Kyoto University

About: Kyoto University is a education organization based out in Kyoto, Japan. It is known for research contribution in the topics: Catalysis & Population. The organization has 85837 authors who have published 217215 publications receiving 6526826 citations. The organization is also known as: Kyōto University & Kyōto daigaku.

ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats

Abstract: Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce neuronal cell death. However, the molecular mechanism of polyQ-induced cell death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and cell death. These findings suggest that ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases.

Reaction-diffusion model as a framework for understanding biological pattern formation

Abstract: The Turing, or reaction-diffusion (RD), model is one of the best-known theoretical models used to explain self-regulated pattern formation in the developing animal embryo. Although its real-world relevance was long debated, a number of compelling examples have gradually alleviated much of the skepticism surrounding the model. The RD model can generate a wide variety of spatial patterns, and mathematical studies have revealed the kinds of interactions required for each, giving this model the potential for application as an experimental working hypothesis in a wide variety of morphological phenomena. In this review, we describe the essence of this theory for experimental biologists unfamiliar with the model, using examples from experimental studies in which the RD model is effectively incorporated.

An endothelial receptor for oxidized low-density lipoprotein

Abstract: Endothelial dysfunction or activation elicited by oxidatively modified low-density lipoprotein (Ox-LDL) has been implicated in the pathogenesis of atherosclerosis1–4, characterized by intimal thickening and lipid deposition in the arteries. Ox-LDL and its lipid constituents impair endothelial production of nitric oxide, and induce the endothelial expression of leukocyte adhesion molecules and smooth-muscle growth factors, which may be involved in atherogenesis5–7. Vascular endothelial cells in culture8,9 and in vivo10,11 internalize and degrade Ox-LDL through a putative receptor-mediated pathway that does not involve macrophage scavenger receptors12–15. Here we report the molecular cloning, using expression cloning strategy, of an Ox-LDL receptor from vascular endothelial cells. The cloned receptor is a membrane protein that belongs structurally to the C-type lectin family, and is expressed in vivo in vascular endothelium and vascular-rich organs.

Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.

Abstract: The ligands for programmed cell death 1 (PD-1), an immunoinhibitory receptor belonging to CD28/cytotoxic T lymphocyte antigen 4 family, are PD-1 ligand 1 and 2 (PD-Ls) Recent reports suggest that the aberrant expression of PD-Ls on tumor cells impairs antitumor immunity, resulting in the immune evasion of the tumor cells Although an inverse correlation between the expression level of PD-Ls and patients' prognosis has been reported for several malignant tumors, the follow-up period was limited because of the lack of the antibody (Ab) applicable to paraffin-embedded specimens Here we generated a new Ab against PD-1 ligand 1 (PD-L1) and analyzed the expression level of PD-Ls in human ovarian cancer using paraffin-embedded specimens Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression Although patients with higher expression of PD-1 ligand 2 also had a poorer prognosis, the difference was not statistically significant A significant inverse correlation was observed between PD-L1 expression and the intraepithelial CD8+ T lymphocyte count, suggesting that PD-L1 on tumor cells directly suppresses antitumor CD8+ T cells Multivariate analysis showed the expression of PD-L1 on tumor cells and intraepithelial CD8+ T lymphocyte count are independent prognostic factors The PD-1/PD-L pathway can be a good target for restoring antitumor immunity in ovarian cancer