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4-quinolones inhibit biotransformation of caffeine.

The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels. The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect. The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.

Adult↗

Prediction of probable pathways of folding in globular proteins.

A method is described for the prediction of probable folding pathways of globular proteins, based on the analysis of distance maps. It is applicable to proteins of unknown spatial structure but known amino acid sequence as well as to proteins of known structure. It is based on an objective procedure for the determination of the boundary of compact regions that contain high densities of interresidue contacts on the distance map of a globular protein. The procedure can be used both with contact maps derived from a known three-dimensional protein structure and with predicted contact maps computed by means of a statistical procedure from the amino acid sequence alone. The computed contact map can also be used to predict the location of compact short-range structures, viz. alpha-helices and beta-turns, thereby complementing other statistical predictive procedures. The method provides an objective basis for the derivation of a theoretically predicted pathway of protein folding, proposed by us earlier [Tanaka and Scheraga (1977) Macromolecules 10, 291-304; Némethy and Scheraga (1979) Proc. Natl. Acad. Sci., U.S.A. 76, 6050-6054].

Adenylate Kinase↗

Hypercycles versus parasites in the origin of life: model dependence in spatial hypercycle systems.

Spatial hypercycle systems can be modelled by means of cellular automata or partial differential equations. In either model, two dimensional spirals or clusters can be formed. Different models give rise to slightly different spatial structures, but the response to parasites is fundamentally different: In cellular automata the hypercycle is resistant to parasites that are fatal in a partial differential equations model. In three dimensions scroll rings correspond to the two dimensional spirals. Numerical simulations on a partial differential equations model indicate that the scroll rings are unstable: The contract by a power law and disappear. Therefore, in three dimensions clusters seem to be the best candidate for the hypercycle resistant to parasites.

Computer Simulation↗

Ethanol modulates the ionic permeability of sodium channels in rat sensory neurons.

The effects of ethanol on tetrodotoxin-sensitive (TTXs) and tetrodotoxin-resistant (TTXr) sodium channels in rat spinal ganglia were studied using a patch-clamp method. Application of ethanol (10 and 100 mM) to both sides of membranes resulted in decreases in the reversion potentials of both types of sodium channels. In the case of TTXr channels, ethanol decreased their selectivity in relation to Na ions and altered the sequence of ion selectivity of these channels for different cations from row X to row XI of the Eisenman selectivity classification. It is suggested that this change in ion selectivity is associated with ethanol-induced disruption of hydrogen bonds which stabilize the spatial structure of ion channel macromolecules, which may lead to changes in the steric parameters of the pores formed by these channels.

Animals↗

Aboriginal migration and labour market programs.

"Despite the potential for government employment policies both to encourage and preclude migration among the Aboriginal workforce, little is known about the impacts of such policies. This paper seeks to construct a base line for identifying these impacts by establishing the spatial structure of labour migration among the Aboriginal and Torres Strait Islander population. It makes use of 1986 Census data to describe the volume and pattern of net and gross flows of working-age Aborigines and Islanders through the national settlement system, distinguishing between movements in remote and closely settled parts of the country. Full determination of the links between policy and migration flows awaits comparison with 1991 Census results."

Australia↗

Identification of binding epitope of a monoclonal antibody (Z12) against human TNF-alpha using computer modeling and deletion mutant technique.

The genes of the heavy and light chain variable region (VH, VL) of Z12 antibody against hTNF-alpha were cloned, and according to the translated sequence of amino acids, the spatial structures of VH and VL domains were modeled by using homology-based modeling method, followed by constructing the whole three-dimensional structure of Fv fragment. The complex model of Fv interacting with hTNF-alpha was gained with computer-guided molecular docking method, based on which, it was predicted that the epitope recognized by Z12 was from 141 to 146 of hTNF-alpha. hTNF-alpha molecule was divided into two fragments of N-terminal region from 1 to 91 and C-terminal region from 92 to 157 with prokaryotic expression. The measured results suggested that the antigenic epitope recognized by Z12 antibody was located in the C-terminal region 92-157 of hTNF-alpha, proving the predicted result reliable preliminarily. Further experimental results showed that after hTNF-a 141-146 residues were deleted, Z12 antibody almost lost the ability to recognize the mutant, suggesting that the amino acid residues from 141 to 146 of hTNF-alpha were specially recognized by Z12 antibody.

