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Sample records for dynamics underlying neurite

  1. Neurite-specific Ca2+ dynamics underlying sound processing in an auditory interneurone.

    PubMed

    Baden, T; Hedwig, B

    2007-01-01

    Concepts on neuronal signal processing and integration at a cellular and subcellular level are driven by recording techniques and model systems available. The cricket CNS with the omega-1-neurone (ON1) provides a model system for auditory pattern recognition and directional processing. Exploiting ON1's planar structure we simultaneously imaged free intracellular Ca(2+) at both input and output neurites and recorded the membrane potential in vivo during acoustic stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed the onset spike rate of ON1, while the final Ca(2+) level depended on the mean spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations and only gradually in the axon and the cell body. Ca(2+) levels were particularly high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive K(+) current this may exhibit a specific control over the cell's electrical response properties. In all cellular compartments presentation of species-specific calling song caused distinct oscillations of the Ca(2+) level in the chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated hyperpolarization of ON1 suppressed background spike activity between chirps, acting as a noise filter. During directional auditory processing, the functional interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition was demonstrated. Upon stimulation with different sound frequencies, the dendrites, but not the axonal arborizations, demonstrated a tonotopic response profile. This mirrored the dominance of the species-specific carrier frequency and resulted in spatial filtering of high frequency auditory inputs. PMID:17443773

  2. Neurite, a Finite Difference Large Scale Parallel Program for the Simulation of Electrical Signal Propagation in Neurites under Mechanical Loading

    PubMed Central

    García-Grajales, Julián A.; Rucabado, Gabriel; García-Dopico, Antonio; Peña, José-María; Jérusalem, Antoine

    2015-01-01

    With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite—explicit and implicit—were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented

  3. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  4. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    PubMed

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  5. New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition.

    PubMed

    Oda, Yoshimi; Nakashima, Souichi; Nakamura, Seikou; Yano, Mamiko; Akiyama, Masanori; Imai, Kayo; Kimura, Tomohito; Nakata, Akiko; Tani, Miyuki; Matsuda, Hisashi

    2016-07-01

    The methanolic extract of Lawsonia inermis L. (henna) showed accelerative effects on nerve growth factor-induced neurite outgrowth in PC12 cells under non-fasting conditions. To elucidate the active constituents responsible for the neuronal differentiation, we conducted a search of the constituents and examined their accelerative effects on neurite outgrowth in PC12 cells. We isolated a new acetophenone glycoside, inermioside A, which exerted a significant accelerative effect on neurite outgrowth. We also confirmed the activities of nine known compounds, including quercetin and lalioside. In addition, we found that quercetin, one of the active constituents, increased Vav3 mRNA expression. PMID:26936787

  6. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism

    PubMed Central

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1±0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80±0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  7. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

    PubMed

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  8. Dynamic peripheral traction forces balance stable neurite tension in regenerating Aplysia bag cell neurons

    PubMed Central

    Hyland, Callen; Mertz, Aaron F.; Forscher, Paul; Dufresne, Eric

    2014-01-01

    Growth cones of elongating neurites exert force against the external environment, but little is known about the role of force in outgrowth or its relationship to the mechanical organization of neurons. We used traction force microscopy to examine patterns of force in growth cones of regenerating Aplysia bag cell neurons. We find that traction is highest in the peripheral actin-rich domain and internal stress reaches a plateau near the transition between peripheral and central microtubule-rich domains. Integrating stress over the area of the growth cone reveals that total scalar force increases with area but net tension on the neurite does not. Tensions fall within a limited range while a substantial fraction of the total force can be balanced locally within the growth cone. Although traction continuously redistributes during extension and retraction of the peripheral domain, tension is stable over time, suggesting that tension is a tightly regulated property of the neurite independent of growth cone dynamics. We observe that redistribution of traction in the peripheral domain can reorient the end of the neurite shaft. This suggests a role for off-axis force in growth cone turning and neuronal guidance. PMID:24825441

  9. Dynamic peripheral traction forces balance stable neurite tension in regenerating Aplysia bag cell neurons.

    PubMed

    Hyland, Callen; Mertz, Aaron F; Forscher, Paul; Dufresne, Eric

    2014-01-01

    Growth cones of elongating neurites exert force against the external environment, but little is known about the role of force in outgrowth or its relationship to the mechanical organization of neurons. We used traction force microscopy to examine patterns of force in growth cones of regenerating Aplysia bag cell neurons. We find that traction is highest in the peripheral actin-rich domain and internal stress reaches a plateau near the transition between peripheral and central microtubule-rich domains. Integrating stress over the area of the growth cone reveals that total scalar force increases with area but net tension on the neurite does not. Tensions fall within a limited range while a substantial fraction of the total force can be balanced locally within the growth cone. Although traction continuously redistributes during extension and retraction of the peripheral domain, tension is stable over time, suggesting that tension is a tightly regulated property of the neurite independent of growth cone dynamics. We observe that redistribution of traction in the peripheral domain can reorient the end of the neurite shaft. This suggests a role for off-axis force in growth cone turning and neuronal guidance. PMID:24825441

  10. NeuronGrowth, a software for automatic quantification of neurite and filopodial dynamics from time-lapse sequences of digital images.

    PubMed

    Fanti, Zian; Martinez-Perez, M Elena; De-Miguel, Francisco F

    2011-10-01

    We developed NeuronGrowth, a software for the automatic quantification of extension and retraction of neurites and filopodia, from time-lapse sequences of two-dimensional digital micrographs. NeuronGrowth requires a semiautomatic characterization of individual neurites in a reference frame, which is then used for automatic tracking and measurement of every neurite over the whole image sequence. Modules for sequence alignment, background subtraction, flat field correction, light normalization, and cropping have been integrated to improve the quality of the analysis. Moreover, NeuronGrowth incorporates a deconvolution filter that corrects the shadow-cast effect of differential interference contrast (DIC) images. NeuronGrowth was tested by analyzing the formation of outgrowth patterns by individual leech neurons cultured under two different conditions. Phase contrast images were obtained from neurons plated on CNS homogenates and DIC images were obtained from similar neurons plated on ganglion capsules as substrates. Filopodia were measured from fluorescent growth-cones of chick dorsal root ganglion cells. Quantitative data of neurite extension and retraction obtained by three different users applying NeuronGrowth and two other manually operated software packages were similar. However, NeuronGrowth required less user participation and had a better time performance when compared with the other software packages. NeuronGrowth may be used in general to quantify the dynamics of tubular structures such as blood vessels. NeuronGrowth is a free plug-in for the free software ImageJ and can be downloaded along with a user manual, a troubleshooting section and other information required for its use from http://www.ifc.unam.mx or http://www.ifc.unam.mx/ffm/index.html. PMID:21913334

  11. Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells.

    PubMed

    Cooper, Robert J; Spitzer, Nadja

    2015-05-01

    Silver nanoparticles (AgNPs) have potent antimicrobial properties at concentrations far below those that cause cytotoxic and genotoxic effects in eukaryotic cells. This property has resulted in the widespread use of AgNPs in consumer products, leading to environmental exposures at sub-lethal levels through ingestion and inhalation. Although the toxicity of AgNPs has been well characterized, effects of environmentally relevant exposures have not been extensively investigated in spite of studies that suggest accumulation of silver in tissues, including brain. To assess the sublethal effects of AgNPs on neural cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricles proliferate and migrate via the rostral migratory stream to the olfactory bulb. Once there, they complete differentiation into neurons and glia and integrate into existing circuits. This process of neurogenesis is tightly regulated, and is considered a part of healthy brain function. We found that 1.0 μg/mL AgNP exposure in cultured differentiating NSCs induced the formation of f-actin inclusions, indicating a disruption of actin function. These inclusions did not co-localize with AgNPs, and therefore do not represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in neurite extension and branching in live cells, cytoskeleton-mediated processes vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may contribute to documented deficits in brain function following AgNP exposure. PMID:25952507

  12. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    NASA Astrophysics Data System (ADS)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  13. PAK-PIX interactions regulate adhesion dynamics and membrane protrusion to control neurite outgrowth.

    PubMed

    Santiago-Medina, Miguel; Gregus, Kelly A; Gomez, Timothy M

    2013-03-01

    The roles of P21-activated kinase (PAK) in the regulation of axon outgrowth downstream of extracellular matrix (ECM) proteins are poorly understood. Here we show that PAK1-3 and PIX are expressed in the developing spinal cord and differentially localize to point contacts and filopodial tips within motile growth cones. Using a specific interfering peptide called PAK18, we found that axon outgrowth is robustly stimulated on laminin by partial inhibition of PAK-PIX interactions and PAK function, whereas complete inhibition of PAK function stalls axon outgrowth. Furthermore, modest inhibition of PAK-PIX stimulates the assembly and turnover of growth cone point contacts, whereas strong inhibition over-stabilizes adhesions. Point mutations within PAK confirm the importance of PIX binding. Together our data suggest that regulation of PAK-PIX interactions in growth cones controls neurite outgrowth by influencing the activity of several important mediators of actin filament polymerization and retrograde flow, as well as integrin-dependent adhesion to laminin. PMID:23321640

  14. Triggering of high-speed neurite outgrowth using an optical microheater

    PubMed Central

    Oyama, Kotaro; Zeeb, Vadim; Kawamura, Yuki; Arai, Tomomi; Gotoh, Mizuho; Itoh, Hideki; Itabashi, Takeshi; Suzuki, Madoka; Ishiwata, Shin’ichi

    2015-01-01

    Optical microheating is a powerful non-invasive method for manipulating biological functions such as gene expression, muscle contraction, and cell excitation. Here, we demonstrate its potential usage for regulating neurite outgrowth. We found that optical microheating with a water-absorbable 1,455-nm laser beam triggers directional and explosive neurite outgrowth and branching in rat hippocampal neurons. The focused laser beam under a microscope rapidly increases the local temperature from 36 °C to 41 °C (stabilized within 2 s), resulting in the elongation of neurites by more than 10 μm within 1 min. This high-speed, persistent elongation of neurites was suppressed by inhibitors of both microtubule and actin polymerization, indicating that the thermosensitive dynamics of these cytoskeletons play crucial roles in this heat-induced neurite outgrowth. Furthermore, we showed that microheating induced the regrowth of injured neurites and the interconnection of neurites. These results demonstrate the efficacy of optical microheating methods for the construction of arbitrary neural networks. PMID:26568288

  15. The cytoskeleton and neurite initiation

    PubMed Central

    Flynn, Kevin C

    2013-01-01

    Neurons begin their life as simple spheres, but can ultimately assume an elaborate morphology with numerous, highly arborized dendrites, and long axons. This is achieved via an astounding developmental progression which is dependent upon regulated assembly and dynamics of the cellular cytoskeleton. As neurites emerge out of the soma, neurons break their spherical symmetry and begin to acquire the morphological features that define their structure and function. Neurons regulate their cytoskeleton to achieve changes in cell shape, velocity, and direction as they migrate, extend neurites, and polarize. Of particular importance, the organization and dynamics of actin and microtubules directs the migration and morphogenesis of neurons. This review focuses on the regulation of intrinsic properties of the actin and microtubule cytoskeletons and how specific cytoskeletal structures and dynamics are associated with the earliest phase of neuronal morphogenesis—neuritogenesis. PMID:24002528

  16. Dendrite and Axon Specific Geometrical Transformation in Neurite Development

    PubMed Central

    Mironov, Vasily I.; Semyanov, Alexey V.; Kazantsev, Victor B.

    2016-01-01

    We propose a model of neurite growth to explain the differences in dendrite and axon specific neurite development. The model implements basic molecular kinetics, e.g., building protein synthesis and transport to the growth cone, and includes explicit dependence of the building kinetics on the geometry of the neurite. The basic assumption was that the radius of the neurite decreases with length. We found that the neurite dynamics crucially depended on the relationship between the rate of active transport and the rate of morphological changes. If these rates were in the balance, then the neurite displayed axon specific development with a constant elongation speed. For dendrite specific growth, the maximal length was rapidly saturated by degradation of building protein structures or limited by proximal part expansion reaching the characteristic cell size. PMID:26858635

  17. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    SciTech Connect

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  18. Analysis of slow-onset neurite formation in NG108-15 cells: implications for a unified model of neurite elongation.

    PubMed

    Smalheiser, N R

    1989-01-01

    When undifferentiated NG108-15 cells are plated onto polylysine coated Petri dishes in serum-free medium, they form neurites within 1-4 h if plated in the presence of laminin or 5'-deoxy-5'-methylthioadenosine (rapid-onset neurites). In the absence of such agents, serum-deprived NG108-15 cells extend axon-like neurites onto polylysine over several days; here we characterize the dynamic behavior of this slow-onset outgrowth pattern in detail. Individual cells plated on laminin expressed a gradual multipolar-to-unipolar transition due to rapid-onset neurites becoming remodelled into the appearance of slow-onset neurites. This phenomenon reflected the selective stabilization of certain rapid-onset neurites, along with the restriction of motility to their distal tips. Based upon the properties and interactions of both rapid- and slow-onset neurites in NG108-15 cells, a unified model for neurite formation is presented. PMID:2917412

  19. Neurite development in PC12 cells cultured on nanopillars and nanopores with sizes comparable with filopodia

    PubMed Central

    Haq, Furqan; Anandan, Venkatramani; Keith, Charles; Zhang, Guigen

    2007-01-01

    We investigated the effect of nanoscale topography on neurite development in pheochromocytoma (PC12 cells) by culturing the cells on substrates having nanoscale pillars and pores with sizes comparable with filipodia. We found that cells on nanopillars and nanopores developed fewer and shorter neurites than cells on smooth substrates, and that cells on nanopores developed more and longer neurites than cells on nanopillars. These results suggest that PC12 cells were spatially aware of the difference in the nanoscale structures of the underlying substrates and responded differently in their neurite extension. This finding points to the possibility of using nanoscale topographic features to control neurite development in neurons. PMID:17722518

  20. Polyester with Pendent Acetylcholine-Mimicking Functionalities Promotes Neurite Growth.

    PubMed

    Wang, Shaofei; Jeffries, Eric; Gao, Jin; Sun, Lijie; You, Zhengwei; Wang, Yadong

    2016-04-20

    Successful regeneration of nerves can benefit from biomaterials that provide a supportive biochemical and mechanical environment while also degrading with controlled inflammation and minimal scar formation. Herein, we report a neuroactive polymer functionalized by covalent attachment of the neurotransmitter acetylcholine (Ach). The polymer was readily synthesized in two steps from poly(sebacoyl diglyceride) (PSeD), which previously demonstrated biocompatibility and biodegradation in vivo. Distinct from prior acetylcholine-biomimetic polymers, PSeD-Ach contains both quaternary ammonium and free acetyl moieties, closely resembling native acetylcholine structure. The polymer structure was confirmed via (1)H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Hydrophilicity, charge, and thermal properties of PSeD-Ach were determined by tensiometer, zetasizer, differential scanning calorimetry, and thermal gravimetric analysis, respectively. PC12 cells exhibited the greatest proliferation and neurite outgrowth on PSeD-Ach and laminin substrates, with no significant difference between these groups. PSeD-Ach yielded much longer neurite outgrowth than the control polymer containing ammonium but no the acetyl group, confirming the importance of the entire acetylcholine-like moiety. Furthermore, PSeD-Ach supports adhesion of primary rat dorsal root ganglions and subsequent neurite sprouting and extension. The sprouting rate is comparable to the best conditions from previous report. Our findings are significant in that they were obtained with acetylcholine-like functionalities in 100% repeating units, a condition shown to yield significant toxicity in prior publications. Moreover, PSeD-Ach exhibited favorable mechanical and degradation properties for nerve tissue engineering application. Humidified PSeD-Ach had an elastic modulus of 76.9 kPa, close to native neural tissue, and could well recover from cyclic dynamic compression. PSeD-Ach showed a gradual in

  1. Rho-associated protein kinase modulates neurite extension by regulating microtubule remodeling and vinculin distribution

    PubMed Central

    Chen, Ke’en; Zhang, Wenbin; Chen, Jing; Li, Sumei; Guo, Guoqing

    2013-01-01

    Rho-associated protein kinase is an essential regulator of cytoskeletal dynamics during the process of neurite extension. However, whether Rho kinase regulates microtubule remodeling or the distribution of adhesive proteins to mediate neurite outgrowth remains unclear. By specifically modulating Rho kinase activity with pharmacological agents, we studied the morpho-dynamics of neurite outgrowth. We found that lysophosphatidic acid, an activator of Rho kinase, inhibited neurite outgrowth, which could be reversed by Y-27632, an inhibitor of Rho kinase. Meanwhile, reorganization of microtubules was noticed during these processes, as indicated by their significant changes in the soma and growth cone. In addition, exposure to lysophosphatidic acid led to a decreased membrane distribution of vinculin, a focal adhesion protein in neurons, whereas Y-27632 recruited vinculin to the membrane. Taken together, our data suggest that Rho kinase regulates rat hippocampal neurite growth and microtubule formation via a mechanism associated with the redistribution of vinculin. PMID:25206623

  2. Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro.

