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PubMed1987

Seven structurally different murine monoclonal galactan-specific antibodies show identity in their galactosyl-binding subsite arrangements.

The constants of association of seven monoclonal antibodies--each capable of binding a tetrasaccharide fragment of a linear beta(1,6)-D-galactopyranan--were measured with a series of galactosyl-ligands some of which carried deoxy-fluoro groups at selected locations. In these oligosaccharide ligands, the galactosyl residues bearing a fluorine-instead of a hydroxyl-group, cannot bind to the highest-binding subsite, which requires hydrogen-bonding. This forces a shift in the saccharide contact-residues, and in this way the relative affinities of the antibody subsites for individual galactosyl residues could be evaluated and compared with those of the four subsites investigated earlier. Correlation of sequence data, spatial structure of J 539 and binding behaviour leads to the exclusion of the third complementarity determining region (CDR) of the H-chain as partaking in the binding, and shows that the galactopyranan antigen probably binds along the lower periphery of the H-L interface of the antibodies, and does so in a groove-type fashion. Each of the seven antibodies has four subsites C, A, B and D in going from the H-to the L-chain, and the relative affinity for "their" galactosyl residue decreases in the order A greater than B greater than C greater than D. The single sugar-binding subsite A accounts for ca 50% of the total binding free energy of the maximally binding tetrasaccharide determinant in all cases.

Amino Acid Sequence↗

PubMed2004

Molecular modelling of the nucleotide-binding domain of Wilson's disease protein: location of the ATP-binding site, domain dynamics and potential effects of the major disease mutations.

WNDP (Wilson's disease protein) is a copper-transporting ATPase that plays an essential role in human physiology. Mutations in WNDP result in copper accumulation in tissues and cause a severe hepato-neurological disorder known as Wilson's disease. Several mutations were surmised to affect the nucleotide binding and hydrolysis by WNDP; however, how the nucleotides bind to normal and mutated WNDP remains unknown. To aid such studies, we performed the molecular modelling of the spatial structure and dynamics of the ATP-binding domain of WNDP and its interactions with ATP. The three-dimensional models of this domain in two conformations were built using the X-ray structures of the Ca2+-ATPase in the E1 and E2 states. To study the functional aspects of the models, they were subjected to long-term molecular dynamics simulations in an explicit solvent; similar calculations were performed for the ATP-binding domain of Ca2+-ATPase. In both cases, we found large-scale motions that lead to significant changes of distances between several functionally important residues. The ATP docking revealed two possible modes of ATP binding: via adenosine buried in the cleft near residues H1069, R1151 and D1164, and via phosphate moiety 'anchored' by H-bonds with residues in the vicinity of catalytic D1027. Furthermore, interaction of ATP with both sites occurs if they are spatially close to each other. This may be achieved after relative domain motions of the 'closure' type observed in molecular dynamics simulations. The results provide a framework for analysis of disease mutations and for future mutagenesis studies.

Adenosine Triphosphatases↗

PubMed2004

Backward masking and the central performance drop.

Kehrer [Spatial Vision 2 (1987) 247] found that texture discrimination performance sometimes peaks in the parafovea rather than at the fovea, and he referred to this phenomenon as the central performance drop (CPD). Kehrer used a backward mask to limit performance and Morikawa [Vision Res. 40 (2000) 3517] argued that in some cases the temporal aspects of the backward mask may be critical to the emergence of the CPD. In one experiment Morikawa showed that the CPD does not emerge when a simultaneous noise-mask (different from the mask used by Kehrer) is used to limit performance. In another experiment Morikawa showed that unmasked texture displays comprising short lines do not elicit the CPD. In both cases, changes in the temporal aspects of the texture displays were accompanied by changes in the spatial structure of the mask or stimulus. For the spatio-temporal theory of the CPD to be sustained one would have to show that noise masks elicit a CPD when used as backward masks and that the short-line textures elicit a CPD when followed by backward masks. Our evidence provides little if any support for either of these predictions. Furthermore, an analysis of a simple filter-rectify-filter model of texture segmentation shows that a greatly attenuated CPD is to be expected when a noise mask is used as a source of spatial noise.