Animals↗

Look-ahead fixations: anticipatory eye movements in natural tasks.

During performance of natural tasks subjects sometimes fixate objects that are manipulated several seconds later. Such early looks are known as "look-ahead fixations" (Pelz and Canosa in Vision Res 41(25-26):3587-3596, 2001). To date, little is known about their function. To investigate the possible role of these fixations, we measured fixation patterns in a model-building task. Subjects assembled models in two sequences where reaching and grasping were interrupted in one sequence by an additional action. Results show look-ahead fixations prior to 20% of the reaching and grasping movements, occurring on average 3 s before the reach. Their frequency was influenced by task sequence, suggesting that they are purposeful and have a role in task planning. To see if look-aheads influenced the subsequent eye movement during the reach, we measured eye-hand latencies and found they increased by 122 ms following a look-ahead to the target. The initial saccades to the target that accompanied a reach were also more accurate following a look-ahead. These results demonstrate that look-aheads influence subsequent visuo-motor coordination, and imply that visual information on the temporal and spatial structure of the scene was retained across intervening fixations and influenced subsequent movement programming. Additionally, head movements that accompanied look-aheads were significantly smaller in amplitude (by 10 degrees) than those that accompanied reaches to the same locations, supporting previous evidence that head movements play a role in the control of hand movements. This study provides evidence of the anticipatory use of gaze in acquiring information about objects for future manipulation.

Adult↗

Representation of the visual field in the lateral intraparietal area of macaque monkeys: a quantitative receptive field analysis.

The representation of the visual field in the primate lateral intraparietal area (LIP) was examined, using a rapid, computer-driven receptive field (RF) mapping procedure. RF characteristics of single LIP neurons could thus be measured repeatedly under different behavioral conditions. Here we report data obtained using a standard ocular fixation task during which the animals were required to monitor small changes in color of the fixated target. In a first step, statistical analyses were conducted in order to establish the experimental limits of the mapping procedure on 171 LIP neurons recorded from three hemispheres of two macaque monkeys. The characteristics of the receptive fields of LIP neurons were analyzed at the single cell and at the population level. Although for many neurons the assumption of a simple two-dimensional gaussian profile with a central area of maximal excitability at the center and progressively decreasing response strength at the periphery can represent relatively accurately the spatial structure of the RF, about 19% of the cells had a markedly asymmetrical shape. At the population level, we observed, in agreement with prior studies, a systematic relation between RF size and eccentricity. However, we also found a more accentuated overrepresentation of the central visual field than had been previously reported and no marked differences between the upper and lower visual representation of space. This observation correlates with an extension of the definition of LIP from the posterior third of the lateral intraparietal sulcus to most of the middle and posterior thirds. Detailed histological analyses of the recorded hemispheres suggest that there exists, in this newly defined unitary functional cortical area, a coarse but systematic topographical organization in area LIP that supports the distinction between its dorsal and ventral regions, LIPd and LIPv, respectively. Paralleling the physiological data, the central visual field is mostly represented in the middle dorsal region and the visual periphery more ventral and posterior. An anteroposterior gradient from the lower to the upper visual field representations can also be identified. In conclusion, this study provides the basis for a reliable mapping method in awake monkeys and a reference for the organization of the properties of the visual space representation in an area LIP extended with respect to the previously described LIP and showing a relative emphasis of central visual field.

Animals↗

Comparison of responses to electrical stimulation and whisker deflection using two different voltage-sensitive dyes in mouse barrel cortex in vivo.

