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PubMed1999

Passive normalization of synaptic integration influenced by dendritic architecture.

We examined how biophysical properties and neuronal morphology affect the propagation of individual postsynaptic potentials (PSPs) from synaptic inputs to the soma. This analysis is based on evidence that individual synaptic activations do not reduce local driving force significantly in most central neurons, so each synapse acts approximately as a current source. Therefore the spread of PSPs throughout a dendritic tree can be described in terms of transfer impedance (Z(c)), which reflects how a current applied at one location affects membrane potential at other locations. We addressed this topic through four lines of study and uncovered new implications of neuronal morphology for synaptic integration. First, Z(c) was considered in terms of two-port theory and contrasted with dendrosomatic voltage transfer. Second, equivalent cylinder models were used to compare the spatial profiles of Z(c) and dendrosomatic voltage transfer. These simulations showed that Z(c) is less affected by dendritic location than voltage transfer is. Third, compartmental models based on morphological reconstructions of five different neuron types were used to calculate Z(c), input impedance (Z(N)), and voltage transfer throughout the dendritic tree. For all neurons, there was no significant variation of Z(c) with location within higher-order dendrites. Furthermore, Z(c) was relatively independent of synaptic location throughout the entire cell in three of the five neuron types (CA3 interneurons, CA3 pyramidal neurons, and dentate granule cells). This was quite unlike Z(N), which increased with distance from the soma and was responsible for a parallel decrease of voltage transfer. Fourth, simulations of fast excitatory PSPs (EPSPs) were consistent with the analysis of Z(c); peak EPSP amplitude varied <20% in the same three neuron types, a phenomenon that we call "passive synaptic normalization" to underscore the fact that it does not require active currents. We conclude that the presence of a long primary dendrite, as in CA1 or neocortical pyramidal cells, favors substantial location-dependent variability of somatic PSP amplitude. In neurons that lack long primary dendrites, however, PSP amplitude at the soma will be much less dependent on synaptic location.

Algorithms↗
PubMed1998

[Dendrites, neurons and simulation models].

The dendritic tree, this morphologically remarkably structured and typically diversified portion of the neuron reveals gradually its till recently little known complex functional possibilities. The size of the dendritic membrane participates in the latter similarly as their morphological pattern and their electronic structure which has a marked effect also due to its passive cable properties on the spread and interaction of potential changes on the membrane. Moreover the presence of a complex, differentiated mosaic of ion channels of different types provides dendrites with non-linearities with a wide scope of dynamic phenomena and active properties. The dendritic membrane can e.g. actively reinforce signals proceeding along the thin dendrite fibres and may make the development of action potentials or their retrograde movement from the membrane of the cell body possible. The possible operations above the spatial and temporal structures of signals equipped by differently located excitation and inhibition synapses are enriched by the action of ions entering via ion channels into the cell when the membrane potential changes. Manifestations of neuroplasticity lend these properties further temporal and functional dimensions. The neuron is no longer a one-way polarized and passive transmitter of synaptic input signals four output action potentials; it is a complicated non-linear hierarchic dynamic system with possible complex temporal and spatial analogue signal transformations in dendritic structures. New findings are the result of the cooperative use of empirical and theoretical procedures based on the morphophysiological methods with a high differentiating capacity and the methodology of studies of dynamic systems and computer simulation.

Action Potentials↗
PubMed1995

Spatial distribution and temporal change in cytosolic pH and [Ca2+] in resting and activated single human platelets.

In human platelets, a rapid rise in cytoplasmic Ca2+ and slower rise in cytoplasmic pH follow stimulation by thrombin. With the Ca2+ probe Fura-2 and the pH probe SNARF-1 for digitized fluorescence microscopy, we studied simultaneously the distribution and changes with time of [pH]i and [Ca2+]i in individual human platelets. In platelets coloaded with both probes, the probes had no detectable fluorescence at each other's excitation wavelength. The monovalent cation ionophore, nigericin (2 microM), produced a homogeneous rise in pH but no change in [Ca2+]. Platelets, in contact with glass, spread and developed an irregular, apparently mutually independent rise in both [Ca2+] and pH. Stimulation of platelets by thrombin 1.0 U/ml elevated [Ca2+]i and produced slow alkalinization without initial acidification. Replacement of extracellular Na+ by choline abolished thrombin-induced alkalinization, but had no effect on thrombin-induced [Ca2+]i elevation. ADP 10 microM caused a rapid rise of [Ca2+]i and transient alkalinization. Most stimulated platelets developed a gradient in pH, that was highest in the center. ADP and thrombin caused oscillation of [Ca2+]i but not of [pH]i. We conclude that alkalinization in stimulated platelets, presumably involving Na+/H+ antiport, is not essential for the rise of [Ca2+]i that may accompany it.