    PubMed

    Boato, Francesco; Hechler, Daniel; Rosenberger, Karen; Lüdecke, Doreen; Peters, Eva M; Nitsch, Robert; Hendrix, Sven

    2011-01-01

    Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices. PMID:22200088

  3. Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro

    PubMed Central

    2011-01-01

    Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices. PMID:22200088

  4. The influence of ensheathing cells on olfactory receptor cell neurite outgrowth in vitro.

    PubMed

    Kafitz, K W; Greer, C A

    1998-11-30

    We previously reported that laminin substrates increased primary (1 degree) neurite outgrowth from olfactory receptor cells (ORCs) in vitro. To further explore mechanisms underlying the outgrowth of ORC neurites, we have cocultured ORCs with the ensheathing cells (ENSH) from the olfactory nerve. ORCs were plated either: (i) directly on monolayers of ENSH (prepared with minor modifications as reported by Doucette and Devon, or (ii) on coverslips suspended above the ENSH monolayer to investigate diffusible trophic influences of ENSH. In addition, ORCs were cocultured with either olfactory bulb glia (OBG) or hippocampal astrocytes (HG) or grown on either laminin (LN) substrates or poly-L-lysine (PLL) controls. The length of ORC neurites was determined after 48 hr in vitro. Immunocytochemical characterization of the ENSH cultures for p75 nerve growth factor (NGF) receptor and glial fibrillary acidic protein (GFAP) revealed that those cultures contained more than 80% ENSH. In OBG cultures approximately 10% and in HG cultures no cells with ENSH characteristics were found. All cells with ENSH characteristics were also LN-immunoreactive. After 48 hr in culture ORCs had the longest 1 degree neurites when they were cocultured with ENSH. No significant differences in the 1 degree neurite length were found comparing ORCs grown directly on ENSH and ORCs physically separated from ENSH. ORCs cultured on HG and on EHS-LN showed no significant differences in the ORC 1 degree neurite length, but on both substrates the ORC 1 degree neurites were significantly shorter than on ENSH. The length of the ORC secondary neurites did not vary significantly in the different culture conditions. Our results suggest that while LN appears to contribute to ORC neurite extension, additional diffusible factors released from ENSH are likely to be further determinants of neurite outgrowth. Because the OBG and HG cocultures did not influence ORC neurite outgrowth as significantly as did the ENSH, it

  5. HMG-CoA reductase inhibition causes neurite loss by interfering with geranylgeranylpyrophosphate synthesis.

    PubMed

    Schulz, Joachim G; Bösel, Julian; Stoeckel, Magali; Megow, Dirk; Dirnagl, Ulrich; Endres, Matthias

    2004-04-01

    To determine whether neurite outgrowth depends upon the mevalonate pathway, we blocked mevalonate synthesis in nerve growth factor-treated PC12 cells or primary cortical neurones with atorvastatin, a 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and substituted different intermediates of the mevalonate pathway. We show that HMG-CoA reductase inhibition causes a profound reduction of neurite length, neurite loss and ultimatively cell death in undifferentiated and pre-differentiated PC12 cells and also in rat primary cortical neurones. Geranylgeranylpyrophosphate, but not farnesylpyrophosphate, squalene or cholesterol, completely compensated for the lack of mevalonate. Our data indicate that, under HMG-CoA reductase inhibition, geranylgeranylpyrophosphate rather than farnesylpyrophosphate or cholesterol is critical for neurite outgrowth and/or maintenance. Loss of neurites is an early manifestation of various neurodegenerative disorders, and dysfunction of isoprenylation might play a role in their pathogenesis. PMID:15030386

  6. Controlling Neurite Outgrowth with Patterned Substrates

    PubMed Central

    Yang, In Hong; Co, Carlos C.; Ho, Chia-Chi

    2011-01-01

    In vivo, neurons form neurites, one of which develops into the axon while others become dendrites. While this neuritogenesis process is well programmed in vivo, there are limited methods to control the number and location of neurite extension in vitro. Here we report a method to control neuritogenesis by confining neurons in specific regions using cell resistant poly(oligoethyleneglycol methacrylate-co-methacrylic acid (OEGMA-co-MA)) or poly(ethyleneglycol-block-lactic acid) PEG-PLA. Line patterned substrates reduce multiple extension of neurites and stimulate bi-directional neurite budding for PC12 and cortical neurons. PC12 cells on 20 and 30 µm line patterns extended one neurite in each direction along the line pattern while cortical neuron on 20 and 30 µm line patterns extended one or two neurites in each direction along the line pattern. Statistical analysis of neurite lengths revealed that PC12 cells and cortical neurons on line patterns extend longer neurites. The ability to guide formation of neurites on patterned substrates is useful for generating neural networks and promoting neurite elongation. PMID:21484989

  7. Guidance of dorsal root ganglion neurites and Schwann cells by isolated Schwann cell topography on poly(dimethyl siloxane) conduits and films

    NASA Astrophysics Data System (ADS)

    Richardson, J. A.; Rementer, C. W.; Bruder, Jan M.; Hoffman-Kim, D.

    2011-08-01

    Biomimetic replicas of cellular topography have been utilized to direct neurite outgrowth. Here, we cultured postnatal rat dorsal root ganglion (DRG) explants in the presence of Schwann cell (SC) topography to determine the influence of SC topography on neurite outgrowth. Four distinct poly(dimethyl siloxane) conduits were fabricated within which DRG explants were cultured. To determine the contribution of SC topographical features to neurite guidance, the extent of neurite outgrowth into unpatterned conduits, conduits with randomly oriented SC replicas, and conduits with SC replicas parallel or perpendicular to the conduit long axis was measured. Neurite directionality and outgrowth from DRG were also quantified on two-dimensional SC replicas with orientations corresponding to the four conduit conditions. Additionally, live SC migration and neurite extension from DRG on SC replicas were examined as a first step toward quantification of the interactions between live SC and navigating neurites on SC replicas. DRG neurite outgrowth and morphology within conduits and on two-dimensional SC replicas were directed by the underlying SC topographical features. Maximal neurite outgrowth and alignment to the underlying features were observed into parallel conduits and on parallel two-dimensional substrates, whereas the least extent of outgrowth was observed into perpendicular conduits and on perpendicular two-dimensional replica conditions. Additionally, neurites on perpendicular conditions turned to extend along the direction of underlying SC topography. Neurite outgrowth exceeded SC migration in the direction of the underlying anisotropic SC replica after two days in culture. This finding confirms the critical role that SC have in guiding neurite outgrowth and suggests that the mechanism of neurite alignment to SC replicas depends on direct contact with cellular topography. These results suggest that SC topographical replicas may be used to direct and optimize neurite

  8. Magnetotail dynamics under isobaric constraints

    NASA Technical Reports Server (NTRS)

    Birn, Joachim; Schindler, Karl; Janicke, Lutz; Hesse, Michael

    1994-01-01

    Using linear theory and nonlinear MHD simulations, we investigate the resistive and ideal MHD stability of two-dimensional plasma configurations under the isobaric constraint dP/dt = 0, which in ideal MHD is equivalent to conserving the pressure function P = P(A), where A denotes the magnetic flux. This constraint is satisfied for incompressible modes, such as Alfven waves, and for systems undergoing energy losses. The linear stability analysis leads to a Schroedinger equation, which can be investigated by standard quantum mechanics procedures. We present an application to a typical stretched magnetotail configuration. For a one-dimensional sheet equilibrium characteristic properties of tearing instability are rediscovered. However, the maximum growth rate scales with the 1/7 power of the resistivity, which implies much faster growth than for the standard tearing mode (assuming that the resistivity is small). The same basic eigen-mode is found also for weakly two-dimensional equilibria, even in the ideal MHD limit. In this case the growth rate scales with the 1/4 power of the normal magnetic field. The results of the linear stability analysis are confirmed qualitatively by nonlinear dynamic MHD simulations. These results suggest the interesting possibility that substorm onset, or the thinning in the late growth phase, is caused by the release of a thermodynamic constraint without the (immediate) necessity of releasing the ideal MHD constraint. In the nonlinear regime the resistive and ideal developments differ in that the ideal mode does not lead to neutral line formation without the further release of the ideal MHD constraint; instead a thin current sheet forms. The isobaric constraint is critically discussed. Under perhaps more realistic adiabatic conditions the ideal mode appears to be stable but could be driven by external perturbations and thus generate the thin current sheet in the late growth phase, before a nonideal instability sets in.

  9. Intracellular calcium and cyclic nucleotide levels modulate neurite guidance by microtopographical substrate features.

    PubMed

    Li, Shufeng; Tuft, Bradley; Xu, Linjing; Polacco, Marc; Clarke, Joseph C; Guymon, C Allan; Hansen, Marlan R

    2016-08-01

    Micro- and nanoscale surface features have emerged as potential tools to direct neurite growth into close proximity with next generation neural prosthesis electrodes. However, the signaling events underlying the ability of growth cones to respond to topographical features remain largely unknown. Accordingly, this study probes the influence of [Ca(2+) ]i and cyclic nucleotide levels on the ability of neurites from spiral ganglion neurons (SGNs) to precisely track topographical micropatterns. Photopolymerization and photomasking were used to generate micropatterned methacrylate polymer substrates. Dissociated SGN cultures were plated on the micropatterned surfaces. Calcium influx and release from internal stores were manipulated by elevating extracellular K(+) , maintenance in calcium-free media, or bath application of various calcium channel blockers. Cyclic nucleotide activity was increased by application of cpt-cAMP or 8-Br-cGMP. Elevation of [Ca(2+) ]i by treatment of cultures with elevated potassium reduced neurite alignment to physical microfeatures. Maintenance of cultures in Ca(2+) -free medium or treatment with the non-selective voltage-gated calcium channel blocker cadmium or L-type Ca(2+) channel blocker nifedipine did not signficantly alter SGN neurite alignment. By contrast, ryanodine or xestospongin C, which block release of internal calcium stores via ryanodine-sensitive channels or inositol-1,4,5-trisphosphate receptors respectively, each significantly decreased neurite alignment. Cpt-cAMP significantly reduced neurite alignment while 8-Br-cGMP significantly enhanced neurite alignment. Manipulation of [Ca(2+) ]i or cAMP levels significantly disrupts neurite guidance while elevation of cGMP levels increases neurite alignment. The results suggest intracellular signaling pathways similar to those recruited by chemotactic cues are involved in neurite guidance by topographical features. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2037

  10. Neurite Outgrowth on Nanofiber Scaffolds with Different Orders, Structures, and Surface Properties

    PubMed Central

    Xie, Jingwei; MacEwan, Matthew R.; Li, Xiaoran; Sakiyama-Elbert, Shelly E.; Xia, Younan

    2009-01-01

    Electrospun nanofibers can be readily assembled into various types of scaffolds for applications in neural tissue engineering. The objective of this study is to examine and understand the unique patterns of neurite outgrowth from primary dorsal root ganglia (DRG) cultured on scaffolds of electrospun nanofibers having different orders, structures, and surface properties. We found that the neurites extended radially outward from the DRG main body without specific directionality when cultured on a nonwoven mat of randomly oriented nanofibers. In contrast, the neurites preferentially extended along the long axis of fiber when cultured on a parallel array of aligned nanofibers. When seeded at the border between regions of aligned and random nanofibers, the same DRG simultaneously expressed aligned and random neurite fields in response to the underlying nanofibers. When cultured on a double-layered scaffold where the nanofibers in each layer were aligned along a different direction, the neurites were found to be dependent on the fiber density in both layers. This bi-axial pattern clearly demonstrates that neurite outgrowth can be influenced by nanofibers in different layers of a scaffold, rather than the topmost layer only. Taken together, these results will provide valuable information pertaining to the design of nanofiber scaffolds for neuroregenerative applications, as well as the effects of topology on neurite outgrowth, growth cone guidance, and axonal regeneration. PMID:19397333

  11. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    PubMed

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. PMID:27163199

  12. Semi-automatic quantification of neurite fasciculation in high-density neurite images by the Neurite Directional Distribution Analysis (NDDA)

    PubMed Central

    Hopkins, Amy M; Wheeler, Brandon; Staii, Cristian; Kaplan, David L.; Atherton, Timothy J.

    2014-01-01

    Background Bundling of neurite extensions occur during nerve development and regeneration. Understanding the factors that drive neurite bundling is important for designing biomaterials for nerve regeneration toward the innervation target and preventing nociceptive collateral sprouting. High-density neuron cultures including dorsal root ganglia explants are employed for in vitro screening of biomaterials designed to control directional outgrowth. Although some semiautomated image processing methods exist for quantification of neurite outgrowth, methods to quantify axonal fasciculation in terms of direction of neurite outgrowth are lacking. New Method This work presents a semi-automated program to analyze micrographs of high-density neurites; the program aims to quantify axonal fasciculation by determining the orientational distribution function of the tangent vectors of the neurites and calculating its Fourier series coefficients (‘c’ values). Results We found that neurite directional distribution analysis (NDDA) of fasciculated neurites yielded ‘c’ values of ≥ ~0.25 whereas branched outgrowth led to statistically significant lesser values of <~0.2. The ‘c’ values correlated directly to the width of neurite bundles and indirectly to the number of branching points. Comparison with Existing Methods Information about the directional distribution of outgrowth is lost in simple counting methods or achieved laboriously through manual analysis. The NDDA supplements previous quantitative analyses of axonal bundling using a vector-based approach that captures new information about the directionality of outgrowth. Conclusion The NDDA is a valuable addition to open source image processing tools available to biomedical researchers offering a robust, precise approach to quantification of imaged features important in tissue development, disease, and repair. PMID:24680908

  13. Immobilized laminin concentration gradients on electrospun fiber scaffolds for controlled neurite outgrowth.

    PubMed

    Zander, Nicole E; Beebe, Thomas P

    2014-03-01

    Neuronal process growth is guided by extrinsic environmental cues such as extracellular matrix (ECM) proteins. Recent reports have described that the growth cone extension is superior across gradients of the ECM protein laminin compared to growth across uniformly distributed laminin. In this work, the authors have prepared gradients of laminin on aligned electrospun nanofibers for use as substrates for neuronal growth. The substrates therefore presented both topographical and chemical guidance cues. Step gradients were prepared by the controlled robotic immersion of plasma-treated polycaprolactone fibers reacted with N-hydroxysuccinimide into the protein solution. The gradients were analyzed using x-ray photoelectron spectroscopy and confocal laser scanning microscopy. Gradients with a dynamic range of protein concentrations were successfully generated and neurite outgrowth was evaluated using neuronlike pheochromocytoma cell line 12 (PC12) cells. After 10 days of culture, PC12 neurite lengths varied from 32.7 ± 14.2 μm to 76.3 ± 9.1 μm across the protein concentration gradient. Neurite lengths at the highest concentration end of the gradient were significantly longer than neurite lengths observed for cells cultured on samples with uniform protein coverage. Gradients were prepared both in the fiber direction and transverse to the fiber direction. Neurites preferentially aligned with the fiber direction in both cases indicating that fiber alignment has a more dominant role in controlling neurite orientation, compared to the chemical gradient. PMID:24739010

  14. Self-aligned Schwann cell monolayers demonstrate an inherent ability to direct neurite outgrowth

    NASA Astrophysics Data System (ADS)

    Seggio, A. M.; Narayanaswamy, A.; Roysam, B.; Thompson, D. M.

    2010-08-01

    In vivo nerve guidance channel studies have identified Schwann cell (SC) presence as an integral factor in axonal number and extension in an injury site, and in vitro studies have provided evidence that oriented SCs can direct neurite outgrowth. However, traditional methods used to create oriented SC monolayers (e.g. micropatterns/microtopography) potentially introduce secondary guidance cues to the neurons that are difficult to de-couple. Although SCs expanded on uniform laminin-coated coverslips lack a global orientation, the monolayers contain naturally formed regions of locally oriented cells that can be used to investigate SC-mediated neurite guidance. In this work, novel image analysis techniques have been developed to quantitatively assess local neurite orientation with respect to the underlying regional orientation of the Schwann cell monolayer. Results confirm that, in the absence of any secondary guidance cues, a positive correlation exists between neurite outgrowth and regional orientation of the SC monolayer. Thus, SCs alone possess an inherent ability to direct neurite outgrowth, and expansion of the co-culture-based quantitative method described can be used to further deconstruct specific biomolecular mechanisms of neurite guidance.

  15. Sonic hedgehog stimulates neurite outgrowth in a mechanical stretch model of reactive-astrogliosis

    PubMed Central

    Berretta, Antonio; Gowing, Emma K.; Jasoni, Christine L.; Clarkson, Andrew N.

    2016-01-01

    Although recovery following a stroke is limited, undamaged neurons under the right conditions can establish new connections and take on-board lost functions. Sonic hedgehog (Shh) signaling is integral for developmental axon growth, but its role after injury has not been fully examined. To investigate the effects of Shh on neuronal sprouting after injury, we used an in vitro model of glial scar, whereby cortical astrocytes were mechanically traumatized to mimic reactive astrogliosis observed after stroke. This mechanical trauma impaired neurite outgrowth from post-natal cortical neurons plated on top of reactive astrocytes. Addition of Shh to the media, however, resulted in a concentration-dependent increase in neurite outgrowth. This response was inhibited by cyclopamine and activated by oxysterol 20(S)-hydroxycholesterol, both of which modulate the activity of the Shh co-receptor Smoothened (Smo), demonstrating that Shh-mediated neurite outgrowth is Smo-dependent. In addition, neurite outgrowth was not associated with an increase in Gli-1 transcription, but could be inhibited by PP2, a selective inhibitor of Src family kinases. These results demonstrate that neurons exposed to the neurite growth inhibitory environment associated with a glial scar can be stimulated by Shh, with signaling occurring through a non-canonical pathway, to overcome this suppression and stimulate neurite outgrowth. PMID:26902390

  16. SOCS3 induces neurite differentiation and promotes neuronal cell survival.

    PubMed

    Mishra, Kanchan Kumar; Gupta, Sakshi; Banerjee, Kakoli

    2016-06-01

    Cytokines and growth factors play an important role in neuronal survival as well as cell death. The family of suppressors of cytokine signalling (SOCS) proteins, which includes SOCS1-7 and cytokine-induced suppressor (CIS), has been shown to act as negative regulators of cytokine-induced signalling. In this report, we highlight the role of SOCS3 in regulating neuronal differentiation and survival. We observed increased SOCS3 expression upon differentiation of PC12 cells as well as neural stem cells. SOCS3 overexpression upregulated differentiation of both neural stem cells and PC12 cells even in the absence of NGF, as evidenced by enhanced neurite outgrowth and upregulation of GAP43, marker associated with neurite outgrowth. siRNA-mediated silencing of SOCS3 confirmed the potential role of SOCS3 in neuritogenesis. We observed that, SOCS3-induced neurite differentiation was mediated via the PI3 kinase pathway. Another interesting observation was that SOCS3 overexpression promoted neuronal cell survival under H2 O2 -mediated stress indicating its fundamental role in cell survival. In conclusion, our results indicate that SOCS3 promotes differentiation and survival of neural cells and could be potentially useful in future therapy for treatment of neurodegenerative disorders. © 2016 IUBMB Life, 68(6):468-476, 2016. PMID:27118613

  17. Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures

    PubMed Central

    Khankan, Rana R.; Wanner, Ina B.; Phelps, Patricia E.

    2015-01-01

    The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged by meningeal fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite outgrowth of postnatal cerebral cortical neurons was assessed on three substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like cultures, and scar-like cultures with OECs. Initial results showed that OECs enhanced total neurite outgrowth of cortical neurons in a scar-like environment by 60%. We then asked if the neurite growth-promoting properties of OECs depended on direct alignment between neuronal and OEC processes. Neurites that aligned with OECs were nearly three times longer when they grew on inhibitory meningeal fibroblast areas and twice as long on reactive astrocyte zones compared to neurites not associated with OECs. Our results show that OECs can independently enhance neurite elongation and that direct OEC-neurite cell contact can provide a permissive substrate that overcomes the inhibitory nature of the reactive astrocyte scar border and the fibroblast-rich spinal cord lesion core. PMID:25863021

  18. Behavior of soil anchors under dynamic loads

    SciTech Connect

    Picornell, M.; Olague, B.

    1997-07-01

    Helical anchors placed in a cohesionless soil in a laboratory setting were tested under static and dynamic loads. The dynamic tests were performed after subjecting the anchors to a seating load. The dynamic load had an intensity that changed in sinusoidal fashion and was superimposed to the static seating loads. Although, the anchors have a static pull-out capacity, when the dynamic loads are applied the anchor experiences additional deformations for each load cycle. The deformations per cycle are initially high but then decrease to a nearly constant rate. Eventually, the constant rate increases suddenly accelerating until failure. This failure can take place even at small fractions of the static pull-out capacity. The rate of deformation per load cycle is found to increase for larger seating loads and for larger dynamic pulsating loads. The results of this study shows that the designer can only adjust loads to decrease the deformation rate to suit the design life of the structure.

  19. MECHANICS OF CRACK BRIDGING UNDER DYNAMIC LOADS

    SciTech Connect

    N. SRIDHAR; ET AL

    2001-02-01

    A bridging law for fiber reinforced composites under dynamic crack propagation conditions has been derived. Inertial effects in the mechanism of fiber pullout during dynamic propagation of a bridged crack are critically examined for the first time. By reposing simple shear lag models of pullout as problems of dynamic wave propagation, the effect of the frictional coupling between the fibers and the matrix is accounted for in a fairly straightforward way. The solutions yield the time-dependent relationship between the crack opening displacement and the bridging traction. Engineering criteria and the role of material and geometrical parameters for significant inertial effects are identified.

  20. Strength of concrete structures under dynamic loading

    NASA Astrophysics Data System (ADS)

    Kumpyak, O. G.; Galyautdinov, Z. R.; Kokorin, D. N.

    2016-01-01

    The use of elastic supports is one the efficient methods of decreasing the dynamic loading. The paper describes the influence of elastic supports on the stress-strain state of steel concrete structures exposed to one-time dynamic loading resulting in failure. Oblique bending beams on elastic supports and their elastic, elastoplastic, and elastoplastic consolidation behavior are considered in this paper. For numerical calculations the developed computer program is used based on the finite element method. Research findings prove high efficiency of elastic supports under dynamic loading conditions. The most effective behavior of elastic supports is demonstrated at the elastoplastic stage. A good agreement is observed between the theoretical and experimental results.

  1. Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients’ neurons

    PubMed Central

    Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu K.; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Plötz, Sonja; Boyer, Leah; Marchetto, Maria C.N.; Aigner, Stefan; Sticht, Heinrich; Groemer, Teja W.; Hehr, Ute; Lampert, Angelika; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Gage, Fred H.; Winner, Beate

    2014-01-01

    The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients. PMID:24381312

  2. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

    NASA Astrophysics Data System (ADS)

    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

  3. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements.

    PubMed

    Wood, Matthew D; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m(-1)) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca(2+)) or PBS (no Ca(2+)). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata. PMID:19494423

  4. Pure neuritic leprosy: Current status and relevance.

    PubMed

    Rao, P Narasimha; Suneetha, Sujai

    2016-01-01

    Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients. PMID:27088926

  5. Neurite outgrowth enhancement by jiadifenolide: possible targets.

    PubMed

    Shenvi, R A

    2016-04-01

    Covering: 1860-2016A mechanistic link may exist between convulsant plant substances typified by picrotoxinin, and 'neurotrophic' sesquiterpenes like jiadifenolide. Picrotoxinin elicits convulsion by anion blockade of the Cys-loop family of neurotransmitter-gated ion channels. These same receptors mediate neuronal development and neurite outgrowth prior to synapse formation. Due to its structural homology with picrotoxin and anisatin, it is possible that jiadifenolide enhances NGF-stimulated neurite outgrowth by modulation of the Cys-loop family of receptors. PMID:26891462

  6. Differential Intensity-dependent Effects of Magnetic Stimulation on the Longest Neurites and Shorter Dendrites in Neuroscreen-1 Cells

    PubMed Central

    Lin, Ching-Yi; Huang, Whitney J.; Li, Kevin; Swanson, Roy; Cheung, Brian; Lin, Vernon W.; Lee, Yu-Shang

    2015-01-01

    OBJECTIVE Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. APPROACH To test our hypotheses, we examined the effects of MS on neurite growth of Neuroscreen-1 (NS-1) cells over pulse frequencies of 1, 5 and 10 Hz at field intensities controlled by machine output (MO). Cells were treated with either 30% or 40% MO and received either maximal or minimal MS-induced current-density. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (~5%) electromagnetic current density while the remaining area (zone 2) received maximal (~95%) current density. Plated NS-1 cells were exposed to MS twice per day for 3 days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). MAIN RESULTS We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in the bolstering of the longest neurite outgrowth, mainly seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. SIGNIFICANCE These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating

  7. Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

    NASA Astrophysics Data System (ADS)

    Lin, Ching-Yi; Huang, Whitney J.; Li, Kevin; Swanson, Roy; Cheung, Brian; Lin, Vernon W.; Lee, Yu-Shang

    2015-04-01

    Objective. Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. Approach. To test our hypotheses, we examined the effects of MS on neurite growth of neuroscreen-1 (NS-1) cells over the pulse frequencies of 1, 5 and 10 Hz at field intensities controlled via machine output (MO). Cells were treated with either 30% or 40% MO. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (∼5%) electromagnetic current density while the remaining area (zone 2) received maximal (∼95%) current density. Plated NS-1 cells were exposed to MS twice per day for three days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). Main results. We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in bolstering longest neurite outgrowth, best seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. Significance. These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating its use into potential therapeutic strategies.

  8. Fabrication of conductive NGF-conjugated polypyrrole-poly(l-lactic acid) fibers and their effect on neurite outgrowth.

    PubMed

    Zeng, Jingwen; Huang, Zhongbing; Yin, Guangfu; Qin, Jiabang; Chen, Xianchun; Gu, Jianwen

    2013-10-01

    In order to fabricate a tissue scaffold with the neurotrophic and electrical activities, conductive nerve growth factor (NGF)-conjugated polypyrrole-poly(l-lactic acid) (PPy-PLLA) composite fibers were prepared by oxidation polymerization and EDC chemistry with poly-l-lysine. PPy nanoparticles (∼70nm diameter) accumulated on PLLA fiber surface to form a rough thick shell (∼200nm thickness). These NGF-conjugated PPy-PLLA fibers could support PC12 neurite outgrowth and extension. Especially, 40% and 74% increase in PC12 neurite outgrowth and extension, respectively, could be obtained under electrical stimulation of 100mV/cm voltages through the composite fibers. A mechanism for the interaction between neurite extension and the NGF-conjugated PPy-PLLA fibers under electro-stimulation was proposed, to explain the synergistic effect of the rough PPy shell, conjugated NGF and electricity on neurite outgrowth and elongation. PMID:23759386

  9. Wave Journal Bearings Under Dynamic Loads

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Dimofte, Florin

    2002-01-01

    The dynamic behavior of the wave journal bearing was determined by running a three-wave bearing with an eccentrically mounted shaft. A transient analysis was developed and used to predict numerical data for the experimental cases. The three-wave journal bearing ran stably under dynamic loads with orbits well inside the bearing clearance. The orbits were almost circular and nearly free of the influence of, but dynamically dependent on, bearing wave shape. Experimental observations for both the absolute bearing-housing-center orbits and the relative bearing-housing-center-to-shaft-center orbits agreed well with the predictions. Moreover, the subsynchronous whirl motion generated by the fluid film was found experimentally and predicted theoretically for certain speeds.

  10. Noise facilitates transcriptional control under dynamic inputs.

    PubMed

    Kellogg, Ryan A; Tay, Savaş

    2015-01-29

    Cells must respond sensitively to time-varying inputs in complex signaling environments. To understand how signaling networks process dynamic inputs into gene expression outputs and the role of noise in cellular information processing, we studied the immune pathway NF-κB under periodic cytokine inputs using microfluidic single-cell measurements and stochastic modeling. We find that NF-κB dynamics in fibroblasts synchronize with oscillating TNF signal and become entrained, leading to significantly increased NF-κB oscillation amplitude and mRNA output compared to non-entrained response. Simulations show that intrinsic biochemical noise in individual cells improves NF-κB oscillation and entrainment, whereas cell-to-cell variability in NF-κB natural frequency creates population robustness, together enabling entrainment over a wider range of dynamic inputs. This wide range is confirmed by experiments where entrained cells were measured under all input periods. These results indicate that synergy between oscillation and noise allows cells to achieve efficient gene expression in dynamically changing signaling environments. PMID:25635454

  11. Nanostructured Polyaniline Coating on ITO Glass Promotes the Neurite Outgrowth of PC 12 Cells by Electrical Stimulation.

    PubMed

    Wang, Liping; Huang, Qianwei; Wang, Jin-Ye

    2015-11-10

    A conducting polymer polyaniline (PANI) with nanostructure was synthesized on indium tin oxide (ITO) glass. The effect of electrical stimulation on the proliferation and the length of neurites of PC 12 cells was investigated. The dynamic protein adsorption on PANI and ITO surfaces in a cell culture medium was also compared with and without electrical stimulation. The adsorbed proteins were characterized using SDS-PAGE. A PANI coating on ITO surface was shown with 30-50 nm spherical nanostructure. The number of PC 12 cells was significantly greater on the PANI/ITO surface than on ITO and plate surfaces after cell seeding for 24 and 36 h. This result confirmed that the PANI coating is nontoxic to PC 12 cells. The electrical stimulation for 1, 2, and 4 h significantly enhanced the cell numbers for both PANI and ITO conducting surfaces. Moreover, the application of electrical stimulation also improved the neurite outgrowth of PC 12 cells, and the number of PC 12 cells with longer neurite lengths increased obviously under electrical stimulation for the PANI surface. From the mechanism, the adsorption of DMEM proteins was found to be enhanced by electrical stimulation for both PANI/ITO and ITO surfaces. A new band 2 (around 37 kDa) was observed from the collected adsorbed proteins when PC 12 cells were cultured on these surfaces, and culturing PC 12 cells also seemed to increase the amount of band 1 (around 90 kDa). When immersing PANI/ITO and ITO surfaces in a DMEM medium without a cell culture, the number of band 3 (around 70 kDa) and band 4 (around 45 kDa) proteins decreased compared to that of PC 12 cell cultured surfaces. These results are valuable for the design and improvement of the material performance for neural regeneration. PMID:25992643

  12. Dynamic Strength Ceramic Nanocomposites Under Pulse Loading

    NASA Astrophysics Data System (ADS)

    Skripnyak, Evgeniya G.; Skripnyak, Vladimir V.; Vaganova, Irina K.; Skripnyak, Vladimir A.

    2015-06-01

    Multi-scale computer simulation approach has been applied to research of strength of nanocomposites under dynamic loading. The influence of mesoscopic substructures on the dynamic strength of ceramic and hybrid nanocomposites, which can be formed using additive manufacturing were numerically investigated. At weak shock wave loadings the shear strength and the spall strength of ceramic and hybrid nanocomposites depends not only phase concentration and porosity, but size parameters of skeleton substructures. The influence of skeleton parameter on the shear strength and the spall strength of ceramic nanocomposites with the same concentration of phases decreases with increasing amplitude of the shock pulse of microsecond duration above the double amplitude of the Hugoniot elastic limit of nanocomposites. This research carried out in 2014 -2015 was supported by grant from The Tomsk State University Academic D.I. Mendeleev Fund Program and also Ministry of Sciences and Education of Russian Federation (State task 2014/223, project 1943, Agreement 14.132.

  13. Dynamic Epistasis under Varying Environmental Perturbations

    PubMed Central

    Barker, Brandon; Xu, Lin; Gu, Zhenglong

    2015-01-01

    Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current knowledge for epistatic dynamics under multiple conditions is limited by the technological difficulties in experimentally screening epistatic relations among genes. We explored this issue by applying flux balance analysis to simulate epistatic landscapes under various environmental perturbations. Specifically, we looked at gene-gene epistatic interactions, where the mutations were assumed to occur in different genes. We predicted that epistasis tends to become more positive from glucose-abundant to nutrient-limiting conditions, indicating that selection might be less effective in removing deleterious mutations in the latter. We also observed a stable core of epistatic interactions in all tested conditions, as well as many epistatic interactions unique to each condition. Interestingly, genes in the stable epistatic interaction network are directly linked to most other genes whereas genes with condition-specific epistasis form a scale-free network. Furthermore, genes with stable epistasis tend to have similar evolutionary rates, whereas this co-evolving relationship does not hold for genes with condition-specific epistasis. Our findings provide a novel genome-wide picture about epistatic dynamics under environmental perturbations. PMID:25625594

  14. Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways.

    PubMed

    Phan, Chia-Wei; Lee, Guan-Serm; Hong, Sok-Lai; Wong, Yuin-Teng; Brkljača, Robert; Urban, Sylvia; Abd Malek, Sri Nurestri; Sabaratnam, Vikineswary

    2014-12-01

    Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways. PMID:25288148

  15. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    SciTech Connect

    Pizzurro, Daniella M.; Dao, Khoi; Costa, Lucio G.

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  16. An algorithm for neurite outgrowth reconstruction

    NASA Technical Reports Server (NTRS)

    Weaver, Christina M.; Pinezich, John D.; Lindquist, W. Brent; Vazquez, Marcelo E.

    2003-01-01

    We present a numerical method which provides the ability to analyze digitized microscope images of retinal explants and quantify neurite outgrowth. Few parameters are required as input and limited user interaction is necessary to process an entire experiment of images. This eliminates fatigue related errors and user-related bias common to manual analysis. The method does not rely on stained images and handles images of variable quality. The algorithm is used to determine time and dose dependent, in vitro, neurotoxic effects of 1 GeV per nucleon iron particles in retinal explants. No neurotoxic effects are detected until 72 h after exposure; at 72 h, significant reductions of neurite outgrowth occurred at doses higher than 10 cGy.

  17. Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures.

    PubMed

    Stiegler, Nina V; Krug, Anne K; Matt, Florian; Leist, Marcel

    2011-05-01

    Chemicals that specifically alter human neurite outgrowth pose a hazard for the development of the nervous system. The identification of such compounds remains a major challenge, especially in a human test system. To address this issue, we developed an imaging-based procedure in LUHMES human neuronal precursor cells to quantify neurite growth of unfixed cultures. Live imaging allowed the simultaneous evaluation of cell viability and neurite outgrowth within one culture dish. The procedure was used to test the hypothesis that inhibitors of specific pathways can impair neurite outgrowth without affecting cell viability. Although the cells were grown at high density to allow extensive networking, overall neurite growth in this complex culture was quantified with a signal-to-noise ratio of > 50. Compounds such as U0126 slowed the extension of neuronal processes at concentrations > 4 times lower than those causing cell death. High numbers of individual viable cells without neurites were identified under such conditions, and neurite outgrowth recovered after washout of the chemical. Also an extension-promoting compound, Y-27632, was identified by this unique multiparametric imaging approach. Finally, the actions of unspecific cytotoxicants such as menadione, cadmium chloride, and sodium dodecyl sulfate were tested to evaluate the specificity of the new assay. We always found a ratio of EC50 (cell death)/EC50 (neurites) < 4 for such chemicals. The described novel test system may thus be useful both for high-throughput screens to identify neuritotoxic agents and for their closer characterization concerning mode of action, compound interactions, or the reversibility of their effects. PMID:21342877

  18. Optimizing neurotrophic factor combinations for neurite outgrowth

    NASA Astrophysics Data System (ADS)

    Deister, C.; Schmidt, C. E.

    2006-06-01

    Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml-1 NGF and 10 ng ml-1 of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 ± 53% increase over untreated DRGs and increased the longest neurite length to 2031 ± 97 µm compared to 916 ± 64 µm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

  19. Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

    SciTech Connect

    Wang, Yingchun; Yang, Feng; Fu, Yi; Huang, Xiahe; Wang, Wei; Jiang, Xining; Gritsenko, Marina A.; Zhao, Rui; Monroe, Matthew E.; Pertz, Olivier C.; Purvine, Samuel O.; Orton, Daniel J.; Jacobs, Jon M.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2011-05-20

    Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.

  20. Dynamic Strength of Tantalum under impact

    NASA Astrophysics Data System (ADS)

    Glam, Benny; Werdiger, Meir; Pistinner, Shlomi

    2013-06-01

    Plane impact experiments of double shock and shock-rarefaction in Tantalum were carried out in a gas gun. VISAR diagnostics has been implemented to measure the particle velocity and the free surface velocity. The VISAR information was utilized to study the dynamic strength of Tantalum under compression and tension. The pressure in the experiments was below 35 GPa. In this pressure range the dominant mechanism is expected to be dislocation motion. A 1-d hydrodynamic code was used in order to match various strength models. As expected, both the Johnson-Cook and the Guinan-Steinberg models do not reproduce the experimental results. Therefore in this paper we compare the Zerilli-Armstrong model which has been recently calibrated at strain rate of 6 x 103 s-1 using the split Kowalsky-Hopkinson bar to our experimental results at strain rate of 106 s-1.

  1. Eigenvector dynamics under perturbation of modular networks

    NASA Astrophysics Data System (ADS)

    Sarkar, Somwrita; Chawla, Sanjay; Robinson, P. A.; Fortunato, Santo

    2016-06-01

    Rotation dynamics of eigenvectors of modular network adjacency matrices under random perturbations are presented. In the presence of q communities, the number of eigenvectors corresponding to the q largest eigenvalues form a "community" eigenspace and rotate together, but separately from that of the "bulk" eigenspace spanned by all the other eigenvectors. Using this property, the number of modules or clusters in a network can be estimated in an algorithm-independent way. A general argument and derivation for the theoretical detectability limit for sparse modular networks with q communities is presented, beyond which modularity persists in the system but cannot be detected. It is shown that for detecting the clusters or modules using the adjacency matrix, there is a "band" in which it is hard to detect the clusters even before the theoretical detectability limit is reached, and for which the theoretically predicted detectability limit forms the sufficient upper bound. Analytic estimations of these bounds are presented and empirically demonstrated.

  2. Reliability of dynamic systems under limited information.

    SciTech Connect

    Field, Richard V., Jr.; Grigoriu, Mircea

    2006-09-01

    A method is developed for reliability analysis of dynamic systems under limited information. The available information includes one or more samples of the system output; any known information on features of the output can be used if available. The method is based on the theory of non-Gaussian translation processes and is shown to be particularly suitable for problems of practical interest. For illustration, we apply the proposed method to a series of simple example problems and compare with results given by traditional statistical estimators in order to establish the accuracy of the method. It is demonstrated that the method delivers accurate results for the case of linear and nonlinear dynamic systems, and can be applied to analyze experimental data and/or mathematical model outputs. Two complex applications of direct interest to Sandia are also considered. First, we apply the proposed method to assess design reliability of a MEMS inertial switch. Second, we consider re-entry body (RB) component vibration response during normal re-entry, where the objective is to estimate the time-dependent probability of component failure. This last application is directly relevant to re-entry random vibration analysis at Sandia, and may provide insights on test-based and/or model-based qualification of weapon components for random vibration environments.

  3. Stochastic Dynamics Underlying Cognitive Stability and Flexibility

    PubMed Central

    Ueltzhöffer, Kai; Armbruster-Genç, Diana J. N.; Fiebach, Christian J.

    2015-01-01

    dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences. PMID:26068119

  4. Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

    PubMed

    Ueltzhöffer, Kai; Armbruster-Genç, Diana J N; Fiebach, Christian J

    2015-06-01

    dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences. PMID:26068119

  5. Facile micropatterning of dual hydrogel systems for 3D models of neurite outgrowth

    PubMed Central

    Curley, J L; Moore, M J

    2011-01-01

    Understanding how microenvironmental factors influence neurite growth is important to inform studies in nerve regeneration, plasticity, development, and neurophysiology. In vitro models attempting to more accurately mimic the physiological environment by provision of a 3D growth matrix may provide useful foundations. Some limitations of thick 3D culture models include hampered solute transport, less-robust neurite growth than on 2D substrates, and difficulty in achieving spatial control of growth. To this end, we describe a 3D dual hydrogel model for embryonic rat day 15 dorsal root ganglion tissue explant growth using a digital micro-mirror device for dynamic mask projection photolithography. The photolithography method developed allowed simple, reproducible, one-step fabrication of thick hydrogel constructs on a variety of substrates, including permeable cell culture inserts. The relationships between projected mask size, crosslinked hydrogel resolution, and gel thickness were characterized, and resolution was found generally to decrease with increasing gel thickness. Cell viability in thick (481 μm) hydrogel constructs was significantly greater on permeable supports than glass, suggesting transport limitations were somewhat alleviated. The observed neurite growth was abundant and occurred in a spatially controlled manner throughout the 3D environment, a crucial step in the quest for a more effective biomimetic model of neurite outgrowth. PMID:21936043

  6. Facile micropatterning of dual hydrogel systems for 3D models of neurite outgrowth.

    PubMed

    Curley, J Lowry; Moore, Michael J

    2011-12-15

    Understanding how microenvironmental factors influence neurite growth is important to inform studies in nerve regeneration, plasticity, development, and neurophysiology. In vitro models attempting to more accurately mimic the physiological environment by provision of a 3D growth matrix may provide useful foundations. Some limitations of thick 3D culture models include hampered solute transport, less-robust neurite growth than on 2D substrates, and difficulty in achieving spatial control of growth. To this end, we describe a 3D dual hydrogel model for embryonic rat day 15 dorsal root ganglion tissue explant growth using a digital micromirror device for dynamic mask projection photolithography. The photolithography method developed allowed simple, reproducible, one-step fabrication of thick hydrogel constructs on a variety of substrates, including permeable cell culture inserts. The relationships between projected mask size, crosslinked hydrogel resolution, and gel thickness were characterized, and resolution was found generally to decrease with increasing gel thickness. Cell viability in thick (481 μm) hydrogel constructs was significantly greater on permeable supports than glass, suggesting transport limitations were somewhat alleviated. The observed neurite growth was abundant and occurred in a spatially controlled manner throughout the 3D environment, a crucial step in the quest for a more effective biomimetic model of neurite outgrowth. PMID:21936043

  7. Fabrication of Aligned Conducting PPy-PLLA Fiber Films and Their Electrically Controlled Guidance and Orientation for Neurites.

    PubMed

    Zou, Yuanwen; Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Pu, Ximing; He, Da

    2016-05-25

    Electrically conductive biomaterial scaffolds have great potential in neural tissue regeneration. In this work, an aligned conductive fibrous scaffold was prepared by electrospinning PLLA on rotating collector and chemical oxidation polymerization of pyrrole (PPy) codoped with poly(glutamic acid)/dodecyl benzenesulfonic acid sodium. The characterization results of composition, structure and mechanics of fiber films show that the existence of weak polar van der Waals' force between PPy coating and PLLA fibers. The resistivity of aligned rough PPy-PLLA fiber film (about 800 nm of fiber diameter) at the perpendicular and parallel directions is 0.971 and 0.874 Ω m, respectively. Aligned rough PPy-PLLA fiber film could guide the extension of 68% PC12 neurites along the direction of fiber axis. Under electrostimulation (ES) of 100, 200, and 400 mV/cm, median neurite lengths of differentiated PC12 on aligned fiber-films are 128, 149, and 141 μm, respectively. Furthermore, under ES of 100, 200, and 400 mV/cm, the alignment rate of neurite along the electropotential direction (angle between neurite and electropotential direction ≤10°) on random fibers film are 17, 23, and 28%, respectively, and the alignment rate of neurites along the fiber axis (angle between neurite and fiber axis ≤10°) on aligned fibers film reach to 76, 83, and 79%, respectively, indicating that the combination of ES and rough conducting aligned structure could adjust the alignment of cellular neurites along the direction of the fiber axis or electropotential. PMID:27172537

  8. Controlled neuronal cell patterning and guided neurite growth on micropatterned nanofiber platforms

    NASA Astrophysics Data System (ADS)

    Malkoc, Veysi; Gallego-Perez, Daniel; Nelson, Tyler; Lannutti, John J.; Hansford, Derek J.

    2015-12-01

    Patterning neuronal cells and guiding neurite growth are important for applications such as prosthetics, cell based biosensors, and tissue engineering. In this paper, a microdevice is presented that provides neuronal cell patterning and guided neurite growth on a collagen coated gelatin/PCL nanofiber mat. The pattern consisted of a grid of polystyrene microwells/nodes to confine the cell bodies and orthogonal grooves to guide neurite growth from each node. Vacuum assisted cell seeding was used to localize cell bodies in the microwells and physically separate the cells during seeding. The electrospun nanofiber mats under the polystyrene microstructures were coated with collagen to enhance the cellular attachment and enhance differentiation. We evaluated the performance of our device using adhesion, viability, and differentiation assays of neuron-like PC12 cells compared to controls for vacuum seeding, spatial isolation and guidance, and collagen coating of the fibers. The device provided PC12 cell patterning with increased adhesion, differentiation, and guided neurite outgrowth compared to controls, demonstrating its potential for in vitro neuronal cell patterning studies.

  9. Stochastic game dynamics under demographic fluctuations

    PubMed Central

    Huang, Weini; Hauert, Christoph; Traulsen, Arne

    2015-01-01

    Frequency-dependent selection and demographic fluctuations play important roles in evolutionary and ecological processes. Under frequency-dependent selection, the average fitness of the population may increase or decrease based on interactions between individuals within the population. This should be reflected in fluctuations of the population size even in constant environments. Here, we propose a stochastic model that naturally combines these two evolutionary ingredients by assuming frequency-dependent competition between different types in an individual-based model. In contrast to previous game theoretic models, the carrying capacity of the population, and thus the population size, is determined by pairwise competition of individuals mediated by evolutionary games and demographic stochasticity. In the limit of infinite population size, the averaged stochastic dynamics is captured by deterministic competitive Lotka–Volterra equations. In small populations, demographic stochasticity may instead lead to the extinction of the entire population. Because the population size is driven by fitness in evolutionary games, a population of cooperators is less prone to go extinct than a population of defectors, whereas in the usual systems of fixed size the population would thrive regardless of its average payoff. PMID:26150518

  10. Stochastic game dynamics under demographic fluctuations.

    PubMed

    Huang, Weini; Hauert, Christoph; Traulsen, Arne

    2015-07-21

    Frequency-dependent selection and demographic fluctuations play important roles in evolutionary and ecological processes. Under frequency-dependent selection, the average fitness of the population may increase or decrease based on interactions between individuals within the population. This should be reflected in fluctuations of the population size even in constant environments. Here, we propose a stochastic model that naturally combines these two evolutionary ingredients by assuming frequency-dependent competition between different types in an individual-based model. In contrast to previous game theoretic models, the carrying capacity of the population, and thus the population size, is determined by pairwise competition of individuals mediated by evolutionary games and demographic stochasticity. In the limit of infinite population size, the averaged stochastic dynamics is captured by deterministic competitive Lotka-Volterra equations. In small populations, demographic stochasticity may instead lead to the extinction of the entire population. Because the population size is driven by fitness in evolutionary games, a population of cooperators is less prone to go extinct than a population of defectors, whereas in the usual systems of fixed size the population would thrive regardless of its average payoff. PMID:26150518

  11. The combinatorics of neurite self-avoidance.

    PubMed

    Forbes, Elizabeth M; Hunt, Jonathan J; Goodhill, Geoffrey J

    2011-11-01

    During neural development in Drosophila, the ability of neurite branches to recognize whether they are from the same or different neurons depends crucially on the molecule Dscam1. In particular, this recognition depends on the stochastic acquisition of a unique combination of Dscam1 isoforms out of a large set of possible isoforms. To properly interpret these findings, it is crucial to understand the combinatorics involved, which has previously been attempted only using stochastic simulations for some specific parameter combinations. Here we present closed-form solutions for the general case. These reveal the relationships among the key variables and how these constrain possible biological scenarios. PMID:21732864

  12. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling

    PubMed Central

    Gu, Tingting; Zhao, Tao; Hewes, Randall S.

    2014-01-01

    Summary Although the growth capacity of mature neurons is often limited, some neurons can shift through largely unknown mechanisms from stable maintenance growth to dynamic, organizational growth (e.g. to repair injury, or during development transitions). During insect metamorphosis, many terminally differentiated larval neurons undergo extensive remodeling, involving elimination of larval neurites and outgrowth and elaboration of adult-specific projections. Here, we show in the fruit fly, Drosophila melanogaster (Meigen), that a metamorphosis-specific increase in insulin signaling promotes neuronal growth and axon branching after prolonged stability during the larval stages. FOXO, a negative effector in the insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon cell-targeted expression of dominant-negative constructs for other components of the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K) also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO), stimulated overgrowth. Interestingly, InR displayed little effect on larval CCAP/bursicon neuron growth, in contrast to its strong effects during metamorphosis. Manipulations of insulin signaling in many other peptidergic neurons revealed generalized growth stimulation during metamorphosis, but not during larval development. These findings reveal a fundamental shift in growth control mechanisms when mature, differentiated neurons enter a new phase of organizational growth. Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation. PMID:24357229

  13. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

    PubMed Central

    Cras, P; Kawai, M; Lowery, D; Gonzalez-DeWhitt, P; Greenberg, B; Perry, G

    1991-01-01

    Senile plaques are polymorphous beta-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This beta-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for the abnormal filaments characteristic of neurofibrillary pathology. In the neocortex of nondemented individuals with senile plaques but spared of neurofibrillary pathology, dystrophic neurites in senile plaques showed only APP accumulation. In contrast, in the brains of Alzheimer patients, virtually all APP-immunoreactive neurites also showed immunoreactivity with ubiquitin, tau, and phosphorylated neurofilaments. The presence of tau and neurofilament epitopes in dystrophic neurites in senile plaques was correlated with the extent of neurofibrillary pathology in the surrounding brain tissue. Accumulation of APP and the formation of neurofibrillary pathology in senile plaque neurites are therefore distinct phenomena. Our findings suggest that APP accumulation in senile plaque neurites occurs prior to tau accumulation and is therefore more closely related to appearance of neuritic dystrophy. Images PMID:1652752

  14. Biophysical mechanisms underlying olfactory receptor neuron dynamics

    PubMed Central

    Nagel, Katherine I.; Wilson, Rachel I.

    2010-01-01

    Odor responses of olfactory receptor neurons (ORNs) exhibit complex dynamics. Using genetics and pharmacology, we show that these dynamics in Drosophila ORNs can be separated into sequential steps, corresponding to transduction and spike generation. Each of these steps contributes distinct dynamics. Transduction dynamics can be largely explained by a simple kinetic model of ligand-receptor interactions, together with an adaptive feedback mechanism that slows transduction onset. Spiking dynamics are well-described by a differentiating linear filter that is stereotyped across odors and cells. Genetic knock-down of sodium channels reshapes this filter, implying that it arises from the regulated balance of intrinsic conductances in ORNs. Complex responses can be understood as a consequence of how the stereotyped spike filter interacts with odor- and receptor-specific transduction dynamics. However, in the presence of rapidly fluctuating natural stimuli, spiking simply increases the speed and sensitivity of encoding. PMID:21217763

  15. Experimental and computational models of neurite extension at a choice point in response to controlled diffusive gradients

    NASA Astrophysics Data System (ADS)

    Catig, G. C.; Figueroa, S.; Moore, M. J.

    2015-08-01

    Ojective. Axons are guided toward desired targets through a series of choice points that they navigate by sensing cues in the cellular environment. A better understanding of how microenvironmental factors influence neurite growth during development can inform strategies to address nerve injury. Therefore, there is a need for biomimetic models to systematically investigate the influence of guidance cues at such choice points. Approach. We ran an adapted in silico biased turning axon growth model under the influence of nerve growth factor (NGF) and compared the results to corresponding in vitro experiments. We examined if growth simulations were predictive of neurite population behavior at a choice point. We used a biphasic micropatterned hydrogel system consisting of an outer cell restrictive mold that enclosed a bifurcated cell permissive region and placed a well near a bifurcating end to allow proteins to diffuse and form a gradient. Experimental diffusion profiles in these constructs were used to validate a diffusion computational model that utilized experimentally measured diffusion coefficients in hydrogels. The computational diffusion model was then used to establish defined soluble gradients within the permissive region of the hydrogels and maintain the profiles in physiological ranges for an extended period of time. Computational diffusion profiles informed the neurite growth model, which was compared with neurite growth experiments in the bifurcating hydrogel constructs. Main results. Results indicated that when applied to the constrained choice point geometry, the biased turning model predicted experimental behavior closely. Results for both simulated and in vitro neurite growth studies showed a significant chemoattractive response toward the bifurcated end containing an NGF gradient compared to the control, though some neurites were found in the end with no NGF gradient. Significance. The integrated model of neurite growth we describe will allow

  16. Real-time detection of neurite outgrowth using microfluidic device

    NASA Astrophysics Data System (ADS)

    Kim, Samhwan; Jang, Jongmoon; Choi, Hongsoo; Moon, Cheil

    2013-05-01

    We developed a simple method for real-time detection of the neurite outgrowth using microfluidic device. Our microfluidic device contains three compartmentalized channels which are for cell seeding, hydrogel and growth factors. Collagen gel is filled in the middle channel and pheochromocytoma (PC12) cells are seeded in the left channel. To induce differentiation of PC12 cells, 50 ng/ml to1000 ng/ml of nerve growth factor (NGF) is introduced into the right channel. After three days of NGF treatment, PC12 cells begin to extend neurites and formed neurite network from sixth day. Quantification of neurite outgrowth is analyzed by measuring the total area of neurites. On sixth day, the area is doubled compared to the area on third day and increases by 20 times on ninth day.

  17. Graphene substrate for inducing neurite outgrowth.

    PubMed

    Lee, Jeong Soon; Lipatov, Alexey; Ha, Ligyeom; Shekhirev, Mikhail; Andalib, Mohammad Nahid; Sinitskii, Alexander; Lim, Jung Yul

    2015-05-01

    A few recent studies demonstrated that graphene may have cytocompatibility with several cell types. However, when assessing cell behavior on graphene, there has been no precise control over the quality of graphene, number of graphene layers, and substrate surface coverage by graphene. In this study, using well-controlled monolayer graphene film substrates we tested the cytocompatibility of graphene for human neuroblastoma (SH-SY5Y) cell culture. A large-scale monolayer graphene film grown on Cu foils by chemical vapor deposition (CVD) could be successfully transferred onto glass substrates by wet transfer technique. We observed that graphene substrate could induce enhanced neurite outgrowth, both in neurite length and number, compared with control glass substrate. Interestingly, the positive stimulatory effect by graphene was achieved even in the absence of soluble neurogenic factor, retinoic acid (RA). Key genes relevant to cell neurogenesis, e.g., neurofilament light chain (NFL), were also upregulated on graphene. Inhibitor studies suggested that the graphene stimulation of cellular neurogenesis may be achieved through focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) cascades. Our data indicate that graphene may be exploited as a platform for neural regenerative medicine, and the suggested molecular mechanism may provide an insight into the graphene control of neural cells. PMID:25778866

  18. An assay to image neuronal microtubule dynamics in mice

    PubMed Central

    Kleele, Tatjana; Marinković, Petar; Williams, Philip R.; Stern, Sina; Weigand, Emily E.; Engerer, Peter; Naumann, Ronald; Hartmann, Jana; Karl, Rosa M.; Bradke, Frank; Bishop, Derron; Herms, Jochen; Konnerth, Arthur; Kerschensteiner, Martin; Godinho, Leanne; Misgeld, Thomas

    2014-01-01

    Microtubule dynamics in neurons play critical roles in physiology, injury and disease and determine microtubule orientation, the cell biological correlate of neurite polarization. Several microtubule binding proteins, including end-binding protein 3 (EB3), specifically bind to the growing plus tip of microtubules. In the past, fluorescently tagged end-binding proteins have revealed microtubule dynamics in vitro and in non-mammalian model organisms. Here, we devise an imaging assay based on transgenic mice expressing yellow fluorescent protein-tagged EB3 to study microtubules in intact mammalian neurites. Our approach allows measurement of microtubule dynamics in vivo and ex vivo in peripheral nervous system and central nervous system neurites under physiological conditions and after exposure to microtubule-modifying drugs. We find an increase in dynamic microtubules after injury and in neurodegenerative disease states, before axons show morphological indications of degeneration or regrowth. Thus increased microtubule dynamics might serve as a general indicator of neurite remodelling in health and disease. PMID:25219969

  19. Increase in Growth Cone Size Correlates with Decrease in Neurite Growth Rate

    PubMed Central

    Ren, Yuan

    2016-01-01

    Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L-lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 μm2. The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth. PMID:27274874

  20. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

    PubMed

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-05-10

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  1. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

    PubMed Central

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-01-01

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  2. Matrix interactions modulate neurotrophin-mediated neurite outgrowth and pathfinding

    PubMed Central

    Madl, Christopher M.; Heilshorn, Sarah C.

    2015-01-01

    Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathfinding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treatment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathfinding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive matrices promoted more faithful neurite pathfinding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration. PMID:26170800

  3. Dynamics of social balance under temporal interaction

    NASA Astrophysics Data System (ADS)

    Nishi, Ryosuke; Masuda, Naoki

    2014-08-01

    Real social contacts are often intermittent such that a link between a pair of nodes in a social network is only temporarily used. The effects of such temporal networks on social dynamics have been investigated for several phenomenological models such as epidemic spreading, linear diffusion processes, and nonlinear oscillations. Here, we numerically investigate nonlinear social balance dynamics in such a situation. Social balance is a classical psychological theory, which dictates that a triad is balanced if the three agents are mutual friends or if the two of them are the friends of each other and hostile to the other agent. We show that the social balance dynamics is slowed down on the temporal complete graph as compared to the corresponding static complete graph.

  4. Mechanical stress activates neurites and somata of myenteric neurons

    PubMed Central

    Kugler, Eva M.; Michel, Klaus; Zeller, Florian; Demir, Ihsan E.; Ceyhan, Güralp O.; Schemann, Michael; Mazzuoli-Weber, Gemma

    2015-01-01

    The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut. PMID:26441520

  5. Mechanical stress activates neurites and somata of myenteric neurons.

    PubMed

    Kugler, Eva M; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Schemann, Michael; Mazzuoli-Weber, Gemma

    2015-01-01

    The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut. PMID:26441520

  6. Evolution of entanglement under echo dynamics

    SciTech Connect

    Prosen, Tomaz; Znidaric, Marko; Seligman, Thomas H.

    2003-04-01

    Echo dynamics and fidelity are often used to discuss stability in quantum-information processing and quantum chaos. Yet fidelity yields no information about entanglement, the characteristic property of quantum mechanics. We study the evolution of entanglement in echo dynamics. We find qualitatively different behavior between integrable and chaotic systems on one hand and between random and coherent initial states for integrable systems on the other. For the latter the evolution of entanglement is given by a classical time scale. Analytic results are illustrated numerically in a Jaynes-Cummings model.