Adult↗

PubMed1978

Gastric chemoceptive projections to fasciculus solitarius and its dipole field structure.

The gastric branch of the vagus nerve, close to the stomach was stimulated electrically and the evoked potentials recorded from the fasciculus solitarius of frog within the stereotaxic coordinates P 4.1-4.6; L 0.5-0.8 and V 0.3-0.5. A predominantly monophasic negative potential, the amplitude (1.0-3.0 mV) of which rises with increase in stimulus strength up to 6 V, could be recorded. From the velocity of conduction (30 m/sec) it appears that the gastric afferent fibres belong to Group A. The depth-recording resulted in the reversal of the negative sign of the potential at depth beyond 180-200 mu. The significance of the appearance of a positive potential and the cellular configuration of the area of fasciculus is discussed in the context of a possible dipole that might exist in the spatial structure from which the depth-recording has been made.

Animals↗

PubMed1986

Regional economic disparities and population change in Morocco.

"The paper examines patterns of population change in Morocco for the decade 1971-1981. They do not mirror those which might have been expected in view of the national economic and spatial structure of this country. The differences are attributed to international economic forces which have transcended national forces in shaping population patterns in parts of the country."

Africa↗

PubMed2006

Century-long synchrony of fossil algae in a chain of Canadian prairie lakes.

Synchronous fluctuations in limnological variables among lakes may signal that large-scale environmental factors regulate lake ecosystem structure, yet most estimates of temporal coherence are based on short (<25 yr) time series, and little is known of how synchrony varies among biological taxa or of the causes of temporal coherence. Here we used time series of 13 fossil pigments from diverse algal groups in seven lakes of the climatically sensitive Northern Great Plains to demonstrate that algal synchrony (S) during the 20th century arose mainly from interdecadal increases in algal abundance rather than from interannual coherence. Synchrony of time series differed greatly among algal taxonomic groups (S = 0.0-0.75) and was not usually spatially structured, but decreased 83% following removal of long-term trends using exponential models or first-difference calculations. Overall, coherence was greatest for labile compounds chl a (S = 0.53) and fucoxanthin (S = 0.75), possibly reflecting the influence of postdepositional degradation processes on fossil time series. However, analysis of chemically stable pigments also indicated that synchrony was great for cryptophytes (as alloxanthin, S = 0.42) and diatoms (diatoxanthin, S = 0.37), taxa that bloom in spring. In contrast, synchrony of total algal abundance was low (beta-carotene, pheophytin a, S < 0.10), reflecting low interannual coherence of summer taxa including colonial cyanobacteria and chlorophytes. Unexpectedly, past variations in climate, resource use, and urbanization explained >85% of algal variation in individual lakes, but only 35% of synchronous algal fluctuations, suggesting that the factors controlling algal synchrony differ from those regulating algal abundance.

Ecosystem↗

PubMedDate not supplied

Magnetoencephalography and its Achilles' heel.

Magnetoencephalography (MEG) has practically unlimited temporal resolution. Fundamental physical reasons, however, restrict the capability of MEG to separate simultaneously active sources. After a brief tutorial introduction into MEG, various aspects of spatial resolution are reviewed with the help of examples. First the estimation of a single current dipole is examined. A consideration of the resolution field shows that the spatial selectivity of the estimated dipole moment is highly dependent on methodological issues. A subsequent consideration of various two-dipole configurations illustrates how the topography of the magnetic field depends on the distance between the two dipoles and their relative orientations. The resolution fields associated with the estimation of the dipole moments reveal a strong interference for closely spaced dipoles. A simple model suggests that the standard deviations of the estimated moments are inversely proportional to the distance of the dipoles. Spatial information provided by techniques like functional magnetic resonance imaging (fMRI) could help to overcome problems resulting from the limited spatial resolution of MEG (multimodal integration). But a straightforward synthesis, according to the principle that fMRI provides the spatial structure of the sources and MEG adds the temporal information, is probably doomed to failure in many situations. A serious dilemma, among other problems, is that the fMRI signal generally represents a temporal integral over several seconds: The knowledge that a certain brain region was active sometime or other is not necessarily helpful for disentangling the MEG activity within a specified short time window. An intriguing fact is that the spatio-temporal pattern of the MEG signals can be considered as a signature of the brain which is suitable for hypothesis testing with high temporal and spatial resolution.