Adenosine Diphosphate↗
PubMed1998

Dynamics of Cytoplasmic Incompatability with Multiple Wolbachia Infections.

Wolbachia infections occur in many arthropods. These matrilineally inherited bacteria cause cytoplasmic incompatibility, in which a cross produces no offspring when between an infected male and an uninfected female. Some populations harbour multiple Wolbachia strains. Females fail to produce offspring when crossed to a male with a strain that the female lacks. Prior theoretical work showed that a panmictic population cannot maintain polymorphism for different strains when each female carries only a single strain. A few authors suggested that doubly infected females can stabilize multistrain polymorphism, but conditions for invasion and location of stable equilibrium were not analysed in detail. For two strains, I describe the conditions under which a multiply infected class can spread. Spread of the doubly infected type stabilizes polymorphism of the singly infected classes. This analysis also suggests an interesting extension to higher multiplicity of infection. For an arbitrary number of strains, N, a panmictic population cannot maintain different classes with N-1 infections unless the class with N infections is also present. This pyramid of polymorphism may explain the puzzling diversity of incompatibility types observed in some Culex mosquitos. Multiple infection also has interesting consequences for the dynamics of spatial variation and reproductive isolation.Copyright 1998 Academic Press Limited

Journal Article↗
PubMed1994

External four-channel tocography during delivery.

OBJECTIVE: A four-channel tocographic technique was developed in order to improve present knowledge of spatial uterine motility. METHOD: Fifty-four women were monitored during labor. Four pressure transducers were attached in a square around the umbilicus. RESULTS: The origin of uterine contractions was generally determined to be in the upper right segment of the uterus. The rate of operative deliveries was decreased in the case of predominant upper right origin of labor. Most of the contractions with clear propagation patterns originated on the upper right side, continued to the left and then spread to the lower right part of the uterus. The highest relative intensity was also measured on the upper right side. CONCLUSION: Predominant upper right origin of labor may be important for unassisted or spontaneous delivery.

Adult↗
PubMedDate not supplied

Imaging of complex NMR spectra.

The Point Spread Function (PSF) in NMR imaging is the result of both the line broadening due to magnet field inhomogeneity and the intrinsic spectrum of the nucleus at resonance. In the case of proton imaging, the line broadening dominates the small chemical shifts and the spectral lines are not resolved. This is not generally the case with other nuclei having strong chemical shifts and the PSF then has a complex structure. During imaging, the complex PSF is convolved with the spatial distribution of the nucleus at resonance and this leads to halo artifacts which are dependent on the imaging technique employed. The images due to the ensemble of spectral lines can be separated in principle by deconvolution of the data with the PSF before reconstruction. In the special case where the complex PSF is spatially independent, it can be obtained from the Free Induction Decay (FID) data produced in the absence of a spatially encoding gradient field. This technique has been successfully applied to in-vivo imaging of exogenous perfluorocarbon material.

Animals↗
PubMedDate not supplied

The effect of finite spatial resolution on the measurement of cardiac phantom wall thickness in single photon emission computerized tomographic imaging.