  7. Nerve abscess in primary neuritic leprosy.

    PubMed

    Rai, Dheeraj; Malhotra, Hardeep Singh; Garg, Ravindra Kumar; Goel, Madhu Mati; Malhotra, Kiran Preet; Kumar, Vijay; Singh, Arun Kumar; Jain, Amita; Kohli, Neera; Singh, Shailesh Kumar

    2013-06-01

    Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis. PMID:24171239

  8. Purines in neurite growth and astroglia activation.

    PubMed

    Heine, Claudia; Sygnecka, Katja; Franke, Heike

    2016-05-01

    The mammalian nervous system is a complex, functional network of neurons, consisting of local and long-range connections. Neuronal growth is highly coordinated by a variety of extracellular and intracellular signaling molecules. Purines turned out to be an essential component of these processes. Here, we review the current knowledge about the involvement of purinergic signaling in the regulation of neuronal development. We particularly focus on its role in neuritogenesis: the formation and extension of neurites. In the course of maturation mammals generally lose their ability to regenerate the central nervous system (CNS) e.g. after traumatic brain injury; although, spontaneous regeneration still occurs in the peripheral nervous system (PNS). Thus, it is crucial to translate the knowledge about CNS development and PNS regeneration into novel approaches to enable neurons of the mature CNS to regenerate. In this context we give a general overview of growth-inhibitory and growth-stimulatory factors and mechanisms involved in neurite growth. With regard to neuronal growth, astrocytes are an important cell population. They provide structural and metabolic support to neurons and actively participate in brain signaling. Astrocytes respond to injury with beneficial or detrimental reactions with regard to axonal growth. In this review we present the current knowledge of purines in these glial functions. Moreover, we discuss organotypic brain slice co-cultures as a model which retains neuron-glia interactions, and further presents at once a model for CNS development and regeneration. In summary, the purinergic system is a pivotal factor in neuronal development and in the response to injury. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:26498067

  9. Dynamics Explorer twin spacecraft under evaluation tests

    NASA Technical Reports Server (NTRS)

    Redmond, C.

    1981-01-01

    The Dynamics Explorer A and B satellites designed to explore the interactive processes occuring between the magnetosphere and Earth's ionosphere, upper atmosphere, and plasmasphere are described. Effects of these interactions, satellite orbits, data collecting antennas, solar power systems, axes, configurations, and Earth based command, control and data display systems are mentioned.

  10. Dynamics of Turing Patterns under Spatiotemporal Forcing

    NASA Astrophysics Data System (ADS)

    Rüdiger, S.; Míguez, D. G.; Muñuzuri, A. P.; Sagués, F.; Casademunt, J.

    2003-03-01

    We study, both theoretically and experimentally, the dynamical response of Turing patterns to a spatiotemporal forcing in the form of a traveling-wave modulation of a control parameter. We show that from strictly spatial resonance, it is possible to induce new, generic dynamical behaviors, including temporally modulated traveling waves and localized traveling solitonlike solutions. The latter make contact with the soliton solutions of Coullet [

    Phys. Rev. Lett.PRLTAO0031-9007 56, 724 (1986)
    ] and generalize them. The stability diagram for the different propagating modes in the Lengyel-Epstein model is determined numerically. Direct observations of the predicted solutions in experiments carried out with light modulations in the photosensitive chlorine dioxide-iodine-malonic acid reaction are also reported.

  11. Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.

    PubMed

    Civiero, Laura; Cirnaru, Maria Daniela; Beilina, Alexandra; Rodella, Umberto; Russo, Isabella; Belluzzi, Elisa; Lobbestael, Evy; Reyniers, Lauran; Hondhamuni, Geshanthi; Lewis, Patrick A; Van den Haute, Chris; Baekelandt, Veerle; Bandopadhyay, Rina; Bubacco, Luigi; Piccoli, Giovanni; Cookson, Mark R; Taymans, Jean-Marc; Greggio, Elisa

    2015-12-01

    Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21-activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2 mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2-mediated pathophysiology. We propose p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease (PD). In health, PAK6 regulates neurite complexity in the brain and LRRK2 is required for its function, (a) whereas PAK6 is aberrantly activated in LRRK2-linked PD brain (b) suggesting that LRRK2 toxicity is mediated by PAK6. PMID:26375402

  12. Fluid flow dynamics under location uncertainty

    NASA Astrophysics Data System (ADS)

    Mémin, Etienne

    2014-03-01

    We present a derivation of a stochastic model of Navier Stokes equations that relies on a decomposition of the velocity fields into a differentiable drift component and a time uncorrelated uncertainty random term. This type of decomposition is reminiscent in spirit to the classical Reynolds decomposition. However, the random velocity fluctuations considered here are not differentiable with respect to time, and they must be handled through stochastic calculus. The dynamics associated with the differentiable drift component is derived from a stochastic version of the Reynolds transport theorem. It includes in its general form an uncertainty dependent "subgrid" bulk formula that cannot be immediately related to the usual Boussinesq eddy viscosity assumption constructed from thermal molecular agitation analogy. This formulation, emerging from uncertainties on the fluid parcels location, explains with another viewpoint some subgrid eddy diffusion models currently used in computational fluid dynamics or in geophysical sciences and paves the way for new large-scales flow modelling. We finally describe an applications of our formalism to the derivation of stochastic versions of the Shallow water equations or to the definition of reduced order dynamical systems.

  13. Nucleosome repositioning underlies dynamic gene expression.

    PubMed

    Nocetti, Nicolas; Whitehouse, Iestyn

    2016-03-15

    Nucleosome repositioning at gene promoters is a fundamental aspect of the regulation of gene expression. However, the extent to which nucleosome repositioning is used within eukaryotic genomes is poorly understood. Here we report a comprehensive analysis of nucleosome positions as budding yeast transit through an ultradian cycle in which expression of >50% of all genes is highly synchronized. We present evidence of extensive nucleosome repositioning at thousands of gene promoters as genes are activated and repressed. During activation, nucleosomes are relocated to allow sites of general transcription factor binding and transcription initiation to become accessible. The extent of nucleosome shifting is closely related to the dynamic range of gene transcription and generally related to DNA sequence properties and use of the coactivators TFIID or SAGA. However, dynamic gene expression is not limited to SAGA-regulated promoters and is an inherent feature of most genes. While nucleosome repositioning occurs pervasively, we found that a class of genes required for growth experience acute nucleosome shifting as cells enter the cell cycle. Significantly, our data identify that the ATP-dependent chromatin-remodeling enzyme Snf2 plays a fundamental role in nucleosome repositioning and the expression of growth genes. We also reveal that nucleosome organization changes extensively in concert with phases of the cell cycle, with large, regularly spaced nucleosome arrays being established in mitosis. Collectively, our data and analysis provide a framework for understanding nucleosome dynamics in relation to fundamental DNA-dependent transactions. PMID:26966245

  14. Dynamics of Hyperbranched Polymers under Confinement

    NASA Astrophysics Data System (ADS)

    Androulaki, Krystallenia; Chrissopoulou, Kiriaki; Anastasiadis, Spiros H.; Prevosto, Daniele; Labardi, Massimiliano

    2015-03-01

    The effect of severe confinement on the dynamics of three different generations of hyperbranched polyesters (Boltorns) is investigated by Dielectric Spectroscopy. The polymers are intercalated within the galleries of natural Na+-MMT, thus, forming 1nm polymer films confined between solid walls. The Tg's of the polymers determined by DSC show a clear dependence on the generation whereas the transition is completely suppressed when all the polymer chains are intercalated. The dynamic investigation of the bulk polymers reveals two sub-Tg processes, with similar behavior for the three polymers with the segmental relaxation observed above the Tg of each. For the nanocomposites, where all polymers are severely confined, the dynamics show significant differences compared to that of the bulk polymers. The sub-Tg processes are similar for the three generations but significantly faster and with weaker temperature dependence than those in the bulk. The segmental process appears at temperatures below the bulk polymer Tg, it exhibits an Arrhenius temperature dependence and shows differences for the three generations. A slow process that appears at higher temperatures is due to interfacial polarization. Co-financed by the EU and Greek funds through the Operational Program ``Education and Lifelong Learning'' of the NSRF-Research Funding Program: THALES-Investing in knowledge society through the Eur. Social Fund (MIS 377278) and COST Action MP0902-COINAPO.

  15. Preparation of embryonic retinal explants to study CNS neurite growth.

    PubMed

    Hanea, Sonia T; Shanmugalingam, Ushananthini; Fournier, Alyson E; Smith, Patrice D

    2016-05-01

    This protocol outlines the preparation of embryonic mouse retinal explants, which provides an effective technique to analyze neurite outgrowth in central nervous system (CNS) neurons. This validated ex vivo system, which displays limited neuronal death, is highly reproducible and particularly amenable to manipulation. Our previously published studies involving embryonic chick or adult mouse retinal explants were instrumental in the preparation of this protocol; aspects of these previous techniques were combined, adopted and optimized. This protocol thus permits more efficient analysis of neurite growth. Briefly, the retina is dissected from the embryonic mouse eye using precise techniques that take into account the small size of the embryonic eye. The approach applied ensures that the retinal ganglion cell (RGC) layer faces the adhesion substrate on coated cover slips. Neurite growth is clear, well-delineated and readily quantifiable. These retinal explants can therefore be used to examine the neurite growth effects elicited by potential therapeutic agents. PMID:27072342

  16. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

    PubMed

    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. PMID:27255817

  17. Natural neural projection dynamics underlying social behavior

    PubMed Central

    Gunaydin, Lisa A.; Grosenick, Logan; Finkelstein, Joel C.; Kauvar, Isaac V.; Fenno, Lief E.; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J.; Airan, Raag D.; Zalocusky, Kelly A.; Tye, Kay M.; Anikeeva, Polina; Malenka, Robert C.; Deisseroth, Karl

    2014-01-01

    Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics. PMID:24949967

  18. Dynamics of evolutionary radiation under ecological neutrality.

    PubMed

    Suzuki, Takanori Mizuno; Chiba, Satoshi

    2016-10-01

    The most spectacular phenomenon of evolutionary biota is the explosive radiation that occurs in depauperate environments in which there are fewer competitors and predators, such as oceanic islands and crater lakes. Adaptation to divergent niches has been proposed as a major cause for this accelerated speciation. Here, we show that neutral mutation, genetic drift, and neutral community dynamics are sufficient to lead to radiation. In addition, these processes yield overshooting dynamics with a decline in species richness in the later stages of radiation. We constructed an ecologically neutral model for a community on an island with a uniform environment. For the speciation process, we introduced a null model with minimal assumptions in which the incompatibilities between alleles in different lineages evolve by a random accumulation of mutations via genetic drift. Our simulations showed that the speciation rate, extinction rate and genetic variation of the species colonizing the island rapidly increased to a sharp peak followed by a decrease that approached zero. Because the extinction rate reached a peak later than the speciation rate, the species richness initially increased, but declined in the later stage, exhibiting "overshooting". The highest species richness was found for the largest island at the largest initial population size. Accordingly, speciation is accelerated by the large population size of depauperate biota, whereas it is decelerated with increasing species richness from the decreasing population size. Explosive radiation without ecological divergence can occur in depauperate environments via neutral stochastic processes. PMID:27297287

  19. Natural neural projection dynamics underlying social behavior.

    PubMed

    Gunaydin, Lisa A; Grosenick, Logan; Finkelstein, Joel C; Kauvar, Isaac V; Fenno, Lief E; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J; Airan, Raag D; Zalocusky, Kelly A; Tye, Kay M; Anikeeva, Polina; Malenka, Robert C; Deisseroth, Karl

    2014-06-19

    Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. PMID:24949967

  20. Dynamics of active cellular response under stress

    NASA Astrophysics Data System (ADS)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  1. Serum- and substratum-dependent modulation of neuritic growth.

    PubMed

    Skaper, S D; Selak, I; Varon, S

    1983-01-01

    Explants of embryonic day 8 (E8) chicken dorsal root ganglia (DRG) have been cultured with medium containing serum or the serum-free supplement N1 on one of three substrata: collagen, polyornithine (PORN), or PORN exposed to a polyornithine-binding neurite-promoting factor (PNPF-PORN). Replicate cultures were maintained with or without nerve growth factor (NGF). NGF elicited its classical neuritic outgrowth on all three substrata in serum-containing or serum-free medium. In the absence of NGF, however, a gradation of increasing neurite growth was seen with: PNPF-PORN greater than PORN greater than collagen. This response occurred in both media. In addition, the neuritic halo in each instance was markedly more developed in the absence of serum, especially on PNPF-PORN. Nonneuronal behaviors reflected both serum and substratum influences: thus, nonneuronal outgrowth consisted mainly of flat cells with serum and collagen, was nonexistent with serum and PORN or PNPF-PORN, and involved mostly Schwann-like scattered cells in the absence of serum on any one substratum. The serum-dependent behaviors of ganglionic neurites were examined further with explants from chicken E11 sympathetic ganglia. A single substratum was used (PORN), without exogenous trophic factor. Neurite outgrowth was depressed by the presence of fetal calf serum, thus supporting the generality of this phenomenon. Lastly, PC12 cells, a clonal line of rat pheochromocytoma, will grow neurites in the presence of NGF after 48 hr in serum-free, but not serum-containing media. Addition of serum to serum-free cultures at this time results in the rapid and complete retraction of neurites. PMID:6876195

  2. Human central nervous system myelin inhibits neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Roder, J; Roach, A; Lozano, A

    1996-05-13

    In vitro and animal studies have identified molecules in mammalian CNS myelin which inhibit neuritic extension and which may be responsible, at least in part, for the lack of axonal regeneration after injury in the injured brain, optic nerve and spinal cord. To determine whether such inhibitory activity may be present in human CNS myelin, we used a bioassay to characterize neurite outgrowth on this substrate. Human CNS myelin strongly inhibited neuritic outgrowth from newborn rat dorsal root ganglion neurons and NG-108-15 cells, a neuroblastoma-glioma hybrid cell line. Similar but less potent inhibitory activity was identified in human gray matter. The CNS myelin inhibition of neuritic outgrowth appeared to be dependent on direct contact between the myelin substrate and neurites. The inhibitory activity in human CNS myelin closely resembled that described in adult rodents. Inhibition of neurite growth by human CNS myelin in this in vitro bioassay mirrors the lack of regeneration in vivo and can be used as a model to develop strategies designed to enhance axonal regeneration and neural recovery. PMID:8782892

  3. Space Station flexible dynamics under plume impingement

    NASA Astrophysics Data System (ADS)

    Williams, Trevor

    1993-12-01

    Assembly of the Space Station requires numerous construction flights by the Space Shuttle. A particularly challenging problem is that of control of each intermediate station configuration when the shuttle orbiter is approaching it to deliver the next component. The necessary braking maneuvers cause orbiter thruster plumes to impinge on the station, especially its solar arrays. This in turn causes both overall attitude errors and excitation of flexible-body vibration modes. These plume loads are predicted to lead to CMG saturation during the approach of the orbiter to the SC-5 station configuration, necessitating the use of the station RCS jets for desaturation. They are also expected to lead to significant excitation of solar array vibrations. It is therefore of great practical importance to investigate the effects of plume loads on the flexible dynamics of station configuration SC-5 as accurately as possible. However, this system possesses a great many flexible modes (89 below 5 rad/s), making analysis time-consuming and complicated. Model reduction techniques can be used to overcome this problem, reducing the system model to one which retains only the significant dynamics, i.e. those which are strongly excited by the control inputs or plume disturbance forces and which strongly couple with the measured outputs. The particular technique to be used in this study is the subsystem balancing approach which was previously developed by the present investigator. This method is very efficient computationally. Furthermore, it gives accurate results even for the difficult case where the structure has many closed-spaced natural frequencies, when standard modal truncation can give misleading results. Station configuration SC-5 is a good example of such a structure.

  4. Space Station flexible dynamics under plume impingement

    NASA Technical Reports Server (NTRS)

    Williams, Trevor

    1993-01-01

    Assembly of the Space Station requires numerous construction flights by the Space Shuttle. A particularly challenging problem is that of control of each intermediate station configuration when the shuttle orbiter is approaching it to deliver the next component. The necessary braking maneuvers cause orbiter thruster plumes to impinge on the station, especially its solar arrays. This in turn causes both overall attitude errors and excitation of flexible-body vibration modes. These plume loads are predicted to lead to CMG saturation during the approach of the orbiter to the SC-5 station configuration, necessitating the use of the station RCS jets for desaturation. They are also expected to lead to significant excitation of solar array vibrations. It is therefore of great practical importance to investigate the effects of plume loads on the flexible dynamics of station configuration SC-5 as accurately as possible. However, this system possesses a great many flexible modes (89 below 5 rad/s), making analysis time-consuming and complicated. Model reduction techniques can be used to overcome this problem, reducing the system model to one which retains only the significant dynamics, i.e. those which are strongly excited by the control inputs or plume disturbance forces and which strongly couple with the measured outputs. The particular technique to be used in this study is the subsystem balancing approach which was previously developed by the present investigator. This method is very efficient computationally. Furthermore, it gives accurate results even for the difficult case where the structure has many closed-spaced natural frequencies, when standard modal truncation can give misleading results. Station configuration SC-5 is a good example of such a structure.

  5. Neural Dynamics Underlying Event-Related Potentials

    NASA Technical Reports Server (NTRS)

    Shah, Ankoor S.; Bressler, Steven L.; Knuth, Kevin H.; Ding, Ming-Zhou; Mehta, Ashesh D.; Ulbert, Istvan; Schroeder, Charles E.

    2003-01-01

    There are two opposing hypotheses about the brain mechanisms underlying sensory event-related potentials (ERPs). One holds that sensory ERPs are generated by phase resetting of ongoing electroencephalographic (EEG) activity, and the other that they result from signal averaging of stimulus-evoked neural responses. We tested several contrasting predictions of these hypotheses by direct intracortical analysis of neural activity in monkeys. Our findings clearly demonstrate evoked response contributions to the sensory ERP in the monkey, and they suggest the likelihood that a mixed (Evoked/Phase Resetting) model may account for the generation of scalp ERPs in humans.

  6. Granular dynamics under shear with deformable boundaries

    NASA Astrophysics Data System (ADS)

    Geller, Drew; Backhaus, Scott; Ecke, Robert

    2015-03-01

    Granular materials under shear develop complex patterns of stress as the result of granular positional rearrangements under an applied load. We consider the simple planar shear of a quasi two-dimensional granular material consisting of bi-dispersed nylon cylinders confined between deformable boundaries. The aspect ratio of the gap width to total system length is 50, and the ratio of particle diameter to gap width is about 10. This system, designed to model a long earthquake fault with long range elastic coupling through the plates, is an interesting model system for understanding effective granular friction because it essentially self tunes to the jamming condition owing to the hardness of the grains relative to that of the boundary material, a ratio of more than 1000 in elastic moduli. We measure the differential strain displacements of the plates, the inhomogeneous stress distribution in the plates, the positions and angular orientations of the individual grains, and the shear force, all as functions of the applied normal stress. There is significant stick-slip motion in this system that we quantify through our quantitative measurements of both the boundary and the grain motion, resulting in a good characterization of this sheared 2D hard sphere system.

  7. Concentration Dynamics of Nanoparticles under a Periodic Light Field

    NASA Astrophysics Data System (ADS)

    Livashvili, A. I.; Krishtop, V. V.; Bryukhanova, T. N.; Kostina, G. V.

    Using a system of heat and mass balance equations, we study the dynamics of the concentration of nanoparticles in nanofluids under the influence of a periodic light field. The review will be based on the thermal convection.

