Analysis of the mechanisms of interaction between generators of cyclic motor reactions and inputs from suprasegmental systems

The simulation mathematical model of neuronal generator systems was used for analyzing the interaction between inputs from descending (afferent) systems and generators of scratching (locomotion). The data obtained indicate that in cases when generators of cyclic motor reactions influence the effectiveness of synaptic transmission from the fibers of descending (or afferent) systems, the differences in the main characteristics of signals that are produced by these generators themselves and those that come to them are emphasized. These data allow us to conclude that the system supplying interaction between inputs from suprasegmental (afferent) fiber systems and generators of locomotion of scratching can be interpreted as an adaptive filter which processes spatial and temporal information coming to the spinal cord via different suprasegmental or primary afferent inputs and allows generators of cyclic motor reactions to correct their functioning in accordance with changing external conditions.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 211–215, May–June, 1993.     

Neural network comparing two-rate-encoded inputs entering in parallel

Presented computational model of a neural network is able to compare two regular input frequencies. The comparison is based on detection of inter-spike interval differences of the two frequencies. This detection is continuous and the network dynamically changes its output according to the changes in the input frequencies. The entire network is composed of biologically plausible parts. A combination of such simple comparators might be involved in the information processing in the central nervous system.     

Pigment spectra and intermolecular interaction potentials in glasses and proteins

A model is proposed for chromophore optical spectra in solids over a wide range of temperatures and pressures. Inhomogeneous band shapes and their pressure dependence, as well as baric shift coefficients of spectral lines, selected by the frequency, were derived using Lennard-Jones potentials of the ground and excited states. Quadratic electron-phonon coupling constants, describing the thermal shift and broadening of zero-phonon lines, were also calculated. Experimentally, thermal shift and broadening of spectral holes were studied between 5 and 40 K for a synthetic pigment, chlorin, embedded in polymer hosts. The baric effects on holes were determined by applying hydrostatic He gas pressure up to 200 bar, at 6 K. Absorption spectra of pheophytin a, chlorophyll a, and beta-carotene in polymers and plant photosystem II CP47 complex were measured between 5 (or 77) and 300 K, and subject to Voigtian deconvolution. A narrowing of inhomogeneous bandwidth with increasing temperature, predicted on the basis of hole behavior, was observed as the shrinking of Gaussian spectral component. The Lorentzian broadening was ascribed to optical dephasing up to 300 K in transitions with weak to moderate linear electron-phonon coupling strength. The thermal broadening is purely Gaussian in multiphonon transitions (S(2) band of beta-carotene, Soret bands of tetrapyrrolic pigments), and the Lorentz process appears to be suppressed, indicating a lack of exponential dephasing. Density, polarity, polarizability, compressibility, and other local parameters of the pigment binding sites in biologically relevant systems can be deduced from spectroscopic data, provided that sufficient background information is available.     

Possible organization pattern of interaction between the generators of cyclic motor activity and inputs from supraspinal and afferent systems

Possible organization patterns of scratching and locomotor generators that allow interpretation of experimentally demonstrated reorganizations in temporal parameters of these generator activities after electrical stimulation of descending and peripheral afferent systems were analyzed with application of mathematical simulation of neuronal generator systems. The results obtained led to the conclusion that patterns of such reorganizations influenced by signals from suprasegmental and/or peripheral systems may be determined by only two factors: 1) the structure of synaptic connections between interneuronal functional groups underlying these generator associations, and 2) the structure of connections between these groups of interneurons and fibers from suprasegmental and peripheral afferent sources. The existence of inhibitory-excitatory actions from descending and afferent systems upon the neurons of locomotor or scratching generator half-centers is a sufficient condition to ensure phasic changes in the sensitivity of these generators to supraspinal and afferent signals. The locomotor generator, unlike the scratching generator, is apparently characterized by a more complex organization of connections between functional neuronal groupings and descending fibers.Translated from Neirofiziologiya, Vol. 25, No. 1, pp. 45–50, January–February, 1993.     

