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PubMed2005

Evidence for biogenic pyromorphite formation by the nematode Caenorhabditis elegans.

The determination of chemical speciation and spatial distribution is a prerequisite for a mechanistic understanding of contaminant bioavailability and toxicity to an organism. We have employed synchrotron X-ray techniques to study Cu and Pb speciation and spatial distribution in the soil nematode Caenorhabditis elegans. Nematodes were exposed to each metal ion singly or simultaneously in solution for 24 h and were then rinsed thoroughly and preserved in formalin for transportation to the National Synchrotron Light Source. Experiments were conducted at the microprobe beamline X26A employing a focused beam of approximately 10 microm in diameter. Nematodes were mounted in agar gel on Kapton tape. Two-dimensional elemental maps for Cu- and Pb-exposed nematodes were collected in fluorescence mode. Copper was homogeneously distributed throughout the body of the nematode, but Pb exhibited a high degree of localization in the nematode, exclusively in the anterior pharynx region. Detectable localized concentrations of Pb in C. elegans occurred at aqueous exposure concentrations of 2.4 microM. Micro X-ray diffraction of these Pb hotspots gave a diffraction pattern indicating a crystalline Pb solid that was consistent with the Pb phosphate, pyromorphite. Biogenic inorganic phosphate granule formation is relatively common in soil invertebrates; however, these phosphates are typically amorphous, and we believe that this is the first report of crystalline pyromorphite formed internally in an organism.

Animals↗

PubMed2001

Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx43 protein levels and gap junction distribution.

In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels within the ischemic zone followed by a progressive increase after 48 h reperfusion. End-to-end immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myocyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolabelling was more intense and diffuse in hearts subjected to PC before sustained coronary occlusion (compared to non-PC). These data indicate that gap junctions are significantly altered during brief episodes of ischemia. Reorganization of the gap junction complex could contribute to PC-mediated reductions in cardiac arrhythmias.

Animals↗

PubMed1986

Distribution of protein and RNA in the 30S ribosomal subunit.

In Escherichia coli, the small ribosomal subunit has a sedimentation coefficient of 30S, and consists of a 16S RNA molecule of 1541 nucleotides complexed with 21 proteins. Over the last few years, a controversy has emerged regarding the spatial distribution of RNA and protein in the 30S subunit. Contrast variation with neutron scattering was used to suggest that the RNA was located in a central core of the subunit and the proteins mainly in the periphery, with virtually no separation between the centers of mass of protein and RNA. However, these findings are incompatible with the results of efforts to locate individual ribosomal proteins by immune electron microscopy and triangulation with interprotein distance measurements. The conflict between these two views is resolved in this report of small-angle neutron scattering measurements on 30S subunits with and without protein S1, and on subunits reconstituted from deuterated 16S RNA and unlabeled proteins. The results show that (i) the proteins and RNA are intermingled, with neither component dominating at the core or the periphery, and (ii) the spatial distribution of protein and RNA is asymmetrical, with a separation between their centers of mass of about 25 angstroms.

Escherichia coli↗

PubMed1990

Physical model simulations of brain injury in the primate.

Diffuse brain injuries resulting from non-impact rotational acceleration are investigated with the aid of physical models of the skull-brain structure. These models provide a unique insight into the relationship between the kinematics of head motion and the associated deformation of the surrogate brain material. Human and baboon skulls filled with optically transparent surrogate brain tissue are subjected to lateral rotations like those shown to produce diffuse injury to the deep white matter in the brain of the baboon. High-speed cinematography captures the deformations of the grids embedded within the surrogate brain tissue during the applied load. The overall deformation pattern is compared to the pathological portrait of diffuse brain injury as determined from animal studies and autopsy reports. Shear strain and pathology spatial distributions mirror each other. Load levels and resulting surrogate brain tissue deformations are related from one species to the other. Increased primate brain mass magnified the strain amplified without significantly altering the spatial distribution. An empirically-derived value for a critical shear strain associated with the onset of severe diffuse axonal injury in primates is determined, assuming constitutive similarity between baboon and human brain tissue. The primate skull physical model data and the critical shear strain associated with the threshold for severe diffuse axonal injury were used to scale data obtained from previous studies to man, and thus derive a diffuse axonal injury tolerance for rotational acceleration for humans.