  8. Pulsed electromagnetic fields potentiate neurite outgrowth in the dopaminergic MN9D cell line.

    PubMed

    Lekhraj, Rukmani; Cynamon, Deborah E; DeLuca, Stephanie E; Taub, Eric S; Pilla, Arthur A; Casper, Diana

    2014-06-01

    Pulsed electromagnetic fields (PEMF) exert biological effects and are in clinical use to facilitate bone repair and wound healing. Research has demonstrated that PEMF can induce signaling molecules and growth factors, molecules that play important roles in neuronal differentiation. Here, we tested the effects of a low-amplitude, nonthermal, pulsed radiofrequency signal on morphological neuronal differentiation in MN9D, a dopaminergic cell line. Cells were plated in medium with 10% fetal calf serum. After 1 day, medium was replaced with serum-containing medium, serum-free medium, or medium supplemented with dibutyryl cyclic adenosine monophosphate (Bt2 cAMP), a cAMP analog known to induce neurite outgrowth. Cultures were divided into groups and treated with PEMF signals for either 30 min per day or continuously for 15 min every hour for 3 days. Both serum withdrawal and Bt2 cAMP significantly increased neurite length. PEMF treatment similarly increased neurite length under both serum-free and serum-supplemented conditions, although to a lesser degree in the presence of serum, when continuous treatments had greater effects. PEMF signals also increased cell body width, indicating neuronal maturation, and decreased protein content, suggesting that this treatment was antimitotic, an effect reversed by the inhibitor of cAMP formation dideoxyadenosine. Bt2 cAMP and PEMF effects were not additive, suggesting that neurite elongation was achieved through a common pathway. PEMF signals increased cAMP levels from 3 to 5 hr after treatment, supporting this mechanism of action. Although neuritogenesis is considered a developmental process, it may also represent the plasticity required to form and maintain synaptic connections throughout life. PMID:24523147

  9. Dynamical evolution of sand ripples under water.

    PubMed

    Stegner, A; Wesfreid, J E

    1999-10-01

    We have performed an experimental study on the evolution of sand ripples formed under the action of an oscillatory flow. An annular sand-water cell was used in order to investigate a wide range of parameters. The sand ripples follow an irreversible condensation mechanism from small to large wavelength until a final state is reached. The wavelength and the shape of these stable sand patterns are mainly governed by the fluid displacement and the static angle of the granular media. A strong hysteresis affects the evolution of steep ripples. When the acceleration of the sand bed reaches a critical value, the final pattern is modified by the superficial fluidization of the sand layer. PMID:11970264

  10. FGF inhibits neurite outgrowth over monolayers of astrocytes and fibroblasts expressing transfected cell adhesion molecules.

    PubMed

    Williams, E J; Mittal, B; Walsh, F S; Doherty, P

    1995-11-01

    We have cultured cerebellar neurons on monolayers of cortical astrocytes in control medium or medium containing recombinant basic fibroblast growth factor (FGF). FGF was found to inhibit neurite outgrowth, with a significant effect seen at 0.5 ng/ml and a maximal effect at 10 ng/ml. FGF increased the production of arachidonic acid (AA) in cerebellar neurons, and when added directly to cultures or generated endogenously via activation of phospholipase A2 using melittin, this second messenger could mimic the inhibitory effect of FGF. FGF and AA could also specifically inhibit neurite outgrowth stimulated by three cell adhesion molecules (NCAM, N-cadherin and L1) expressed in transfected fibroblasts, or in the case of L1 bound to a tissue culture substratum. These data demonstrate that, in certain cellular contexts, FGF can act as an inhibitory cue for axonal growth and that arachidonic acid is the second messenger responsible for this activity. We discuss the possibility that arachidonic acid inhibits neurite outgrowth by desensitising the second messenger pathway underlying neuronal responsiveness to cell adhesion molecules. PMID:8586663

  11. Neuroprotective effects of ginsenoside Rb1 on hippocampal neuronal injury and neurite outgrowth

    PubMed Central

    Liu, Juan; He, Jing; Huang, Liang; Dou, Ling; Wu, Shuang; Yuan, Qionglan

    2014-01-01

    Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta (25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta (25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta (25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta (25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta (25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling. PMID:25206916

  12. Stochastic population dynamics under resource constraints

    NASA Astrophysics Data System (ADS)

    Gavane, Ajinkya S.; Nigam, Rahul

    2016-06-01

    This paper investigates the population growth of a certain species in which every generation reproduces thrice over a period of predefined time, under certain constraints of resources needed for survival of population. We study the survival period of a species by randomizing the reproduction probabilities within a window at same predefined ages and the resources are being produced by the working force of the population at a variable rate. This randomness in the reproduction rate makes the population growth stochastic in nature and one cannot predict the exact form of evolution. Hence we study the growth by running simulations for such a population and taking an ensemble averaged over 500 to 5000 such simulations as per the need. While the population reproduces in a stochastic manner, we have implemented a constraint on the amount of resources available for the population. This is important to make the simulations more realistic. The rate of resource production then is tuned to find the rate which suits the survival of the species. We also compute the mean life time of the species corresponding to different resource production rate. Study for these outcomes in the parameter space defined by the reproduction probabilities and rate of resource production is carried out.

  13. Blurred Star Image Processing for Star Sensors under Dynamic Conditions

    PubMed Central

    Zhang, Weina; Quan, Wei; Guo, Lei

    2012-01-01

    The precision of star point location is significant to identify the star map and to acquire the aircraft attitude for star sensors. Under dynamic conditions, star images are not only corrupted by various noises, but also blurred due to the angular rate of the star sensor. According to different angular rates under dynamic conditions, a novel method is proposed in this article, which includes a denoising method based on adaptive wavelet threshold and a restoration method based on the large angular rate. The adaptive threshold is adopted for denoising the star image when the angular rate is in the dynamic range. Then, the mathematical model of motion blur is deduced so as to restore the blurred star map due to large angular rate. Simulation results validate the effectiveness of the proposed method, which is suitable for blurred star image processing and practical for attitude determination of satellites under dynamic conditions. PMID:22778666

  14. Crack tip blunting and cleavage under dynamic conditions

    NASA Astrophysics Data System (ADS)

    Rajan, V. P.; Curtin, W. A.

    2016-05-01

    In structural materials with both brittle and ductile phases, cracks often initiate within the brittle phase and propagate dynamically towards the ductile phase. The macroscale, quasistatic toughness of the material thus depends on the outcome of this microscale, dynamic process. Indeed, dynamics has been hypothesized to suppress dislocation emission, which may explain the occurrence of brittle transgranular fracture in mild steels at low temperatures (Lin et al., 1987). Here, crack tip blunting and cleavage under dynamic conditions are explored using continuum mechanics and molecular dynamics simulations. The focus is on two questions: (1) whether dynamics can affect the energy barriers for dislocation emission and cleavage, and (2) what happens in the dynamic "overloaded" situation, in which both processes are energetically possible. In either case, dynamics may shift the balance between brittle cleavage and ductile blunting, thereby affecting the intrinsic ductility of the material. To explore these effects in simulation, a novel interatomic potential is used for which the intrinsic ductility is tunable, and a novel simulation technique is employed, termed as a "dynamic cleavage test", in which cracks can be run dynamically at a prescribed energy release rate into a material. Both theory and simulation reveal, however, that the intrinsic ductility of a material is unaffected by dynamics. The energy barrier to dislocation emission appears to be identical in quasi-static and dynamic conditions, and, in the overloaded situation, ductile crack tip behavior ultimately prevails since a single emission event can blunt and arrest the crack, preventing further cleavage. Thus, dynamics cannot embrittle a ductile material, and the origin of brittle failure in certain alloys (e.g., mild steels) appears unrelated to dynamic effects at the crack tip.

  15. Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons

    PubMed Central

    Koch, J C; Bitow, F; Haack, J; d'Hedouville, Z; Zhang, J-N; Tönges, L; Michel, U; Oliveira, L M A; Jovin, T M; Liman, J; Tatenhorst, L; Bähr, M; Lingor, P

    2015-01-01

    Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (αSyn-WT), a protein associated with PD, and its mutant variants αSyn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of αSyn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of αSyn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with αSyn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all αSyn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by αSyn-WT and -A53T but not by αSyn-A30P. Correspondingly, colocalization of αSyn and the autophagy marker LC3 was reduced for αSyn-A30P compared with the other αSyn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both αSyn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that αSyn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered. PMID:26158517

  16. Shoc2/Sur8 Protein Regulates Neurite Outgrowth

    PubMed Central

    Leon, Gonzalo; Sanchez-Ruiloba, Lucia; Perez-Rodriguez, Andrea; Gragera, Teresa; Martinez, Natalia; Hernandez, Silvia; Anta, Berta; Calero, Olga; Garcia-Dominguez, Carlota A.; Dura, Lara M.; Peña-Jimenez, Daniel; Castro, Judit; Zarich, Natasha; Sanchez-Gomez, Pilar; Calero, Miguel; Iglesias, Teresa; Oliva, Jose L.; Rojas, Jose M.

    2014-01-01

    The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth. PMID:25514808

  17. Decentralized optimal control of dynamical systems under uncertainty

    NASA Astrophysics Data System (ADS)

    Gabasov, R.; Dmitruk, N. M.; Kirillova, F. M.

    2011-07-01

    The problem of optimal control of a group of interconnected dynamical objects under uncertainty is considered. The cases are examined in which the centralized control of the group of objects is impossible due to delay in the channel for information exchange between the group members. Optimal self-control algorithms in real time for each dynamical object are proposed. Various types of a priori and current information about the behavior of the group members and about uncertainties in the system are examined. The proposed methods supplement the earlier developed optimal control methods for an individual dynamical system and the methods of decentralized optimal control of deterministic objects. The results are illustrated with examples.

  18. Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation.

    PubMed

    Bica, Laura; Liddell, Jeffrey R; Donnelly, Paul S; Duncan, Clare; Caragounis, Aphrodite; Volitakis, Irene; Paterson, Brett M; Cappai, Roberto; Grubman, Alexandra; Camakaris, James; Crouch, Peter J; White, Anthony R

    2014-01-01

    Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato)-copper complex, Cu(II)(gtsm) on neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal-related cultures. We found that Cu(II)(gtsm) induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato) complex, Cu(II)(atsm), but at a higher concentration. Induction of neurite elongation by Cu(II)(gtsm) was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II)(gtsm) treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II)(gtsm) inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor) resulted in analogous elongation of neurites compared to 50 nM Cu(II)(gtsm), suggesting a potential link between Cu(II)(gtsm)-mediated phosphatase inhibition and neurogenerative outcomes. PMID:24587210

  19. Material Stiffness Effects on Neurite Alignment to Photopolymerized Micropatterns

    PubMed Central

    2015-01-01

    The ability to direct neurite growth into a close proximity of stimulating elements of a neural prosthesis, such as a retinal or cochlear implant (CI), may enhance device performance and overcome current spatial signal resolution barriers. In this work, spiral ganglion neurons (SGNs), which are the target neurons to be stimulated by CIs, were cultured on photopolymerized micropatterns with varied matrix stiffnesses to determine the effect of rigidity on neurite alignment to physical cues. Micropatterns were generated on methacrylate thin film surfaces in a simple, rapid photopolymerization step by photomasking the prepolymer formulation with parallel line–space gratings. Two methacrylate series, a nonpolar HMA-co-HDDMA series and a polar PEGDMA-co-EGDMA series, with significantly different surface wetting properties were evaluated. Equivalent pattern periodicity was maintained across each methacrylate series based on photomask band spacing, and the feature amplitude was tuned to a depth of 2 μm amplitude for all compositions using the temporal control afforded by the UV curing methodology. The surface morphology was characterized by scanning electron microscopy and white light interferometry. All micropatterned films adsorb similar amounts of laminin from solution, and no significant difference in SGN survival was observed when the substrate compositions were compared. SGN neurite alignment significantly increases with increasing material modulus for both methacrylate series. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa). The ability to understand neurite response to engineered physical cues and mechanical properties such as matrix stiffness will allow the development of advanced biomaterials that direct de novo neurite growth to address the spatial signal resolution limitations of current neural prosthetics. PMID:25211120

  20. Material stiffness effects on neurite alignment to photopolymerized micropatterns.

    PubMed

    Tuft, Bradley W; Zhang, Lichun; Xu, Linjing; Hangartner, Austin; Leigh, Braden; Hansen, Marlan R; Guymon, C Allan

    2014-10-13

    The ability to direct neurite growth into a close proximity of stimulating elements of a neural prosthesis, such as a retinal or cochlear implant (CI), may enhance device performance and overcome current spatial signal resolution barriers. In this work, spiral ganglion neurons (SGNs), which are the target neurons to be stimulated by CIs, were cultured on photopolymerized micropatterns with varied matrix stiffnesses to determine the effect of rigidity on neurite alignment to physical cues. Micropatterns were generated on methacrylate thin film surfaces in a simple, rapid photopolymerization step by photomasking the prepolymer formulation with parallel line-space gratings. Two methacrylate series, a nonpolar HMA-co-HDDMA series and a polar PEGDMA-co-EGDMA series, with significantly different surface wetting properties were evaluated. Equivalent pattern periodicity was maintained across each methacrylate series based on photomask band spacing, and the feature amplitude was tuned to a depth of 2 μm amplitude for all compositions using the temporal control afforded by the UV curing methodology. The surface morphology was characterized by scanning electron microscopy and white light interferometry. All micropatterned films adsorb similar amounts of laminin from solution, and no significant difference in SGN survival was observed when the substrate compositions were compared. SGN neurite alignment significantly increases with increasing material modulus for both methacrylate series. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa). The ability to understand neurite response to engineered physical cues and mechanical properties such as matrix stiffness will allow the development of advanced biomaterials that direct de novo neurite growth to address the spatial signal resolution limitations of current neural prosthetics. PMID:25211120

  1. The role of calsyntenin-3 in dystrophic neurite formation in Alzheimer's disease brain.

    PubMed

    Uchida, Yoko; Gomi, Fujiya

    2016-03-01

    β-Amyloid (Aβ) oligomers may play an important role in the early pathogenesis of Alzheimer's disease: cognitive impairment caused by synaptic dysfunction. Dystrophic neurites surrounding Aβ plaques, another pathological feature of Alzheimer's disease, are plaque-associated neuritic alterations preceding the appearance of synaptic loss. In the present review, we focus on the mechanism of dystrophic neurite formation by Aß oligomers, and discuss the neurotoxic role of Aβ-induced calsyntenin-3 in mediating dystrophic neurite formation. PMID:27018282

  2. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

    PubMed

    Gan, Guangming; Lv, Huihui; Xie, Wei

    2014-01-01

    In Drosophila, ventral nerve cord (VNC) occupies most of the larval central nervous system (CNS). However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV) neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV) neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV) neurites have mixed vesicles and some T-bar structures; Large vesicle (LV) neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P) phase, they have mitochondria, microtubules or big dark vesicles in the second (S) phase, and they contain immature synaptic features in the third (T) phase. The subsequent bifurcate (B) phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M) phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo development

  3. Laminar stream of detergents for subcellular neurite damage in a microfluidic device: a simple tool for the study of neuroregeneration

    NASA Astrophysics Data System (ADS)

    Lee, Chang Young; Romanova, Elena V.; Sweedler, Jonathan V.

    2013-06-01

    Objective. The regeneration and repair of damaged neuronal networks is a difficult process to study in vivo, leading to the development of multiple in vitro models and techniques for studying nerve injury. Here we describe an approach for generating a well-defined subcellular neurite injury in a microfluidic device. Approach. A defined laminar stream of sodium dodecyl sulfate (SDS) was used to damage selected portions of neurites of individual neurons. The somata and neurites unaffected by the SDS stream remained viable, thereby enabling the study of neuronal regeneration. Main results. By using well-characterized neurons from Aplysia californica cultured in vitro, we demonstrate that our approach is useful in creating neurite damage, investigating neurotrophic factors, and monitoring somata migration during regeneration. Supplementing the culture medium with acetylcholinesterase (AChE) or Aplysia hemolymph facilitated the regeneration of the peptidergic Aplysia neurons within 72 h, with longer (p < 0.05) and more branched (p < 0.05) neurites than in the control medium. After the neurons were transected, their somata migrated; intriguingly, for the control cultures, the migration direction was always away from the injury site (7/7). In the supplemented cultures, the number decreased to 6/8 in AChE and 4/8 in hemolymph, with reduced migration distances in both cases. Significance. The SDS transection approach is simple and inexpensive, yet provides flexibility in studying neuroregeneration, particularly when it is important to make sure there are no retrograde signals from the distal segments affecting regeneration. Neurons are known to not only be under tension but also balanced in terms of force, and the balance is obviously disrupted by transection. Our experimental platform, verified with Aplysia, can be extended to mammalian systems, and help us gain insight into the role that neurotrophic factors and mechanical tension play during neuronal regeneration.

  4. Progression of damage and fracture in composites under dynamic loading

    NASA Technical Reports Server (NTRS)

    Minnetyan, Levon; Murthy, Pappu L. N.; Chamis, Christos C.

    1990-01-01

    A new computational simulation method is presented to evaluate the dynamic aspects of composite structural response and durability that have not been simulated previously. Composite structural behavior under any loading condition, geometry, composite system, laminate configuration, and boundary conditions can now be simulated. Structural degradation, delamination, fracture, and damage propagation are included in the simulation. An angle-plied composite plate structure under normal impact loading is used as an example to demonstrate the versatility of the simulation method.

  5. Organic Photovoltaics and Bioelectrodes Providing Electrical Stimulation for PC12 Cell Differentiation and Neurite Outgrowth.

    PubMed

    Hsiao, Yu-Sheng; Liao, Yan-Hao; Chen, Huan-Lin; Chen, Peilin; Chen, Fang-Chung

    2016-04-13

    Current bioelectronic medicines for neurological therapies generally involve treatment with a bioelectronic system comprising a power supply unit and a bioelectrode device. Further integration of wireless and self-powered units is of practical importance for implantable bioelectronics. In this study, we developed biocompatible organic photovoltaics (OPVs) for serving as wireless electrical power supply units that can be operated under illumination with near-infrared (NIR) light, and organic bioelectronic interface (OBEI) electrode devices as neural stimulation electrodes. The OPV/OBEI integrated system is capable to provide electrical stimulation (ES) as a means of enhancing neuron-like PC12 cell differentiation and neurite outgrowth. For the OPV design, we prepared devices incorporating two photoactive material systems--β-carotene/N,N'-dioctyl-3,4,9,10-perylenedicarboximide (β-carotene/PTCDI-C8) and poly(3-hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM)--that exhibited open circuit voltages of 0.11 and 0.49 V, respectively, under NIR light LED (NLED) illumination. Then, we connected OBEI devices with different electrode gaps, incorporating biocompatible poly(hydroxymethylated-3,4-ethylenedioxythiophene), to OPVs to precisely tailor the direct current electric field conditions during the culturing of PC12 cells. This NIR light-driven OPV/OBEI system could be engineered to provide tunable control over the electric field (from 220 to 980 mV mm(-1)) to promote 64% enhancement in the neurite length, direct the neurite orientation on chips, or both. The OPV/OBEI integrated systems under NIR illumination appear to function as effective power delivery platforms that should meet the requirements for wirelessly offering medical ES to a portion of the nervous system; they might also be a key technology for the development of next-generation implantable bioelectronics. PMID:26999636

  6. Dynamic Tensile Strength of Coal under Dry and Saturated Conditions

    NASA Astrophysics Data System (ADS)

    Zhao, Yixin; Liu, Shimin; Jiang, Yaodong; Wang, Kai; Huang, Yaqiong

    2016-05-01

    The tensile failure characterization of dry and saturated coals under different impact loading conditions was experimentally investigated using a Split Hopkinson pressure bar. Indirect dynamic Brazilian disc tension tests for coals were carried out. The indirect tensile strengths for different bedding angles under different impact velocities, strain rates and loading rates are analyzed and discussed. A high-speed high-resolution digital camera was employed to capture and record the dynamic failure process of coal specimens. Based on the experimental results, it was found that the saturated specimens have stronger loading rate dependence than the dry specimens. The bedding angle has a smaller effect on the dynamic indirect tensile strength compared to the impact velocity. Both shear and tensile failures were observed in the tested coal specimens. Saturated coal specimens have higher indirect tensile strength than dry ones.

