Denitrifying bacteria of genus Alcaligenes isolated from soil]

The organism isolated is a small non-sporulating Gram-negative rod, motile by means of peritrichous flagellae. It is an oxidase-positive chemo-organotroph utilizing O2,NO-3,NO-2 and N2O as resiratory substrates. Primary alcohols as well as numerous organic and amino acids are utilized as carbon and energy sources. Carbohydrates are not assimilated. Poly-beta-hydroxybutyrate is accumulated intracellularly. The bacterium is assigned to the genus Alcaligenes and its phenotype characteristics are compared with those of A. faecalis.     

Similar paracrystals of endoplasmic reticulum in the photoemitters and the photoreceptors of scale-worms

Summary Paracrystals of tubular endoplasmic reticulum are the characteristic of the luminous cells in the elytra of polynoïd worms, and they are the sources of luminescence as well as of fluorescence. Structurally similar paracrystals are now found to be the main constituent of the lens in the eyes of all the Aphroditidae.     

Possible biological effects of electric and magnetic parameters in the environment

The features and intensities of electric and magnetic fields in the environment are described. Natural as well as technical constant and variable fields are considered in the light of their possible biological effects. The upper limits of the various fields are discussed. Results of laboratory measurements and also of epidemiological investigations are presented. The question is raised whether atmospheric small ions can cause a biological effect.     

Substanzen mit askarizider Wirkung

Summary Some substances with toxic properties againstAscaris lumbricoides are described. Three of them are as effective as Thymol.     

Beyond heuristics and biases: A contingency model of judgemental forecasting

The conflicting viewpoints about the quality of judgemental forecasts are examined and a model is proposed that attempts to resolve the conflict. The model sees forecasts as contingent upon the repertory of forecasting strategies that the forecaster brings to the forecasting task, the strategy that he or she selects as a function of the characteristics of the task, and the rigour with which he or she applies the strategy as a function of the motivating characteristics of the environment in which the task is encountered. The implications of differences in subjects' and experimenters' assumptions about which strategies are appropriate in experimental studies are examined, as are the implications of the differences between the motivating aspects of experimental and applied settings on both performance and on the generatizability of the results of experiments to applied judgemental forecasting.     

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.     

Integrin antagonists

Integrins are a family of cell surface glycoproteins that mediate numerous cell-cell and cell-matrix interactions and are involved in biological processes such as tissue morphogenesis, leukocyte recirculation and migration, wound healing, blood clotting and immune response. Aberrant cell adhesion has been implicated in the pathogenesis of several diseases, including a number of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease and asthma, as well as cancer and coronary heart disease. As such integrins are seen as excellent targets for the development of therapeutic agents. This report begins with an examination of the structure of integrin molecules and their ligands and then goes on to review the current state of development of antiintegrin antagonists. Received 13 April 1999; received after revision 28 May 1999; accepted 28 May 1999     

Syndecan family of cell surface proteoglycans: Developmentally regulated receptors for extracellular effector molecules

Syndecans are a family of integral membrane proteoglycans with conserved membrane-spanning and intracellular domains but with structurally distinct extracellular domains (ectodomains). They are known to function as heparan sulphate co-receptors in fibroblast growth factor signalling as well as to link cells directly to the extracellular matrix. These and other biological activities of syndecans involve specific interactions of the heparan sulphate side chains of syndecans with cytokines and extracellular matrix proteins. Four different vertebrate syndecans, designated as syndecans 1–4 (or syndecan, fibroglycan, N-syndecan and amphiglycan, respectively), are known. During embryonic development, syndecans have specific and highly regulated expression patterns that are distinct from the expression in adult tissue, suggesting an active role in morphogenetic processes. The developmental expression of syndecans is particularly intense in mesenchymal condensates and at epithelium mesenchyme interfaces, where a number of heparan sulphate-binding cytokines and matrix components are also expressed in a regulated manner, ofter spatially and temporally co-ordinated with the syndecan expression. Recent evidence indicates that the regulation of heparan sulphate fine structure (mainly the number and arrangement of sulphate groups along the polymer) provides a mechanism for the cellular control of syndecan-protein interactions. Furthermore, morphogenetically active cytokines such as fibroblast growth factor-2 and transforming growth factor-β participate in the regulation of syndecan expression and glycosaminoglycan structure. This review discusses the developmental expression and binding functions of syndecans as well as the molecular regulation of specific heparan sulphate-protein interactions.     

