bluuebunny/crossref_metadata_2025 huggingface dataset:
Time–resolved capacitance measurements: monitoring exocytosis in single cells
Authors: Lindau Manfred
Published: March 2009

Many cells release preformed material contained in secretory granules by exocytosis. Exocytosis is a specialized means of secretion in which the granules fuse with the plasma membrane and thereby discharge their contents through the fusion pores. This mechanism mediates, for example, the formation of the fertilization envelope in eggs, the release of neurotransmitters and neuropeptides by neurons, the release of a variety of enzymes and mediators by mast cells and granulocytes or the secretion of hormones by endocrine cells. Classical methods for investigating exocytosis usually measure release of secreted material.
Microscopic behaviour of DNA during electrophoresis: electrophoretic orientation
Authors: Nordén Bengt , Elvingson Christer , Jonsson Mats , Åkerman Björn
Published: March 2009

The study of the behaviour of DNA when subjected to electric fields poses several intriguing problems of fundamental physico-chemical importance. Electric field (Kerr effect) orientation of DNA in free solution as well as migration of DNA in gel electrophoresis are two well-established, but so far rather separate, research fields. Whereas the first one has been generally concerned with basic structural and dynamical properties of DNA (Charney, 1988), the second is closely related to techniques of molecular biology (for a review on DNA electrophoresis, see stellwagen 1987).
DNA–carcinogen interaction: covalent DNA-adducts of benzo(a)pyrene 7, 8-dihydrodiol 9, 10-epoxides studied by biochemical and biophysical techniques
Authors: Gräslund Astrid , Jernström Bengt
Published: March 2009

Exposure to various chemicals, either due to occupation or lifestyle, is considered to be a major contributing factor to tumour formation in man (Higginson, 1969; Doll & Peto, 1981). An important and prevalent class of potent carcinogenic compounds present in the environment is polycyclic aromatic hydrocarbons (PAHs), which are found in various petroleum and combustion products derived from heat and power generation and motor vehicle exhausts (Baum, 1978). Furthermore, since PAHs are generally formed by pyrolysis of organic matters such as tobacco smoking and certain procedures of food preparation, the PAH exposure to humans is extensive.
The application of the molecular replacement method to thede novodetermination of protein structure
Authors: Lawrence Michael C.
Published: March 2009

The determination of a novel protein structure by X-ray diffraction is seldom straightforward. Three hurdles present themselves (i) the protein must be purified in sufficient quantity to allow crystallization trials, (ii) crystals must be grown to adequate size and must diffract to a resolution that will allow atomic detail to be revealed, and (iii) phases must be determined for the diffracted X-ray beams in order that an initial electron-density map may be calculated.
RNA structure and NMR spectroscopy
Authors: Varani Gabriele , Tinoco Ignacio
Published: March 2009

RNA molecules perform a wide variety of biological functions, from enzymic activity to storage and propagation of genetic information.
Methodology of magnetic resonance imaging
Authors: Ernst R. R.
Published: March 2009

A survey of magnetic resonance imaging techniques is presented. Emphasis is put on the basic types of measurement procedures rather than, discussing all variants proposed so far. The general experimental procedure consists of two phases, the preconditioning period and the image formation period. While the preconditioning period determines the image contrast, the image formation process is responsible for image resolution. Means to improve sensitivity and to minimize measurement time are discussed.
Sequence-specific assignments and their use in NMR studies of DNA structure
Authors: Reid B. R.
Published: March 2009

There has been a surge of recent interest, reflected by a sharp increase in the number of publications, in the area of high-resolution nuclear magnetic resonance (NMR) studies of DNA. The goal of many of these studies is to monitor the structure of biologically important DNA sequences directly in solution; the impetus for such studies was the realization, from early single-crystal X-ray structures, that nearest-neighbor context effects are a major determinant of local structure in short double-helical DNAs (Dickerson & Drew, 1981; Dickerson, 1983). Thus, instead of the previously assumed regular averaged structure of the double helix derived from fibre diffraction analysis, the more interesting concept emerged that specific sequence-dependent distortions from ‘classical’ DNA structure might be responsible for the recognition of such sequences by a variety of ligands such as repressors, polymerases, drugs, etc.
The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains
Authors: Walker John E.
Published: March 2009

The inner membranes of mitochondria contain three multi-subunit enzyme complexes that act successively to transfer electrons from NADH to oxygen, which is reduced to water (Fig. I). The first enzyme in the electron transfer chain, NADH:ubiquinone oxidoreductase (or complex I), is the subject of this review. It removes electrons from NADH and passes them via a series of enzyme-bound redox centres (FMN and Fe-S clusters) to the electron acceptor ubiquinone. For each pair of electrons transferred from NADH to ubiquinone it is usually considered that four protons are removed from the matrix (see section 4.1 for further discussion of this point).
Cryo-electron microscopy of vitrified specimens
Authors: Dubochet Jacques , Adrian Marc , Chang Jiin-Ju , Homo Jean-Claude , Lepault Jean , McDowall Alasdair W. , Schultz Patrick
Published: March 2009

