Temporal and Spatial Cellular Distribution of Neural Crest Derivatives and Alpha Cells during Islet Development

Recent studies have revealed that signals from neural crest (NC) derivatives regulate the mass, proliferation, and maturation of beta cells in developing fetal pancreas. However, little is known about the cellular distribution of NC derivatives during pancreatic development or the process whereby the developing islets are enclosed. We studied the temporal and spatial distribution of NC derivatives and endocrine cells at each developmental stage. At embryonic day 10.5 (E10.5) of mouse embryo, NC derivatives that migrated to the prospective pancreatic region were distributed in close proximity to pancreatic epithelial cells. As development advanced, most NC derivatives progressively surrounded endocrine rather than exocrine cells, and were distributed in closer proximity to alpha cells rather than to beta cells. At E20, approximately 70% of the NC derivatives enclosing endocrine cells were distributed in close proximity to alpha cells. Moreover, the expression of SynCAM, a Ca2+-independent homophilic trans-cell adhesion molecule, was confirmed from E16.5 on and was more remarkable at the cell boundaries of alpha cells and NC derivatives. These findings suggest that NC derivatives might be distributed in close proximity to alpha cells as a result of homophilic binding of SynCAM expressed by alpha cells and NC derivatives during islet development

RNAi-Mediated Knockdown Showing Impaired Cell Survival in Drosophila Wing Imaginal Disc

The genetically amenable organism Drosophila melanogaster has been estimated to have 14,076 protein coding genes in the genome, according to the flybase release note R5.13 (http://flybase.bio.indiana.edu/static_pages/docs/release_notes.html). Recent application of RNA interference (RNAi) to the study of developmental biology in Drosophila has enabled us to carry out a systematic investigation of genes affecting various specific phenotypes. In order to search for genes supporting cell survival, we conducted an immunohistochemical examination in which the RNAi of 2,497 genes was independently induced within the dorsal compartment of the wing imaginal disc. Under these conditions, the activities of a stress-activated protein kinase JNK (c-Jun N-terminal kinase) and apoptosis-executing factor Caspase-3 were monitored. Approximately half of the genes displayed a strong JNK or Caspase-3 activation when their RNAi was induced. Most of the JNK activation accompanied Caspase-3 activation, while the opposite did not hold true. Interestingly, the area activating Caspase-3 was more broadly seen than that activating JNK, suggesting that JNK is crucial for induction of non-autonomous apoptosis in many cases. Furthermore, the RNAi of essential factors commonly regulating transcription and translation showed a severe and cell-autonomous apoptosis but also elicited another apoptosis at an adjacent area in a non-autonomous way. We also found that the frequency of apoptosis varies depending on the tissues

The position of institutional repository in Japanese university libraries by comparison with "digital library"

DRFIC2008 Poster Session No.16DRFIC2008 ポスターセッション資料 16

The position of institutional repository in Japanese university libraries by comparison with "digital library"

DRFIC2008 Poster Session Recap one-minute oral presentation No.16DRFIC2008 ポスターセッションまとめ 口頭プレゼンテーション資料 16

Porphyromonas gingivalis Mfa1 Induces Chemokine and Cell Adhesion Molecules in Mouse Gingival Fibroblasts via Toll-Like Receptors

Porphyromonas gingivalis Mfa1 fimbriae are thought to act as adhesion factors and to direct periodontal tissue destruction but their immunomodulatory actions are poorly understood. Here, we investigated the effect of Mfa1 stimulation on the immune and metabolic mechanisms of gingival fibroblasts from periodontal connective tissue. We also determined the role of Toll-like receptor (TLR) 2 and TLR4 in Mfa1 recognition. Mfa1 increased the expression of genes encoding chemokine (C-X-C motif) ligand (CXCL) 1, CXCL3, intercellular adhesion molecule (ICAM) 1 and Selectin endothelium (E) in gingival fibroblasts, but did not have a significant effect on genes that regulate metabolism. Mfa1-stimulated up-regulation of genes was significantly suppressed in Tlr4 siRNA-transfected cells compared with that in control siRNA-transfected cells, which indicates that recognition by TLR4 is essential for immunomodulation by Mfa1. Additionally, suppression of Tlr2 expression partially attenuated the stimulatory effect of Mfa1. Overall, these results help explain the involvement of P. gingivalis Mfa1 fimbriae in the progression of periodontal disease

A scoring evaluation for the practical introduction of guideline‐directed medical therapy in heart failure patients

Abstract Aims The guideline‐directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial‐proven medications for every patient in the real world. Methods and results A simple GDMT score was created, according to the combination of GDMT drugs (renin–angiotensin system inhibitors, beta‐blockers, mineralocorticoid receptor antagonists, and sodium–glucose transporter 2 inhibitors) administration and their dosage (0–9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n = 1054] were retrospectively analysed (excluding those with in‐hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all‐cause death, HF readmission, and composite outcome (HF readmission and all‐cause death) (P < 0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis. Conclusions The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients