Influence fields: a quantitative framework for representation and analysis of active dendrites

Rathour RK, Narayanan R. Influence fields: a quantitative framework for representation and analysis of active dendrites. J Neurophysiol 107: 2313-2334, 2012. First published January 18, 2012; doi:10.1152/jn.00846.2011.-Neuronal dendrites express numerous voltage-gated ion channels (VGICs), typically with spatial gradients in their densities and properties. Dendritic VGICs, their gradients, and their plasticity endow neurons with information processing capabilities that are higher than those of neurons with passive dendrites. Despite this, frameworks that incorporate dendritic VGICs and their plasticity into neurophysiological and learning theory models have been far and few. Here, we develop a generalized quantitative framework to analyze the extent of influence of a spatially localized VGIC conductance on different physiological properties along the entire stretch of a neuron. Employing this framework, we show that the extent of influence of a VGIC conductance is largely independent of the conductance magnitude but is heavily dependent on the specific physiological property and background conductances. Morphologically, our analyses demonstrate that the influences of different VGIC conductances located on an oblique dendrite are confined within that oblique dendrite, thus providing further credence to the postulate that dendritic branches act as independent computational units. Furthermore, distinguishing between active and passive propagation of signals within a neuron, we demonstrate that the influence of a VGIC conductance is spatially confined only when propagation is active. Finally, we reconstruct functional gradients from VGIC conductance gradients using influence fields and demonstrate that the cumulative contribution of VGIC conductances in adjacent compartments plays a critical role in determining physiological properties at a given location. We suggest that our framework provides a quantitative basis for unraveling the roles of dendritic VGICs and their plasticity in neural coding, learning, and homeostasis.

A touch of history and a peep into the future of the lipid-quinone known as coenzyme Q and ubiquinone

Coenzyme Q (ubiquinone), a fully substituted benzoquinone with polyprenyl side chain, participates in many cellular redox activities. Paradoxically it was discovered only in 1957, albeit being ubiquitous. It required a person, F. L. Crane, a place, Enzyme Institute, Madison, USA, and a time when D. E. Green was directing vigorous research on mitochondria. Located at the transition of 2-electron flavoproteins and 1-electron cytochrome carriers, it facilitates electron transfer through the elegant Q-cycle in mitochondria to reduce O-2 to H2O, and to H2O2, now a significant signal-transducing agent, as a minor activity in shunt pathway (animals) and alternative oxidase (plants). The ability to form Q-radical by losing an electron and a proton was ingeniously used by Mitchell to explain the formation of the proton gradient, considered the core of energy transduction, and also in acidification in vacuoles. Known to be a mobile membrane constituent (microsomes, plasma membrane and Golgi apparatus), allowing it to reach multiple sites, coenzyme Q is expected to have other activities. Coenzyme Q protects circulating lipoproteins being a better lipid antioxidant than even vitamin E. Binding to proteins such as QPS, QPN, QPC and uncoupling protein in mitochondria, QA and QB in the reaction centre in R. sphaeroides, and disulfide bond-forming protein in E. coli (possibly also in Golgi), coenzyme Q acquires selective functions. A characteristic of orally dosed coenzyme Q is its exclusive absorption into the liver, but not the other tissues. This enrichment of Q is accompanied by significant decrease of blood pressure and of serum cholesterol. Inhibition of formation of mevalonate, the common precursor in the branched isoprene pathway, by the minor product, coenzyme Q, decreases the major product, cholesterol. Relaxation of contracted arterial smooth muscle by a side-chain truncated product of coenzyme Q explains its effect of decreasing blood pressure. Extensive clinical studies carried out on oral supplements of coenzyine Q, initially by K. Folkers and Y. Yamamura and followed many others, revealed a large number of beneficial effects, significantly in cardiovascular diseases. Such a variety of effects by this lipid quinone cannot depend on redox activity alone. The fat-soluble vitamins (A, D, E and K) that bear structural relationship with coenzyme Q are known to be active in their polar forms. A vignette of modified forms of coenzyme Q taking active role in its multiple effects is emerging.

Self-Assembly and Catalytic Activity of Metal Nanoparticles Immobilized in Polymer Membrane Prepared via Layer-by-Layer Approach

Densely packed nanoparticles distributed in a stable and robust thin film is a highly preferred system for utilizing the various applications of nanoparticles. Here, we report covalent bond mediated layer-by-layer (LbL) self-assembled thin films of nanoparticles embedded in polymer membrane. Polymer with complementary functional group is utilized for fabrication of thin film via covalent bonding. UV-visible spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to monitor the growth of LbL thin film. Subsequently, the composite thin film is used for catalysis of an organic electron transfer reaction of p-nitrophenol to p-aminophenol by sodium borohydride. The catalytic activity of these composite films is assayed multiple times, proving its applicability as a catalyst. The kinetic data obtained by monitoring reduction of p-nitrophenol suggest that the reaction rates are directly related to the sizes of the nanoparticle and porosity of the membrane.

A drop of active matter

We study theoretically the hydrodynamics of a fluid drop containing oriented filaments endowed with active contractile or extensile stresses and placed on a solid surface. The active stresses alter qualitatively the wetting properties of the drop, leading to new spreading laws and novel static drop shapes. Candidate systems for testing our predictions include cytoskeletal extracts with motors and ATP, suspensions of bacteria or pulsatile cells, or fluids laden with artificial self-propelled colloids.

Differential modulation of intracellular survival of cytosolic and vacuolar pathogens by curcumin

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.

A Single-Stage Water-Gas Shift Reaction over Highly Active and Stable Si- and Al-Substituted Pt/CeO2 Catalysts

Ce0.88Si0.1Pt0.02O2-d and Ce0.88Al0.1Pt0.02O2-d catalysts were synthesized by using a low-temperature sonochemical method and characterized by using XRD, TEM, XPS, FTIR, and BET surface analyzer. The catalytic activities of these compounds were investigated for the watergas shift reaction in the temperature range of 140-440 degrees C. The substitution of Si in Ce0.98Pt0.02O2-d increased the releasing capacity of lattice oxygen, whereas the substitution of Al decreased the reducibility of Ce0.98Pt0.02O2-d, as evidenced by hydrogen temperature-programmed reduction studies. However, both the catalysts showed a considerable improvement in terms of activity and stability compared to Ce0.98Pt0.02O2-d. The combined activity measurement and characterization results suggest that the increase in the oxygen vacancy, which acts as a dissociation center for water, is the primary reason for the improvement in the activity of modified Ce0.98Pt0.02O2-d. Both the catalysts are 100?% selective toward H2 production, and approximately 99?% conversion of CO to CO2 was observed at 260 and 270 degrees C for Ce0.88Si0.1Pt0.02O2-d and Ce0.88Al0.1Pt0.02O2-d, respectively. These catalysts do not deactivate during the daily startup/shutdown operations and are sustainable even after prolonged reaction. Notably, these catalysts do not require any pretreatment or activation during startup/shutdown operations.

Active Sequential Hypothesis Testing with Application to a Visual Search Problem

We consider a visual search problem studied by Sripati and Olson where the objective is to identify an oddball image embedded among multiple distractor images as quickly as possible. We model this visual search task as an active sequential hypothesis testing problem (ASHT problem). Chernoff in 1959 proposed a policy in which the expected delay to decision is asymptotically optimal. The asymptotics is under vanishing error probabilities. We first prove a stronger property on the moments of the delay until a decision, under the same asymptotics. Applying the result to the visual search problem, we then propose a ``neuronal metric'' on the measured neuronal responses that captures the discriminability between images. From empirical study we obtain a remarkable correlation (r = 0.90) between the proposed neuronal metric and speed of discrimination between the images. Although this correlation is lower than with the L-1 metric used by Sripati and Olson, this metric has the advantage of being firmly grounded in formal decision theory.