Brain↗

PubMed2006

Homogenization dynamics and introduction routes of invasive freshwater fish in the Iberian Peninsula.

Nonnative invasive species are one of the main global threats to biodiversity. The understanding of the traits characterizing successful invaders and invasion-prone ecosystems is increasing, but our predictive ability is still limited. Quantitative information on biotic homogenization and particularly its temporal dynamics is even scarcer. We used freshwater fish distribution data in the Iberian Peninsula in four periods (before human intervention, 1991, 1995, and 2001) to assess the temporal dynamics of biotic homogenization among river basins. The percentage of introduced species among fish faunas has increased in recent times (from 41.8% in 1991 to 52.5% in 2001), leading to a clear increase in the similarity of community composition among basins. The mean Jaccard's index increase (a measure of biotic homogenization) from the pristine situation to the present (17.1%) was similar to that for Californian fish but higher than for other studies. However, biotic homogenization was found to be a temporally dynamic process, with finer temporal grain analyses detecting transient stages of biotic differentiation. Introduced species assemblages were spatially structured along a latitudinal gradient in the Iberian Peninsula, with species related to sport fishing being characteristic of northern basins. Although the comparison of fish distributions in the Iberian Peninsula and France showed significant and generalized biotic homogenization, nonnative assemblages of northeastern Iberian basins were more similar to those of France than to those of the rest of the Iberian Peninsula, indicating a main introduction route. Species introduced to the Iberian Peninsula tended to be mainly piscivores or widely introduced species that previously had been introduced to France. Our results indicate that the simultaneous analysis of the spatial distribution of introduced assemblages (excluding native species that reflect other biogeographical patterns) and their specific traits can be an effective tool to detect introduction and invasion routes and to predict future invaders from donor regions.

Animals↗

PubMed1991

Effects of ions on vanadate-induced photocleavage of myosin subfragment 1.

Myosin subfragment 1 (S1) is cleaved by near-ultraviolet irradiation in the presence of vanadate at three sites located at 23, 31 and 74 kDa from the N-terminus. Since vanadate is considered to be a good structural analogue of phosphate, it is assumed that the cleavage sites participate in forming the phosphate-binding site(s) of S1. In this work, the effect of various ions on the vanadate-induced photocleavage of S1 was studied. Monovalent anions were found to inhibit photocleavage in the 50-200 mM range. The inhibition is more expressed at a site 74 kDa from the N-terminus than at the 23-kDa and 31-kDa sites. The inhibitory effect of the monovalent anions increases in the order acetate = F- less than Cl- less than Br- less than I- = SCN-. The order of the inhibitory effect is identical to the protein-structure-damaging effect of monovalent anions in the von Hippel series [von Hipel, P. H. & Wong, K. Y. (1964) Science 145, 577-581]. Therefore, it is assumed that decreased photocleavage is due to local perturbations of structure, especially at the 74-kDa site, in addition to increased ionic strength. Divalent anions, sulfate and thiosulfate, strongly inhibit photocleavage at 2 mM. The inhibition is very pronounced at the 23-kDa and 31-kDa sites, while the 74-kDa site is hardly affected. Since photocleavage at the 23-kDa and 31-kDa sites is regulated jointly and independently from cleavage at the 74-kDa site, it is assumed that S1 has two distinct phosphate-binding sites: the regions of the 23-kDa and 31-kDa cleavage sites, which are proximal to each other in the spatial structure, participate in forming the first phosphate-binding site, while the 74-kDa site is part of the second binding site. Sulfate was also found to inhibit the trapping of vanadate and to facilitate its release from the S1-MgADP-Vi (Vi, inorganic vanadate) complex. Photocleavage of S1 takes place at all three sites, both in the presence or absence of divalent cations, indicating that these, including Mg2+, are not essential for cleavage.