OBJECTIVE: To devise and validate a method of estimating accurately myocardial wall thickness from cardiac images acquired with single photon emission tomography (SPECT). MATERIALS AND METHODS: We simulated the imaging process by convolving a spatial resolution function, experimentally determined for a clinical SPECT system, with rectangular profiles mimicking the myocardial walls for different thicknesses and separations. Wall thicknesses were estimated by fitting the resulting profiles to a linear superposition of two offset Gaussians. The method was validated by extensive computer simulation and by testing on real phantom images. RESULTS: Accurate estimates of the wall thickness of SPECT phantoms were obtained when the estimated thickness (using fitting to Gaussians) was deconvolved with the point spread function (PSF) of the imaging system using a look-up table. CONCLUSIONS: This method is a novel method of estimating wall thickness from cardiac images. It is particularly useful for small separations (e.g. at end systole and/or towards the apex of the heart) of walls that are narrow compared to the PSF of the imaging system.

Computer Simulation↗
PubMed1997

Impact of cytoplasmic calcium buffering on the spatial and temporal characteristics of intercellular calcium signals in astrocytes.

The impact of calcium buffering on the initiation and propagation of mechanically elicited intercellular Ca2+ waves was studied using astrocytes loaded with different exogenous, cell membrane-permeant Ca2+ chelators and a laser scanning confocal or video fluorescence microscope. Using an ELISA with a novel antibody to BAPTA, we showed that different cell-permeant chelators, when applied at the same concentrations, accumulate to the same degree inside the cells. Loading cultures with BAPTA, a high Ca2+ affinity chelator, almost completely blocked calcium wave occurrence. Chelators having lower Ca2+ affinities had lesser affects, as shown in their attenuation of both the radius of spread and propagation velocity of the Ca2+ wave. The chelators blocked the process of wave propagation, not initiation, because large [Ca2+]i increases elicited in the mechanically stimulated cell were insufficient to trigger the wave in the presence of high Ca2+ affinity buffers. Wave attenuation was a function of cytoplasmic Ca2+ buffering capacity; i.e., loading increasing concentrations of low Ca2+ affinity buffers mimicked the effects of lesser quantities of high-affinity chelators. In chelator-treated astrocytes, changes in calcium wave properties were independent of the Ca2+-binding rate constants of the chelators, of chelation of other ions such as Zn2+, and of effects on gap junction function. Slowing of the wave could be completely accounted for by the slowing of Ca2+ ion diffusion within the cytoplasm of individual astrocytes. The data obtained suggest that alterations in Ca2+ buffering may provide a potent mechanism by which the localized spread of astrocytic Ca2+ signals is controlled.

Animals↗
PubMed1998

Calculation of the spatial variation of relative biological effectiveness in a therapeutic proton field for eye treatment.

The relative biological effectiveness (RBE) of protons under conditions suitable for eye treatment has been studied. A complete three-dimensional modelling of the beam delivery system has been performed. Proton Monte Carlo transport calculations have been performed to obtain the proton energy distributions at different positions in a water phantom including the influence of range shifter, modulator wheel, scattering foils and collimators. A beam with a kinetic energy of 68 MeV +/- 250 keV has been simulated with respect to the HMI-Berlin eye treatment facility. The dependence of the RBE on absorbed dose and position within a spread-out Bragg peak (SOBP) has been investigated with the track structure model. Due to a decreasing proton energy with depth, the energy transfer per pathlength within the SOBP increases, affecting the RBE. An RBE increasing with depth as well as with decreasing absorbed dose has been found for the endpoint inactivation of V79 and CH2B2 hamster cells. RBE values at the distal end of the SOBP up to 1.3 and 1.5 have been found at a dose of 14 Gy and 2 Gy respectively. Within the SOBP plateau, no lateral variation of RBE has been found for a given depth. The model used offers the possibility of introducing a variable RBE in treatment planning.

Animals↗
PubMed1992

Kinetics of diffusion in a spherical cell. I. No solute buffering.

Realistic neuron models that involve effects of concentration changes of second messengers on ion channels must include processes such as diffusion and solute buffering. These processes, which span a wide range of spatial and temporal scales, may impose a severe computational burden. In this paper and its companion, we examine the kinetics of diffusion and present methods for stimulating it accurately and efficiency. The problem of calcium diffusion in a spherical cell is used as a device to demonstrate the practical application of our analysis. However, the scope of these papers is not limited to this problem. The same analysis that we apply and concerns that we raise are germane to the spread of any second messenger, and can be adapted to other geometries. The focus of this paper is the simplest case: diffusion in the absence of solute buffering. This analysis also applies whenever buffering is so fast that it is instantaneous compared to diffusion, or so slow that concentration gradients have dissipated before substantial buffering takes place. The second paper investigates the more difficult situation where diffusion and buffering occur at comparable rates. In the absence of buffering, concentration changes produced by diffusion can be fit by an infinite series of exponential terms. We show how to design a model with N + 1 compartments that fits the N slowest terms of this series exactly in a shell just inside the cell membrane.