Identification of Active Sources in Single-Channel Convolutive Mixtures Using Known Source Models

We address the problem of identifying the constituent sources in a single-sensor mixture signal consisting of contributions from multiple simultaneously active sources. We propose a generic framework for mixture signal analysis based on a latent variable approach. The basic idea of the approach is to detect known sources represented as stochastic models, in a single-channel mixture signal without performing signal separation. A given mixture signal is modeled as a convex combination of known source models and the weights of the models are estimated using the mixture signal. We show experimentally that these weights indicate the presence/absence of the respective sources. The performance of the proposed approach is illustrated through mixture speech data in a reverberant enclosure. For the task of identifying the constituent speakers using data from a single microphone, the proposed approach is able to identify the dominant source with up to 8 simultaneously active background sources in a room with RT60 = 250 ms, using models obtained from clean speech data for a Source to Interference Ratio (SIR) greater than 2 dB.

Site-specific N-Linked Glycosylation of Receptor Guanylyl Cyclase C Regulates Ligand Binding, Ligand-mediated Activation and Interaction with Vesicular Integral Membrane Protein 36, VIP36

Guanylyl cyclase C (GC-C) is a multidomain, membrane-associated receptor guanylyl cyclase. GC-C is primarily expressed in the gastrointestinal tract, where it mediates fluid-ion homeostasis, intestinal inflammation, and cell proliferation in a cGMP-dependent manner, following activation by its ligands guanylin, uroguanylin, or the heat-stable enterotoxin peptide (ST). GC-C is also expressed in neurons, where it plays a role in satiation and attention deficiency/hyperactive behavior. GC-C is glycosylated in the extracellular domain, and differentially glycosylated forms that are resident in the endoplasmic reticulum (130 kDa) and the plasma membrane (145 kDa) bind the ST peptide with equal affinity. When glycosylation of human GC-C was prevented, either by pharmacological intervention or by mutation of all of the 10 predicted glycosylation sites, ST binding and surface localization was abolished. Systematic mutagenesis of each of the 10 sites of glycosylation in GC-C, either singly or in combination, identified two sites that were critical for ligand binding and two that regulated ST-mediated activation. We also show that GC-C is the first identified receptor client of the lectin chaperone vesicular integral membrane protein, VIP36. Interaction with VIP36 is dependent on glycosylation at the same sites that allow GC-C to fold and bind ligand. Because glycosylation of proteins is altered in many diseases and in a tissue-dependent manner, the activity and/or glycan-mediated interactions of GC-C may have a crucial role to play in its functions in different cell types.

AN EXPERIMENTAL STUDY ON EFFERVESCENT ATOMIZATION OF BIO-OIL FUELS

This paper presents the work on detailed characterization of effervescent spray of Jatropha and Pongamia pure plant oils. The spray characteristics of these biofuels are compared with those of diesel. Both macroscopic and microscopic spray characteristics at different injection pressures and gas-to-liquid ratio (GLR) have been studied. The particle/droplet imaging analysis (PDIA) technique along with direct imaging methods are used for the purpose of spray characterization. Due to their higher viscosity, pure plant oils showed poor atomization compared to diesel and a blend of diesel and pure plant oil at a given GLR. Pure plant oil sprays showed a lower spray cone angle when compared to diesel and blends at lower GLRs. However, the difference is not significant at higher GLRs. Droplet size measurements at 100 mm downstream of the exit orifice showed reduction in Sauter mean diameter (SMD) diameter with increase in GLR. A radial variation in the SMD is observed for the blend and pure plant oils. Pure oils showed a larger variation when compared to the blend. Spray unsteadiness has been characterized based on the image-to-image variation in the mean droplet diameter and fluctuations in the spray cone angle. Results showed that pure plant oil sprays are more unsteady at lower GLRs when compared to diesel and blend. A critical GLR is identified at which the spray becomes steady. The three regimes of spray operation, namely ``steady spray,'' ``pulsating spray,'' and ``spray and unbroken liquid jet'' are identified in the injection pressure-GLR parameter space for these pure plant oils. Two-phase flow imaging inside the exit orifice shows that for the pure plant oils, the flow is highly transient at low GLRs and the bubbly, slug, and annular two-phase flow regimes are all observed. However, at higher GLRs where the spray is steady, only the annular flow regime is observed.

