A novel potent vasoconstrictor peptide produced by vascular endothelial cells

An endothelium-derived 21-residue vasoconstrictor peptide, endothelin, has been isolated, and shown to be one of the most potent vasoconstrictors known. Cloning and sequencing of preproendothelin complementary DNA shows that mature endothelin is generated through an unusual proteolytic processing, and regional homologies to a group of neurotoxins suggest that endothelin is an endogenous modulator of voltage-dependent ion channels. Expression of the endothelin gene is regulated by several vasoactive agents, indicating the existence of a novel cardiovascular control system.     

OCIAD2 activates γ-secretase to enhance amyloid β production by interacting with nicastrin

The gamma (γ)-secretase holoenzyme is composed of four core proteins and cleaves APP to generate amyloid beta (Aβ), a key molecule that causes major neurotoxicity during the early stage of Alzheimer’s disease (AD). However, despite its important role in Aβ production, little is known about the regulation of γ-secretase. OCIAD2, a novel modulator of γ-secretase that stimulates Aβ production, and which was isolated from a genome-wide functional screen using cell-based assays and a cDNA library comprising 6,178 genes. Ectopic expression of OCIAD2 enhanced Aβ production, while reduction of OCIAD2 expression suppressed it. OCIAD2 expression facilitated the formation of an active γ-secretase complex and enhanced subcellular localization of the enzyme components to lipid rafts. OCIAD2 interacted with nicastrin to stimulate γ-secretase activity. OCIAD2 also increased the interaction of nicastrin with C99 and stimulated APP processing via γ-secretase activation, but did not affect Notch processing. In addition, a cell-permeable Tat-OCIAD2 peptide that interfered with the interaction of OCIAD2 with nicastrin interrupted the γ-secretase-mediated AICD production. Finally, OCIAD2 expression was significantly elevated in the brain of AD patients and PDAPP mice. This study identifies OCIAD2 as a selective activator of γ-secretase to increase Aβ generation.     

日本和美国的基础设施管理经验及教训研究(英文)

经过20世纪后期大量的建设后,面临着诸如桥梁破坏等新问题。同时,由于全球气候变暖现象,21世纪的基础设施管理制度必须建立在符合总成本效益比最小和防止全球变暖的条件下。文章介绍了日本和美国对社会基础设施的一些管理制度和经验。     

Plasma cyclic 3′,5′-guanosine monophosphate and cyclic 3′,5′-adenosine monophosphate response to methacholine in man

Summary Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man.     

Live imaging of yeast Golgi cisternal maturation

There is a debate over how protein trafficking is performed through the Golgi apparatus. In the secretory pathway, secretory proteins that are synthesized in the endoplasmic reticulum enter the early compartment of the Golgi apparatus called cis cisternae, undergo various modifications and processing, and then leave for the plasma membrane from the late (trans) cisternae. The cargo proteins must traverse the Golgi apparatus in the cis-to-trans direction. Two typical models propose either vesicular transport or cisternal progression and maturation for this process. The vesicular transport model predicts that Golgi cisternae are distinct stable compartments connected by vesicular traffic, whereas the cisternal maturation model predicts that cisternae are transient structures that form de novo, mature from cis to trans, and then dissipate. Technical progress in live-cell imaging has long been awaited to address this problem. Here we show, by the use of high-speed three-dimensional confocal microscopy, that yeast Golgi cisternae do change the distribution of resident membrane proteins from the cis nature to the trans over time, as proposed by the maturation model, in a very dynamic way.     

Stability of magnesite and its high-pressure form in the lowermost mantle

Carbonates are important constituents of marine sediments and play a fundamental role in the recycling of carbon into the Earth's deep interior via subduction of oceanic crust and sediments. Study of the stability of carbonates under high pressure and temperature is thus important for modelling the carbon budget in the entire Earth system. Such studies, however, have rarely been performed under appropriate lower-mantle conditions and no experimental data exist at pressures greater than 80 GPa (refs 3-6). Here we report an in situ X-ray diffraction study of the stability of magnesite (MgCO(3)), which is the major component of subducted carbonates, at pressure and temperature conditions approaching those of the core-mantle boundary. We found that magnesite transforms to an unknown form at pressures above approximately 115 GPa and temperatures of 2,100-2,200 K (depths of approximately 2,600 km) without any dissociation, suggesting that magnesite and its high-pressure form may be the major hosts for carbon throughout most parts of the Earth's lower mantle.     

7-Dehydrosterols in prothoracic glands of the silkworm,Bombyx mori

Summary Sterol analysis of prothoracic glands of the silkworm,Bombyx mori revealed the presence of 7-dehydrocampesterol and 7-dehydrositosterol together with 7-dehydrocholesterol. It was also found that the amounts of these 7-dehydrosterols were increased in proportion to the ecdysone titer.     

Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes

The ezrin-radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.     

NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats

Acidic amino acids, such as glutamate and aspartate, are thought to be excitatory transmitters in the cerebral neocortex and hippocampus. Receptors for these amino acids can be classified into at least three types on the basis of their agonists. Quisqualate-preferring receptors and kainate-preferring receptors are implicated in the mediation of synaptic transmission in many regions including the hippocampus and visual cortex, whereas N-methyl-D-aspartate (NMDA)-preferring receptors are thought to be involved in modulating synaptic efficacy, for example in longterm potentiation, a form of synaptic plasticity in the hippocampus. In the visual cortex of the cat and monkey, it is well established that synaptic plasticity, estimated by susceptibility of binocular responsiveness of cortical neurons to monocular visual deprivation, disappears after the 'critical' period of postnatal development. Here we report that during the critical period in young kittens, a selective NMDA-receptor antagonist blocks visual responses of cortical neurons much more effectively than it does in the adult cat. This suggests that NMDA receptors may be involved in establishing synaptic plasticity in the kitten visual cortex.     

Purification of alpha-ketoaldehyde dehydrogenase from the human liver and its possible significance in the control of glycation

Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.