Animals↗
PubMed2026

Evolutionary history of Jamestown Canyon virus reveals complex multi-vector ecology.

Jamestown Canyon virus (JCV) is a historically understudied mosquito-borne virus of increasing concern in North America. We generated 658 whole-genome JCV sequences from northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997 to 2022. Then, we applied phylodynamic methods to demonstrate how mosquito phenology structures the maintenance and evolution of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s, and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of &#x223c;3 &#xd7; 10-5 substitutions per site per year (s/s/y), making it one of the slowest-evolving known RNA viruses, because the virus spends &#x223c;10 months per year in evolutionary stasis while overwintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of &#x223c;30-60 km2/year, which is more similar to slow-moving tick-borne viruses than to other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contributed to periodic bursts of spatial diffusion and amplification within seasons. We demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework for rapidly advancing our evolutionary and ecological knowledge of understudied viruses.

Animals↗
PubMed2004

A PCE groundwater plume discharging to a river: influence of the streambed and near-river zone on contaminant distributions.

An investigation of a tetrachloroethene (PCE) groundwater plume originating at a dry cleaning facility on a sand aquifer and discharging to a river showed that the near-river zone strongly modified the distribution, concentration, and composition of the plume prior to discharging into the surface water. The plume, streambed concentration, and hydrogeology were extensively characterized using the Waterloo profiler, mini-profiler, conventional and driveable multilevel samplers (MLS), Ground Penetrating Radar (GPR) surveys, streambed temperature mapping (to identify discharge zones), drivepoint piezometers, and soil coring and testing. The plume observed in the shallow streambed deposits was significantly different from what would have been predicted based on the characteristics of the upgradient plume. Spatial and temporal variations in the plume entering the near-river zone contributed to the complex contaminant distribution observed in the streambed where concentrations varied by factors of 100 to 5000 over lateral distances of less than 1 to 3.5 m. Low hydraulic conductivity semi-confining deposits and geological heterogeneities at depth below the streambed controlled the pattern of groundwater discharge through the streambed and influenced where the plume discharged into the river (even causing the plume to spread out over the full width of the streambed at some locations). The most important effect of the near-river zone on the plume was the extensive anaerobic biodegradation that occurred in the top 2.5 m of the streambed, even though essentially no biodegradation of the PCE plume was observed in the upgradient aquifer. Approximately 54% of the area of the plume in the streambed consisted solely of PCE transformation products, primarily cis-1,2-dichloroethene (cDCE) and vinyl chloride (VC). High concentrations in the interstitial water of the streambed did not correspond to high groundwater-discharge zones, but instead occurred in low discharge zones and are likely sorbed or retarded remnants of past high-concentration plume discharges. The high-concentration areas (up to 5529 microg/l of total volatile organics) in the streambed are of ecological concern and represent potential adverse exposure locations for benthic and hyporheic zone aquatic life, but the effect of these exposures on the overall health of the river has yet to be determined. Even if the upgradient source of PCE is remediated and additional PCE is prevented from reaching the streambed, the high-concentration deposits in the streambed will likely take decades to hundreds of years to flush completely clean under natural conditions because these areas have low vertical groundwater flow velocities and high retardation factors. Despite high concentrations of contaminants in the streambed, PCE was detected in the surface water only rarely due to rapid dilution in the river and no cDCE or VC was detected. Neither the sampling of surface water nor the sampling of the groundwater from the aquifer immediately adjacent to the river gave an accurate indication of the high concentrations of PCE biodegradation products present in the streambed. Sampling of the interstitial water of the shallow streambed deposits is necessary to accurately characterize the nature of plumes discharging to rivers.

Biodegradation, Environmental↗
PubMed2004

Separable enhancer sequences regulate the expression of the neural bHLH transcription factor neurogenin 1.

