Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic

Members of the opioid receptor family of G-protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system, where they have key roles in nociception and analgesia. Unlike the 'classical' opioid receptors, δ, κ and μ (δ-OR, κ-OR and μ-OR), which were delineated by pharmacological criteria in the 1970s and 1980s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, also known as ORL-1) was discovered relatively recently by molecular cloning and characterization of an orphan GPCR. Although it shares high sequence similarity with classical opioid GPCR subtypes (～60%), NOP has a markedly distinct pharmacology, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. Here we report the crystal structure of human NOP, solved in complex with the peptide mimetic antagonist compound-24 (C-24) (ref. 4), revealing atomic details of ligand-receptor recognition and selectivity. Compound-24 mimics the first four amino-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to the binding of these peptides. The X-ray structure also shows substantial conformational differences in the pocket regions between NOP and the classical opioid receptors κ (ref. 5) and μ (ref. 6), and these are probably due to a small number of residues that vary between these receptors. The NOP-compound-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.     

Identification of precoccinellin in the ladybird beetle,Coleomegilla maculata

Zusammenfassung Isolierung und Strukturzuteilung für ein Alkaloid ausColeomegilla maculata (Coleoptera: Curculionidae).

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Coleoptera: Curculionidae.

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In cooperation with the Mississippi Agricultural and Forestry Experiment Station, Mississippi State, Mississippi 39762. Received for publication.

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Mention of a proprietary product does not necessarily imply endorsement of this product by the USDA.     

Fibre type composition of single motor units during synapse elimination in neonatal rat soleus muscle

Skeletal motor neurones innervate the specialized 'types' of fibres comprising most mammalian muscles in a characteristic fashion: each motor neurone forms a 'motor unit' by innervating a set of fibres all of the same type. Because the type expression of adult muscle fibres is plastic and apparently controlled by their innervation, each motor neurone is thought to impose a common type differentiation on all the fibres in its motor unit. However, the situation in developing muscles cannot be this simple. Muscle fibres in neonates receive synaptic input from several motor neurones and achieve the adult, single innervation only after a period of 'synapse elimination. Despite this polyneuronal innervation, differentiated fibre types are present in neonatal muscles. This means either that the motor neurones polyneuronally innervate fibres in a random fashion and type expression is not determined by innervation or that the polyneuronal innervation is ordered in such a way that each fibre could receive unambiguous instructions for type differentiation. We have investigated these possibilities here by determining the fibre type composition of motor units in neonatal rat soleus muscle. We find that even during the time of polyneuronal innervation each motor neurone confines its innervation to largely one of two fibre types present in the muscle. Therefore, some mechanism during early development segregates the synapses of two groups of soleus motor neurones onto two separate populations of soleus muscle fibres.     

Novel form of growth cone motility involving site-directed actin filament assembly.

Regulation of cytoskeletal structure and motility by extracellular signals is essential for all directed forms of cell movement and underlies the developmental process of axonal guidance in neuronal growth cones. Interaction with polycationic microbeads can trigger morphogenic changes in neurons and muscle cells normally associated with formation of pre- and postsynaptic specializations. Furthermore, when various types of microscopic particles are applied to the lamellar surface of a neuronal growth cone or motile cell they often exhibit retrograde movement at rates of 1-6 microns min-1 (refs 3-6). There is strong evidence that this form of particle movement results from translocation of membrane proteins associated with cortical F-actin networks, not from bulk retrograde lipid flow and may be a mechanism behind processes such as cell locomotion, growth cone migration and capping of cell-surface antigens. Here we report a new form of motility stimulated by polycationic bead interactions with the growth-cone membrane surface. Bead binding rapidly induces intracellular actin filament assembly, coincident with a production of force sufficient to drive bead movements. These extracellular bead movements resemble intracellular movements of bacterial parasites known to redirect host cell F-actin assembly for propulsion. Our results suggest that site-directed actin filament assembly may be a widespread cellular mechanism for generating force at membrane-cytoskeletal interfaces.     

Variation in intestinal serotonin levels,and the effect of reserpine in sprague-dawley rats from different sources

Zusammenfassung Es wurde ein statistisch gesicherter unterschiedlicher Serotoningehalt im Darmtraktus zweier unabhängig gezüchteter Rattengruppen von Sprague-Dawley Abstammung und ihre unterschiedliche Ansprechbarkeit auf die Serotonin entleerende Wirkung des Reserpins gefunden.     

外耦合布拉格光栅5um量子级联激光器

窄带宽的AlGaAs/GaAs布拉格光栅耦合到InP的半导体量子级联激光器从而产生稳定的激光频谱,其激 光谱线宽度在1纳米左右。如果不加光栅，非稳定的自由激射的激光器的谱线宽度有30nm左右。隔离的分布式布 拉格光栅可以独立调谐几个纳米。