Animals↗

PubMed2004

Spectral correlation studies of emotional states in humans.

Utilization of a new approach to EEG analysis, i.e., spectral correlation, allowed significant differences in the spatial distribution of correlational relationships in spectral power to be identified for emotions of different qualities, i.e., anger and fear. In conditions of fear, the topographic distribution of intracortical connections in the delta range was more extensive and included the frontal, central, temporal, parietal, and occipital areas. The emotion of anger induced changes in the pattern of the spatial distribution of intracortical connections in the alpha frequency range, such that a powerful frontal focus of connections formed in the frontal areas. The largest number of connections in the beta2 band (22 highly significant connections) was seen for the emotion of anger. Thus, generalization of connections in the high-frequency EEG ranges occurred in anger, while this was not characteristic of fear.

Adult↗

PubMed2006

A functional response model of a predator population foraging in a patchy habitat.

1. Functional response models (e.g. Holling's disc equation) that do not take the spatial distributions of prey and predators into account are likely to produce biased estimates of predation rates. 2. To investigate the consequences of ignoring prey distribution and predator aggregation, a general analytical model of a predator population occupying a patchy environment with a single species of prey is developed. 3. The model includes the density and the spatial distribution of the prey population, the aggregative response of the predators and their mutual interference. 4. The model provides explicit solutions to a number of scenarios that can be independently combined: the prey has an even, random or clumped distribution, and the predators show a convex, sigmoid, linear or no aggregative response. 5. The model is parameterized with data from an acarine predator-prey system consisting of Phytoseiulus persimis and Tetranychus urticae inhabiting greenhouse cucumbers. 6. The model fits empirical data quite well and much better than if prey and predators were assumed to be evenly distributed among patches, or if the predators were distributed independently of the prey. 7. The analyses show that if the predators do not show an aggregative response it will always be an advantage to the prey to adopt a patchy distribution. On the other hand, if the predators are capable of responding to the distribution of prey, then it will be an advantage to the prey to be evenly distributed when its density is low and switch to a more patchy distribution when its density increases. The effect of mutual interference is negligible unless predator density is very high. 8. The model shows that prey patchiness and predator aggregation in combination can change the functional response at the population level from type II to type III, indicating that these factors may contribute to stabilization of predator-prey dynamics.

Animals↗

PubMed2003

[Orderly structural organization of intrahemispheric interzonal connections in the cat visual cortex].

The study was aimed at morphometric analysis of cluster organization of neurons, forming interzonal cortico-cortical connections within the visual cortex. The study employed the technique based on horseradish peroxidase retrograde transport and methods of mathematical analysis of spatial distribution of labeled cells. The quantitative characteristics of cell distribution were obtained including cluster volume and linear dimensions, distances between their centers of gravity, periodicity and distribution along cortical surface. Age-related peculiarities in the distribution of initial cells of cortical interzonal connections were found. It was demonstrated that adult cluster organization pattern was established by the end of the second postnatal month. Quantitative differences in the spatial distribution of neuronal groups in the visual cortical areas 17 and 18 were determined.

Animals↗

PubMed1996

Visualization of autophosphorylation of Ca2+/calmodulin-dependent protein kinase II in hippocampal slices.

We describe a method for visualizing the relative spatial distribution of autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) in neuronal subcompartments within hippocampal slices. The method employs a monoclonal antibody recognizing only autophosphorylated CaMKII, and an affinity-purified polyclonal rabbit antisera recognizing only nonphosphorylated CaMK II (Patton et al. (1993) Mol. Biol. Cell, 4: 159-172). 50 microns sections cut from fixed 500 microns hippocampal slices are double-labeled with these antibodies bound by secondary antibodies coupled to fluorescein and Cy3, respectively. The distribution of the two antigens in identical optical sections is recorded by dual channel confocal laser scanning microscopy (CLSM). The digital images are analyzed with the program MacPhase to determine the relative levels of staining with antibodies to phosphokinase and antibodies to nonphosphokinase in subcellular domains of neurons. Comparison of data from paired control and experimental slices reveals the spatial distributions of changes in levels of autophosphorylated CaMKII produced by pharmacological treatments. We are able to detect and spatially resolve differences in levels of autophosphorylation of CaMK II between slices subjected to Ca2+ depletion (low autophosphorylation) and slices treated with a phosphatase inhibitor (high autophosphorylation).

