Orientierte Kristallabscheidung (Epitaxie) auf pflanzlichen Zellwänden

Summary Oriented overgrowth (epitaxy) of the needle-like crystals of pentachlorophenol on the surface of the cell walls of parenchyma is described. By means of this epitaxy it is possible to obtain an insight into the orientation of the cellulose microfibrils on the wall surface of plant cells.     

Instruments and rules: R. B. Woodward and the tools of twentieth-century organic chemistry

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation — such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy — through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of ‘rule-based’ theories; and in an increased focus on synthesis, at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This ‘Instrumental Revolution’ in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward (1917–1979) provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry.     

Resculpting the binding pocket of APC superfamily LeuT-fold amino acid transporters

Amino acid transporters are essential components of prokaryote and eukaryote cells, possess distinct physiological functions, and differ markedly in substrate specificity. Amino acid transporters can be both drug targets and drug transporters (bioavailability, targeting) with many monogenic disorders resulting from dysfunctional membrane transport. The largest collection of amino acid transporters (including the mammalian SLC6, SLC7, SLC32, SLC36, and SLC38 families), across all kingdoms of life, is within the Amino acid-Polyamine-organoCation (APC) superfamily. The LeuT-fold is a paradigm structure for APC superfamily amino acid transporters and carriers of sugars, neurotransmitters, electrolytes, osmolytes, vitamins, micronutrients, signalling molecules, and organic and fatty acids. Each transporter is specific for a unique sub-set of solutes, specificity being determined by how well a substrate fits into each binding pocket. However, the molecular basis of substrate selectivity remains, by and large, elusive. Using an integrated computational and experimental approach, we demonstrate that a single position within the LeuT-fold can play a crucial role in determining substrate specificity in mammalian and arthropod amino acid transporters within the APC superfamily. Systematic mutation of the amino acid residue occupying the equivalent position to LeuT V104 titrates binding pocket space resulting in dramatic changes in substrate selectivity in exemplar APC amino acid transporters including PAT2 (SLC36A2) and SNAT5 (SLC38A5). Our work demonstrates how a single residue/site within an archetypal structural motif can alter substrate affinity and selectivity within this important superfamily of diverse membrane transporters.     

Magnetische Kernresonanz und Festkörperphysik

Summary Nuclear magnetic resonance (NMR) deals with isotopes possessing a nuclear magnetic dipole moment. The nuclei are used as probes to explore the internal magnetic fields in solids. Thus NMR has become a new tool in solid-state physics. Some typical examples of the application of NMR to solid-state problems are discussed.The location and orientation of water molecules in crystals are determined by NMR with relative ease. The second moment of an NMR line shape yields information on the structure as well as on the mobility of the atoms. The various types of resonance frequency shifts may be used for the understanding of the interactions and bonds in the solid and the dynamics of the crystal lattice.Very important are nuclei possessing both a magnetic dipole and an electric quadrupole moment. They serve as very sensitive detectors of the internal electric fields prevailing in solids. Apart from further structural information, NMR spectra influenced by electric quadrupole interaction may be used for studying such topics as aluminium-silicon ordering in feldspars or phase transitions in ferroelectrics.The utility of NMR in treating problems of the bonding is exemplified by showing that the covalent effects in the alkali halides are very small.Some investigations of ferromagnetism, antiferromagnetism and superconductivity are mentioned.     

Calcium and disease: molecular determinants of calcium crystal deposition diseases

Deposition of basic calcium phosphate (hydroxyapatite, octacalcium phosphate and tricalcium phosphate) (BCP) and crystalline calcium pyrophosphate dihydrate (CPPD) is associated with a variety of aging-related pathologies, including osteoarthritis, cartilage degeneration and pseudogout. These diseases of calcium deposition serve as some of the best-studied examples of how calcium-regulated changes in gene expression can directly lead to pathogenic consequences. Tissue damage can result when crystals stimulate cells to release matrix-degrading molecules or secrete cytokines that stimulate the release of matrix-degrading molecules. Exposure of cultured cells to crystals induces expression of cellular proto-oncogenes such as c-fos, c-myc and c-jun, by a calcium-dependent mechanism, and this response can be blocked by a potential therapeutic compound, phosphocitrate. Activation of the c-fos and c-jun genes is directly involved in expression of metalloproteinases such as collagenase and stromelysin, suggesting that crystal-mediated activation of these genes is directly involved in pathogenesis. In this review recent advances in the molecular mechanisms responsible for crystal-mediated cell activation are discussed.     