Cryo-electron microscopy of vitrified specimens was just emerging as a practical method when Richard Henderson proposed that we should teach an EMBO course on the new technique. The request seemed to come too early because at that moment the method looked more like a laboratory game than a useful tool. However, during the months which ellapsed before the start of the course, several of the major difficulties associated with electron microscopy of vitrified specimens found surprisingly elegant solutions or simply became non-existent. The course could therefore take place under favourable circumstances in the summer of 1983. It was repeated the following years and cryo-electron microscopy spread rapidly. Since that time, water, which was once the arch enemy of all electronmicroscopists, became what it always was in nature – an integral part of biological matter and a beautiful substance.
Structure and dynamics of polypeptides and proteins in lipid membranes
Authors: Vogel Horst
Published: March 2009

The elucidation of the molecular mechanisms whereby ions and polar molecules are translocated across the hydrophobic barrier of a lipid bilayer in biological membranes is one of the most challenging problems in biological research. Specific membrane proteins, such as pumps, carriers and channels, play the central role in the various translocation pathways. Recent progress in expression cloning has provided the sequence of a number of biologically important membrane proteins and in principle the door is open to investigate every protein which might be of importance in the central signal transduction and transport processes. Unfortunately, to date there are only a few examples where the three-dimensional structure of membrane proteins are known at atomic resolution. The photosynthetic reaction centres from purple bacteria (Deisenhoferet al.1985), bacteriorhodopsin (Hendersonet al.1990) and the large porin channel ofRhodobacter capsulata(Weisset al.1991). According to these structural data membrane proteins seem to fold in general in membrane-spanning α-helices and β-strands in order to saturate hydrogen bonds. Only these two motifs seem to form stable structures which can be in contact with the hydrophobic lipid interior of a membrane.
Theoretical perspectives on ion-channel electrostatics: continuum and microscopic approaches
Authors: Partenskii Michael B. , Jordan Peter C.
Published: March 2009

Peter Läuger introduced me (P.C.J.) to the field of ion-channel electrostatics while I was a sabbatical visitor at Konstanz in 1978–79. Läuger pointed out that the relative conductance of hydrophobic ions through phosphatidyl choline (PC) and glyceryl monooleate (GMO) membranes differed by a factor of about 100 (Hladky & Haydon, 1973), quite consistent with the difference in the water-membrane potential differences in the two systems (Pickar & Benz, 1978). However, cation conductance through gramicidin channels spanning these membranes only differs by a factor of 2–3 (Bamberg et al. 1976). Why? It is the pursuit of an answer to this question which led me into my researches in this field.
Luminescence spectroscopic approaches in studying cell surface dynamics
Authors: Matkó Janos , Szöllösi Janos , Trón Lajos , Damjanovich Sandor
Published: March 2009

The major elements of membranes, such as proteins, lipids and polysaccharides, are in dynamic interaction with each other (Albertset al.1983). Protein diffusion in the lipid matrix of the membrane, the lipid diffusion and dynamic domain formation below and above their transition temperature from gel to fluid state, have many functional implications. This type of behaviour of membranes is often summarized in one frequently used word membrane fluidity (coined by Shinitzky & Henkart, 1979). The dynamic behaviour of the cell membrane includes rotational, translational and segmental movements of membrane elements (or their domain-like associations) in the plane of, and perpendicular to the membrane. The ever changing proximity relationships form a dynamic pattern of lipids, proteins and saccharide moieties and are usually described as ‘cell-surface dynamics’ (Damjanovichet al.1981). The knowledge about the above defined behaviour originates from experiments performed mostly on cytoplasmic membranes of eukaryotic cells. Nevertheless numerous data are available also on the mitochondrial and nuclear membranes, as well as endo (sarco-)plasmic reticulum (Martonosi, 1982; Slater, 1981; Siekevitz, 1981).
Mutational studies of protein structures and their stabilities
Authors: Shortle David
Published: March 2009

The fundamental relationship between structure and function has served to guide investigations into the workings of living systems at all levels - from the whole organism to individual cells on down to individual molecules. When X-ray crystallography began to reveal the three-dimensional structures of proteins like myoglobin, lysozyme and RNase A, protein chemists were well prepared to draw inferences about functional mechanisms from the precise positioning of amino acid residues they could see. The close proximity between an amino acid side chain and a chemical group on a bound ligand strongly suggests a functional role for that side chain in binding affinity and specificity. Likewise, the nearly universal finding of large clusters of hydrophobic side chains buried in the core of proteins strongly supports a major functional role of hydrophobic interactions in protein folding and stability. Even though eminently plausible hypotheses like these, grounded in the most fundamental principles of chemistry and the logic of structure–function relationships, become widely accepted and make their way into textbooks, protein chemists have felt compelled to search for ways to test them and put them on a more quantitative basis.
Two-dimensional crystallization of membrane proteins
Authors: Kühlbrandt W.
Published: March 2009

