Kyushu University

About: Kyushu University is a education organization based out in Fukuoka, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 68284 authors who have published 135190 publications receiving 3055928 citations. The organization is also known as: Kyūshū Daigaku.

Germline gain-of-function mutations in RAF1 cause Noonan syndrome

Abstract: Noonan syndrome is characterized by short stature, facial dysmorphia and a wide spectrum of congenital heart defects1,2. Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause ∼60% of cases of Noonan syndrome3,4,5,6,7,8,9. However, the gene(s) responsible for the remainder are unknown. We have identified five different mutations in RAF1 in ten individuals with Noonan syndrome; those with any of four mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy (HCM), whereas affected individuals with mutations leading to changes in the CR3 domain did not. Cells transfected with constructs containing Noonan syndrome–associated RAF1 mutations showed increased in vitro kinase and ERK activation, and zebrafish embryos with morpholino knockdown of raf1 demonstrated the need for raf1 for the development of normal myocardial structure and function. Thus, our findings implicate RAF1 gain-of-function mutations as a causative agent of a human developmental disorder, representing a new genetic mechanism for the activation of the MAPK pathway.

Digital photoswitching of fluorescence based on the photochromism of diarylethene derivatives at a single-molecule level.

Abstract: Photochromic reactions of diarylethene derivatives were detected at a single-molecule level by using a fluorescence technique. Fluorescent photoswitching molecules in which photochromic diarylethene and fluorescent bis(phenylethynyl)anthracene units are linked through an adamantyl spacer were synthesized, and switching of fluorescence upon irradiation with UV and visible light was followed in solution as well as on polymer films at the single-molecule level. Although in solution the fluorescence intensity gradually changed upon irradiation with UV and visible light, digital on/off switching between two discrete states was observed at the single-molecule level. The “on”- and “off”-times were dependent on the power of UV and visible light. When the power of UV and visible light was increased, the average on- and off-times became short in proportion to the reciprocal power of the light. The response-times were found to show distribution. The distribution of the on- and off-times is considered to reflect the ...

Early human atherosclerosis : Accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration

Abstract: Objective— The present study was designed to clarify the morphological features of early human atherosclerosis and to determine whether specific extracellular matrix proteoglycans play a role in early atherogenesis. Methods and Results— Step and serial sections were obtained from right coronary arteries with no or early atherosclerosis. Atherosclerosis was classified into 4 grades according to the amount of lipid deposition. Coronary arteries with Grade 0 showed diffuse intimal thickening (DIT) with no lipid deposits. The extracellular matrix proteoglycans, biglycan and decorin, were localized in the outer layer of DIT. Most cases of Grade 1 and Grade 2 exhibited fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima. As lipid grades increased, macrophages increased in number and were present in the deeper layers. Most cases of Grade 3 exhibited pathologic intimal thickening (PIT) with extracellular lipids underneath a layer of foam cell macrophages. Conclusions— In early human coronary atherosclerosis, fatty streaks develop via extracellular deposition of lipids associated with specific types of proteoglycans in the outer layer of preexisting DIT. As the amount of the lipid increases in fatty streaks, macrophages infiltrate toward the deposited lipid to form PIT with foam cells.

The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily

Abstract: The let-23 gene is required for induction of the Caenorhabditis elegans vulva. It is shown that let-23 encodes a putative tyrosine kinase of the epidermal growth factor receptor subfamily. Thus, let-23 might encode the receptor for the inductive signal required for vulval development. Because let-23 acts upstream of let-60 ras in the vulval determination pathway, the identification of the let-23 product provides support for a link in vivo between tyrosine kinase growth factor receptors and ras proteins in a pathway of cell-type determination.

Blue light activates the plasma membrane H(+)-ATPase by phosphorylation of the C-terminus in stomatal guard cells.

Abstract: The opening of stomata, which is driven by the accumulation of K(+) salt in guard cells, is induced by blue light (BL). The BL activates the H(+) pump; however, the mechanism by which the perception of BL is transduced into the pump activation remains unknown. We present evidence that the pump is the plasma membrane H(+)-ATPase and that BL activates the H(+)-ATPase via phosphorylation. A pulse of BL (30 s, 100 micromol/m(2)/s) increased ATP hydrolysis by the plasma membrane H(+)-ATPase and H(+) pumping in Vicia guard cell protoplasts with a similar time course. The H(+)-ATPase was phosphorylated reversibly by BL, and the phosphorylation levels paralleled the ATP hydrolytic activity. The phosphorylation occurred exclusively in the C-termini of H(+)-ATPases on both serine and threonine residues in two isoproteins of H(+)-ATPase in guard cells. An endogenous 14-3-3 protein was co-precipitated with H(+)-ATPase, and the recombinant 14-3-3 protein bound to the phosphorylated C-termini of H(+)-ATPases. These findings demonstrate that BL activates the plasma membrane H(+)-ATPase via phosphorylation of the C-terminus by a serine/threonine protein kinase, and that the 14-3-3 protein has a key role in the activation.