Active-contour-based automated image quantitation techniques for Western Blot analysis

Western Blot analysis is an analytical technique used in Molecular Biology, Biochemistry, Immunogenetics and other Molecular Biology studies to separate proteins by electrophoresis. The procedure results in images containing nearly rectangular-shaped blots. In this paper, we address the problem of quantitation of the blots using automated image processing techniques. We formulate a special active contour (or snake) called Oblong, which locks on to rectangular shaped objects. Oblongs depend on five free parameters, which is also the minimum number of parameters required for a unique characterization. Unlike many snake formulations, Oblongs do not require explicit gradient computations and therefore the optimization is carried out fast. The performance of Oblongs is assessed on synthesized data and Western Blot Analysis images.

Live Soap: Stability, Order, and Fluctuations in Apolar Active Smectics

We construct a hydrodynamic theory of noisy, apolar active smectics in bulk suspension or on a substrate. Unlike purely orientationally ordered active fluids, active apolar smectics can be dynamically stable in Stokesian bulk suspensions. Smectic order in these systems is quasilong ranged in dimension d = 2 and long ranged in d = 3. We predict reentrant Kosterlitz-Thouless melting to an active nematic in our simplest model in d = 2, a nonzero second-sound speed parallel to the layers in bulk suspensions, and that there are no giant number fluctuations in either case. We also briefly discuss possible instabilities in these systems. DOI: 10.1103/PhysRevLett.110.118102

Quantitative interactions between the A-type K+ current and inositol trisphosphate receptors regulate intraneuronal Ca2+ waves and synaptic plasticity

Key points center dot Active calcium signal propagation occurs when an initial calcium trigger elicits calcium release through endoplasmic reticulum (ER) receptors. A high concentration of the calcium trigger in thin-calibre dendrites would suppress release of calcium through hippocampal inositol trisphosphate receptors (InsP3Rs). center dot Could the high-density expression of A-type K+ channels in thin-calibre dendrites be a mechanism for inhibiting this suppression, thereby restoring the utility of the ER as a substrate for active calcium propagation? center dot Quantitative analyses involving experimentally constrained models reveal a bell-shaped dependence of calcium released through InsP3Rs on the A-type K+ channel density, during the propagation of a calcium wave. center dot A-type K+ channels regulated the relative contribution of ER calcium to the induction of synaptic plasticity in the presence of model metabotropic glutamate receptors. center dot These results identify a novel form of interaction between active dendrites and the ER membrane and suggest that A-type K+ channels are ideally placed for inhibiting the suppression of InsP3Rs in thin-calibre dendrites. Abstract The A-type potassium current has been implicated in the regulation of several physiological processes. Here, we explore a role for the A-type potassium current in regulating the release of calcium through inositol trisphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampal pyramidal neurons. To do this, we constructed morphologically realistic, conductance-based models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density ofA-type potassium channels, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendritic diameter and that wave initiation occurred at branch points as a consequence of a high surface area to volume ratio of oblique dendrites. Furthermore, analogous to the role ofA-type potassium channels in regulating spike latency, we found that an increase in the density ofA-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (mGluR) signalling components and a calcium-controlled plasticity rule into our model and demonstrate thatthe presence of mGluRs induced a leftward shift in a BienenstockCooperMunro-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. Our results establish a novel form of interaction between active dendrites and the ER membrane, uncovering a powerful mechanism that could regulate biophysical/biochemical signal integration and steer the spatiotemporal spread of signalling microdomains through changes in dendritic excitability.

Regulation of lipid biosynthesis, sliding motility, and biofilm formation by a membrane-anchored nucleoid-associated protein of mycobacterium tuberculosis

Bacteria use a number of small basic proteins for organization and compaction of their genomes. By their interaction with DNA, these nucleoid-associated proteins (NAPs) also influence gene expression. Rv3852, a NAP of Mycobacterium tuberculosis, is conserved among the pathogenic and slow-growing species of mycobacteria. Here, we show that the protein predominantly localizes in the cell membrane and that the carboxy-terminal region with the propensity to form a transmembrane helix is necessary for its membrane localization. The protein is involved in genome organization, and its ectopic expression in Mycobacterium smegmatis resulted in altered nucleoid morphology, defects in biofilm formation, sliding motility, and change in apolar lipid profile. We demonstrate its crucial role in regulating the expression of KasA, KasB, and GroEL1 proteins, which are in turn involved in controlling the surface phenotypes in mycobacteria.