We examined the spatial structure of noise in optical recordings made with two commonly used voltage-sensitive dyes (RH795 and RH1691) in mouse barrel cortex in vivo, and determined that the signal-to-noise ratio of the two dyes was comparable when averaging over barrel-sized areas, or at single pixels distant from large blood vessels. We examined the spatiotemporal development of whisker- and electrically-evoked optical responses by quantifying the area of activated cortical surface as a function of time. Whisker and electrical stimuli activated cortical areas between 0.2-2.0 mm(2) depending on intensity. More importantly, both types of activation recruited cortical area at similar rates and showed a linear relationship between the maximal activated area and the peak rate of increase of the activated area. We propose a general rule of supragranular cortical activation in which the initial spreading speed of the response determines the total activated area, independent of the type of activation. Finally, despite comparable single-response kinetics, we observed greater paired-pulse depression of whisker-evoked responses relative to electrically-evoked responses.

Animals↗

Termite symbiotic systems: efficient bio-recycling of lignocellulose.

Termites thrive in great abundance in terrestrial ecosystems and play important roles in biorecycling of lignocellulose. Together with their microbial symbionts, they efficiently decompose lignocellulose. In so-called lower termites, a dual decomposing system, consisting of the termite's own cellulases and those of its gut protists, was elucidated at the molecular level. Higher termites degrade cellulose apparently using only their own enzymes, because of the absence of symbiotic protists. Termite gut prokaryotes efficiently support lignocellulose degradation. However, culture-independent molecular studies have revealed that the majority of these gut symbionts have not yet been cultivated, and that the gut symbiotic community shows a highly structured spatial organization. In situ localization of individual populations and their functional interactions are important to understand the nature of symbioses in the gut. In contrast to cellulose, lignin degradation does not appear to be important in the gut of wood-feeding termites. Soil-feeding termites decompose humic substances in soil at least partly, but little is known about the decomposition. Fungus-growing termites are successful in the almost complete decomposition of lignocellulose in a sophisticated cooperation with basidiomycete fungi cultivated in their nest. A detailed understanding of efficient biorecycling systems, such as that for lignocellulose, and the symbioses that provide this efficiency will benefit applied microbiology and biotechnology.

Animals↗

Land management in the American southwest: a state-and-transition approach to ecosystem complexity.

State-and-transition models are increasingly being used to guide rangeland management. These models provide a relatively simple, management-oriented way to classify land condition (state) and to describe the factors that might cause a shift to another state (a transition). There are many formulations of state-and-transition models in the literature. The version we endorse does not adhere to any particular generalities about ecosystem dynamics, but it includes consideration of several kinds of dynamics and management response to them. In contrast to previous uses of state-and-transition models, we propose that models can, at present, be most effectively used to specify and qualitatively compare the relative benefits and potential risks of different management actions (e.g., fire and grazing) and other factors (e.g., invasive species and climate change) on specified areas of land. High spatial and temporal variability and complex interactions preclude the meaningful use of general quantitative models. Forecasts can be made on a case-by-case basis by interpreting qualitative and quantitative indicators, historical data, and spatially structured monitoring data based on conceptual models. We illustrate how science- based conceptual models are created using several rangeland examples that vary in complexity. In doing so, we illustrate the implications of designating plant communities and states in models, accounting for varying scales of pattern in vegetation and soils, interpreting the presence of plant communities on different soils and dealing with our uncertainty about how those communities were assembled and how they will change in the future. We conclude with observations about how models have helped to improve management decision-making.

Conservation of Natural Resources↗

Learning cortical topography from spatiotemporal stimuli.

Stimulus representation is a functional interpretation of early sensory cortices. Early sensory cortices are subject to stimulus-induced modifications. Common models for stimulus-induced learning within topographic representations are based on the stimuli's spatial structure and probability distribution. Furthermore, we argue that average temporal stimulus distances reflect the stimuli's relatedness. As topographic representations reflect the stimuli's relatedness, the temporal structure of incoming stimuli is important for the learning in cortical maps. Motivated by recent neurobiological findings, we present an approach of cortical self-organization that additionally takes temporal stimulus aspects into account. The proposed model transforms average interstimulus intervals into representational distances. Thereby, neural topography is related to stimulus dynamics. This offers a new time-based interpretation of cortical maps. Our approach is based on a wave-like spread of cortical activity. Interactions between dynamics and feedforward activations lead to shifts of neural activity. The psychophysical saltation phenomenon may represent an analogue to the shifts proposed here. With regard to cortical plasticity, we offer an explanation for neurobiological findings that other models cannot explain. Moreover, we predict cortical reorganizations under new experimental, spatiotemporal conditions. With regard to psychophysics, we relate the saltation phenomenon to dynamics and interaction in early sensory cortices and predict further effects in the perception of spatiotemporal stimuli.