In spite of several great breakthroughs, the overall rate of progress in determining high-resolution structures of membrane proteins has been slow. This is entirely due to the scarcity of suitable, well-ordered crystals. Most membrane proteins are multimeric complexes with a composite molecular mass in excess of 50000 Da which puts them outside the range of current solution NMR techniques. For the foreseeable future, detailed information about the structure of large membrane proteins will therefore depend on crystallographic methods.
The active transport of ions in plant cells
Authors: MacRobbie E. A. C.
Published: March 2009

In a recent review of the transport of salts and water across multicellular secretory tissues in animals (Keynes, 1969), a summary was given of the various types of active transport of ions necessary to explain the experimental observations in a very wide range of tissues, and five basic types of ion pump were discussed. The question of whether plants and animals have any common mechanisms for the transport of salts and water was specifically excluded. The original aim of the present review was to survey the types of ion pump found in plant cells and tissues, and to compare these with those found in animals. Its aims narrowed very considerably in writing. It now reviews ion transport processes in giant algal cells, and tries to assess progress towards understanding the mechanisms involved. It indicates the existence of similar ion transports in higher plant cells, but it does not present a complete review of the experimental work on higher plants.
Evolution of higher-organism DNA
Authors: Kohne David E.
Published: March 2009

A great deal of information about evolutionary events and processes has been inferred from careful studies of fossil records. Other forms of evidence have also contributed greatly to the understanding of evolution. Comparative biochemistry (Florkin, 1949), immunology (Boyden, 1942), protein sequencing (Dayoff, 1969; Anfinsen, 1959), and early DNA studies (McCarthy & Bolton, 1963; Schildkraut, Marmur & Doty, 1961) have for the most part corroborated earlier evolutionary findings, and at the same time provided new understanding of molecular processes in evolution. Of these approaches the comparison of DNA seems most promising since a relatively precise quantitative comparison can be made of all of the genetic material of different species.
The structure of cornea
Authors: Worthington C. R.
Published: March 2009

The anatomy and physiology of cornea has been described in reviews (Maurice, 1969; Davson, 1980). We are primarily concerned with the structure of the stroma of cornea. There are two levels of organization in the stroma: the collagen fibrils and the lamellae. Each lamella contains an array of collagen fibrils which appear as long thin cylinders in electron micrographs. The lamellae are parallel to the cornea surface and are at right angles to the light direction. Adjacent lamellae are approximately at right angles to each other. There are many lamellae (about 200) in the thickness of the stroma so that the different lamellae have on the average all possible orientations.
Characterization of the distribution of internal motions in the basic pancreatic trypsin inhibitor using a large number of internal NMR probes
Authors: Wagner Gerhard
Published: March 2009

The experimental observations described in this article indicated that a distribution of many different fluctuations is present in a globular protein. These fluctuations were characterized by observation of many natural internal probes such as the labile peptide protons and the aromatic side chains. The conditions which are necessary to get reactions of the internal probes have been discussed in detail. The structural interpretation of the data was facilitated by the development and the use of new NMR techniques which provided the identification of the resonances of all the labile peptide protons. With NOE measurements a distinction between correlated and uncorrelated exchange events was obtained. This enabled us to elucidate the exchange mechanism over a wide range of p2H and temperature and to classify different subsets of fluctuations with respect to their lifetimes. It was further demonstrated that a change of external conditions such as temperature, p2H or pressure can change the distribution of fluctuations in the protein. The mechanisms responsible for rotation of internal aromatic side chains were also found to change with temperature, and mechanistic aspects of these fluctuations were discussed.
Membrane fusion proteins of enveloped animal viruses
Authors: White Judith , Kielian Margaret , Helenius Ari
Published: March 2009

In a living cell membrane-bound compartments are continuously either separated or united through fusion reactions, and literally thousands of such reactions take place every minute. The formation of membrane vesicles from pre-existing membranes, and their fusion with specific acceptor membranes, constitute a prerequisite for the transport of most impermeant molecules and macromolecules into the cell by endocytosis, out of the cell by exocytosis, and between the cellular organelles (Palade, 1975; Silverstein, 1978; Evered & Collins, 1982). Less frequent, but equally crucial, are fusion events in fertilization, cell division, polykaryon formation, enucleation, etc. (for reviews see Poste & Nicholson, 1978). Although a great deal is known about the properties and consequences of individual forms of membrane fusion in cellular systems, and about fusion in artificial lipid membranes, the molecular basis for the reactions remain largely unclear.
Chaos in biological systems
Authors: Olsen Lars Folke , Degn Hans
Published: March 2009

