SABERTOOTH: protein structural alignment based on a vectorial structure representation

Background  

The task of computing highly accurate structural alignments of proteins in very short computation time is still challenging. This is partly due to the complexity of protein structures. Therefore, instead of manipulating coordinates directly, matrices of inter-atomic distances, sets of vectors between protein backbone atoms, and other reduced representations are used. These decrease the effort of comparing large sets of coordinates, but protein structural alignment still remains computationally expensive.     

LIGAND: database of chemical compounds and reactions in biological pathways

LIGAND is a composite database comprising three sections: COMPOUND for the information about metabolites and other chemical compounds, REACTION for the collection of substrate–product relations representing metabolic and other reactions, and ENZYME for the information about enzyme molecules. The current release (as of September 7, 2001) includes 7298 compounds, 5166 reactions and 3829 enzymes. In addition to the keyword search provided by the DBGET/LinkDB system, a substructure search to the COMPOUND and REACTION sections is now available through the World Wide Web (http://www.genome.ad.jp/ligand/). LIGAND may be also downloaded by anonymous FTP (ftp://ftp.genome.ad.jp/pub/kegg/ligand/).     

A novel strategy for site-directed chemical reactions in single stranded DNA--absorption and NMR spectroscopic studies of model compounds.

A new and simple model enabling a chemical species to be brought to a preselected site in single strand DNA is reported. Two oligonucleotides containing a propanediol linkage were hybridized to their complementary sequences with an extra-base opposite the propanediol derivative. Absorption studies results shown that the addition of a bisacridine derivative strongly increased the stabilities of both duplexes when added in a 1:1 ratio. NMR studies on one of these duplexes brought evidence of the intercalation of the bisacridine at the position involving the propanediol linkage. These results suggest that this system could be used to target a specific reaction at a preselected position using the bisacridine derivative as carrier for the reactive species.     

The mechanism of coupling chemical and physical reactions by the calcium ATPase of sarcoplasmic reticulum and other coupled vectorial systems

The coupling of the chemical reaction of ATP hydrolysis to the transport of calcium from the cytoplasm into the lumen of sarcoplasmic reticulum vesicles can be defined by a set of rules that define alternating changes in the specificities of the enzyme for catalysis of chemical and physical reactions.     

A spatially explicit representation of conservation agriculture for application in global change studies

Conservation agriculture (CA) is widely promoted as a sustainable agricultural management strategy with the potential to alleviate some of the adverse effects of modern, industrial agriculture such as large‐scale soil erosion, nutrient leaching and overexploitation of water resources. Moreover, agricultural land managed under CA is proposed to contribute to climate change mitigation and adaptation through reduced emission of greenhouse gases, increased solar radiation reflection, and the sustainable use of soil and water resources. Due to the lack of official reporting schemes, the amount of agricultural land managed under CA systems is uncertain and spatially explicit information about the distribution of CA required for various modeling studies is missing. Here, we present an approach to downscale present‐day national‐level estimates of CA to a 5 arcminute regular grid, based on multicriteria analysis. We provide a best estimate of CA distribution and an uncertainty range in the form of a low and high estimate of CA distribution, reflecting the inconsistency in CA definitions. We also design two scenarios of the potential future development of CA combining present‐day data and an assessment of the potential for implementation using biophysical and socioeconomic factors. By our estimates, 122–215 Mha or 9%–15% of global arable land is currently managed under CA systems. The lower end of the range represents CA as an integrated system of permanent no‐tillage, crop residue management and crop rotations, while the high estimate includes a wider range of areas primarily devoted to temporary no‐tillage or reduced tillage operations. Our scenario analysis suggests a future potential of CA in the range of 533–1130 Mha (38%–81% of global arable land). Our estimates can be used in various ecosystem modeling applications and are expected to help identifying more realistic climate mitigation and adaptation potentials of agricultural practices.     

Antifungal chemical compounds identified using a C. elegans pathogenicity assay

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.     

On a global representation of dynamical characteristics in ESS-models

ESS-models are considered in the frame of adequate dynamical systems. This leads to a method of global representation of the dynamical characteristics, which allows for a comprehensive view on the relations among ESS-matrices. As an extension of ESS-models, the concept of ESS-models with changing matrix is introduced, which, in applications, makes use of such global representations. In particular, structurally stable and “catastrophic” cases can be identified and their significance in the context of ESS-models can be clarified. As a complete result for the case of two strategies a surface representation is obtained, which is an analogue to the elementary “cusp catastrophe”. These concepts are applied in a model that describes directed evolution of a behavioural component to a certain limit.     

Vanadium compounds as therapeutic agents: Some chemical and biochemical studies

The behaviour of three vanadium(V) systems, namely the pyridinone (V^V-dmpp), the salicylaldehyde (V^V-salDPA) and the pyrimidinone (V^V-MHCPE) complexes, is studied in aqueous solutions, under aerobic and physiological conditions using ⁵¹V NMR, EPR and UV-Visible (UV-Vis) spectroscopies. The speciations for the V^V-dmpp and V^V-salDPA have been previously reported. In this work, the system V^V-MHCPE is studied by pH-potentiometry and ⁵¹V NMR. The results indicate that, at pH ca. 7, the main species present are (V^VO₂)L₂ and (V^VO₂)LH₋₁ (L = MHCPE⁻) and hydrolysis products, similar to those observed in aqueous solutions of V^V-dmpp. The latter species is protonated as the pH decreases, originating (V^VO₂)L and (V^VO₂)LH. All the V^V-species studied are stable in aqueous media with different compositions and at physiological pH, including the cell culture medium. The compounds were screened for their potential cytotoxic activity in two different cell lines. The toxic effects were found to be incubation time and concentration dependent and specific for each compound and type of cells. The HeLa tumor cells seem to be more sensitive to drug effects than the 3T3-L1 fibroblasts. According to the IC₅₀ values and the results on reversibility to drug effects, the V^V-species resulting from the V^V-MHCPE system show higher toxicity in the tumor cells than in non-tumor cells, which may indicate potential antitumor activity.     