Structural and biological aspects of carotenoid cleavage

Apo-carotenoid compounds such as retinol (vitamin A) are involved in a variety of cellular processes and are found in all kingdoms of life. Instead of being synthesized from small precursors, they are commonly produced by oxidative cleavage and subsequent modification of larger carotenoid compounds. The cleavage reaction is catalyzed by a family of related enzymes, which convert specific substrate double bonds to the corresponding aldehydes or ketones. The individual family members differ in their substrate preference and the position of the cleaved double bond, giving rise to a remarkable number of products starting from a limited number of carotenoid substrate molecules. The recent determination of the structure of a member of this family has provided insight into the reaction mechanism, showing how substrate specificity is achieved. This review will focus on the biochemistry of carotenoid oxygenases and the structural determinants of the cleavage reaction.     

Über die Gestalt von Fadenmolekülen in Lösung

Summary Some arguments put forward byG. Bier in a recent article in order to supportH. Staudinger's assumption that chain molecules in solution should behave like straight rigid rods are examined. It is shown that the assumptions made byG. Bier are largely arbitrary. The main argument is the assumption that the C-C-bond in long chain molecules should not show any rotation. As far as this point is concerned, attention is drawn to some recent publications showing that the viscosity of shape of chain molecules can be determined by experiment (specific viscosity and double refraction of flow at high velocity gradients). According to these determinations the time necessary for a complete change of shape, using partially free rotation, is of the order of 10^–5–10^–3 seconds for molecules like nitrocellulose or polystyrene up to degrees of polymerization of several thousands and for viscosities of the solvent of the order of 10^–2 poises.     

Degradation of collagen by the cariogenic bacteria, Streptococcus mutans

The behaviour of cariogenic Bacteria (Streptococcus mutans) is studied with regard to collagen, which represents 90% of the dentine organic matrix. Collagenase activity of cariogenic Bacteria is measured with radioactive precursors and gel electrophoresis and compared to reference bacterial collagenase (Clostridium histolyticum). Labelled collagen substrate has been prepared with two different methods: extraction by 0,5 M acetic acid from young Rat skin, previously labelled with L-proline 14C, or reduction by Na B3H4. Both collagen sutstrates have been incubated for 2 h in Terleckyj medium in which the Streptococcus mutans have been inoculated. The experiments show a proteolytic activity of Streptococcus Mutans on the collagen substrate.     

Ni2MnGa铁磁形状记忆材料

铁磁形状记忆合金 (FSMA)是在一定温度范围马氏体相稳定同时又具铁磁性的一类特殊的形状记忆合金。Ni2MnGa铁磁形状记忆合金近年来成为呈现磁场驱动大应变的新型驱动材料 ,这些应变来自磁场诱发马氏体孪晶的重排 ,而不是磁场对奥氏体至马氏体相变的作用。孪晶变体的重排在宏观上呈现为正或切应变 ,一非化学计量比Ni2 MnGa单晶于室温加 0 .4T磁场能产生6 %的应变 ,Ni Mn Ga单晶在高至 15 0Hz的交变磁场仍可得到 2 .5 %的应变。本文阐述了与这种磁控形状记忆效应相关的孪晶界迁动的磁学和晶体学理论。马氏体相的大磁晶各向异性能使磁化沿c轴方向有利 ,穿过孪晶界c轴刚好转动 90度 ,同时 ,这个孪晶界也构成了约 90度的畴界。在各向异性的情况下 ,孪晶界的迁动仅有相邻孪晶变体的Zeeman能差驱动 ,μ0 ΔMis·Hi。磁场和外应力对应变的影响通过对一简单的自由能表达式取极小值来表示 ,自由能表达式包括Zeeman能、磁晶各向异性能和外应力以及在某些情况下需考虑的内部弹性能 ,模型的所有参数可通过应力 应变曲线和磁化曲线测量得到。铁磁形状记忆合金的磁场诱发应变可类比传统热弹性形状记忆效应 ,与更为人们所熟知的磁致伸缩现象不同。     