Animals↗

PubMed1989

The Functional Organization of the Olivo-Cerebellar System as Examined by Multiple Purkinje Cell Recordings.

Multiple recordings from Purkinje cells in the rat cerebellum allowed the mechanism responsible for the activation of rows of synchronous complex spikes to be investigated. By determining the spatial distribution of the climbing fibre reflex that follows electrical microstimulation of the cerebellar cortex, it was shown that the mechanism for the simultaneity of firing was the electrotonic interactions between neurons in the inferior olive (IO). The spatial organization of the complex spike activity was shown to be regulated by GABAergic inhibitory input into the IO, probably arising from the cerebellar nuclear neurons. The rostro-caudal organizion of the complex spike activity following physiological stimulation (tactile stimulation of the upper and lower lip) demonstrated the same spatial distribution of synchronous activity in the cerebellar cortex as did the spontaneous activity and this was also disrupted by GABA blockers. Finally, complex spike responses to physiological stimulation indicate that the IO is capable of gating sensory inputs in accordance with its intrinsic autorhythmicity and that strong peripheral stimuli reset the oscillatory properties of the IO. The functional implications of the synchronicity and of the temporo-spatial organizion of complex spikes in the cerebellar cortex are discussed in the context of motor coordination and timing.

Journal Article↗

PubMed1993

A stochastic model for adhesion-mediated cell random motility and haptotaxis.

The active migration of blood and tissue cells is important in a number of physiological processes including inflammation, wound healing, embryogenesis, and tumor cell metastasis. These cells move by transmitting cytoplasmic force through membrane receptors which are bound specifically to adhesion ligands in the surrounding substratum. Recently, much research has focused on the influence of the composition of extracellular matrix and the distribution of its components on the speed and direction of cell migration. It is commonly believed that the magnitude of the adhesion influences cell speed and/or random turning behavior, whereas a gradient of adhesion may bias the net direction of the cell movement, a phenomenon known as haptotaxis. The mechanisms underlying these responses are presently not understood. A stochastic model is presented to provide a mechanistic understanding of how the magnitude and distribution of adhesion ligands in the substratum influence cell movement. The receptor-mediated cell migration is modeled as an interrelation of random processes on distinct time scales. Adhesion receptors undergo rapid binding and transport, resulting in a stochastic spatial distribution of bound receptors fluctuating about some mean distribution. This results in a fluctuating spatio-temporal pattern of forces on the cell, which in turn affects the speed and turning behavior on a longer time scale. The model equations are a system of nonlinear stochastic differential equations (SDE's) which govern the time evolution of the spatial distribution of bound and free receptors, and the orientation and position of the cell. These SDE's are integrated numerically to simulate the behavior of the model cell on both a uniform substratum, and on a gradient of adhesion ligand concentration. Furthermore, analysis of the governing SDE system and corresponding Fokker-Planck equation (FPE) yields analytical expressions for indices which characterize cell movement on multiple time scales in terms of cell cytomechanical, morphological, and receptor binding and transport parameters. For a uniform adhesion ligand concentration, this analysis provides expressions for traditional cell movement indices such as mean speed, directional persistence time, and random motility coefficient. In a small gradient of adhesion, a perturbation analysis of the FPE yields a constitutive cell flux expression which includes a drift term for haptotactic directional cell migration. The haptotactic drift contains terms identified as contributions from directional orientation bias (taxis), kinesis, and orthotaxis, of which taxis appears to be predominant given estimates of the model parameters.

Animals↗

PubMed1992

Relation between recovery sequence estimated from body surface potentials and T wave shape in patients with negative T waves and normal subjects.