The size of the intermolecular energy funnel in protein-protein interactions

Revealing the fundamental principles of protein interactions is essential for the basic knowledge of molecular processes and designing better predictive tools. Protein docking procedures allow systematic sampling of intermolecular energy landscapes, revealing the distribution of energy basins and their characteristics. A systematic search docking procedure GRAMM-X was applied to a comprehensive nonredundant database of nonobligate protein-protein complexes to determine the size of the intermolecular energy funnel. The unbound structures were simulated using rotamer library. The procedure generated grid-based matches, based on a smoothed Lennard-Jones potential, and minimized them off the grid with the same potential. The minimization generated a distribution of distances, based on a variety of metrics, between the grid-based and the minimized matches. The metric selected for the analysis, ligand interface RMSD, provided three independent estimates of the funnel size: based on the distribution amplitude for the near-native matches, deviation from random, and correlation with the energy values. The three methods converge to similar estimates of approximately 6-8 A ligand interface RMSD. The results indicated dependence of the funnel size on the type of the complex (smaller for antigen-antibody, medium for enzyme-inhibitor, and larger for the rest of the complexes) and the funnel size correlation with the size of the interface. Guidelines for the optimal sampling of docking coordinates, based on the funnel size estimates, were explored.     

Global inputs of biological nitrogen fixation in agricultural systems

Biological dinitrogen (N₂) fixation is a natural process of significant importance in world agriculture. The demand for accurate determinations of global inputs of biologically-fixed nitrogen (N) is strong and will continue to be fuelled by the need to understand and effectively manage the global N cycle. In this paper we review and update long-standing and more recent estimates of biological N₂ fixation for the different agricultural systems, including the extensive, uncultivated tropical savannas used for grazing. Our methodology was to combine data on the areas and yields of legumes and cereals from the Food and Agriculture Organization (FAO) database on world agricultural production (FAOSTAT) with published and unpublished data on N₂ fixation. As the FAO lists grain legumes only, and not forage, fodder and green manure legumes, other literature was accessed to obtain approximate estimates in these cases. Below-ground plant N was factored into the estimations. The most important N₂-fixing agents in agricultural systems are the symbiotic associations between crop and forage/fodder legumes and rhizobia. Annual inputs of fixed N are calculated to be 2.95 Tg for the pulses and 18.5 Tg for the oilseed legumes. Soybean (Glycine max) is the dominant crop legume, representing 50% of the global crop legume area and 68% of global production. We calculate soybean to fix 16.4 Tg N annually, representing 77% of the N fixed by the crop legumes. Annual N₂ fixation by soybean in the U.S., Brazil and Argentina is calculated at 5.7, 4.6 and 3.4 Tg, respectively. Accurately estimating global N₂ fixation for the symbioses of the forage and fodder legumes is challenging because statistics on the areas and productivity of these legumes are almost impossible to obtain. The uncertainty increases as we move to the other agricultural-production systems—rice (Oryza sativa), sugar cane (Saccharum spp.), cereal and oilseed (non-legume) crop lands and extensive, grazed savannas. Nonetheless, the estimates of annual N₂ fixation inputs are 12–25 Tg (pasture and fodder legumes), 5 Tg (rice), 0.5 Tg (sugar cane), <4 Tg (non-legume crop lands) and <14 Tg (extensive savannas). Aggregating these individual estimates provides an overall estimate of 50–70 Tg N fixed biologically in agricultural systems. The uncertainty of this range would be reduced with the publication of more accurate statistics on areas and productivity of forage and fodder legumes and the publication of many more estimates of N₂ fixation, particularly in the cereal, oilseed and non-legume crop lands and extensive tropical savannas used for grazing.     

