ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

Magnetic shape-memory effects in a crystal

Magnetic fields affect the motion of electrons and the orientation of spins in solids, but are thought to have little impact on crystal structure, particularly in compounds with low magnetic susceptibility, such as antiferromagnets. Here we describe an unexpected magnetic effect on crystal shape, in which the direction of the crystal's axes are swapped and the shape changes when a magnetic field is applied; this in turn induces curious memory effects in resistivity and magnetic susceptibility. Ironically, this phenomenon occurs in one of the most well-studied two-dimensional antiferromagnets, La(2-x)Sr(x)CuO(4).     

Calcitonin gene related peptide stimulates adenylate cyclase activity in rat striated muscle

Summary Rat calcitonin gene related peptide (CGRP) and salmon calcitonin (CT) stimulated adenylate cyclase activity in a dose-dependent manner in the rat diaphragm and in the kidney. The ED₅₀ value of rat CGRP was lower and that of salmon CT was higher in the diaphragm than in the kidney. These results suggest that CGRP stimulates adenylate cyclase activity in the striated muscle by reacting with sites distinct from the site in the kidney.     

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.     

四川华蓥二叠-三叠系界线剖面稳定碳同位素变化特征及其生物地球化学循环成因

对四川华蓥楼房湾剖面稳定碳同位素进行的研究表明,该地区二叠-三叠系界线附近碳同位素变化趋势与全球变化基本一致。早三叠世早期ΔB平均值高于晚二叠世晚期,指示海水中磷酸盐浓度的增大和初级生产力的繁盛。从晚二叠世末期开始δ13Ccarb的缓慢降低是由大规模火山作用以及陆地风化作用加强造成的;早三叠世最早期δ13Ccarb和δ13Corg的快速同步降低所代表的全球碳循环变化主要受控于生物集群绝灭的主幕及海平面上升引起的底部缺氧水上涌。总之,二叠-三叠纪之交碳同位素变化是火山作用、海平面变化、海洋和陆地生物集群绝灭以及缺氧水上涌等因素综合作用的结果。     

安徽东至早奥陶世红花园组生物礁:奥陶纪生物大辐射前的微生物礁

通过对安徽东至建新剖面红花园组的生物礁、微生物岩进行研究,发现蓝绿菌类Girvanella在生物礁中大量分布,是生物礁的主要造礁成分。其他造礁生物包括瓶筐虫、石海绵、腹足类、腕足类、棘皮类等。Girvanella以散乱分布、包壳、组成内碎屑以及与海绵伴生等4种方式在本区生物礁中存在,并且在生物礁成礁过程中以生物本体矿化作用及粘结、捕获颗粒的作用形成生物礁格架;瓶筐虫及石海绵为生物礁中的居住者,因此,生物礁性质为瓶筐虫/石海绵-微生物礁,微生物起到了主要的造礁作用。此外红花园组典型含生物礁沉积序列是由底部的生屑灰岩基底、中部的海绵层(少量微生物岩)及顶部的微生物岩组成的。通过与其他地区同时代生物礁的对比发现,东至建新剖面红花园组中瓶筐虫/石海绵-微生物礁的发育及微生物的繁盛是全球性的,是由于底栖生物扰动对潮下带微生物发育影响尚未彰显造成的。     

Perlecan is essential for cartilage and cephalic development.

Perlecan, a large, multi-domain, heparan sulfate proteoglycan originally identified in basement membrane, interacts with extracellular matrix proteins, growth factors and receptors, and influences cellular signalling. Perlecan is present in a variety of basement membranes and in other extracellular matrix structures. We have disrupted the gene encoding perlecan (Hspg2) in mice. Approximately 40% of Hspg2-/- mice died at embryonic day (E) 10.5 with defective cephalic development. The remaining Hspg2-/- mice died just after birth with skeletal dysplasia characterized by micromelia with broad and bowed long bones, narrow thorax and craniofacial abnormalities. Only 6% of Hspg2-/- mice developed both exencephaly and chondrodysplasia. Hspg2-/- cartilage showed severe disorganization of the columnar structures of chondrocytes and defective endochondral ossification. Hspg2-/- cartilage matrix contained reduced and disorganized collagen fibrils and glycosaminoglycans, suggesting that perlecan has an important role in matrix structure. In Hspg2-/- cartilage, proliferation of chondrocytes was reduced and the prehypertrophic zone was diminished. The abnormal phenotypes of the Hspg2-/- skeleton are similar to those of thanatophoric dysplasia (TD) type I, which is caused by activating mutations in FGFR3 (refs 7, 8, 9), and to those of Fgfr3 gain-of-function mice. Our findings suggest that these molecules affect similar signalling pathways.     

日本传统“诗吟”中单个反射声优选时延与自相关函数的关系

研究在日本传统“诗吟”表演中，在干信号中加上适当时延的单个反射声是否更为有利．专业“诗吟”表演者嗓音中对典型的“节”的吟唱是该种表演艺术的一种独特的吟咏方式．对此及对“节”外内容的吟唱都在消音室中加以录音．文中通过成对比较法试验得出了主观优选的标度值．结果表明，在聆听对“节”的吟唱时，听者更喜欢在干信号中加上延时为10～30ms的单个反射声，而在聆听对“节”外内容的吟唱时，加上单个反射声与否对听者而言并无显著的差别．文中对此项发现从吟唱“节”的声源信号的自相关函数的包络特征上加以讨论．     

Ferroelectricity from iron valence ordering in the charge-frustrated system LuFe2O4

Ferroelectric materials are widely used in modern electric devices such as memory elements, filtering devices and high-performance insulators. Ferroelectric crystals have a spontaneous electric polarization arising from the coherent arrangement of electric dipoles (specifically, a polar displacement of anions and cations). First-principles calculations and electron density analysis of ferroelectric materials have revealed that the covalent bond between the anions and cations, or the orbital hybridization of electrons on both ions, plays a key role in establishing the dipolar arrangement. However, an alternative model-electronic ferroelectricity-has been proposed in which the electric dipole depends on electron correlations, rather than the covalency. This would offer the attractive possibility of ferroelectric materials that could be controlled by the charge, spin and orbital degrees of freedom of the electron. Here we report experimental evidence for ferroelectricity arising from electron correlations in the triangular mixed valence oxide, LuFe(2)O(4). Using resonant X-ray scattering measurements, we determine the ordering of the Fe(2+) and Fe(3+) ions. They form a superstructure that supports an electric polarization consisting of distributed electrons of polar symmetry. The polar ordering arises from the repulsive property of electrons-electron correlations-acting on a frustrated geometry.