BACKGROUND: Advances in analytical methods of the epicardial electrical potentials allowed us to demonstrate spatial distributions of local recovery. Because local recovery will be reflected in events on body surface ECG mapping, abnormalities in recovery sequence that may be responsible for the origin of negative T waves can be detected from body surface potentials. METHODS AND RESULTS: Eighty-seven unipolar ECGs were recorded simultaneously from the entire thorax in patients having negative T waves on left anterior precordial leads and in normal subjects. These included 40 patients with anterior myocardial infarction (MI), 21 patients with left ventricular hypertrophy (LVH), and 44 male volunteers. We measured Tmax time, defined as the instant of maximal first derivative of the T wave as the index of local recovery (Wyatt's method). Parameters related to T wave potentials were positive T wave amplitude, negative T wave amplitude, and T integral. Significant correlations were observed between the Tmax time and each of the T wave potentials. The T wave potentials were dependent on Tmax times. In the anterior MI, the late Tmax times were located on the upper left anterior chest and early Tmax times on the lower right lateral chest. In the LVH, the area showing a delayed recovery was displaced in a left downward direction compared with anterior MI. CONCLUSIONS: Body surface Tmax time distributions clearly separate two negative T wave groups, i.e., anterior MI and LVH. Appearance of the negative T waves correlates well with the presence of the area with delayed Tmax time on the spatial distribution.

Adult↗

PubMed1993

Optical assessment of spatial patterning of strength-duration relationship for vagal responses in the early embryonic chick brainstem.

The spatial patterning of strength-duration relationship for neural responses to vagus nerve stimulation in the early embryonic chick brainstem preparation was assessed by means of an optical method for monitoring neural activity using a voltage-sensitive dye. Intact brainstem, and brainstem slice preparations, together with the attached vagus nerve, were dissected from 6- to 8-day (d)-old chick embryos. They were stained with a voltage-sensitive merocyanine-rhodanine dye (NK2761). Application of depolarizing square current pulses to the vagus nerve fibers using a micro-suction electrode evoked voltage-related optical (absorption) responses in the brainstem. The optical responses were recorded simultaneously from 127 contiguous sites in both the intact and slice preparations, using a 12 x 12-element photodiode array. The amplitude of the evoked signals and the extent of the response area depended on the strength and duration of the stimulating current pulse. Thus, we determined the threshold current strength needed to evoke the fast spike-like optical signal, corresponding to the action potential, in response to vagal stimulation at a given duration, and we obtained strength-duration curves for 100-200 contiguous regions in the preparation. The strength-duration curves could be apparently fitted by the empirical formula of Weiss. From these curves we obtained the rheobasic currents as a possible indication of neural responsiveness to peripheral vagus stimulation, and we constructed the map of the spatial distribution of the rheobasic currents. The rheobasic current is smallest in the central region of the response area, and it is distributed in a layered pattern of increasing value. In accordance with such a pattern, the minimum rheobasic current decreased and the response area expanded developmentally. The results suggest that the ordered patterns of spatial distributions of the size of the axon, the specific membrane resistance, sodium channel activity, and other electrophysiological factors underlie the initial process of functional organization of the dorsal motor nucleus within the brainstem during early embryonic development.

Animals↗

PubMed2002

Distribution patterns of over-represented k-mers in non-coding yeast DNA.

MOTIVATION: Over-represented k-mers in genomic DNA regions are often of particular biological interest. For example, over-represented k-mers in co-regulated families of genes are associated with the DNA binding sites of transcription factors. To measure over-representation, we introduce a statistical background model based on single-mismatches, and apply it to the pooled 500 bp ORF Upstream Regions (USRs) of yeast. More importantly, we investigate the context and spatial distribution of over-represented k-mers in yeast USRs. RESULTS: Single and double-stranded spatial distributions of most over-represented k-mers are highly non-random, and predominantly cluster into a small number of classes that are robust with respect to over-representation measures. Specifically, we show that the three most common distribution patterns can be related to DNA structure, function, and evolution and correspond to: (a) homologous ORF clusters associated with sharply localized distributions; (b) regulatory elements associated with a symmetric broad hill-shaped distribution in the 50-200 bp USR; and (c) runs of As, Ts, and ATs associated with a broad hill-shaped distribution also in the 50-200 bp USR, with extreme structural properties. Analysis of over-representation, homology, localization, and DNA structure are essential components of a general data-mining approach to finding biologically important k-mers in raw genomic DNA and understanding the 'lexicon' of regulatory regions.