  7. Deciphering and prediction of plant dynamics under field conditions.

    PubMed

    Izawa, Takeshi

    2015-04-01

    Elucidation of plant dynamics under fluctuating natural environments is a challenging goal in plant physiology. Recently, using a computer statistics integrating a series of transcriptome data of field-grown rice leaves during an entire crop season and several corresponding environmental data such as solar radiation and ambient temperature, most parts of transcriptome have been modeled. This reveals the detailed contributions of developmental timing, circadian clocks and each environmental factor to transcriptome dynamics in the field and can predict transcriptome dynamics under given environments. Furthermore, some traits such as flowering time in natural environments have been shown to be predicted by mathematical models based on gene-networks parameterized with data obtained in the laboratory, and phenology models refined by knowledge of molecular genetics. New molecular physiology is beginning in plant science. PMID:25706440

  8. Dynamic MRI of the TMJ under physical load

    PubMed Central

    Hopfgartner, A J; Tymofiyeva, O; Ehses, P; Rottner, K; Boldt, J; Richter, E-J; Jakob, P M

    2013-01-01

    Objectives: The objective of this study was to examine the kinematics of structures of the temporomandibular joint (TMJ) under physiological load while masticating. Methods: Radial MRI was chosen as a fast imaging method to dynamically capture the motions of the joint’s anatomy. The technique included a golden ratio-based increment angle and a sliding window reconstruction. The measurements were performed on 22 subjects with and without deformation/displacement of the intra-articular disc while they were biting on a cooled caramel toffee. Results: The reconstructed dynamic images provided sufficient information about the size and localization of the disc as well as the change of the intra-articular distance with and without loading. Conclusions: The feasibility of the golden ratio-based radial MRI technique to dynamically capture the anatomy of the TMJ under physical load was demonstrated in this initial study. PMID:23975114

  9. Protein displacements under external forces: An atomistic Langevin dynamics approach

    NASA Astrophysics Data System (ADS)

    Gnandt, David; Utz, Nadine; Blumen, Alexander; Koslowski, Thorsten

    2009-02-01

    We present a fully atomistic Langevin dynamics approach as a method to simulate biopolymers under external forces. In the harmonic regime, this approach permits the computation of the long-term dynamics using only the eigenvalues and eigenvectors of the Hessian matrix of second derivatives. We apply this scheme to identify polymorphs of model proteins by their mechanical response fingerprint, and we relate the averaged dynamics of proteins to their biological functionality, with the ion channel gramicidin A, a phosphorylase, and neuropeptide Y as examples. In an environment akin to dilute solutions, even small proteins show relaxation times up to 50 ns. Atomically resolved Langevin dynamics computations have been performed for the stretched gramicidin A ion channel.

  10. Soil Moisture Dynamics under Corn, Soybean, and Perennial Kura Clover

    NASA Astrophysics Data System (ADS)

    Ochsner, T.; Venterea, R. T.

    2009-12-01

    Rising global food and energy consumption call for increased agricultural production, whereas rising concerns for environmental quality call for farming systems with more favorable environmental impacts. Improved understanding and management of plant-soil water interactions are central to meeting these twin challenges. The objective of this research was to compare the temporal dynamics of soil moisture under contrasting cropping systems suited for the Midwestern region of the United States. Precipitation, infiltration, drainage, evapotranspiration, soil water storage, and freeze/thaw processes were measured hourly for three years in field plots of continuous corn (Zea mays L.), corn/soybean [Glycine max (L.) Merr.] rotation, and perennial kura clover (Trifolium ambiguum M. Bieb.) in southeastern Minnesota. The evapotranspiration from the perennial clover most closely followed the temporal dynamics of precipitation, resulting in deep drainage which was reduced up to 50% relative to the annual crops. Soil moisture utilization also continued later into the fall under the clover than under the annual crops. In the annual cropping systems, crop sequence influenced the soil moisture dynamics. Soybean following corn and continuous corn exhibited evapotranspiration which was 80 mm less than and deep drainage which was 80 mm greater than that of corn following soybean. These differences occurred primarily during the spring and were associated with differences in early season plant growth between the systems. In the summer, soil moisture depletion was up to 30 mm greater under corn than soybean. Crop residue also played an important role in the soil moisture dynamics. Higher amounts of residue were associated with reduced soil freezing. This presentation will highlight key aspects of the soil moisture dynamics for these contrasting cropping systems across temporal scales ranging from hours to years. The links between soil moisture dynamics, crop yields, and nutrient leaching

  11. Myelin from MAG-deficient mice is a strong inhibitor of neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Li, C; Roder, J; Lozano, A

    1996-03-22

    Myelin-associated glycoprotein (MAG) has potent neurite outgrowth inhibitory activity in vitro. To assess the importance of MAG in the neurite outgrowth inhibitory activity in CNS myelin, we used an in vitro bioassay to characterize neurite growth on CNS myelin derived from mice carrying a null mutation of the MAG gene. Myelin proteins from MAG-deficient mice inhibited neurite outgrowth to a similar degree to the wild-type CNS myelin. These results suggest that CNS myelin molecules other than MAG exert strong inhibitory effects on the growth of neurites. PMID:8724661

  12. Fetal calf serum-mediated inhibition of neurite growth from ciliary ganglion neurons in vitro.

    PubMed

    Davis, G E; Skaper, S D; Manthorpe, M; Moonen, G; Varon, S

    1984-01-01

    Embryonic chick ciliary ganglion (CG) neurons cultured in fetal calf serum-containing medium have been previously reported to extend neurites on polyornithine (PORN) substrata precoated with a neurite-promoting factor (PNPF) from rat schwannoma-conditioned medium. On PORN substrata alone, however, no neuritic growth occurred. This was interpreted as evidence that PORN was an incompetent substratum for ciliary neuritic growth. In this study, we now find that an untreated PORN substratum allows neuritic growth in serum-free defined medium. When PNPF was added to PORN, a more rapid and extensive neuritic response occurred. After 5 hr of culture, a 60% neuritic response occurred on PNPF/PORN, whereas no neurons initiated neurites until 10-12 hr on PORN. The inhibitory effect of fetal calf serum noted above on PORN could be obtained in part by pretreating the substratum with serum for 1 hr. Maximal inhibitory effects in the PORN pretreatment were achieved after 30 min and were not further improved by treatments up to 4 hr. Bovine serum albumin was also found to inhibit neurite growth on PORN to about 60% of the inhibition obtained by an equivalent amount of serum protein. Fetal calf serum was shown to cause a 15% reduction in the percentage of neurons bearing neurites after its addition to 18-hr serum-free PORN cultures and to cause statistically significant reductions in neurite lengths measured 2 hr later. PMID:6481819

  13. Thermomechanical behavior of EUV pellicle under dynamic exposure conditions

    NASA Astrophysics Data System (ADS)

    Goldfarb, Dario L.; Bloomfield, Max O.; Colburn, Matthew

    2016-03-01

    The utilization of EUV pellicles as protective layers for EUV masks requires the use of refractory materials that can tolerate large temperature excursions due to the non-negligible absorption of EUV radiation during exposure. Additionally, the mechanical stress induced on the EUV pellicle by the thermal load is dependent on the thermal expansion of the material which can be responsible for transient wrinkling. In this study, an ultrathin (20 nm), free-standing membrane based on silicon nitride is utilized as a learning vehicle to understand the material requirements of EUV pellicles under dynamic exposure conditions that are typical of commercial EUV scanners. First, the nanoscale radiative properties (emissivity) and thermo-mechanical failure temperature of the dielectric film under vacuum conditions are experimentally investigated utilizing a pulsed ArF (193 nm) probing laser. The silicon nitride membrane is found to be marginally compatible with an equivalent 80W EUV source power under steady state illumination conditions. Next, the thermal behavior of the EUV pellicle under dynamic exposure conditions is simulated using a finite element solver. The transient temperature profile and stress distribution across the membrane under stationary state conditions are extracted for an equivalent 60W EUV power source and the pellicle wrinkling due to heating and consequent impact on CD uniformity is estimated. The present work provides a generalized methodology to anticipate the thermal response of a EUV pellicle under realistic exposure conditions.

  14. A subset of chicken statoacoustic ganglion neurites are repelled by Slit1 and Slit2

    PubMed Central

    Battisti, Andrea C.; Fantetti, Kristen N.; Moyers, Bryan A.; Fekete, Donna M.

    2014-01-01

    Mechanosensory hair cells in the chicken inner ear are innervated by bipolar afferent neurons of the statoacoustic ganglion (SAG). During development, individual SAG neurons project their peripheral process to only one of eight distinct sensory organs. These neuronal subtypes may respond differently to guidance cues as they explore the periphery in search of their target. Previous gene expression data suggested that Slit repellants might channel SAG neurites into the sensory primordia, based on the presence of robo transcripts in the neurons and the confinement of slit transcripts to the flanks of the prosensory domains. This led to the prediction that excess Slit proteins would impede the outgrowth of SAG neurites. As predicted, axonal projections to the primordium of the anterior crista were reduced 2-3 days after electroporation of either slit1 or slit2 expression plasmids into the anterior pole of the otocyst on embryonic day 3 (E3). The posterior crista afferents, which normally grow through and adjacent to slit expression domains as they are navigating towards the posterior pole of the otocyst, did not show Slit responsiveness when similarly challenged by ectopic delivery of slit to their targets. The sensitivity to ectopic Slits shown by the anterior crista afferents was more the exception than the rule: responsiveness to Slits was not observed when the entire E4 SAG was challenged with Slits for 40 hours in vitro. The corona of neurites emanating from SAG explants was unaffected by the presence of purified human Slit1 and Slit2 in the culture medium. Reduced axon outgrowth from E8 olfactory bulbs cultured under similar conditions for 24 hours confirmed bioactivity of purified human Slits on chicken neurons. In summary, differential sensitivity to Slit repellents may influence the directional outgrowth of otic axons toward either the anterior or posterior otocyst. PMID:24456709

  15. A method of measuring dynamic strain under electromagnetic forming conditions.

    PubMed

    Chen, Jinling; Xi, Xuekui; Wang, Sijun; Lu, Jun; Guo, Chenglong; Wang, Wenquan; Liu, Enke; Wang, Wenhong; Liu, Lin; Wu, Guangheng

    2016-04-01

    Dynamic strain measurement is rather important for the characterization of mechanical behaviors in electromagnetic forming process, but it has been hindered by high strain rate and serious electromagnetic interference for years. In this work, a simple and effective strain measuring technique for physical and mechanical behavior studies in the electromagnetic forming process has been developed. High resolution (∼5 ppm) of strain curves of a budging aluminum tube in pulsed electromagnetic field has been successfully measured using this technique. The measured strain rate is about 10(5) s(-1), which depends on the discharging conditions, nearly one order of magnitude of higher than that under conventional split Hopkins pressure bar loading conditions (∼10(4) s(-1)). It has been found that the dynamic fracture toughness of an aluminum alloy is significantly enhanced during the electromagnetic forming, which explains why the formability is much larger under electromagnetic forging conditions in comparison with conventional forging processes. PMID:27131683

  16. A method of measuring dynamic strain under electromagnetic forming conditions

    NASA Astrophysics Data System (ADS)

    Chen, Jinling; Xi, Xuekui; Wang, Sijun; Lu, Jun; Guo, Chenglong; Wang, Wenquan; Liu, Enke; Wang, Wenhong; Liu, Lin; Wu, Guangheng

    2016-04-01

    Dynamic strain measurement is rather important for the characterization of mechanical behaviors in electromagnetic forming process, but it has been hindered by high strain rate and serious electromagnetic interference for years. In this work, a simple and effective strain measuring technique for physical and mechanical behavior studies in the electromagnetic forming process has been developed. High resolution (˜5 ppm) of strain curves of a budging aluminum tube in pulsed electromagnetic field has been successfully measured using this technique. The measured strain rate is about 105 s-1, which depends on the discharging conditions, nearly one order of magnitude of higher than that under conventional split Hopkins pressure bar loading conditions (˜104 s-1). It has been found that the dynamic fracture toughness of an aluminum alloy is significantly enhanced during the electromagnetic forming, which explains why the formability is much larger under electromagnetic forging conditions in comparison with conventional forging processes.

  17. Phase separated microstructure and dynamics of polyurethane elastomers under strain

    NASA Astrophysics Data System (ADS)

    Iacob, Ciprian; Padsalgikar, Ajay; Runt, James

    The molecular mobility of polyurethane elastomers is of the utmost importance in establishing physical properties for uses ranging from automotive tires and shoe soles to more sophisticated aerospace and biomedical applications. In many of these applications, chain dynamics as well as mechanical properties under external stresses/strains are critical for determining ultimate performance. In order to develop a more complete understanding of their mechanical response, we explored the effect of uniaxial strain on the phase separated microstructure and molecular dynamics of the elastomers. We utilize X-ray scattering to investigate soft segment and hard domain orientation, and broadband dielectric spectroscopy for interrogation of the dynamics. Uniaxial deformation is found to significantly perturb the phase-separated microstructure and chain orientation, and results in a considerable slowing down of the dynamics of the elastomers. Attenuated total reflectance Fourier transform infrared spectroscopy measurements of the polyurethanes under uniaxial deformation are also employed and the results are quantitatively correlated with mechanical tensile tests and the degree of phase separation from small-angle X-ray scattering measurements.

  18. Dynamical weakening by fluidization under oscillatory viscous flows

    NASA Astrophysics Data System (ADS)

    Valverde, Jose Manuel

    2015-11-01

    Dynamical weakening of granular materials plays a critical role on diverse geological events such as seismic faulting and landslides. A common feature in the dynamics of these processes is the development of fluid-solid relative flows, which could lead to fluidization by hydrodynamic viscous stresses. This work is focused on analyzing hydrodynamic fluidization under oscillatory viscous flows as a possible driving mechanism for dynamical weakening. The theoretical estimations and experimental observations presented and reviewed suggest that fluidization can be greatly promoted by oscillatory viscous flows, which are usually expected in geological events involving vibration of granular materials in viscous fluids. Fluidization under oscillatory viscous flows may occur at not excessively large vibration velocities of fine particles in gases or relatively larger particles in liquids or supercritical fluids. In particular, the enhancement of fluidization by high-frequency vibrations would be a powerful mechanism to promote dynamical weakening of fine powders in dry fault gouges, failure of liquid- (or supercritical fluid-) saturated beds, and sustained fluidization of pyroclastic flows and lahars.

  19. Dynamic control of a bistable wing under aerodynamic loading

    NASA Astrophysics Data System (ADS)

    Bilgen, Onur; Arrieta, Andres F.; Friswell, Michael I.; Hagedorn, Peter

    2013-02-01

    The aerodynamic evaluation of a dynamic control technique applied to a bistable unsymmetrical cross-ply composite plate with surface bonded piezoelectric actuators is presented. The plate is clamped on one end to form a low-aspect-ratio wing. A previously proposed dynamic control method, utilizing bending resonance in different stable equilibrium positions, is used to induce snap-through between the two equilibrium states. Compared to quasi-static actuation, driving the bistable plate near resonance using surface bonded piezoelectric materials requires, theoretically, a lower peak excitation voltage to achieve snap-through. First, a set of extensive wind tunnel experiments are conducted on the passive bistable wing to understand the change in the dynamic behavior under various aerodynamic conditions. The passive wing demonstrated sufficient bending stiffness to sustain its shape under aerodynamic loading while preserving the desired bistable behavior. Next, by the use of the resonant control technique, the plate is turned into an effectively monostable structure, or alternatively, both stable equilibrium positions can be reached actively from the other stable equilibrium. Dynamic forward and reverse snap-through is demonstrated in the wind tunnel which shows both the effectiveness of the piezoelectric actuation as well as the load carrying capability of both states of the bistable wing.

  20. MiR-93 Targeting EphA4 Promotes Neurite Outgrowth from Spinal Cord Neurons.

    PubMed

    Chen, Xiaogang; Yang, Huilin; Zhou, Xiaoqing; Zhang, Lin; Lu, Xiaoqing

    2016-04-01

    The failure of neurite outgrowth in the adult mammalian spinal cord injury is thought to be attributed to the intrinsic growth ability of mature neurons. Ephrin/Eph system is a major growth regulator of many axonal guidance processes. EphA4 is expressed specifically in traumatic central nervous system (CNS) and dynamically regulate target gene expression, suggesting that it may be associated with neural regeneration. Here, we found an alteration in temporal expression of miR-93 following a contusive spinal cord injury (SCI) in adult rats. The messenger RNA (mRNA) expression level of miR-93 was upregulated and the protein expression levels of EphA4, p-Ephexin, and active RhoA were all decreased in traumatic spinal cord relative to those with an intact spinal cord. Infection of cultured spinal cord neurons (SCNs) with miR-93 mimic led to neuronal growth promotion and decreased levels of EphA4, p-Ephexin, and active RhoA protein expression. Dual-luciferase reporter assay confirmed that miR-93 bound to the three prime untranslated region (3' UTR) of EphA4 and inhibited the expression of EphA4 mRNA. These findings provide evidence that miR-93 inhibits EphA4 expression, decreased EphA4 expression could promote neurite outgrowth in SCNs due to reduced levels of p-Ephexin and active RhoA. PMID:26798048

  1. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    SciTech Connect

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-11-01

    production and neuronal cell death. • BBR activates IGF-1/Akt/GSK-3β signaling under normal and high glucose conditions. • BBR enhances HO-1 and NGF expression through stimulating Nrf2 translocation. • BBR promotes neurite outgrowth through Nrf2-dependent pathway.

  2. Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons

    PubMed Central

    Huang, Liang; Liu, Li-feng; Liu, Juan; Dou, Ling; Wang, Ge-ying; Liu, Xiao-qing; Yuan, Qiong-lan

    2016-01-01

    Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25–35 (Aβ25–35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25–35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25–35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25–35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25–35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387

  3. Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.

