バンドウ フリョ シュウヨウジョ ノ ドイツヘイ ガ オオアサヒコ ジンジャ ケイダイ ニ ツクッタ ハシ ト コウエン

German prisoners in the Bandō prisoner-of-war (POW) camp made bridges and a park in the forest of the Ooasahiko-Jinja Shrine during 1917-1919. Details of the constructions were a 15 m-long wood bridge and five small wood bridges, four stone bridges, road with a total length of 1,130 m, stone embankments, slopes, two flights of stone steps with a length of 8 m and 3 m according to the record written by Adolf Deutschmann who planned and directed the work. Two stone bridges called Doitsu-bashi (German bridge) and Megane-bashi (glasses bridge) remain and the Doitsu-bashi has been designated as a cultural asset of Tokushima prefecture. However, other constructions have been disappeared or became unclear now. In this study, we tried to clarify their precise place and history using an old map of the Ooasahiko-Jinja Shrine, photos and pictures of German prisoners, and interview to an old resident who participated in improvement of the forest around 1970. Results indicated that the road and the stone bridge still remain in some part. In addition to Adolf Deutschmann we found that Max Bunge was an important member of the work. He has not been noticed in previous studies of the Bandō POW camp, although he was a famous person in the German community in Qingdao by some heroic behaviors, and that he became a mayor of his hometown Heiligenhafen after he was released from the camp. He wrote about beautiful nature of the shrine’s forest and about his sympathy to faith of Japanese pilgrims who he saw during construction work

Single-cell transcriptome atlas of Drosophila gastrula 2.0

ショウジョウバエ原腸胚における1細胞遺伝子発現アトラスを作成 --ゲノム情報による発生制御の解明に向けた基盤的リソース--. 京都大学プレスリリース. 2023-07-11.During development, positional information directs cells to specific fates, leading them to differentiate with their own transcriptomes and express specific behaviors and functions. However, the mechanisms underlying these processes in a genome-wide view remain ambiguous, partly because the single-cell transcriptomic data of early developing embryos containing accurate spatial and lineage information are still lacking. Here, we report a single-cell transcriptome atlas of Drosophila gastrulae, divided into 77 transcriptomically distinct clusters. We find that the expression profiles of plasma-membrane-related genes, but not those of transcription-factor genes, represent each germ layer, supporting the nonequivalent contribution of each transcription-factor mRNA level to effector gene expression profiles at the transcriptome level. We also reconstruct the spatial expression patterns of all genes at the single-cell stripe level as the smallest unit. This atlas is an important resource for the genome-wide understanding of the mechanisms by which genes cooperatively orchestrate Drosophila gastrulation

CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity

CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs. Consistent with this, ODN2395-mediated activation of DCs was significantly attenuated in Cxcl14-knockout mice. CXCL14 bound CpG ODN with high affinity at pH 7.5, but not at pH 6.0, thereby enabling efficient delivery of CpG ODN to TLR9 in the endosome/lysosome. Furthermore, the CXCL14-CpG ODN complex specifically bound to high affinity CXCL14 receptors on DCs. Thus, CXCL14 serves as a specific carrier of CpG DNA to sensitize TLR9-mediated immunosurveillance

CXCL14 Deficiency in Mice Attenuates Obesity and Inhibits Feeding Behavior in a Novel Environment

BACKGROUND: CXCL14 is a chemoattractant for macrophages and immature dendritic cells. We recently reported that CXCL14-deficient (CXCL14(-/-)) female mice in the mixed background are protected from obesity-induced hyperglycemia and insulin resistance. The decreased macrophage infiltration into visceral adipose tissues and the increased insulin sensitivity of skeletal muscle contributed to these phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed a comprehensive study for the body weight control of CXCL14(-/-) mice in the C57BL/6 background. We show that both male and female CXCL14(-/-) mice have a 7-11% lower body weight compared to CXCL14(+/-) and CXCL14(+/+) mice in adulthood. This is mainly caused by decreased food intake, and not by increased energy expenditure or locomotor activity. Reduced body weight resulting from the CXCL14 deficiency was more pronounced in double mutant CXCL14(-/-)ob/ob and CXCL14(-/-)A(y) mice. In the case of CXCL14(-/-)A(y) mice, oxygen consumption was increased compared to CXCL14(+/-)A(y) mice, in addition to the reduced food intake. In CXCL14(-/-) mice, fasting-induced up-regulation of Npy and Agrp mRNAs in the hypothalamus was blunted. As intracerebroventricular injection of recombinant CXCL14 did not change the food intake of CXCL14(-/-) mice, CXCL14 could indirectly regulate appetite. Intriguingly, the food intake of CXCL14(-/-) mice was significantly repressed when mice were transferred to a novel environment. CONCLUSIONS/SIGNIFICANCE: We demonstrated that CXCL14 is involved in the body weight control leading to the fully obese phenotype in leptin-deficient or A(y) mutant mice. In addition, we obtained evidence indicating that CXCL14 may play an important role in central nervous system regulation of feeding behavior