Amino Acid Motifs↗

PubMed1991

Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses.

To elucidate the nature of signals that control the level and spatial distribution of mRNAs encoding acetylcholine receptor (AChR), alpha-, beta-, gamma-, delta- and epsilon-subunits in muscle fibers chronic paralysis was induced in rat leg muscles either by surgical denervation or by different neurotoxins that cause disuse of the muscle or selectively block neuromuscular transmission pre- or postsynaptically and cause an increase of AChRs in muscle membrane. After paralysis, the levels and the spatial distributions of the different subunit-specific mRNAs change discoordinately and seem to follow one of three different patterns depending on the subunit mRNA examined. The level of epsilon-subunit mRNA and its accumulation at the end-plate are largely independent on the presence of the nerve or electrical muscle activity. In contrast, the gamma-subunit mRNA level is tightly coupled to innervation. It is undetectable or low in innervated normally active muscle and in innervated but disused muscle, whereas it is abundant along the whole fiber length in denervated muscle or in muscle in which the neuromuscular contact is intact but the release of transmitter is blocked. The alpha-, beta-, and delta-subunit mRNA levels show a different pattern. Highest amounts are always found at end-plate nuclei irrespective of whether the muscle is innervated, denervated, active, or inactive, whereas in extrasynaptic regions they are tightly controlled by innervation partially through electrical muscle activity. The changes in the levels and distribution of gamma- and epsilon-subunit-specific mRNAs in toxin-paralyzed muscle correlate well with the spatial appearance of functional fetal and adult AChR channel subtypes along the muscle fiber. The results suggest that the focal accumulation at the synaptic region of mRNAs encoding the alpha-, beta-, delta-, and epsilon-subunits, which constitute the adult type end-plate channel, is largely determined by at least two different neural factors that act on AChR subunit gene expression of subsynaptic nuclei.

Animals↗

PubMed2004

Modulation of autonomic balance by tumors and viruses.

Autonomic balance, a function generally under host control, is subject to modulation by other signalers. In some cases, modulation of host autonomic function through behavioral and physical stressors exerted by another individual may have negative consequences for the stress recipient by inducing sympathetic bias. Modulation of autonomic function may sometimes benefit one party at the expense of another. Tumors and HIV are examples of illegitimate signalers who may induce host sympathetic bias to promote their own growth and evade host immune surveillance. Paraneoplastic and paraviral syndromes such as hypertrophic osteoarthopathy, QTc prolongation, insomnia, and cachexia could be viewed as epiphenomena related to the tumoral and viral manipulation of host autonomic balance. In a more general framework, other paraneoplastic and paraviral syndromes may represent epiphenomena related to modulation of endocrine, cytokine, and autonomic functions by tumors and viruses to promote their own survival. Spatial distribution of cancers and viruses within the host may reflect affinity for strategic locations that facilitate manipulation of a variety of host functions including autonomic, endocrine, and cytokine regulation. A more general for understanding spatial distribution of diseases based on gradients of autonomic balance in the body are explored. Darwinian perspectives are discussed.

Autonomic Nervous System Diseases↗

PubMed2000

Lead in the southern East China Sea.