Chaos is a widespread and easily recognizable phenomenon that hardly anybody took notice of until recently. The reason may be that chaos has something profoundly counterintuitive about it. It will not fit easily into any familiar cause–effect frame. The best introduction to chaos is by the way of an example. Consider a leaking faucet (Shaw, 1984). When the weight of the accumulating drop exceeds the surface tension the drop falls and a new drop begins to form. If the leak is small and the pressure in the faucet is constant, the time taken for the drop to reach the critical weight is constant. The dripping is perfectly periodic, the period depending on the leak rate. If the leak is slightly increased, the period of dripping will decrease slightly and vice versa. However, somewhere beyond this point the leaking faucet becomes a nuisance. When the leak is increased beyond a certain point the dripping looses its regularity. The time interval between the drops will first alternate periodically between a short and a long time interval. After a further increase of the leak this double periodic pattern will become unstable and change into a new pattern where four different time intervals between the drops alternate periodically. As the leak is further increased the period will double again and again and finally the dripping becomes completely irregular without any repeating pattern. When this occurs we are observing chaos. At the same time we are posed with the problem of understanding how such a ridiculously simple system can show random behaviour.
Hydrogen exchange and structural dynamics of proteins and nucleic acids
Authors: Englander S. Walter , Kallenbach Neville R.
Published: March 2009

Though the structures presented in crystallographic models of macromolecules appear to possess rock-like solidity, real proteins and nucleic acids are not particularly rigid. Most structural work to date has centred upon the native state of macromolecules, the most probable macromolecular form. But the native state of a molecule is merely its most abundant form, certainly not its only form. Thermodynamics requires that all other possible structural forms, however improbable, must also exist, albeit with representation corresponding to the factor exp( —Gi/RT) for each state of free energyGi(see Moelwyn-Hughes, 1961), and one appreciates that each molecule within a population of molecules will in time explore the vast ensemble ofpossiblestructural states.
NMR studies of enzymatic ratesin vitroandin vivoby magnetization transfer
Authors: Alger J. R. , Shulman R. G.
Published: March 2009

Magnetization transfer techniques are specialized NMR experiments which can measure the rate of chemical reactions while concentrations of products and reactants are maintained constant. These techniques are being used to measure the rates of enzyme catalysed reactions in a variety of living systems andin vitro. The magnetization transfer measurementsin vivoof the ATP synthetase and the creatine kinase reactions have been particularly useful in describing rates of major energy transducing reactions involving ATP and phosphocreatine. As a result, a wide range of biomedicai scientists are becoming aware of the potentials of these techniques. The purpose of this review is thus threefold: first, to present a concise, conceptual review of the underlying principles for these non-specialists; secondly, to review the important biochemical applications of the method which have appeared, and thirdly, to discuss potential applications and limitations of the method.
Electron spin polarization of photosynthetic reactants
Authors: Hoff A. J.
Published: March 2009

Photosynthesis is the conversion of the quantum energy of light into the chemical energy of complex organic molecules and organized cellular structures in plants and in some bacteria. The processes of photosynthesis span the time domain of subpicoseconds to the millennia of slow-growing trees, its study brings together such diverse disciplines as photophysics, biochemistry, botany and ecology. In the last few decades tremendous progress has been made in understanding the multivarious chemical reactions that ultimately lead to the fixation of carbon dioxide into organic substance, yet the basic mechanism underlying the conversion of photon energy into chemical energy still remains very much an enigma. These so-called primary reactions which transduce the excitation energy of excited chlorophyll pigments into the potential energy of stabilized, separated charges on electron donor and electron acceptor molecules have been studied with a variety of physical techniques, among which fast optical spectroscopy and electron paramagnetic resonance (EPR) are prominent. This review will highlight one intriguing aspect of EPR, namely that of electron spin polarization (ESP).† It will be shown that ESP of photosynthetic primary reactants offers a unique tool to gain insight in the electrostatic and magnetic interactions that make photosynthesis work. Moreover, it will become apparent that ESP in photosynthesis has several unique traits not (yet) found in ESP of photochemical reactionsin vitro. As such, it may serve as a paradigma of ESP phenomena and will present an absorbing spectacle also for EPR spectroscopists outside photosynthesis.
Calculations of electrostatic interactions in biological systems and in solutions
Authors: Warshel Arieh , Russell Stephen T.
Published: March 2009

Correlating the structure and action of biological molecules requires knowledge of the corresponding relation between structure and energy. Probably the most important factors in such a structure– energy correlation are associated with electrostatic interactions. Thus the key requirement for quantative understanding of the action of biological molecules is the ability to correlate electrostatic interactions with structural information. To appreciate this point it is useful to compare the electrostatic energy of a charged amino acid in a polar solvent to the corresponding van der Waals energy. The electrostatic free energy, ΔGel, can be approximated (as will be shown in Section II) by the Born formula (ΔGel= –(166Q2/ā) (I – I/E)). Where ΔGelis given in kcal/mol,Qis the charge of the given group, in units of electron charge,āis the effective radius of the group, andEis the dielectric constant of the solvent. With an effective radius of charged amino acids of approximately 2 Å, Born's formula gives about – 80 kcal/mol for their energy in polar solvents whereEis larger than 10. This energy is two orders of magnitude larger than the van der Waals interaction of such groups and their surroundings.
Constraints on the accuracy of messenger RNA movement
Authors: Kurland C. G. , Ehrenberg Måns
Published: March 2009