Adenosine Triphosphate↗

PubMed2006

Population structure and gene flow among wild populations of the black muntjac (Muntiacus crinifrons) based on mitochondrial DNA control region sequences.

The black muntjac (Muntiacus crinifrons) is a rare species endemic to China and its current distribution is confined to partial mountain ranges in eastern China. To assess the population structure and gene flow among the extant populations, we sequenced a portion of the mitochondrial control region (424 bp) for 47 samples collected from its current three large populations (Huangshan, Tiammushan and Suichang). A total of 18 unique haplotypes were defined based on 22 polymorphic sites. Of these haplotypes, 15 ones were population-specific and only one haplotype was shared among the three populations. Significant genetic differentiation was detected between Suichang and Huangshan populations (ø(ST)=0.1677, P<0.001) or between Suichang and Tianmushan populations (ø(ST)=0.2002, P<0.001), indicating that the Suichang population may be spatially structured from other two populations along matriline. The Mantel test revealed that this significant differentiation was not driven by geographic distance (P=0.14), implying that genetic divergence of Suichang population might result from recent human disturbances. Phylogenetic analyses suggested the mitochondrial control region haplotypes were split into two well divergent clades (Clade I and Clade II). Interestingly, the two distinct haplotype clades were found to coexist in Suichang area. The nested clade analysis revealed a significant phylogeographic structure among the black muntjac populations (total cladogram: chi2=18.68; P<0.001), which was inferred to result from past fragmentation followed by range expansion. The population expansion was supported by the analysis of mismatch distribution and the tests of neutrality. Therefore, we suggest that the coexistence of distinct haplotypes in Suichang population was induced by historical population expansion after fragmentation and that the current genetic differentiation should be attributed to the reduction of female-mediated gene flow due to recent habitat fragmentation and subsequent loss.

Animals↗

PubMed1984

Growth trends of metropolitan areas in Japan: application of the concept of P-M curve.

"The aim of this paper is to illuminate basic characteristics of metropolitan areas in Japan. [The authors] first delineate the boundaries of ninety-eight Japanese metropolitan areas based on the concept of cut-off point on the P-M curve the idea of which was originally developed by Ogawa in 1957. Secondly, [they] carry out empirical analyses on spatial structure and growth patterns of those metropolitan areas by use of 1960 and 1975 data." The results indicate that the population share of central cities declined from 1960 to 1975.

Asia↗

PubMed1983

Urban squatting and migration in Peninsular Malaysia.

"This article examines some of the links between the phenomena of urban migration and squatter settlements in the Third World city. This will be done by demonstrating that both are outcomes of fundamental social and political forces that have operated on these societies. Migration and squatting are placed in a context of the historical processes that led to the uneven development of Malaysia. The article offers some explanation for the origin of the inequalities observed in spatial structures--in this case urban housing--by focusing on one of the contributory factors, namely migration."

Asia↗

PubMed2003

Cryptic population structure in a large, mobile mammalian predator: the Scandinavian lynx.

The Eurasian lynx (Lynx lynx) is an example of a species that has gone through a severe bottleneck, leading to near extinction in Scandinavia around 1930-- a pattern shared with several other large carnivorous mammals. Here we extend previous genetic analyses of northern European lynx, confirming that lynx from the Scandinavian Peninsula represent a distinct clade differing clearly from European conspecifics. Furthermore, and despite a recent bottleneck and subsequent range expansion, we detect marked genetic differentiation within Scandinavia. This differentiation is largely manifested as a north-south gradient, with a linear increase in the quantity FST/(1 - FST). Aided by computer simulations we find that this pattern is unlikely to have arisen by random genetic drift in the short time since lynx started to expand in the 1950s, suggesting that the spatial structure may predate the bottleneck. Individual-based analyses indicate that, instead of a continuous gradient, Scandinavian lynx may be structured into three more or less distinct groups, possibly corresponding to northern, central and southern subpopulations. The presence of such structuring was unknown previously and was unexpected from general considerations on the mobility of the species, historical data and the absence of geographical barriers. Our study demonstrates how molecular markers may be used to detect cryptic population structure, invisible using traditional methods.

