47 research outputs found
Downsian Positions of Parties and Districts from the Numbers of Votes with Examples of Japanese Congressional Elections 1983 - 2004
This paper proposes, under assumptions of sincere voters with some additional conditions, to calculate the positions of parties and districts by “solving” a system of equations whose left hand sides are theoretical predictions and theright hand sides are the actual numbers of votes gained by the parties in the districts. The positions of parties and prefectures are calculated for the seats for the proportional representation in the Japanese congressional elections 1983 – 2004. The result reveals that the competition in these elections was not between the right and the left, but between the urban and the rural
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Oligodendrocyte Precursor Cells Support Blood-Brain Barrier Integrity via TGF-β Signaling
Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity
Increased RNA transcription of energy source transporters in circulating white blood cells of aged mice
Circulating white blood cells (WBC) contribute toward maintenance of cerebral metabolism and brain function. Recently, we showed that during aging, transcription of metabolism related genes, including energy source transports, in the brain significantly decreased at the hippocampus resulting in impaired neurological functions. In this article, we investigated the changes in RNA transcription of metabolism related genes (glucose transporter 1 [Glut1], Glut3, monocarboxylate transporter 4 [MCT4], hypoxia inducible factor 1-α [Hif1-α], prolyl hydroxylase 3 [PHD3] and pyruvate dehydrogenase kinase 1 [PDK1]) in circulating WBC and correlated these with brain function in mice. Contrary to our expectations, most of these metabolism related genes in circulating WBC significantly increased in aged mice, and correlation between their increased RNA transcription and impaired neurological functions was observed. Bone marrow mononuclear transplantation into aged mice decreased metabolism related genes in WBC with accelerated neurogenesis in the hippocampus. In vitro analysis revealed that cell-cell interaction between WBC and endothelial cells via gap junction is impaired with aging, and blockade of the interaction increased their transcription in WBC. Our findings indicate that gross analysis of RNA transcription of metabolism related genes in circulating WBC has the potential to provide significant information relating to impaired cell-cell interaction between WBC and endothelial cells of aged mice. Additionally, this can serve as a tool to evaluate the change of the cell-cell interaction caused by various treatments or diseases
Association of High-Density Lipoprotein Subclasses with Chronic Kidney Disease Progression, Atherosclerosis, and Klotho.
Atherosclerosis is often a complication of chronic kidney disease (CKD) because of dyslipidemia and CKD-mineral and bone disorder. High-density lipoproteins (HDLs) are grouped into various subclasses composed of multiple proteins and lipids, and their transformation is altered in CKD. We investigated the roles of lipoprotein subclasses in CKD progression, and atherosclerosis, and the relationships with Klotho and fibroblast growth factor (FGF) 23.Seventy-one CKD patients were enrolled in this prospective cohort study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) and lipoprotein particle numbers in 20 lipoprotein fractions were measured by a newly developed high-performance gel permeation chromatography.Diabetic nephropathy was observed in 23.9% of the patients. The mean age was 75.0 years and estimated glomerular filtration rate (eGFR) was 17.2 ml/min./1.73m2. The lipoprotein particle numbers in small HDLs were higher in Stage 4 group than in Stage 5 group (p = 0.002). Multivariate regression analysis adjusted for baseline characteristics showed that the cholesterol proportions in very small HDLs were associated with eGFR change rate [F19 β = -17.63, p = 0.036] and ABI [F19 β = 0.047, p = 0.047] in Stage 4 group, and that serum soluble α-Klotho level was associated with the lipoprotein particle numbers in very small HDLs [F19 β = 0.00026, p = 0.012; F20 β = 0.00041, p = 0.036] in Stage 5 group.This study showed that HDL subclasses are associated with CKD progression, ABI, and Klotho level in CKD-stage-specific manner
Experimental study of WGA binding on the endothelial cell surface in cerebral ischemia
The relationship between the saccharide chain
on the endothelial cell surface and the permeability of
intracerebral blood vessels has been studied. In the present
study, wheat germ agglutinin (WGA) was perfused into
capillaries in the area postrema of the normal Mongolian
gerbil, where the blood brain barrier (BBB) is known to
lack, and into intracerebral blood vessels, the BBB of
which had been destroyed by experimentally induced brain
ischemia. The light microscopic features of the sections
from WGA-perfused brain tissues of the normal gerbil
revealed that most of the blood vessels, including
capillaries in the brain parenchyma, showed positive
findings (the reaction induced a very distinct staining of
the vascular wall) from which the course and structure of
the fine vessels could be determined. The reaction to WGA
on the diaphragma fenestra (DF) in capillaries in the area
postrema was relatively weak, and DF without the reaction
were occasionally revealed by electron microscopy. The
gerbil, in which cerebral ischemia had been induced, also
showed partial defect of the reaction with WGA on the
lumina1 side of the endothelial cells. The results of the
present experiment suggest some degree of correlation
between the saccharide chains, including the specific
monosaccharide of WGA, on the endothelial cell surface
and permeability. It was considered that lectin can be used
as an index for morphological observations, suggesting an
alteration in function of the endothelial cell membrane.
In addition, the perfusion method in this experiment
suggested the possibility of distinguishing pinocytotic
vesicles from pits of cell membranes
eGFR change and cholesterol proportions and lipoprotein particle numbers in lipoprotein fractions.
<p>eGFR change and cholesterol proportions and lipoprotein particle numbers in lipoprotein fractions.</p