Theoretical as well as experimental studies of translational accuracy have most often been concerned with the selection of aminoacyl-tRNA by codon-programmed ribosomes. The selection of the successive codons on the mRNA has received much less attention, probably because it represents both conceptually and experimentally, a much more demanding physical problem. Nevertheless, it would seem that errors in the selection of the codon are potentially much more destructive than errors in selection of aminoacyl-tRNA species. This can be appreciated from the following.
Heteronuclear filters in two-dimensional [1H, 1H]-NMR spectroscopy: combined use with isotope labelling for studies of macromolecular conformation and intermolecular interactions
Authors: Otting Gottfried , Wüthrich Kurt
Published: March 2009

The use of heteronuclear filters enables the editing of complex 1H nuclear magnetic resonance (NMR) spectra into simplified subspectra containing a lesser number of resonance lines, which are then more easily amenable to detailed spectral analysis. This editing is based on the creation of heteronuclear two-spin or multiple-spin coherence and discrimination between protons that do or do not participate in these heteronuclear coherences. In principle, heteronuclear editing can be used in conjunction with one-dimensional or multidimensional 1H-NMR experiments for studies of a wide variety of low-molecular-weight compounds or macromolecular systems, and is implicitely applied in a wide range of heteronuclear NMR experiments with proton detection (e.g. Bax et al. 1983; Griffey & Redfield, 1987). In the present article we shall focus on the use of heteronuclear filters in two-dimensional (2D) [1H, 1H]-NMR experiments. The selection of the material covered was primarily motivated by its impact on the practice of protein structure determination in solution, and on NMR studies of intermolecular interactions with biological macromolecules. Section 2 surveys potential applications of heteronuclear filters in this area. The remainder of the article is devoted to an introduction of the theoretical principles used in heteronuclear filters, and to a detailed description of the experimental implementation of these measurements. In writing the review we tried to minimize redundancy with the recent article in Quarterly Review of Biophysics by Griffey & Redfield (1987) and to concentrate on experiments that were introduced during the period 1986–9.
Voltage clamp and tracer flux data: effects of a restricted extra-cellular space
Authors: Attwell David , Eisner David , Cohen Ira
Published: March 2009

In the original Hodgkin & Huxley analysis of the membrane currents in squid giant axon, the time dependence of the currents was attributed to voltage-dependent changes in the permeability of the membrane to the ions involved. According to this theoretical framework, the time constants for the rate of change of current should be unique functions of the membrane potential, and should be independent of the previous history of the voltage and current flowing. In recent years, however, there has been increasing awareness of the fact that, for many physiological preparations, the space just outside the cell membrane is not in good diffusive contact with thebulkextra-cellular fluid perfusing the preparation. Consequently, when current flows across the cell membrane, there are changes in the ion concentrations in this so-called ‘restricted extra-cellular space’ (RECS).
The molecular structure of adrenergic and dopaminergic substances
Authors: Giesecke Johan , Hebert Hans
Published: March 2009

At the end of the last century it was established that the different nerve cells along a neuronal path do not come into direct physical contact with one another, but that there are narrow gaps between them, called synapses (Sherrington, 1897; Ramón y Cajal, 1906). Elliot (1905) made the basic experimental observation that the propagation of nerve impulses across a synapse might be mediated by specific chemical agents (see Fig. i). Such substances are now called neurotransmitters, and some 20 different compounds putatively responsible for synaptic transmission in different parts of the nervous system are known at present, e.g. a few recently isolated polypeptides. The most extensively studied transmitters are acetylcholine and the catecholamine group, consisting of dopamine (a), noradrenaline (b), and adrenaline (c).
Deuterium labelling in NMR structural analysis of larger proteins
Authors: LeMaster David M.
Published: March 2009

In the last few years since the early NMR structural studies of small proteins such as glucagon (Braunet al.1983) andlacrepresser headpiece (Zuiderweget al.1984) the quality of the structure determinations have improved considerably. Of major importance has been the introduction of phase sensitive detection in the Tl dimension (Stateset al.1982; Marion & Wüthrich, 1983) which has allowed for absorption presentation of 2D data with the resulting enhancement in resolution, accuracy of coupling constant measurements and accuracy of peak volume integrations. Introduction of new pulse sequences, advances in instrumentation and further developments in the structure calculation algorithms have also helped improve the quality of NMR structural analyses of proteins.
Structural studies of protein–nucleic acid interaction: the sources of sequence-specific binding
Authors: Steitz Thomas A.
Published: March 2009