Die Immunoelektrophorese in Agar-Gel

Summary An account is given of Immuno-electrophoresis, as it originated from a combination of electrophoresis in agar-jelly and the various experiences with antigen/antibody reactions in gels. The theoretical background is detailed as well as different techniques. The increased sensitivity has gained us new insight into the composition of body fluids. Finally the limitations are discussed as they are proper to all reactions which have an immuno-chemical basis.     

Oncogenes and angiogenesis: a way to personalize anti-angiogenic therapy?

The acquisition of oncogenic mutations and promotion of angiogenesis are key hallmarks of cancer. These features are often thought of as separate events in tumor progression and the two fields of research have frequently been considered as independent. However, as we highlight in this review, activated oncogenes and deregulated angiogenesis are tightly associated, as mutations in cancer cells can lead to perturbation of the pro- and anti-angiogenic balance thereby causing aberrant angiogenesis. We propose that normalization of the vascular network by targeting oncogenes in the tumor cells might lead to more efficient and sustained therapeutic effects compared to therapies targeting tumor vessels. We discuss how pharmacological inhibition of oncogenes in tumor cells restores a functional vasculature by bystander anti-angiogenic effect. As genetic alterations are tumor-specific, targeted therapy, which potentially blocks the angiogenic program activated by individual oncogenes may lead to personalized anti-angiogenic therapy.     

The Eyes Absent proteins in development and disease

The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.     

Ion channels in plant signaling

Plant ion channel activities are rapidly modulated in response to several environmental and endogenous stimuli such as light, pathogen attack and phytohormones. Electrophysiological as well as pharmacological studies provide strong evidence that ion channels are essential for the induction of specific cellular responses, implicating their tight linkage to signal transduction cascades. Ion channels propagate signals by modulating the membrane potential or by directly affecting cellular ion composition. In addition, they may also be effectors at the end of signaling cascades, as examplified by ion channels which determine the solute content of stomatal guard cells. Plant channels are themselves subject to regulation by a variety of cellular factors, including calcium, pH and cyclic nucleotides. In addition, they appear to be regulated by (de)-phosphorylation events as well as by direct interactions with cytoskeletal and other cellular proteins. This review summarizes current knowledge on the role of ion chan nels in plant signaling.     

Enzymes catalyzing the reduction of aldopentoses and the oxidation of pentitols in Mycobacteria]

M. phlei, grown on synthetic Sauton medium (with 6% glycerol as carbon source), had NADPH- and NADH-aldopentose reductase, as well as NAD-pentitol dehydrogenase activities; some of their properties are studied. These activities are not present in BCG grown on the same medium. All experiments of aldopentose-reductase induction in BCG on a D(+)xylose medium were negative.     

Genetics on the neurodiversity spectrum: Genetic,phenotypic and endophenotypic continua in autism and ADHD

How we ought to diagnose, categorise and respond to spectrum disabilities such as autism and Attention Deficit/Hyperactivity Disorder (ADHD) is a topic of lively debate. The heterogeneity associated with ADHD and autism is described as falling on various continua of behavioural, neural, and genetic difference. These continua are varyingly described either as extending into the general population, or as being continua within a given disorder demarcation. Moreover, the interrelationships of these continua are likewise often vague and subject to diverse interpretations.In this paper, I explore geneticists' and self-advocates’ perspectives concerning autism and ADHD as continua. These diagnoses are overwhelmingly analysed as falling on a continuum or continua of underlying traits, which supports the notion of “the neurodiversity spectrum”, i.e., a broader swath of human neural and behavioural diversity on which some concentrations of different functioning are diagnosed. I offer a taxonomy of conceptions of the genetic, phenotypic, and endophenotypic dimensionality within and beyond these diagnostic categories, and suggest that the spectrum of neurodiversity is characteristically endophenotypic.     