Animals↗

PubMedDate not supplied

[Natural alpha-conotoxins and their synthetic analogues in studies of nicotinic acetylcholine receptors].

alpha-Conotoxins, peptide neurotoxins from poisonous marine snails of the genus Conus that highly specifically block nicotinic acetylcholine receptors (AChRs) of various types, are reviewed. Preliminarily, the structural organization of AChRs of the muscular and neuronal types, their involvement in physiological processes, and their role in various diseases are briefly discussed. In this connection, the necessity of quantitative determination of AChR subtypes using neurotoxins and other approaches is substantiated. The chemical structure, spatial organization, and specificity of alpha-conotoxins are mainly discussed, taking into consideration the recent results on the ability of alpha-conotoxins to interact with muscular or neuronal hetero- and homooligomeric AChRs exhibiting a high species specificity. Particular emphasis is placed upon a thorough characterization of the surfaces of interaction of alpha-conotoxins with AChRs using synthetic analogues of alpha-conotoxins, mutations in AChRs, and pairwise mutations in both alpha-conotoxins and AChRs. The discovery in 2001 of the acetylcholine-binding protein from the pond snail Lymnaea stagnalis and the determination of its crystalline structure led to rapid progress in understanding the structural organization of ligand-binding domains of AChRs with which alpha-conotoxins also interact. We discuss the interaction of various alpha-conotoxins with acetylcholine-binding proteins, the recently reported X-ray structure of the complex of the acetylcholine-binding protein from Aplysia californica with the alpha-conotoxin analogue PnIA, and the application of this structure to the modeling of complexes of alpha-conotoxins with various AChRs.

Animals↗

PubMed2006

Biocomplexity in a highly migratory pelagic marine fish, Atlantic herring.

The existence of biologically differentiated populations has been credited with a major role in conferring sustainability and in buffering overall productivity of anadromous fish population complexes where evidence for spatial structure is uncontroversial. Here, we describe evidence of correlated genetic and life history (spawning season linked to spawning location) differentiation in an abundant and highly migratory pelagic fish, Atlantic herring, Clupea harengus, in the North Sea (NS) and adjacent areas. The existence of genetically and phenotypically diverse stocks in this region despite intense seasonal mixing strongly implicates natal homing in this species. Based on information from genetic markers and otolith morphology, we estimate the proportional contribution by NS, Skagerrak (SKG) and Kattegat and western Baltic (WBS) fish to mixed aggregations targeted by the NS fishery. We use these estimates to identify spatial and temporal differences in life history (migratory behaviour) and habitat use among genetically differentiated migratory populations that mix seasonally. Our study suggests the existence of more complex patterns of intraspecific diversity than was previously recognized. Sustainability may be compromised if such complex patterns are reduced through generalized management (e.g. area closures) that overlooks population differences in spatial use throughout the life cycle.

Animal Migration↗

PubMed1996

Chaos and synchrony in a model of a hypercolumn in visual cortex.

Neurons in cortical slices emit spikes or bursts of spikes regularly in response to a suprathreshold current injection. This behavior is in marked contrast to the behavior of cortical neurons in vivo, whose response to electrical or sensory input displays a strong degree of irregularity. Correlation measurements show a significant degree of synchrony in the temporal fluctuations of neuronal activities in cortex. We explore the hypothesis that these phenomena are the result of the synchronized chaos generated by the deterministic dynamics of local cortical networks. A model of a "hypercolumn" in the visual cortex is studied. It consists of two populations of neurons, one inhibitory and one excitatory. The dynamics of the neurons is based on a Hodgkin-Huxley type model of excitable voltage-clamped cells with several cellular and synaptic conductances. A slow potassium current is included in the dynamics of the excitatory population to reproduce the observed adaptation of the spike trains emitted by these neurons. The pattern of connectivity has a spatial structure which is correlated with the internal organization of hypercolumns in orientation columns. Numerical simulations of the model show that in an appropriate parameter range, the network settles in a synchronous chaotic state, characterized by a strong temporal variability of the neural activity which is correlated across the hypercolumn. Strong inhibitory feedback is essential for the stabilization of this state. These results show that the cooperative dynamics of large neuronal networks are capable of generating variability and synchrony similar to those observed in cortex. Auto-correlation and cross-correlation functions of neuronal spike trains are computed, and their temporal and spatial features are analyzed. In other parameter regimes, the network exhibits two additional states: synchronized oscillations and an asynchronous state. We use our model to study cortical mechanisms for orientation selectivity. It is shown that in a suitable parameter regime, when the input is not oriented, the network has a continuum of states, each representing an inhomogeneous population activity which is peaked at one of the orientation columns. As a result, when a weakly oriented input stimulates the network, it yields a sharp orientation tuning. The properties of the network in this regime, including the appearance of virtual rotations and broad stimulus-dependent cross-correlations, are investigated. The results agree with the predictions of the mean field theory which was previously derived for a simplified model of stochastic, two-state neurons. The relation between the results of the model and experiments in visual cortex are discussed.