Structural studies of DNA-binding proteins and their complexes with DNA have proceeded at an accelerating pace in recent years due to important technical advances in molecular genetics, DNA synthesis, protein crystallography and nuclear magnetic resonance. The last major review on this subject by Pabo & Sauer (1984) summarized the structural and functional studies of the three sequence-specific DNA-binding proteins whose crystal structures were then known, theE. colicatabolite gene activator protein (CAP) (McKay & Steitz, 1981; McKayet al.1982; Weber & Steitz, 1987), acrorepressor from phage λ (Andersonet al.1981), and the DNA-binding proteolytic fragment ofλcIrepressor protein (Pabo & Lewis, 1982) Although crystallographic studies of theE. coli lacrepressor protein were initiated as early as 1971 when it was the only regulatory protein available in sufficient quantities for structural studies (Steitzet al.1974), little was established about the structural aspects of DNA-binding proteins until the structure of CAP was determined in 1980 followed shortly thereafter by the structure ofλcrorepressor and subsequently that of the λ repressor fragment. There are now determined at high resolution the crystal structures of seven prokaryotic gene regulatory proteins or fragments [CAP,λcro,λcIrepressor fragment, 434 repressor fragment (Andersonet al.1987), 434crorepressor (Wolbergeret al.1988),E. coli trprepressor (Schevitzet al.1985),E. coli metrepressor (Raffertyet al.1989)],EcoRI restriction endonuclease (McClarinet al.1986), DNAse I (Suck & Ofner, 1986), the catalytic domain of γδ resolvase (Hatfullet al.1989) and two sequence-independent double-stranded DNA-binding proteins [the Klenow fragment ofE. coliDNA polymerase I (Olliset al.1985) and theE. coliHu protein (Tanakaet al., 1984)].
Environmental intoxicants and their fundamental interactions
Authors: Eisinger J. , Blumberg W. E.
Published: March 2009

The biological sciences are and should be responsive to the needs of medicine: thus the deficiency diseases (e.g. ben-ben and scurvy) stimulated the search for vitamins, just as contagious diseases fathered immunology and the study of antibiotics. It has been said that we live in the era of environmental disease, which suggests that an important fraction of human disease in technological societies is induced by environmental conditions, including some which are more commonly referred to as life styles. While this assessment requires further amplification (see below), it is clear that the sheer number and variety of potentially dangerous environmental agents has become so great that a better understanding of their fundamental interactions with the living system is clearly needed. As of the end of 1977, the American Chemical Society's Chemical Abstract Service contained over four million entities, and it is estimated that there are about 63000 chemicals in common usage. The toxicity of only a very small number of these has been investigated.
Determinants of biodegradability
Authors: Dagley Stanley
Published: March 2009

As a consequence of the activities of modern industry and agriculture, many made-made organic compounds have found their way into our environment, and by persisting there for varying periods of time have caused concern to society. Why do some chemicals persist while others disappear? Detailed answers to this question require an understanding of the degradative segment of the earth's carbon cycle, most of the reactions of which are catalysed by enzymes used by microbes. These organisms owe much of their degradative expertise to their ability to render oxygen gas chemically reactive. This is a process that would be extremely dangerous for any living organism if it were carried out in a haphazard or accidental fashion; but when catalysed and cantrolled by enzymes (oxygenases) of micro-organisms, reaction sequences are started that result in biodegradation of compounds that resist the enzymes of all other living forms.
Structure and distribution of modules in extracellular proteins
Authors: Bork Peer , Downing A. Kristina , Kieffer Bruno , Campbell Iain D.
Published: March 2009

It has become standard practice to compare new amino-acid and nucleotide sequences with existing ones in the rapidly growing sequence databases. This has led to the recurring identification of certain sequence patterns, usually corresponding to less than 300 amino-acids in length. Many of these identifiable sequence regions have been shown to fold up to form a ‘domain’ structure; they are often called protein ‘modules’ (see definitions below). Proteins that contain such modules are widely distributed in biology, but they are particularly common in extracellular proteins.
Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants
Authors: Skulachev Vladimir P.
Published: March 2009

To proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2as well as of one-electron O2reductants such asThese two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of, and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2and the O2reductants when phosphorylating respiration fails to do this job due to lack of ADP.

In particular, it is proposed that some increase in the H+leak of mitochondrial membrane in State 4 lowers, stimulates O2consumption and decreases the level ofwhich otherwise accumulates and serves as one-electron O2reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.
The continuous spread of West Nile virus (WNV): seroprevalence in asymptomatic horses
Authors: ALONSO-PADILLA J. , LOZA-RUBIO E. , ESCRIBANO-ROMERO E. , CÓRDOBA L. , CUEVAS S. , MEJÍA F. , CALDERÓN R. , MILIÁN F. , TRAVASSOS DA ROSA A. , WEAVER S. C. , ESTRADA-FRANCO J. G. , SAIZ J. C.
Published: March 2009

West Nile virus (WNV) was probably introduced in southern and northern Mexico from the USA in two independent events. Since then, WNV activity has been reported in several Mexican states bordering the USA and the Gulf of Mexico, but disease manifestations seen there in humans and equids are quite different to those observed in the USA. We have analysed WNV seroprevalence in asymptomatic, unvaccinated equids from two Mexican states where no data had been previously recorded. WNV IgG antibodies were detected in 31·6% (91/288) of equine sera from Chiapas and Puebla states (53·3% and 8·0%, respectively). Analysis by plaque reduction neutralization test (PRNT) showed good specificity (99·4%) and sensitivity (84·9%) with the ELISA results. Further analyses to detect antibodies against three different flaviviruses (WNV, St Louis encephalitis virus, Ilheus virus) by haemagglutination inhibition (HI) tests on a subset of 138 samples showed that 53% of the 83 HI-positive samples showed specific reaction to WNV. These data suggest continuous expansion of WNV through Mexico.
Tip of the iceberg
Authors: DERIABYN M. V. , HJORTH P. G.
Published: March 2009