Computational inhibitor design against malaria plasmepsins

Plasmepsins are aspartic proteases involved in the degradation of the host cell hemoglobin that is used as a food source by the malaria parasite. Plasmepsins are highly promising as drug targets, especially when combined with the inhibition of falcipains that are also involved in hemoglobin catabolism. In this review, we discuss the mechanism of plasmepsins I–IV in view of the interest in transition state mimetics as potential compounds for lead development. Inhibitor development against plasmepsin II as well as relevant crystal structures are summarized in order to give an overview of the field. Application of computational techniques, especially binding affinity prediction by the linear interaction energy method, in the development of malarial plasmepsin inhibitors has been highly successful and is discussed in detail. Homology modeling and molecular docking have been useful in the current inhibitor design project, and the combination of such methods with binding free energy calculations is analyzed. S. Bjelic, M. Nervall: These authors contributed equally to this work. Received 27 February 2007; received after revision 17 April 2007; accepted 26 April 2007     

Polyreactive antibodies in adaptive immune responses to viruses

B cells express immunoglobulins on their surface where they serve as antigen receptors. When secreted as antibodies, the same molecules are key elements of the humoral immune response against pathogens such as viruses. Although most antibodies are restricted to binding a specific antigen, some are polyreactive and have the ability to bind to several different ligands, usually with low affinity. Highly polyreactive antibodies are removed from the repertoire during B-cell development by physiologic tolerance mechanisms including deletion and receptor editing. However, a low level of antibody polyreactivity is tolerated and can confer additional binding properties to pathogen-specific antibodies. For example, high-affinity human antibodies to HIV are frequently polyreactive. Here we review the evidence suggesting that in the case of some pathogens like HIV, polyreactivity may confer a selective advantage to pathogen-specific antibodies.     

The importance of the forecast

Careful forecasts, as accurate as possible, are central to the successful implementation of policy. There are fundamental reasons why policy makers cannot ‘play by ear’, adjusting policy quickly to each unexpected deviation in economic outcomes. Specific incidents are described where economic policy went awry because of faulty forecasts. The policy process is described in detail to show precisely where the forecast enters. Forecasting as a validation tool for establishing credibility in policy formation is analysed and discussed. Some estimated measure of forecast accuracy is presented, together with commentary on the necessary degrees of precision for successful implementation of policy.     

Highly reactive oxygen species: detection, formation, and possible functions

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies.     

Synthetic genes for the elucidation of glycosylation codes for arabinogalactan-proteins and other hydroxyproline-rich glycoproteins

Hydroxyproline-rich glycoproteins (HRGPs) are ubiquitous architectural components of the growing plant cell wall, accounting for as much as 10-20% of the dry weight. HRGPs are implicated in all aspects of plant growth and development, including responses to stress. The HRGP superfamily contains three major groups which represent a continuum of peptide periodicity and hydroxyproline-O-glycosylation. These groups range from the highly periodic and lightly arabinosylated repetitive proline-rich proteins (PRPs), through the crosslinked extensins which are periodic and highly arabinosylated, to the arabinogalactan-proteins (AGPs) which are the most highly glycosylated and least periodic. The repetitive units are small, often only four- to six-residue-glycosylated modules viewed hypothetically as functional motifs, or glycomodules. The Hyp contiguity hypothesis predicts that Hyp arabinosylation increases with Hyp contiguity and that clustered noncontiguous Hyp residues are sites of arabinogalactan polysaccharide addition in the AGPs and gums. Recent results involving glycosylation site mapping of endogenous HRGPs and HRGP design using synthetic genes have corroborated the hypothesis. The uses of synthetic genes in HRGP glycosylation site mapping and structural/functional analysis are also discussed.