Models, Neurological↗

PubMed2004

Examination of a smallest CELSS (microcosm) through an individual-based model simulation.

Research of the effect of space environment on an ecosystem consisting of plants and animals is essential when they are to be positively used in space. Although there have been experiments on various organisms under space environment in the past, they mainly studied the effect of space environment on an individual organism or a single species. Microcosm is drawing attention as an experimental material of an ecosystem consisting of multiple species. The object in this research is to understand the nature of this network system called ecosystem. Thus, a mixed microorganism culturing system consisting of three types of microorganisms which form a minimum food chain system as a closed ecosystem (chlorella as the producer, bacteria as the decomposer, and rotifer as the consumer) was taken for the subject, on which to research the universal characteristics of ecosystems. From the results of experiments under the terrestrial environment, formation of colonies, which is an ecological structure, has been observed at its mature stage. The organisms form an optimal substance circulation system. Therefore, formation of colonies in simulation models is important. Many attempts have been made to create ecosystem models. For example, the Lotka-Volterra model forms a simultaneous equation with the differential equation expressing predator and prey relationship and many numerical calculations have been conducted on various ecosystems based on expanded L-V models. Conventionally, these top-down methods have been used. However, since this method only describes the average concentration of organisms that are distributed uniformly throughout the system and cannot express the spatial structure of the system, it was difficult to express ecosystem structures like colonies and density distributions. In actual ecosystems, there is heterogeneity in the number of individuals and in substance density, and this is thought to have great significance in ecosystems. Consequently, an individual-based model was used that applies rules to predator-prey relationship, suppression, production, self suppression, etc., of each species. It enabled the emergence of the overall system only by its local rules, and it was possible to reproduce colony generation. In addition, the transition and the ratio of populations for each species match well with experimental results.

Animals↗

PubMed2004

No statistical support for correlation between the positions of protein interaction sites and alternatively spliced regions.

BACKGROUND: Alternative splicing is an efficient mechanism for increasing the variety of functions fulfilled by proteins in a living cell. It has been previously demonstrated that alternatively spliced regions often comprise functionally important and conserved sequence motifs. The objective of this work was to test the hypothesis that alternative splicing is correlated with contact regions of protein-protein interactions. RESULTS: Protein sequence spans involved in contacts with an interaction partner were delineated from atomic structures of transient interaction complexes and juxtaposed with the location of alternatively spliced regions detected by comparative genome analysis and spliced alignment. The total of 42 alternatively spliced isoforms were identified in 21 amino acid chains involved in biomolecular interactions. Using this limited dataset and a variety of sophisticated counting procedures we were not able to establish a statistically significant correlation between the positions of protein interaction sites and alternatively spliced regions. CONCLUSIONS: This finding contradicts a naïve hypothesis that alternatively spliced regions would correlate with points of contact. One possible explanation for that could be that all alternative splicing events change the spatial structure of the interacting domain to a sufficient degree to preclude interaction. This is indirectly supported by the observed lack of difference in the behaviour of relatively short regions affected by alternative splicing and cases when large portions of proteins are removed. More structural data on complexes of interacting proteins, including structures of alternative isoforms, are needed to test this conjecture.

Alternative Splicing↗