We study the stability and dynamics of melting icebergs. Specifically, we address the ‘toppling’ or ‘rollover’ observed for floating icebergs. The rollover is thought to occur because the ocean melts the iceberg from below, causing its overall mass and mass distribution to change with time. We model the evolution of equilibrium positions for a general homogeneous body afloat in an ideal fluid, as this homogeneous body is subjected to ‘melting’, i.e. a slow removal of material from the submerged part. If this process is the dominating melting mechanism, can the likelihood of a toppling be inferred from observing only the above-surface part? We show here that some information about the evolution of stability due to melting can be inferred from the surface geometry of the iceberg.
Mathematical models and reconstruction methods in magneto-acoustic imaging
Authors: AMMARI HABIB , CAPDEBOSCQ YVES , KANG HYEONBAE , KOZHEMYAK ANASTASIA
Published: March 2009

In this paper, we provide the mathematical basis for three different magneto-acoustic imaging approaches (vibration potential tomography, magneto-acoustic tomography with magnetic induction and magneto-acoustic current imaging) and propose new algorithms for solving the inverse problem for each of them.
The space of formal balls and models of quasi-metric spaces
Authors: ALI-AKBARI M. , HONARI B. , POURMAHDIAN M. , REZAII M. M.
Published: March 2009

In this paper we study quasi-metric spaces using domain theory. Our main objective in this paper is to study the maximal point space problem for quasi-metric spaces. Here we prove that quasi-metric spaces that satisfy certain completeness properties, such as Yoneda and Smyth completeness, can be modelled by continuous dcpo's. To achieve this goal, we first study the partially ordered set of formal balls (BX, ⊑) of a quasi-metric space (X, d). Following Edalat and Heckmann, we prove that the order properties of (BX, ⊑) are tightly connected to topological properties of (X, d). In particular, we prove that (BX, ⊑) is a continuous dcpo if (X, d) is algebraic Yoneda complete. Furthermore, we show that this construction gives a model for Smyth-complete quasi-metric spaces. Then, for a given quasi-metric space (X, d), we introduce the partially ordered set of abstract formal balls (BX, ⊑, ≺). We prove that if the conjugate space (X, d−1) of a quasi-metric space (X, d) is right K-complete, then the ideal completion of (BX, ⊑, ≺) is a model for (X, d). This construction provides a model for any Yoneda-complete quasi-metric space (X, d), as well as the Sorgenfrey line, Kofner plane and Michael line.
Optimierung der glykämischen Kontrolle und Dosistitration mit Insulin Glargine (Lantus®) durch frei praktizierende Ärzte in der Schweiz: Resultate des OPTI-LAN Praxiserfahrungsberichtes
Authors: Spirk  , Lareida  , Scheidegger  , Diem
Published: March 2009

Rationale: Nationale und internationale Fachgesellschaften haben Richtwerte für die Blutzuckerkontrolle von Diabetikern ausgearbeitet. Klinische Studien haben gezeigt, dass die glykämische Kontrolle der Typ-2-Diabetiker durch Anpassung der Glargine-Insulindosis (Lantus®) anhand einfacher Titrationsschemen verbessert werden kann. Es ist nicht klar, ob und wie die Empfehlungen der Fachgesellschaften in der täglichen klinischen Praxis in der Schweiz umgesetzt werden. Methodik: Wir haben eine Beobachtungsstudie der gängigen Umsetzung der Empfehlungen zu glykämischen Zielwerten und Insulindosistitration an Diabetikern bei 77 frei praktizierenden Ärzten in den drei Sprachregionen der Schweiz durchgeführt. Die prospektive Erfassung der Daten über einen Behandlungszeitraum von 6 Monaten erfolgte zwischen September 2005 und September 2007. Resultate: Das mittlere Alter der insgesamt 317 eingeschlossenen Patienten war 63 ± 11 Jahre, 137 (43%) waren Frauen und 298 (94%) Typ-2-Diabetiker. Die durchschnittliche Diabetesdauer betrug 8 ± 6 Jahre. Am Anfang der Untersuchung wurde ein mittleres HbA1C von 8.9 ± 1.6% und ein Nüchternblutzuckerspiegel von 10.1 ± 3.2 mmol/l gemessen, trotz Therapie mit mindestens einem oralen Antidiabetikum (bei 83% der Patienten) und/oder Insulin (bei 47% der Patienten). Von den behandelnden Ärzten wurde für 284 (90%) eingeschlossene Patienten als Zielwert ein HbA1C von ≤7% und für 245 (77%) Patienten ein Nüchternblutzuckerziel von ≤7 mmol/l gewählt; eine Empfehlung, die den Richtwerten der Schweizerischen Gesellschaft für Endokrinologie und Diabetologie (SGED) entspricht. 33% der Schweizer Ärzte benutzten für die Insulindosisanpassung das von Riddle et al. erarbeitete Schema; dagegen legten 17% der Ärzte die Anpassung unter Zuhilfenahme des von der Amerikanischen bzw. Europäischen Diabetesgesellschaft vorgeschlagenen Schemas in die Hände des Patienten. Während der 6-monatigen Behandlung mit Insulin Glargine (Lantus®) erreichten 196 (62%) Patienten die von der SGED ausgegebenen Zielwerte für die glykämische Kontrolle. Das HbA1C sank im Durchschnitt um 2.1% (von 8.9 auf 6.8) und der Nüchternblutzucker um 3 mmol/l (von 10.1 auf 7.1). Die Insulindosis musste durchschnittlich um 14 IE (von 16 auf 30) erhöht werden. Insgesamt waren 91% der Patienten mit der Durchführbarkeit der Dosistitration zufrieden; bei 64% der Patienten hat die Therapie mit Lantus® zur Verbesserung ihres Wohlbefindens beigetragen und bei 27% der Patienten blieb das Wohlbefinden unverändert. Konklusion: Die Empfehlungen von SGED zur glykämischen Kontrolle werden in der täglichen Routine von den frei praktizierenden Ärzten in der Schweiz sehr gut umgesetzt. Die Behandlung mit Insulin Glargine (Lantus®) erlaubt ein rasches und adäquates Erreichen der empfohlenen glykämischen Zielwerte und trägt dadurch zur Patientenzufriedenheit bei.
Lateralized Repetition Priming for Unfamiliar Faces
Authors: Martin Douglas , Nind Louise K. , Macrae C. Neil
Published: March 2009