Animals↗

M cells in the rabbit palatine tonsil: the distribution, spatial arrangement and membrane subdomains as defined by confocal lectin histochemistry.

The crypt epithelium of the palatine tonsil contains M cells that play an important role in the uptake of luminal antigens to initiate immune responses. To study the close interaction of M cells, squamous epithelial cells and lymphocytes we used confocal laser scanning microscopy and the lectin from Ulex europaeus (UEA-I), which selectively labels rabbit tonsillar M cells. Confocal serial sections and synthetic section planes showed that the M cells comprise up to 35% of the epithelial cells in the tonsil crypt and completely engulf clusters of two to eight lymphocytes with their apical cytoplasm. These lymphocytes lie in a pocket of the M cell's basolateral membrane that invaginates from one of the lateral aspects and forms a tunnel-like opening. Therefore, the tonsillar M cells closely resemble the M cells of the small and large intestines in their spatial structure, and likewise maintain an intraepithelial compartment for the interaction of lymphocytes, macrophages and antigens. The UEA-I bound intensely to the apical membrane of the M cells and to transcytotic vesicles in the apical cytoplasm. The pocket membrane bound the UEA-I more avidly than the remaining basolateral membrane, suggesting that the basolateral membrane of M cells is subdivided into membrane domains with different compositions of glycoconjugates.

Animals↗

Geographic homogeneity and non-equilibrium patterns of mtDNA sequences in Tuscany, Italy.

The geographical distribution of 49 mtDNA sequences from 22 localities in Southern Tuscany, Italy, was studied by molecular analysis of variance, by a new spatial autocorrelation statistic specifically designed for sequence data and by reconstructing genealogies of haplotypes. All these methods indicated a high homogeneity of populations. Nevertheless, genetic variability showed significant departure from equilibrium expectations, in agreement with the predicted effects of a population expansion. We suggest that a past population expansion that was probably associated with a migrational wave and with local gene flow between localities prevented spatial structuring in Southern Tuscany.

Analysis of Variance↗

Elk winter foraging at fine scale in Yellowstone National Park.

The link between landscape properties and foraging decisions by herbivores remains unclear, but such knowledge is central to the understanding of plant-herbivore dynamics. Our goal was to determine whether fine-scale foraging paths of free-ranging elk (Cervus canadensis) respond to spatial structure of habitats in Yellowstone National Park. During winter 2002 we gathered elk-foraging information by following snow tracks in open habitats located on hillsides and flat terrain. The 21 snow paths surveyed were comprised on average of 15 discrete snow craters connected to each other by relatively straight-line movements. Our analyses revealed two levels of selection: elk chose where to dig, and how much search effort to allocate at digging sites based on habitat characteristics. On hillsides, elk preferentially dug in areas of greater biomass of grasses and forbs, and simply walked through poorer sites without digging. Individuals also searched more intensively, creating larger craters, where food biomass was higher. On flat terrain, crater size decreased with snow depth and increased with snow density. Correlated random walk models usually were adequate to characterize elk movement on flat terrain, but not on hillsides. First, as the number of movements between local foraging areas increased, elk displacements on hillsides became shorter than expected from random patterns. This trend on hillsides was strongly influenced by interindividual variation in movement behavior. Second, elk tended to forage perpendicularly to aspect, resulting in horizontal displacements. Our study demonstrates that free-ranging elk adjust their foraging to fine-scale habitat structure.

