based on the data, we estimated BPSD using gradient boosting decision trees (GBTD), a machine learning technique, and CNN, a type of DNN. As a result of evaluation experiments using approximately five months of data, we were able to demonstrate the possibility of estimating the onset of BPSD for the method using GBDT.

Ror1 plays a crucial role in cancer progression by regulating cell proliferation and migration. Ror1 is expressed abundantly in various types of cancer cells and cancer stem-like cells. However, the molecular mechanisms regulating expression of Ror1 in these cells remain largely unknown. Ror1 and its putative ligand Wnt5a are expressed highly in malignant gliomas, especially in glioblastomas, and the extents of Ror1 expression are correlated positively with poorer prognosis in patients with gliomas. We show that Ror1 expression can be upregulated in glioblastoma cells under spheroid culture, but not adherent culture conditions. Notch and hypoxia signaling pathways have been shown to be activated in spheroid-forming glioblastoma stem-like cells (GSCs), and Ror1 expression in glioblastoma cells is indeed suppressed by inhibiting either Notch or hypoxia signaling. Meanwhile, either forced expression of the Notch intracellular domain (NICD) in or hypoxic culture of glioblastoma cells result in enhanced expression of Ror1 in the cells. Consistently, we show that both NICD and hypoxia-inducible factor 1 alpha bind to upstream regions within the Ror1 gene more efficiently in GSCs under spheroid culture conditions. Furthermore, we provide evidence indicating that binding of Wnt5a to Ror1, upregulated by Notch and hypoxia signaling pathways in GSCs, might promote their spheroid-forming ability. Collectively, these findings indicate for the first time that Notch and hypoxia signaling pathways can elicit a Wnt5a-Ror1 axis through transcriptional activation of Ror1 in glioblastoma cells, thereby promoting their stem cell-like property.

In the brains under pathological conditions, astrocytes become reactive astrocytes that exhibit various context-dependent functions through the regulation of specific signaling pathways and transcriptional mechanisms in response to environmental changes. Reactive astrocytes induced in injured brains begin proliferating and play a role in promoting protection and repair of damaged tissues, but the relationship between the proliferative characteristics and tissue-protective and repair functions of reactive astrocytes remains unclear. Here, we show that growth factor signaling elicited by bFGF and HB-EGF, whose expression is up-regulated in the injured brains, acts synergistically with inflammatory cytokine signaling in astrocytes, thereby markedly up-regulating gene expression of the Ror-family protein Ror2, a receptor for Wnt5a. Activation of Wnt5a-Ror2 signaling in astrocytes results in intracellular accumulation of phosphorylated p62, thereby activating antioxidative transcription factor Nrf2. Finally, we provide evidence demonstrating that forced activation of Wnt5a-Ror2-p62-Nrf2 signaling axis in astrocytes reduces cellular damage caused by hemin, a degradation product of hemoglobin, and promotes repair of the damaged blood brain barrier after brain hemorrhage.

Accumulating evidence demonstrates that bone marrow (BM)-derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a-Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer. Here, we show that CXCL16-CXCR6 signaling is also activated in MSCs through cell-autonomous machinery, leading to upregulated expression of CCL5. We further show that CCR1 and CCR3, receptors of CCL5, are expressed on the surface of MKN45 cells, and that CCL5 secreted from MSCs promotes migration of MKN45 cells presumably via its binding to CCR1/CCR3. These data indicate that cell-autonomous CXCL16-CXCR6 signaling activated in MSCs upregulates expression of CCL5, and that subsequent activation of CCL5-CCR1/3 signaling in MKN45 cells through intercellular machinery can promote migration of MKN45 cells. Collectively, these findings postulate the presence of orchestrated chemokine signaling emanated from MSCs to regulate progression of undifferentiated gastric cancer cells.

Invadopodia on cancer cells play crucial roles in tumor invasion and metastasis by degrading and remodeling the surrounding extracellular matrices and driving cell migration in complex 3D environments. Previous studies have indicated that microtubules (MTs) play a crucial role in elongation of invadopodia, but not their formation, probably by regulating delivery of membrane and secretory proteins within invadopodia. However, the identity of the responsible MT-based molecular motors and their regulation has been elusive. Here, we show that KIF1C, a member of kinesin-3 family, is localized to the tips of invadopodia and is required for their elongation and the invasion of cancer cells. We also found that c-Src phosphorylates tyrosine residues within the stalk domain of KIF1C, thereby enhancing its association with tyrosine phosphatase PTPD1, that in turn activates MT-binding ability of KIF1C, probably by relieving the autoinhibitory interaction between its motor and stalk domains. These findings shed new insights into how c-Src signaling is coupled to the MT-dependent dynamic nature of invadopodia and also advance our understanding of the mechanism of KIF1C activation through release of its autoinhibition.