Channel properties of an insect neuronal acetylcholine receptor protein reconstituted in planar lipid bilayers

A pentameric membrane protein composed of four types of polypeptide has been identified as the minimal structural unit responsible for the electrogenic action of acetylcholine on electrocytes and muscle cells. Because many populations of central and peripheral neurons also have nicotinic acetylcholine receptors (AChRs), considerable effort has recently gone into identifying the neuronal receptor. The central nervous tissue of insects contains very high concentrations of nicotinic AChRs, and we have recently purified an alpha-toxin binding protein, a putative AChR, from neuronal membranes of locusts. It is a component of high relative molecular mass, clearly composed of identical subunits, a structure predicted for an ancestral AChR protein. To verify that the purified polypeptides not only represent ligand binding sites but that they are indeed functional receptors, we have now reconstituted the isolated protein in a planar lipid bilayer. We show that in this system cholinergic agonists activate functional ion channels, that have properties comparable to those exhibited by the peripheral AChRs in vertebrates; thus, for the first time a functional acetylcholine receptor channel has been identified in nerve cells.     

Rapid kinetics of second messenger formation in olfactory transduction

Olfactory transduction is thought to be mediated by a membrane-bound receptor protein initiating a multistep reaction cascade which ultimately leads to a depolarizing generator current. There is considerable evidence for the involvement of adenylate cyclase in vertebrate olfactory transduction, and some data indicate that phospholipase C may have a central role in insect olfaction. However, one must show that odorants not only stimulate enzyme activity but also induce changes in concentrations of relevant second messengers. One important criterion for a candidate second messenger of chemo-electrical transduction is that its formation must precede the onset of the odorant-induced membrane permeability changes which proceed on a subsecond time-scale. Here we report an odorant-induced, transient accumulation of cyclic AMP in isolated olfactory cilia from rats, and the generation of inositol trisphosphate in antennal preparations from insects, both of which show subsecond time courses that are sufficiently rapid to mediate the odorant-regulated permeability of olfactory receptor cells.     

In situ experimental evidence of the fate of a phytodetritus pulse at the abyssal sea floor

More than 50% of the Earth' s surface is sea floor below 3,000 m of water. Most of this major reservoir in the global carbon cycle and final repository for anthropogenic wastes is characterized by severe food limitation. Phytodetritus is the major food source for abyssal benthic communities, and a large fraction of the annual food load can arrive in pulses within a few days. Owing to logistical constraints, the available data concerning the fate of such a pulse are scattered and often contradictory, hampering global carbon modelling and anthropogenic impact assessments. We quantified (over a period of 2.5 to 23 days) the response of an abyssal benthic community to a phytodetritus pulse, on the basis of 11 in situ experiments. Here we report that, in contrast to previous hypotheses, the sediment community oxygen consumption doubled immediately, and that macrofauna were very important for initial carbon degradation. The retarded response of bacteria and Foraminifera, the restriction of microbial carbon degradation to the sediment surface, and the low total carbon turnover distinguish abyssal from continental-slope 'deep-sea' sediments.     

Metallo-β-lactamases: two binding sites for one catalytic metal ion?

During the past few years the results from molecular biological, biochemical, chemical, physical and theoretical approaches expanded the knowledge about metallo-beta-lactamases considerably. The main reason for the attracted interest is a persisting medical problem. Bacteria expressing metallo-beta-lactamases can be resistant to treatment with all the known beta-lactam antibiotics, and they are additionally invulnerable to combined treatment with inhibitors for the wider-spread serine-beta-lactamases. However, clinically useful inhibitors for metallo-beta-lactamases are not yet available. In spite of the rapidly expanding knowledge base a central question is still controversially discussed: is it the mononuclear, the binuclear or the metal-free state which might serve as the physiologically relevant target for inhibitor design? A summary of the present views of the roles and coordination geometries of metal ion(s) in metallo-beta-lactamases is combined with a discussion of the possibly variable metal ion content under physiological conditions.     

Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus

The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses, may be a feature shared by the virulent influenza viruses.     

MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity

Following homozygosity mapping in a single kindred, we identified nonsense and missense mutations in MYO5B, encoding type Vb myosin motor protein, in individuals with microvillus inclusion disease (MVID). MVID is characterized by lack of microvilli on the surface of enterocytes and occurrence of intracellular vacuolar structures containing microvilli. In addition, mislocalization of transferrin receptor in MVID enterocytes suggests that MYO5B deficiency causes defective trafficking of apical and basolateral proteins in MVID.     

The analytical concept of a chemical element in the work of Bergman and Scheele

In Thomas Thomson's System of chemistry of 1802 Bergman and Scheele are actually considered as creators of the analytical concept of an element. With regard to this, a detailed investigation of the work of Bergman and Scheele shows that Thomson's statement contains mistakes as well as inadmissable simplifications and generalizations. It is correct, however, that Bergman in 1774–1777 specifically anticipated in essential aspects the analytical element concept proposed by Lavoisier in 1787–1789.     

锂离子聚合物电池电量的非线性贝叶斯估计(英文)

精确的电量估计对于电池控制系统有着非常重要的意义.为此提出一种新颖的锂离子聚合物电池模型,其电量估计将由非线性贝叶斯推断方法来实现.