Rapid and reversible shape changes of molecular crystals on photoirradiation

The development of actuators based on materials that reversibly change shape and/or size in response to external stimuli has attracted interest for some time. A particularly intriguing possibility is offered by light-responsive materials, which allow remote operation without the need for direct contact to the actuator. The photo-response of these materials is based on the photoisomerization of constituent molecules (typically trans-cis isomerization of azobenzene chromophores), which gives rise to molecular motions and thereby deforms the bulk material. This effect has been used to create light-deformable polymer films and gels, but the response of these systems is relatively slow. Here we report that molecular crystals based on diarylethene chromophores and with sizes ranging from 10 to 100 micrometres exhibit rapid and reversible macroscopic changes in shape and size induced by ultraviolet and visible light. We find that on exposure to ultraviolet light, a single crystal of 1,2-bis(2-ethyl-5-phenyl-3-thienyl)perfluorocyclopentene changes from a square shape to a lozenge shape, whereas a rectangular single crystal of 1,2-bis(5-methyl-2-phenyl-4-thiazolyl)perfluorocyclopentene contracts by about 5-7 per cent. The deformed crystals are thermally stable, and switch back to their original state on irradiation with visible light. We find that our crystals respond in about 25 microseconds (that is, about five orders of magnitude faster than the response time of the azobenzene-based polymer systems) and that they can move microscopic objects, making them promising materials for possible light-driven actuator applications.     

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.     

Interkinetic nuclear migration: beyond a hallmark of neurogenesis

Interkinetic nuclear migration (INM) is an oscillatory nuclear movement that is synchronized with the progression of the cell cycle. The efforts of several researchers, following the first report of INM in 1935, have revealed many of the molecular mechanisms of this fascinating phenomenon linking the timing of the cell cycle and nuclear positioning in tissue. Researchers are now faced with a more fundamental question: is INM important for tissue, particularly brain, development? In this review, I summarize the current understanding of the regulatory mechanisms governing INM, investigations involving several different tissues and species, and possible explanations for how nuclear movement affects cell-fate determination and tissue formation.     

Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta

Eutherian placenta, an organ that emerged in the course of mammalian evolution, provides essential architecture, the so-called feto-maternal interface, for fetal development by exchanging nutrition, gas and waste between fetal and maternal blood. Functional defects of the placenta cause several developmental disorders, such as intrauterine growth retardation in humans and mice. A series of new inventions and/or adaptations must have been necessary to form and maintain eutherian chorioallantoic placenta, which consists of capillary endothelial cells and a surrounding trophoblast cell layer(s). Although many placental genes have been identified, it remains unknown how the feto-maternal interface is formed and maintained during development, and how this novel design evolved. Here we demonstrate that retrotransposon-derived Rtl1 (retrotransposon-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice.     

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.     

G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody

G-protein-coupled receptors are the largest class of cell-surface receptors, and these membrane proteins exist in equilibrium between inactive and active states. Conformational changes induced by extracellular ligands binding to G-protein-coupled receptors result in a cellular response through the activation of G proteins. The A(2A) adenosine receptor (A(2A)AR) is responsible for regulating blood flow to the cardiac muscle and is important in the regulation of glutamate and dopamine release in the brain. Here we report the raising of a mouse monoclonal antibody against human A(2A)AR that prevents agonist but not antagonist binding to the extracellular ligand-binding pocket, and describe the structure of A(2A)AR in complex with the antibody Fab fragment (Fab2838). This structure reveals that Fab2838 recognizes the intracellular surface of A(2A)AR and that its complementarity-determining region, CDR-H3, penetrates into the receptor. CDR-H3 is located in a similar position to the G-protein carboxy-terminal fragment in the active opsin structure and to CDR-3 of the nanobody in the active β(2)-adrenergic receptor structure, but locks A(2A)AR in an inactive conformation. These results suggest a new strategy to modulate the activity of G-protein-coupled receptors.     

PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos

The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.     

UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis

Microglia, brain immune cells, engage in the clearance of dead cells or dangerous debris, which is crucial to the maintenance of brain functions. When a neighbouring cell is injured, microglia move rapidly towards it or extend a process to engulf the injured cell. Because cells release or leak ATP when they are stimulated or injured, extracellular nucleotides are thought to be involved in these events. In fact, ATP triggers a dynamic change in the motility of microglia in vitro and in vivo, a previously unrecognized mechanism underlying microglial chemotaxis; in contrast, microglial phagocytosis has received only limited attention. Here we show that microglia express the metabotropic P2Y6 receptor whose activation by endogenous agonist UDP triggers microglial phagocytosis. UDP facilitated the uptake of microspheres in a P2Y6-receptor-dependent manner, which was mimicked by the leakage of endogenous UDP when hippocampal neurons were damaged by kainic acid in vivo and in vitro. In addition, systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in messenger RNA encoding P2Y6 receptors that colocalized with activated microglia were observed. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and could function as a sensor for phagocytosis by sensing diffusible UDP signals, which is a previously unknown pathophysiological function of P2 receptors in microglia.     

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

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.     

基于人脑相关模型的视觉时间和空间感

一种典型的时间性的感觉是对于闪烁灯光缺失基频的现象.对此可用从信号的自相关函数(ACF)中导出的时间性因子加以描述.此方法与关于复音的音调评价所采用的方法相类似.此外,视觉的空间感,例如纹理感,包括对比、韵律和粗糙度,这些感觉也可用从灰度的ACF中导出的因子加以描述.其主观优选条件已经从其与时间和空间因子的关系中找出.文中还发现大脑的活动与对视觉有关的时间性因子的主观优选具有良好的对应性,当时间因子改变时,左脑的α波形更为显著.该理论结合时间和空间值可应用于实现更佳的视觉环境.此项关于时间性设计的新概念也可应用于建筑与环境设计中,人们可从2001年以来发表于网页http://www.jtdweb.org/中的文献里得到更多的关于JTD的信息.