Hair follicle epidermal stem cells define a niche for tactile sensation

The heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells in tactile sensory unit formation in the mouse hair follicle. Epidermal stem cells in the follicle upper-bulge, where mechanosensory lanceolate complexes innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These epidermal stem cells deposit an ECM protein called EGFL6 into the collar matrix, a novel ECM that tightly ensheathes lanceolate complexes. EGFL6 is required for the proper patterning, touch responses, and αv integrin-enrichment of lanceolate complexes. By maintaining a quiescent original epidermal stem cell niche, the old bulge, epidermal stem cells provide anatomically stable follicle–lanceolate complex interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized epidermal stem cells provide a niche linking the hair follicle and the nervous system throughout the hair cycle

Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16.Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system

CXCL14, CXCR7 expression and CXCR4 splice variant ratio associate with survival and metastases in Ewing sarcoma patients

Animal science

The RhoA GEF Syx Is a Target of Rnd3 and Regulated via a Raf1-Like Ubiquitin-Related Domain

Background: Rnd3 (RhoE) protein belongs to the unique branch of Rho family GTPases that has low intrinsic GTPase activity and consequently remains constitutively active [1,2]. The current consensus is that Rnd1 and Rnd3 function as important antagonists of RhoA signaling primarily by activating the ubiquitous p190 RhoGAP [3], but not by inhibiting the ROCK family kinases. Methodology/Principal Findings: Rnd3 is abundant in mouse embryonic stem (mES) cells and in an unbiased two-step affinity purification screen we identified a new Rnd3 target, termed synectin-binding RhoA exchange factor (Syx), by mass spectrometry. The Syx interaction with Rnd3 does not occur through the Syx DH domain but utilizes a region similar to the classic Raf1 Ras-binding domain (RBD), and most closely related to those in RGS12 and RGS14. We show that Syx behaves as a genuine effector of Rnd3 (and perhaps Rnd1), with binding characteristics similar to p190-RhoGAP. Morpholinooligonucleotide knockdown of Syx in zebrafish at the one cell stage resulted in embryos with shortened anterior-posterior body axis: this phenotype was effectively rescued by introducing mouse Syx1b mRNA. A Rnd3-binding defective mutant of Syx1b mutated in the RBD (E164A/R165D) was more potent in rescuing the embryonic defects than wild-type Syx1b, showing that Rnd3 negatively regulates Syx activity in vivo. Conclusions/Significance: This study uncovers a well defined Rnd3 effector Syx which is widely expressed and directl

Lefty Blocks a Subset of TGFβ Signals by Antagonizing EGF-CFC Coreceptors

Members of the EGF-CFC family play essential roles in embryonic development and have been implicated in tumorigenesis. The TGFβ signals Nodal and Vg1/GDF1, but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We report that the TGFβ signaling antagonist Lefty also acts through an EGF-CFC-dependent mechanism. Lefty inhibits Nodal and Vg1 signaling, but not Activin signaling. Lefty genetically interacts with EGF-CFC proteins and competes with Nodal for binding to these coreceptors. Chimeras between Activin and Nodal or Vg1 identify a 14 amino acid region that confers independence from EGF-CFC coreceptors and resistance to Lefty. These results indicate that coreceptors are targets for both TGFβ agonists and antagonists and suggest that subtle sequence variations in TGFβ signals result in greater ligand diversity

Some enzymes in the cerebrospinal fluid and glyco-conjugates may be useful to diagnose brain disorder

科学研究費補助金研究成果報告書研究種目: 基盤研究(B)研究期間: 2003～2006課題番号: 15390212研究代表者: 西 克治（滋賀医科大学・医学部・教授）研究分担者: 大久保 岩男（滋賀医科大学・医学部・教授）研究分担者: 種子島 章男（滋賀医科大学・医学部・助教授）研究分担者: 山本 好男（滋賀医科大学・医学部・講師）研究分担者: 牛山 郁子（滋賀医科大学・医学部・助手）研究分担者: 高瀬 泉（滋賀医科大学・医学部・助手