Molecular recognition: Models for drug design

The review takes examples, mostly from the recent literature, to illustrate how an understanding of physico-chemical properties and an appreciation of the molecular shape and electronic properties can lead to a better insight into molecular recognition processes. The techniques used to generate 3-dimensional structures of molecules and the influence this information has had on the drug design cycle, are briefly discussed.     

Molecular recognition: models for drug design.

The review takes examples, mostly from the recent literature, to illustrate how an understanding of physico-chemical properties and an appreciation of the molecular shape and electronic properties can lead to a better insight into molecular recognition processes. The techniques used to generate 3-dimensional structures of molecules and the influence this information has had on the drug design cycle, are briefly discussed.     

Structure and function of the GroE chaperone

The Escherichia coli proteins GroEL and GroES were the first chaperones to be studied in detail and have thus become a role model for assisted protein folding in general. A wealth of both structural and functional data on the GroE system has been accumulated over the past years, enabling us now to understand the basic principles of how this fascinating protein-folding machine accomplishes its task. According to the current model, GroE processes a nonnative polypeptide in a cycle consisting of three steps. First, the polypeptide substrate is captured by GroEL. Upon binding of the co-chaperone GroES and ATP, the substrate is then discharged into a unique microenvironment inside of the chaperone, which promotes productive folding. After hydrolysis of ATP, the polypeptide is released into solution. Moreover, GroE may actively increase the folding efficiency, e.g. by unfolding of misfolded protein molecules. The mechanisms underlying these features, however, are yet not well characterized.     

Therapeutic strategies to ameliorate lysosomal storage disorders – a focus on Gaucher disease

The lysosomal storage disorders encompass more than 40 distinct diseases, most of which are caused by the deficient activity of a lysosomal hydrolase leading to the progressive, intralysosomal accumulation of substrates such as sphingolipids, mucopolysaccharides, and oligosaccharides. Here, we primarily focus on Gaucher disease, one of the most prevalent lysosomal storage disorders, which is caused by an impaired activity of glucocerebrosidase, resulting in the accumulation of the glycosphingolipid glucosylceramide in the lysosomes. Enzyme replacement and substrate reduction therapies have proven effective for Gaucher disease cases without central nervous system involvement. We discuss the promise of chemical chaperone therapy to complement established therapeutic strategies for Gaucher disease. Chemical chaperones are small molecules that bind to the active site of glucocerebrosidase variants stabilizing their threedimensional structure in the endoplasmic reticulum, likely preventing their endoplasmic reticulum-associated degradation and allowing their proper trafficking to the lysosome where they can degrade accumulated substrate to effectively ameliorate Gaucher disease. Received 22 September 2005; received after revision 15 December 2006; accepted 2 February 2006     

Secondary metabolites of the chemically rich ascoglossanCyerce nigricans

Summary Two new metabolites of an apparent propionate origin have been isolated from the organic extract of the ascoglossan molluscCyerce nigricans. The proposed structures for the new natural products are based on interpretation of their physical and spectral properties. The new compounds isolated lacked the potent ichthyodeterrent properties of the whole animal extract suggesting that other molecules are involved in the defense of this shell-less mollusc.     

有机功能材料薄膜与器件

具有光、电、磁物理功能的有机材料的出现促进新思想、新概念、新材料的发展；有机功能材料的电子状态、导电机理以及杂质的影响完全有别于无机金属和半导体，因此，在深入探索结构与功能的关系的基础上，有可能开展分子、聚集态以及器件设计的研究。若与有机化合物的结构多样化，良好的加工性、成膜和成纤性等特点相结合，有可能实现无机电子材料所难兼具的电子行为。进而实现“分子电路”的设想。这里，我们对有机功能材料的基本概念、种类，功能材料薄膜的沉积、器件的构筑，分子电子学和分子器件的概念作了一个较为全面的介绍。