Animals↗

Incorporating patterns of disperser behaviour into models of seed dispersal and its effects on estimated dispersal curves.

The processes determining where seeds fall relative to their parent plant influence the spatial structure and dynamics of plant populations and communities. For animal dispersed species the factors influencing seed shadows are poorly understood. In this paper we test the hypothesis that the daily temporal distribution of disperser behaviours, for example, foraging and movement, influences dispersal outcomes, in particular the shape and scale of dispersal curves. To do this, we describe frugivory and the dispersal curves produced by the southern cassowary, Casuarius casuarius, the only large-bodied disperser in Australia's rainforests. We found C. casuarius consumed fruits of 238 species and of all fleshy-fruit types. In feeding trials, seeds of 11 species were retained on average for 309 min (+/-256 SD). Sampling radio-telemetry data randomly, that is, assuming foraging occurs at random times during the day, gives an estimated average dispersal distance of 239 m (+/-207 SD) for seeds consumed by C. casuarius. Approximately 4% of seeds were dispersed further than 1,000 m. However, observation of wild birds indicated that foraging and movement occur more frequently early and late in the day. Seeds consumed early in the day were estimated to receive dispersal distances 1.4 times the 'random' average estimate, while afternoon consumed seeds received estimated mean dispersal distances of 0.46 times the 'random' estimate. Sampling movement data according to the daily distribution of C. casuarius foraging gives an estimated mean dispersal distance of 337 m (+/-194 SD). Most animals' behaviour has a non-random temporal distribution. Consequently such effects should be common and need to be incorporated into seed shadow estimation. Our results point to dispersal curves being an emergent property of the plant-disperser interaction rather than being a property of a plant or species.

Animals↗

Landscape context outweighs local habitat quality in its effects on herbivore dispersal and distribution.

Past studies with spatially structured herbivore populations have emphasized the primacy of intrinsic factors (e.g., patch quality), patch geometry (e.g., patch size and isolation), and more recently landscape context (e.g., matrix composition) in affecting local population abundance and dispersal rate. However, few studies have examined the relative importance of each factor, or how they might interact to affect herbivore abundance or dispersal. Here, we performed a factorial field experiment to examine the independent and interactive effects of patch quality (plant biomass, leaf protein, leaf phenolics) and matrix composition [mudflat or non-host grass (Bromus inermis)] on planthopper (Prokelisia crocea) emigration from host-plant patches (prairie cordgrass, Spartina pectinata). In addition, a field survey was conducted to examine the relative importance of patch quality, geography, and matrix composition on planthopper occupancy and density. In the experiment, we found that rates of emigration from low and intermediate quality patches were, on average, 21% percent higher for patches embedded in brome than mudflat. In contrast, the emigration rate was unaffected by matrix composition in nutrient-rich patches. Within matrix types, plant quality had little effect on emigration. In the survey, planthopper density and the patch occupancy rate of planthoppers increased nonadditively with increasing patch size and the percentage of the surrounding matrix composed of mudflat. This study suggests that landscape-level factors, such as the matrix, may be more important than factors intrinsic to the patches.

Analysis of Variance↗

Revisiting the rDNA sequence diversity of a natural population of the arbuscular mycorrhizal fungus Acaulospora colossica.

In 1999, the diversity of a field population of the arbuscular mycorrhizal (AM) fungus Acaulospora colossica was characterized using DNA sequence data. Since 1999, AM fungal sequences have accumulated rapidly within public databases. Moreover, novel phylogenetic tools have been developed and can be used to interpret the data. A second analysis of those sequences collected in 1999 demonstrates that while the majority of the sequences are, in fact, sequences of A. colossica; a minority of the sequences still cannot be identified with confidence. Those sequences identified as A. colossica can be used to show that (1) the nuclear rDNA ITS regions are remarkably diverse, and (2) sequences isolated from different spores of the same site may be more closely related to each other than to sequences of other sites, so that the genetic diversity of an AM fungal field population may be spatially structured; however, identical sequences can also be recovered from different sites.

DNA, Fungal↗