Ngn1 is a basic helix-loop-helix (bHLH) transcription factor expressed in specific regions within the developing brain and spinal cord, sensory ganglia, and olfactory epithelium. We have identified sequences both 5' and 3' of the mouse ngn1 gene that function in regulating ngn1 expression, and each of these sequences contains distinct regulatory cassettes for different subregions of the expression domain. Enhancers for expression in ngn1 domains of the midbrain, hindbrain, trigeminal ganglia, and ventral-neural tube appear redundant and are spread both 5' and 3' of the ngn1 coding sequence. In contrast, a single discrete dorsal-neural tube enhancer was located in the 5' sequence that is conserved among mouse, human, chick, and zebrafish ngn1 genes. Functionally, this enhancer is both necessary and sufficient for driving expression of a heterologous reporter in transgenic mice specifically to the dorsal domain of ngn1 expression in the spinal neural tube. Thus, sequences are identified that can be used to direct temporally and spatially restricted expression of heterologous genes to the developing neural tube.

Animals↗
PubMed1983

Principles of nuclear magnetic resonance for medical application.

Several important components must be combined to create an effective nuclear magnetic resonance (NMR) imaging system. The most imposing component is the magnet itself, which is most often either resistive or superconducting. In addition, the magnetic field gradient, radiofrequency (RF) coil, spectrometer, computer, and display system are critical factors that require special consideration before selecting an NMR system for a particular clinical usage. Although nuclear magnetic resonance and nuclear decay share a common object of interest (the nucleus), a number of differences between resonance and decay phenomena relating to information content and imaging techniques can be discussed. First, in NMR the frequency, and hence energy, of the detected electromagnetic radiation from a given nuclear type is dependent critically on the magnetic and molecular environment of the stimulated nuclei. This is contrasted to the situation in nuclear decay reactions, where the energy of gamma or positron emission is only weakly dependent on local factors. Thus in NMR, molecular information can be acquired without the use of external tracer molecules. In NMR energy exchange mechanisms (relaxation) take place on a microscopic scale, and hence local information is acquired by measuring relaxation times. Furthermore, the frequency output of an NMR experiment is transmitted to the detector with little change from its surroundings. This again differs from nuclear decay, where the observed spread of detected energies is a complex function of numerous interactions among the emitted radiation, the surrounding matter, and the detector, and energy exchange processes are spread in a random fashion over a large volume. However, this relative lack of interaction with matter in NMRs (RF) output comes at a price of sensitivity, since the energy level is orders of magnitude lower than that of gamma photons. In addition, the much longer wavelengths associated with such low energy radiation (on the order of meters) makes simple collimation used in gamma cameras impossible, and hence more complex means need to be used to locate the emitted signal spatially. Overall, the differences between NMR and nuclear decay are likely to lead to a complementary, rather than conflicting, relationship between the two sciences, with advantages to each depending on the questions being investigated. Which problems are best studied with what technique is an open question at this stage of development of NMR.

Humans↗
PubMed2005

The impact of HIV/AIDS on the control of tuberculosis in India.

Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or more times in East Africa and southern Africa. As HIV continues to spread, warnings have been issued of disastrous AIDS and TB epidemics in "new-wave" countries, including India, which accounts for 20% of all new TB cases arising in the world each year. Here we investigate whether, in the face of the HIV epidemic, India's Revised National TB Control Program (RNTCP) could halve TB prevalence and death rates in the period 1990-2015, as specified by the United Nations Millennium Development Goals. Using a mathematical model to capture the spatial and temporal variation in TB and HIV in India, we predict that, without the RNTCP, HIV would increase TB prevalence (by 1%), incidence (by 12%), and mortality rates (by 33%) between 1990 and 2015. With the RNTCP, however, we expect substantial reductions in prevalence (by 68%), incidence (by 41%), and mortality (by 39%) between 1990 and 2015. In India, 29% of adults but 72% of HIV-positive adults live in four large states in the south where, even with the RNTCP, mortality is expected to fall by only 15% between 1990 and 2015. Nationally, the RNTCP should be able to reverse the increases in TB burden due to HIV but, to ensure that TB mortality is reduced by 50% or more by 2015, HIV-infected TB patients should be provided with antiretroviral therapy in addition to the recommended treatment for TB.