A comparative study on resource allocation and energy efficient job scheduling strategies in large-scale parallel computing systems

In the large-scale parallel computing environment, resource allocation and energy efficient techniques are required to deliver the quality of services (QoS) and to reduce the operational cost of the system. Because the cost of the energy consumption in the environment is a dominant part of the owner’s and user’s budget. However, when considering energy efficiency, resource allocation strategies become more difficult, and QoS (i.e., queue time and response time) may violate. This paper therefore is a comparative study on job scheduling in large-scale parallel systems to: (a) minimize the queue time, response time, and energy consumption and (b) maximize the overall system utilization. We compare thirteen job scheduling policies to analyze their behavior. A set of job scheduling policies includes (a) priority-based, (b) first fit, (c) backfilling, and (d) window-based policies. All of the policies are extensively simulated and compared. For the simulation, a real data center workload comprised of 22385 jobs is used. Based on results of their performance, we incorporate energy efficiency in three policies i.e., (1) best result producer, (2) average result producer, and (3) worst result producer. We analyze the (a) queue time, (b) response time, (c) slowdown ratio, and (d) energy consumption to evaluate the policies. Moreover, we present a comprehensive workload characterization for optimizing system’s performance and for scheduler design. Major workload characteristics including (a) Narrow, (b) Wide, (c) Short, and (d) Long jobs are characterized for detailed analysis of the schedulers’ performance. This study highlights the strengths and weakness of various job scheduling polices and helps to choose an appropriate job scheduling policy in a given scenario.     

A spectroscopic examination on intermolecular interaction of ergosterol with lecithin

The ergosterol and lecithin absorption IR-spectra were studied in a nonpolar anhydrous medium. The thermodynamical and spectral characteristics of dimeric associates and the enthalpy value for trimeric associates of this sterol are determined. Thermodynamical and spectral parameters of ergosterol intermolecular associates with lecithin in a nonpolar anhydrous medium are found. It is established that the intermolecular interaction of lecithin with ergosterol occurs according to the mechanism of hydrogen bond. A conclusion is drawn that the presence of binary bonds and methyl groups in the cyclic and aliphatic parts of the sterol molecule affects greatly the structure of the model membrane and its strength. It is shown that under conditions of the experiment the oxygen of the phosphate group contributes to formation of the molecular associates of lecithin with sterols and not that of the carbonyl group. The obtained experimental data may be at use when studying structural disturbances of native membranes in norm and with different pathologies.     

Analysis of nonlinear physiological systems with single or multiple spike inputs and analogue or spike outputs

This paper outlines an extension of Krausz' (1975) approach to nonlinear analysis of physiological systems with random impulse train inputs. This extension concerns multiple (here two) inputs and spike train outputs in addition to analogue outputs. The respective theoretical formula are given, and the approach is illustrated by experimental data relating to the nonlinear interaction of cat motor units activated with random pulse trains. As outputs are considered muscle tension (as an example for an analogue signal) and discharge frequency of a Ia fibre (as an example for a spike output).     

Kinetics of intermolecular interaction during protein folding of reduced cytochrome c

Kinetics of intermolecular interaction between reduced cytochrome c (Cyt c) protein and solvent during the protein-refolding process is studied by monitoring the time dependence of apparent diffusion coefficient (D) using the pulsed-laser-induced transient grating technique. The refolding was triggered by photoinduced reduction of unfolded Fe(III) Cyt c in 3.5 M guanidine hydrochloride (GdnHCl) solution and the change in the diffusion coefficient was monitored in time domain. The relationship between D and the protein conformations under equilibrium condition were investigated at various GdnHCl concentrations using a photolabeling reagent. The time dependence of the observed transient grating signal was analyzed using these data and two models: a continuous change model of the intermolecular interaction and a two-state model. It was found that the TG signals in various time ranges can be consistently reproduced well by the two-state model. The dynamics of D is expressed well by a single exponential function with a rate constant of 22 +/- 7 s(-1) in a whole time range. The folding process of Cyt c is discussed based on these observations.     

Effects of isotope substitution on intermolecular electron transfer in biological systems

Isotope effects on electron transfer reactions are discussed in terms of the multiphonon radiationless transition theory. The D₂0 substitution effect on the oxidation of cytochrome c (Kihara &; McCray, 1973) is analyzed. On the basis of these results the molecular mechanism for cytochrome c oxidation is proposed.     

Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE-RF

Merlin, the neurofibromatosis 2 tumor suppressor protein, has two major isoforms with alternate C termini and is related to the ERM (ezrin, radixin, moesin) proteins. Regulation of the ERMs involves intramolecular and/or intermolecular head-to-tail associations between family members. We have determined whether merlin undergoes similar interactions, and our findings indicate that the C terminus of merlin isoform 1 is able to associate with its N-terminal domain in a head-to-tail fashion. However, the C terminus of isoform 2 lacks this property. Similarly, the N terminus of merlin can also associate with C terminus of moesin. We have also explored the effect of merlin self-association on binding to the regulatory cofactor of Na(+)-H(+) exchanger (NHE-RF), an interacting protein for merlin and the ERMs. Merlin isoform 2 captures more NHE-RF than merlin isoform 1 in affinity binding assays, suggesting that in full-length merlin isoform 1, the NHE-RF binding site is masked because of the self-interactions of merlin. Treatment with a phospholipid known to decrease self-association of ERMs enhances the binding of merlin isoform 1 to NHE-RF. Thus, although isoform 1 resembles the ERM proteins, which transition between inactive (closed) and active (open) states, isoform 2 is distinct, existing only in the active (open) state and presumably constitutively more available for interaction with other protein partners.     

Evidence showing an intermolecular interaction between KChIP proteins and Taiwan cobra cardiotoxins

Direct protein-protein interaction between Taiwan cobra cardiotoxin3 (CTX3) and potassium channel-interacting proteins (KChIPs) was investigated in the present study. It was found that KChIPs bound with CTX3, in which KChIP and CTX3 formed a 1:1 complex as evidenced by the results of chemical cross-linking. Pull-down assay revealed that the intact EF-hands 3 and 4 of KChIP1 were critical for CTX3-binding. Likewise, removal of EF-hands 3 and 4 distorted the ability of KChIP1 to bind with Kv4.2 N-terminal fragment (KvN) as well as fluorescent probe 8-anilinonaphthalene-1-sulfonate (ANS). In contrast to the interaction between KChIP1 and KvN, the binding of CTX3 to KChIP1 showed a Ca(2+)-independent manner. Fluorescence measurement revealed that CTX3 affected the binding of ANS to Ca(2+)-bound KChIP1, but not Ca(2+)-free KChIP1. Alternatively, KChIP1 simultaneously bound with KvN and CTX3, and the interaction between KChIP1 and KvN was enhanced by CTX3. In terms of the fact that KChIPs regulate the electrophysiological properties of Kv K(+) channel, the potentiality of CTX for this biomedical application could be considered.     

Interaction of pyrrolobenzodiazepine (PBD) ligands with parallel intermolecular G-quadruplex complex using spectroscopy and ESI-MS

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5'GGGGTTGGGG3') designated as d(T(2)G(8)), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T(2)G(8)) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T(2)G(8))(2) and d(T(2)G(8))(4) forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T(2)G(8)) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex.     

Multiscale modeling of biomolecular systems: in serial and in parallel

Considerable progress has been recently achieved in the multiscale modeling of complex biological processes. Multiscale models have now investigated the structure and dynamics of lipid membranes, proteins, peptides and DNA over length and time scales ranging from the atomic to the macroscopic. Serial multiscale methods that parameterize low-resolution coarse-grained models with data from high-resolution models have studied long time or length scale phenomena that cannot be investigated with atomically detailed models. Parallel multiscale methods that directly couple high- and low-resolution models have efficiently explored slow structural transitions and the importance of long-wavelength fluctuations for biological molecules. The success of such models relies upon new theories and methods for constructing accurate multiscale bridges that transfer information between models with different resolutions.     

Concept of energy in biological systems

Beside the concept of material inputs and outputs of components of the representation of biological systems given to us by Rosen, the concept of energy is incorporated. The interaction of material and energy is represented by a cartesian product; and separate material and energetical mappings are considered as the new representation of components. These developments generate aMα category, and it is shown thatMα is isomorphic to theM category of previous developments.