Quantum chemical computations and photophysical spectral features studies of two coumarin compounds

An attempt was made to determine the ground state and excited state dipole moments and quantum chemical computations of two coumarin compounds, namely 3‐hydroxy‐3‐[2‐oxo‐2‐(2‐oxo‐2H‐chromen‐3‐yl)‐ethyl]‐1,3‐dihydro‐indol‐2‐one (3HOCE) and 3‐[2‐(8‐methoxy‐2‐oxo‐2H‐chromen‐3‐yl)‐2‐oxo‐ethylidene]‐1,3‐dihydro‐indol‐2‐one (3MOCE). Both compounds displayed a red shift with enhancement in solvent polarity. The larger excited state dipole moment indicated the more polar nature of the selected compounds in the excited state than in the ground state. Kinetic stability and chemical reactivity of the selected compounds were studied with help of the quantum chemical properties of the compounds such as frontier molecular orbital analysis using density functional theory calculations with B3LYP/6–311+G (d, p) basis sets. Molecular electrostatic potential, Mulliken charges, natural bond orbital, and nonlinear optical properties were further studied. NBO analysis showed proton transfer within the selected donor–acceptor, depicting the large energy of stabilization for the compounds. The calculated Fukui function inferred the local softness and electrophilicity indices of used solute compounds.     

Spacetime representation of global electrocortical activity

A model for global electrocortical activity is developed by considering telencephalonic structures as mass of linked oscillators generating activity with a number of resonant modes. Equations for the signals are written in the comoving frame and then transformed into the laboratory frame. The state transition matrix is obtained in the presence of electric and magnetic fields.     

Quantitative intravital microscopy using a Generalized Polarity concept for kidney studies

In this article, we describe a ratiometric intravital two-photon microscopy technique for studying glomerular permeability and differences in proximal tubule cell reabsorption. This quantitative approach is based on the Generalized Polarity (GP) concept, in which the intensity difference between two fluorescent molecules is normalized to the total intensity produced by the two dyes. After an initial intravenous injection of a mixture of 3-, 40-, and 70-kDa fluorescently labeled dextrans into live Munich-Wistar-Frömter (MWF) rats, we were able to monitor changes in the GP values between any two dyes within local regions of the kidney, including the glomerulus, Bowman's capsule, proximal tubule lumens and proximal tubule cells, and individual capillary vessels. We were able to quantify accumulations of different dextrans in the Bowman's space and in tubular lumens as well as reabsorption by proximal tubular cells at different time points in the same rat. We found that for 6- to 8-wk-old MWF rats that developed spontaneous albuminuria, the 40- and 70-kDa dextrans, with hydrodynamic radii larger than albumin, were differentially filtered, but both were able to pass the glomerular filtration barrier and enter into the urinary space of the Bowman's capsule within a few seconds after intravenous infusion. Using GP image analysis, we found that negatively charged dextrans of both 40 and 70 kDa were better reabsorbed by the proximal tubule cells than the neutrally charged 40-kDa dextran. These results demonstrate the potential power of the GP imaging technique for quantitative studies of glomerular filtration and tubular reabsorption. glomerular permeability; tubular reabsorption; charge selectivity; two-photon excitation; multiphoton     

Three-dimensional representation of chemical gradients

Perspective display techniques are applied to chemical and biochemical data sets. These represent spatially distributed gradients of reactive compounds that participate in pattern-formation processes due to reaction-diffusion or reaction-convection coupling. The patterns form in thin solution layers and are observed as chemical waves in the Belousov-Zhabotinskii reaction, as convection-induced stationary structures during oscillating glycolysis in yeast cytoplasm, and as the diffusive spreading of enzyme-catalyzed metabolic turnover in a substrate layer. The digital data are measured with a two-dimensional spectrophotometer based on a computerized video equipment with high spatial, temporal and intensity resolution. By application of three-dimensional procedures detailed structural properties of chemical and biochemical model systems will be presented yielding localization of reaction and transport events.     

Toxicologic evaluation of individual chemical compounds and complex mixtures using a motile cell test object

The possibility of quantitative prognosis of chemical compounds and complex mixtures toxicity by means of a biotechnical system with suspension of bull spermatozoa sensor was investigated. The concentration of some chemical compounds, inhibiting by half spermatozoa motility has been experimentally determined. A correlation between the values determined and acute toxicity of the compounds tested has been established. The possible use of the biotechnical system for the screening of medical polymer materials has been demonstrated.     

A new method of global search for functional DNA segments using a fractal representation of nucleotide texts]

New global method for computer prediction of functional sites in nucleotide sequences, based on the fractal representation, is presented. Fractal representation of set of sequences (FRS) provides simple way for generating recognitions matrix of functionally similar sequences and simple estimations of its efficiency for searching homologous regions in new sequences. Other advantages of the method are absence of the necessity of sequences alignment during generating based set and searching new homologous regions and small CPU time. Usage of the method illustrated for searching globin and histone genes, for ALU repeats in human genome and long terminal repeats in virus genome.