At present, in most oceans the lead (Pb) biogeochemical cycling has been disturbed by anthropogenic Pb through atmospheric input. The Pb concentrations in the upper water positively correlate with atmospheric input fluxes of Pb. The North Pacific is affected greatly by atmospheric substances via long-range transport from eastern Asia, especially from Mainland China. Mainland China may export considerable amounts of pollutants into the seas via rivers and the atmosphere owing to its recent fast growth in industry and economy. The East China Sea lies in an important geographical position--a transit between Mainland China and the western North Pacific. However, no data are available for seawater concentrations of Pb, a representative element with anthropogenic origin. In this work seawater samples from both 5 and 30-50 m water layers of 15 stations occupied over a cyclonic eddy in the southern East China Sea were analyzed for particulate Pb (PPb) and dissolved Pb (DPb). The Mean concentration of DPb (approximately 128 ng/l) in the southern East China Sea upper waters (< or = 50 m) is approximately several times higher than those in the Pacific; the high DPb concentrations in the southern East China Sea waters correspond to much higher atmospheric supplies of Pb to the East China Sea. Thus, this study partly fills the 'data gap' of the marginal seas. Also, it indicates that the East China Sea may be considerably contaminated by deposited polluted aerosols. Spatial distributions of DPb in the surface water show a tendency of increasing concentrations with distance offshore, that depends on the magnitudes of atmospheric Pb inputs and on particle scavenging processes. In contrast to DPb, spatial distributions of PPb basically display an 'omega'-like picture and a tendency of decreasing concentrations with distance offshore. These are related to riverine and scavenging sources and to the drive by the eddy. Additionally, the residence times of DPb in the surface water were estimated to be about 2 years, agreeing well with the reported data.

Lead↗

PubMed1987

Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents.

Adult male mice were treated with one or two different doses of each of 18 different cytotoxic agents. They were sampled at various times (3-12h) thereafter, and the spatial distributions of cell death in the small intestinal crypts were studied. Dead or dying cells or cells carrying dead cell fragments were examined histologically, and all of these were recorded (for convenience as apoptotic fragments), relative to the cell position in the crypt. Thus, distributions of apoptotic fragments against cell position were determined. A regression analysis of the data obtained at different times after administration of each agent was undertaken and the position of the median of the spatial distribution of presumptive target cells was deduced for each cytotoxic agent. The accuracy of this median value was determined to be +/- 0.5 cell positions. From these median values, the different cytotoxic agents could be divided roughly into three groups: [3H]thymidine, isopropyl-methane-sulphonate, gamma-rays, bleomycin and adriamycin all have their median values (susceptible cells) at cell positions 4 to 6; bischlorethylnitrosourea, actinomycin D, cyclophosphamide and cycloheximide at cell positions 6-8; mechlorethamine, triethylenethiophosphoramide, vincristine, 5-fluorouracil, hydroxyurea and methotrexate at cell positions 8-11. The position of these medians was considered in relation to the killing of clonogenic cells. Preliminary studies on the distributions of dead cells after myleran, cis-platinum and heat (hyperthermia) were also reported. There is a general tendency for antibiotics and radiation to attack the lower cell positions in the crypt. Alkylating agents on the other hand have a somewhat broad spectrum of action. Antimetabolites and a microtubule dissociating agent act on higher cell positions. No difference could be detected between two different forms (sources) of actinomycin D. The changes in the yields of apoptotic and mitotic cells with time and the migration velocities of cells in the crypts carrying apoptotic fragments after exposure to cytotoxics are also presented.

Animals↗

PubMed2003

A methodology to estimate odors around landfill sites: the use of methane as an odor index and its utility in landfill siting.

The estimation of odor production and dispersion from landfill sites is a very complicated task because of the different chemical species that exist in biogas. To site a new landfill, it is necessary to know the distance that odors can travel around the landfill under atmospheric conditions that increase the concentration of pollutants. Although CH4 is an odorless gas, it can be used as an index to determine the dispersion of low-reactivity odorous species around a landfill site. Methane production rates, estimated by biogas production models, were used by an air dispersion model to determine the spatial distribution of CH4 around landfill sites. By utilizing dispersion models under extreme atmospheric conditions, a maximum CH4 concentration around the landfills was determined. Based on the ratio between CH4 and odorous chemical species, the spatial distribution of the concentration of an odorous species was determined for those species with low reactivity in the atmosphere. For odorous species with high reactivity in the atmosphere, a dispersion-reaction model must be used. In this way, the acceptable distance between new landfills and residential areas can be determined. The proposed methodology could be used as a design tool for those who are interested in landfill siting.

Air Pollutants↗