Repetition priming (RP) is the ability to recognize a stimulus more rapidly as a result of prior exposure to the item. Recent research examining the neuroanatomical basis of this effect has demonstrated RP for familiar faces presented to the right but not to the left cerebral hemisphere. Extending this line of enquiry, the current research considered whether similar effects emerge when unfamiliar faces are the stimuli of interest. Using a divided-visual-field methodology, RP for unfamiliar faces in the left and the right hemispheres was assessed. The results revealed that RP: (i) only emerges in the right hemisphere; (ii) is evident regardless of whether the lateralized presentation of unfamiliar faces occurs at study or at test and (iii) occurs only when hair is cropped from the faces. The theoretical implications of these findings are considered.
Automatic Selection of Irrelevant Object Features Through Working Memory
Authors: Soto David , Humphreys Glyn W.
Published: March 2009

Recent research has shown that the contents of working memory (WM) can guide the early deployment of attention in visual search. Here, we assessed whether this guidance occurred for all attributes of items held in WM, or whether effects are based on just the attributes relevant for the memory task. We asked observers to hold in memory just the shape of a coloured object and to subsequently search for a target line amongst distractor lines, each embedded within a different object. On some trials, one of the objects in the search display could match the shape, the colour or both dimensions of the cue, but this object never contained the relevant target line. Relative to a neutral baseline, where there was no match between the memory and the search displays, search performance was impaired when a distractor object matched both the colour and the shape of the memory cue. The implications for the understanding of the interaction between WM and selection are discussed.
Translation Priming Between the Native Language and a Second Language
Authors: Duyck Wouter , Warlop Nele
Published: March 2009

During the last two decades, bilingual research has adopted the masked translation priming paradigm as a tool to investigate the architecture of the bilingual language system. Although there is now a consensus about the existence of forward translation priming (from native language primes (L1) to second language (L2) translation equivalent targets), the backward translation priming effect (from L2 to L1) has only been reported in studies with bilinguals living in an L2 dominant environment. In a lexical decision experiment, we obtained significant translation priming in both directions, with unbalanced Dutch-French bilinguals living in an L1 dominant environment. Also, we demonstrated that these priming effects do not interact with a low-level visual prime feature such as font size. The obtained backward translation priming effect is consistent with the model of bilingual lexicosemantic organization of Duyck and Brysbaert (2004), which assumes strong mappings between L2 word forms and underlying semantic representations.
Like Me or Like Us
Authors: Bianchi Mauro , Machunsky Maya , Steffens Melanie C. , Mummendey Amélie
Published: March 2009

Research has shown abundant evidence for social projection, that is, the tendency to expect similarity between oneself and others ( Krueger, 1998a , 1998b ). This effect is stronger when others constitute an ingroup instead of an outgroup ( Robbins & Krueger, 2005 ). A different line of research has shown evidence for ingroup projection, that is, the tendency to use ingroup instead of outgroup features to define an inclusive category ( Wenzel, Mummendey, Weber, & Waldzus, 2003 ). In this research, we examine whether ingroup (i.e., Germans) projection to an inclusive category (i.e., Europeans) is different from the projection of self-attributes to the same inclusive category. In two studies, German participants rated how typical a series of attributes was for the ingroup, an inclusive category, the self, and an outgroup (i.e., Italians). The attributes varied in their relevance to the groups under consideration. The results showed that ingroup projection is stronger than social projection, but only when typical ingroup attributes are concerned. Moreover, ingroup projection weakened when the image of the ingroup was manipulated to be less positive, while social projection remained stable. These findings imply that ingroup projection is not simply social projection.