AIDS-Related Opportunistic Infections↗
PubMed2004

Axon branching and synaptic bouton phenotypes in GABAergic nonpyramidal cell subtypes.

GABAergic nonpyramidal cells, cortical interneurons, consist of heterogeneous subtypes differing in their axonal field and target selectivity. It remains to be investigated how the diverse innervation patterns are generated and how these spatially complicated, but synaptically specific wirings are achieved. Here, we asked whether a particular cell type obeys a specific branching and bouton arrangement principle or differs from others only in average morphometric values of the morphological template common to nonpyramidal cells. For this purpose, we subclassified nonpyramidal cells within each physiological class by quantitative parameters of somata, dendrites, and axons and characterized axon branching and bouton distribution patterns quantitatively. Each subtype showed a characteristic set of vertical and horizontal bouton spreads around the somata. Each parameter, such as branching angles, internode or interbouton intervals, followed its own characteristic distribution pattern irrespective of subtypes, suggesting that nonpyramidal cells have the common mechanism for formation of the axon branching pattern and bouton arrangement. Fitting of internode and interbouton interval distributions to the exponential indicated their apparent random occurrence. Decay constants of the fitted exponentials varied among nonpyramidal cells, but each subtype expressed a particular set of interbouton and internode interval averages. The distinctive combination of innervation field shape and local axon phenotypes suggests a marked functional difference in the laminar and columnar integration properties of different GABAergic subtypes, as well as the subtype-specific density of inhibited targets.

Analysis of Variance↗
PubMed2006

Proposal of Health Information System (HIS) as tool for the epidemiological surveillance of leishmaniasis in urban areas.

In recent years leishmaniasis has become a serious Public Health problem in Italy. The coexistence of infected dogs, vectors and humans, makes urban areas suitable environment for the spread of this zoonotic disease. With the purpose to improve the current system for the control of leishmaniasis in urban areas, the authors report their experiences carrying out a Health Information System (HIS) for the surveillance of the disease in the city of Messina. The HIS project is built on a dataset containing geographical data on urban environment, census tracts at parish level and data of human and canine leishmaniasis cases reported in the last years. The HIS allows the spatial representation of the disease occurrence and can be used as a novel epidemiological tool to perform area-based surveillance.

Animals↗
PubMed2001

Applicability of the single equivalent point dipole model to represent a spatially distributed bio-electrical source.

Although the single equivalent point dipole model has been used to represent well-localised bio-electrical sources, in realistic situations the source is distributed. Consequently, position estimates of point dipoles determined by inverse algorithms suffer from systematic error due to the non-exact applicability of the inverse model. In realistic situations, this systematic error cannot be avoided, a limitation that is independent of the complexity of the torso model used. This study quantitatively investigates the intrinsic limitations in the assignment of a location to the equivalent dipole due to distributed electrical source. To simulate arrhythmic activity in the heart, a model of a wave of depolarisation spreading from a focal source over the surface of a spherical shell is used. The activity is represented by a sequence of concentric belt sources (obtained by slicing the shell with a sequence of parallel plane pairs), with constant dipole moment per unit length (circumferentially) directed parallel to the propagation direction. The distributed source is represented by N dipoles at equal arc lengths along the belt. The sum of the dipole potentials is calculated at predefined electrode locations. The inverse problem involves finding a single equivalent point dipole that best reproduces the electrode potentials due to the distributed source. The inverse problem is implemented by minimising the chi2 per degree of freedom. It is found that the trajectory traced by the equivalent dipole is sensitive to the location of the spherical shell relative to the fixed electrodes. It is shown that this trajectory does not coincide with the sequence of geometrical centres of the consecutive belt sources. For distributed sources within a bounded spherical medium, displaced from the sphere's centre by 40% of the sphere's radius, it is found that the error in the equivalent dipole location varies from 3 to 20% for sources with size between 5 and 50% of the sphere's radius. Finally, a method is devised to obtain the size of the distributed source during the cardiac cycle.

Computer Simulation↗