    PubMed

    Huang, Liang; Liu, Li-Feng; Liu, Juan; Dou, Ling; Wang, Ge-Ying; Liu, Xiao-Qing; Yuan, Qiong-Lan

    2016-02-01

    Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aβ25-35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25-35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25-35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25-35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25-35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387

  4. Relation of dynamic parameters of brick masonry fragment at fracture under static and dynamic loading

    NASA Astrophysics Data System (ADS)

    Kopanitsa, D. G.; Useinov, E. S.

    2015-01-01

    The article shows the results of experimental analysis of brick masonry fragments under static and dynamic loading. The measurements of fractures and natural vibration frequencies of samples have been carried out in the course of tests. It has been shown that at appearance of inelastic deformations and cracks, there is a change in natural vibration frequencies, received from the analysis of the corresponding spectra. Comparison of results of experiments of brick masonry fragments, received under action of static and dynamic loads has been carried out.

  5. Alignment and Stiffening of Liquid Crystal Elastomers under Dynamic Compression

    NASA Astrophysics Data System (ADS)

    Agrawal, Aditya; Patra, Prabir; Ajayan, Pulickel; Chapman, Walter; Verduzco, Rafael

    2013-03-01

    Biological tissues have the remarkable ability to remodel and repair in response to disease, injury, and mechanical stresses, a phenomenon known ``functional adaptation'' or ``remodeling''. Herein, we report similar behavior in polydomain liquid crystal elastomers. Liquid crystal elastomers dramatically increase in stiffness by up to 90 % under low-amplitude, repetitive (dynamic) compression. By studying a systematic series of materials, we demonstrate that the stiffness increase is directly influenced by the liquid crystal content of the elastomers, the presence of a nematic liquid crystal phase and the use of a dynamic as opposed to static deformation. Through a combination of rheological measurements, polarizing optical microscopy and 2-D X-ray diffraction, we demonstrate that self-stiffening arises due to rotations of the nematic director in response to dynamic compression, and show that the behavior is consistent with the theory for nematic rubber elasticity. Previous work with liquid crystal elastomers has focused primarily on `soft elastic' deformations at large strains, but our findings indicate rich behavior at previously overlooked low-strain, dynamic deformations.

  6. General polytropic dynamic cylinder under self-gravity

    NASA Astrophysics Data System (ADS)

    Lou, Yu-Qing

    2015-12-01

    We explore self-similar hydrodynamics of general polytropic (GP) and isothermal cylinders of infinite length with axial uniformity and axisymmetry under self-gravity. Specific entropy conservation along streamlines serves as the dynamic equation of state. Together with possible axial flows, we construct classes of analytic and semi-analytic non-linear dynamic solutions for either cylindrical expansion or contraction radially by solving cylindrical Lane-Emden equations. By extensive numerical explorations and fitting trials in reference to asymptotes derived for large index n, we infer several convenient empirical formulae for characteristic solution properties of cylindrical Lane-Emden equations in terms of n values. A new type of asymptotic solutions for small x is also derived in the Appendix. These analyses offer hints for self-similar dynamic evolution of molecular filaments for forming protostars, brown dwarfs and gaseous planets and of large-scale gaseous arms or starburst rings in (barred) spiral galaxies for forming young massive stars. Such dynamic solutions are necessary starting background for further three-dimensional (in)stability analysis of various modes. They may be used to initialize numerical simulations and serve as important benchmarks for testing numerical codes. Such GP formalism can be further generalized to include magnetic field for a GP magnetohydrodynamic analysis.

  7. Automated quantification of neurite outgrowth orientation distributions on patterned surfaces

    NASA Astrophysics Data System (ADS)

    Payne, Matthew; Wang, Dadong; Sinclair, Catriona M.; Kapsa, Robert M. I.; Quigley, Anita F.; Wallace, Gordon G.; Razal, Joselito M.; Baughman, Ray H.; Münch, Gerald; Vallotton, Pascal

    2014-08-01

    Objective. We have developed an image analysis methodology for quantifying the anisotropy of neuronal projections on patterned substrates. Approach. Our method is based on the fitting of smoothing splines to the digital traces produced using a non-maximum suppression technique. This enables precise estimates of the local tangents uniformly along the neurite length, and leads to unbiased orientation distributions suitable for objectively assessing the anisotropy induced by tailored surfaces. Main results. In our application, we demonstrate that carbon nanotubes arrayed in parallel bundles over gold surfaces induce a considerable neurite anisotropy; a result which is relevant for regenerative medicine. Significance. Our pipeline is generally applicable to the study of fibrous materials on 2D surfaces and should also find applications in the study of DNA, microtubules, and other polymeric materials.

  8. Dynamic Reasoning under Probabilistic Uncertainty in the Semantic Web

    NASA Astrophysics Data System (ADS)

    Chen, Limin; Shi, Zhongzhi

    Towards a full realization of the Semantic Web as a source of processable information and services, we extend description logic ALCO@ to admit dynamic reasoning under probabilistic uncertainty. In our formalism, the crisp knowledge is encoded in DL-knowledgebase, and the uncertain one is in conditional constraints; atomic actions are represented in terms of their preconditions (conditional constraints) and effects (possibly negated ALCO@-assertions involving only atomic concepts). We also summarize some reasoning tasks in the new formalism and provide algorithms for them. This work is strictly related to the practical need of DL-based reasoning in the Semantic Web and is much closer than the prior formalisms to a practical formalism in the Web setting full of uncertain information and dynamic processing.

  9. Dynamic performance of dissipative dielectric elastomers under alternating mechanical load

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Chen, Hualing; Sheng, Junjie; Liu, Lei; Wang, Yongquan; Jia, Shuhai

    2014-07-01

    This paper presents a theoretical study about the effect of dissipation on the dynamic performance of a dielectric elastomer membrane subject to a combination of mechanical load and voltage. The thermodynamic dissipative model is given and the equation of motion is deduced by a free energy method. It is found that when the applied mechanical load and voltage are static, the membrane may reach a state of equilibrium after the viscoelastic relaxation. When the voltage is static but the mechanical load is sinusoidal, the membrane will resonate at multiple frequencies. The study result indicates that the viscoelasticity can reduce the natural frequency and increase the mean stretch of the dielectric elastomer. After the power source is cut off, the effect of current leakage on dynamic performance under alternating mechanical load is that the natural frequency increases and the mean stretch reduces.

  10. Modeling the Underlying Dynamics of the Spread of Crime

    PubMed Central

    McMillon, David; Simon, Carl P.; Morenoff, Jeffrey

    2014-01-01

    The spread of crime is a complex, dynamic process that calls for a systems level approach. Here, we build and analyze a series of dynamical systems models of the spread of crime, imprisonment and recidivism, using only abstract transition parameters. To find the general patterns among these parameters—patterns that are independent of the underlying particulars—we compute analytic expressions for the equilibria and for the tipping points between high-crime and low-crime equilibria in these models. We use these expressions to examine, in particular, the effects of longer prison terms and of increased incarceration rates on the prevalence of crime, with a follow-up analysis on the effects of a Three-Strike Policy. PMID:24694545

  11. Fluid displacement under elastic membranes: Dynamics and interfacial instabilities

    NASA Astrophysics Data System (ADS)

    Al-Housseiny, Talal; Christov, Ivan; Juel, Anne; Stone, Howard

    2012-11-01

    The spreading of fluids under a flexible membrane is a feature of many systems such as the lateral intrusion of magma under a terrestrial crust, or when blood spreads underneath the skin giving the signature color of bruises. In this work, we investigate the displacement of a viscous fluid by a gas underneath an elastic membrane. We consider a radial Hele-Shaw cell where the upper plate is an elastic sheet. The dynamics of the interface between the injected gas and the displaced fluid are fundamentally modified by the presence of an elastic boundary, which leads to the suppression of viscous fingering below a critical flow rate. We demonstrate theoretically the mechanism of suppression and find the corresponding critical flow rate. In addition, we study the dynamics of a stable (circular) interface propagating underneath an elastic membrane and derive the scaling laws for both the position of the interface and the shape of the elastic membrane. Our theoretical findings agree very well with the experimental results of D. Pihler-Puzovic et al. (PRL 2012). T. T. Al-Housseiny is supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-0646086.

  12. Electromechanical fatigue in IPMC under dynamic energy harvesting conditions

    NASA Astrophysics Data System (ADS)

    Krishnaswamy, Arvind; Roy Mahapatra, D.

    2011-04-01

    Ionic polymer-metal composites (IPMCs) are an interesting subset of smart, multi-functional materials that have shown promises in energy conversion technologies. Being electromechanically coupled, IPMCs can function as dynamic actuators and sensors, transducers for energy conversion and harvesting, as well as artificial muscles for medical and industrial applications. Like all natural materials, even IPMCs undergo fatigue under dynamic load conditions. Here, we investigate the electromechanical fatigue induced in the IPMCs due to the application of cyclic mechanical bending deformation under hydrodynamic energy harvesting condition. Considering the viscoelastic nature of the IPMC, we employ an analytical approach to modeling electromechanical fatigue primarily under the cyclic stresses induced in the membrane. The polymer-metal composite undergoes cyclic softening throughout the fatigue life without attaining a saturated state of charge migration. However, it results in (1) degradation of electromechanical performance; (2) nucleation and growth of microscopic cracks in the metal electrodes; (3) delamination of metal electrodes at the polymer-electrode interface. To understand these processes, we employ a phenomenological approach based on experimentally measured relaxation properties of the IPMC membrane. Electromechanical performance improves significantly with self-healing like properties for a certain range of relaxation time. This is due to reorientation of the backbone polymer chains which eventually leads to a regenerative process with increased charge transport.

  13. Neurite outgrowth on fluorinated polyimide film micropatterned by ion irradiation

    NASA Astrophysics Data System (ADS)

    Okuyama, Y.; Sato, M.; Nagaoka, S.; Kawakami, H.; Suzuki, Y.; Iwaki, M.

    2003-05-01

    In this study, we investigated neurite outgrowth on a fluorinated polyimide film micropatterned by ion irradiation. We used the fluorinated polyimide because of its excellent thermal and mechanical properties and biocompatibility. Rattus norvegicus chromaphin (PC12) cells were used for in vitro studies. The polyimide films were irradiated with He +, Ne + or Kr + at 1 × 10 14 ions/cm 2 using an ion-beam mask. The lines in the mask were 120 and 160 μm wide and 120-160 μm apart. PC12 cells were selectively adhered on the polyimide film micropatterned by Kr +-irradiation. However, the neurite length on the film irradiated by Kr + was shorter than that determined in the film irradiated by He +. On the other hand, neurite outgrowth on the polyimide film micropatterned by He +-irradiation was at least 100 μm in length. This initial study indicated the enhanced outgrowth of PC12 cells on the fluorinated polyimide film micropatterned by ion irradiation.

  14. Stimulation of neurite outgrowth using positively charged hydrogels

    PubMed Central

    Dadsetan, Mahrokh; Knight, Andrew M.; Lu, Lichun; Windebank, Anthony J.; Yaszemski, Michael J.

    2009-01-01

    Autologous nerve grafts are currently the best option for the treatment of segmental peripheral nerve defects. However, autografts have several drawbacks including size mismatch and loss of sensation in the donor nerve’s sensory distribution. In this work, we have investigated the development of a synthetic hydrogel that contains positive charge for use as a substrate for nerve cell attachment and neurite outgrowth in culture. We have demonstrated that modification of oligo-(polyethylene glycol) fumarate (OPF) with a positively charged monomer improves primary sensory rat neuron attachment and differentiation in a dose-dependent manner. Positively charged hydrogels also supported attachment of dorsal root ganglion (DRG) explants that contain sensory neurons, Schwann cells and neuronal support cells. Furthermore, charged hydrogels were analyzed for the appearance of myelinated structures in a co-culture containing DRG neurons and Schwann cells. DRGs and Schwann cells remained viable on charged hydrogels for a time period of three weeks and neurites extended from the DRGs. Sudan black staining revealed that neurites emerging from DRGs were accompanied by migrating Schwann cells. These findings suggest that charged OPF hydrogels are capable of sustaining both primary nerve cells and the neural support cells that are critical for regeneration. PMID:19427689

  15. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Matsumoto, K.; Sato, C.; Naka, Y.; Whitby, R.; Shimizu, N.

    2010-03-01

    Low concentrations (0.11-1.7 µg ml - 1) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 µg ml - 1 CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  16. Metastasis suppressor 1 regulates neurite outgrowth in primary neuron cultures.

    PubMed

    Yu, Juan; Lin, Shuyun; Wang, Mei; Liang, Lijun; Zou, Zijiao; Zhou, Xinfeng; Wang, Meichi; Chen, Ping; Wang, Ying

    2016-10-01

    Metastasis suppressor 1 (MTSS1) or missing in metastasis (MIM) is an actin- and membrane-binding protein with tumor suppressor functions. MTSS1 is important for cell morphology, motility, metastasis. The role of MTSS1 in cell morphology has been widely investigated in non-neuronal tissues; however the role of MTSS1 in neurite outgrowth remains unclear. Here we investigated the effect of MTSS1 on neurite outgrowth in primary cerebellar granule and hippocampal neurons of mouse. We found that overexpression of MTSS1 in cerebellar granule neurons significantly enhanced dendrite elaboration but inhibited axon elongation. This phenotype was significantly reduced by deletion of the Wiskott-Aldrich homology 2 (WH2) motif and point mutation in the insulin receptor substrate p53 (IRSp53) and MIM/MTSS1 homology (IMD) domain. Furthermore, inhibition of Rac1 activity or blocking of phosphatidyl inositol phosphates (PIPs) signaling decreased the effect of MTSS1 markedly. In accordance with the over-expression data, knockdown of MTSS1 in cerebellar granule neurons could increase the axon length but decrease the dendrite length and the number of dendrites. In addition, MTSS1 knock down in embryonic hippocampal neurons suppressed neurite branching and reduced dendrite length. Our findings have demonstrated that MTSS1 modulates neuronal morphology, possibly through a Rac1-PIPs signaling pathway. PMID:27401056

  17. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    PubMed Central

    Li, Yi-sheng; Qin, Li-xia; Liu, Jie; Xia, Wei-liang; Li, Jian-ping; Shen, Hai-lian; Gao, Wei-Qiang

    2016-01-01

    GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases. PMID:27127481

  18. Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

    PubMed Central

    Vernes, Sonja C.; Oliver, Peter L.; Spiteri, Elizabeth; Lockstone, Helen E.; Puliyadi, Rathi; Taylor, Jennifer M.; Ho, Joses; Mombereau, Cedric; Brewer, Ariel; Lowy, Ernesto; Nicod, Jérôme; Groszer, Matthias; Baban, Dilair; Sahgal, Natasha; Cazier, Jean-Baptiste; Ragoussis, Jiannis; Davies, Kay E.; Geschwind, Daniel H.; Fisher, Simon E.

    2011-01-01

    Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections. PMID:21765815

  19. Marginally subcritical dynamics explain enhanced stimulus discriminability under attention

    PubMed Central

    Tomen, Nergis; Rotermund, David; Ernst, Udo

    2014-01-01

    Recent experimental and theoretical work has established the hypothesis that cortical neurons operate close to a critical state which describes a phase transition from chaotic to ordered dynamics. Critical dynamics are suggested to optimize several aspects of neuronal information processing. However, although critical dynamics have been demonstrated in recordings of spontaneously active cortical neurons, little is known about how these dynamics are affected by task-dependent changes in neuronal activity when the cortex is engaged in stimulus processing. Here we explore this question in the context of cortical information processing modulated by selective visual attention. In particular, we focus on recent findings that local field potentials (LFPs) in macaque area V4 demonstrate an increase in γ-band synchrony and a simultaneous enhancement of object representation with attention. We reproduce these results using a model of integrate-and-fire neurons where attention increases synchrony by enhancing the efficacy of recurrent interactions. In the phase space spanned by excitatory and inhibitory coupling strengths, we identify critical points and regions of enhanced discriminability. Furthermore, we quantify encoding capacity using information entropy. We find a rapid enhancement of stimulus discriminability with the emergence of synchrony in the network. Strikingly, only a narrow region in the phase space, at the transition from subcritical to supercritical dynamics, supports the experimentally observed discriminability increase. At the supercritical border of this transition region, information entropy decreases drastically as synchrony sets in. At the subcritical border, entropy is maximized under the assumption of a coarse observation scale. Our results suggest that cortical networks operate at such near-critical states, allowing minimal attentional modulations of network excitability to substantially augment stimulus representation in the LFPs. PMID:25202240

  20. Dynamics of lysozyme and its hydration water under electric field

    SciTech Connect

    Favi, Pelagie M; Zhang, Qiu; O'Neill, Hugh Michael; Mamontov, Eugene; Omar Diallo, Souleymane; Palmer, Jeremy

    2014-01-01

    The effects of static electric field on the dynamics of lysozyme and its hydration water have been investigated by means of incoherent quasi-elastic neutron scattering (QENS). Measurements were performed on lysozyme samples, hydrated respectively with heavy water (D2O) to capture the protein dynamics, and with light water (H2O), to probe the dynamics of the hydration shell, in the temperature range from 210 < T < 260 K. The hydration fraction in both cases was about 0.38 gram of water per gram of dry protein. The field strengths investigated were respectively 0 kV/mm and 2 kV/mm ( 2 106 V/m) for the protein hydrated with D2O and 0 kV and 1 kV/mm for the H2O-hydrated counterpart. While the overall internal protons dynamics of the protein appears to be unaffected by the application of electric field up to 2 kV/mm, likely due to the stronger intra-molecular interactions, there is also no appreciable quantitative enhancement of the diffusive dynamics of the hydration water, as would be anticipated based on our recent observations in water confined in silica pores under field values of 2.5 kV/mm. This may be due to the difference in surface interactions between water and the two adsorption hosts (silica and protein), or to the existence of a critical threshold field value Ec 2 3 kV/mm for increased molecular diffusion, for which electrical breakdown is a limitation for our sample.

  1. Wave packet dynamics under effect of a pulsed electric field

    NASA Astrophysics Data System (ADS)

    da Silva, A. R. C. B.; de Moura, F. A. B. F.; Dias, W. S.

    2016-06-01

    We studied the dynamics of an electron in a crystalline one-dimensional model under effect of a time-dependent Gaussian field. The time evolution of an initially Gaussian wave packet it was obtained through the numerical solution of the time-dependent Schrödinger equation. Our analysis consists of computing the electronic centroid as well as the mean square displacement. We observe that the electrical pulse is able to promote a special kind of displacement along the chain. We demonstrated a direct relation between the group velocity of the wave packet and the applied electrical pulses. We compare those numerical calculations with a semi-classical approach.

  2. Barothropic relaxing media under pressure perturbations: Nonlinear dynamics

    NASA Astrophysics Data System (ADS)

    Kuetche, Victor K.

    2015-12-01

    In this paper, we delve into the dynamics of a barothropic relaxing medium under pressure perturbations originating from blast wave explosions in the milieu. Analyzing the problem within the viewpoint of the Lyakhov formalism of geodynamic systems, we derive a complex-valued nonlinear evolution equation which models the wave propagation of the pressure perturbations within the barothropic medium. As a result, we find that the previous system can be circularly polarized and hence support traveling rotating pressure excitations which profiles strongly depend upon their angular momenta. In the wake of these results, we address some physical implications of the findings alongside their potential applications.

  3. Dynamics of propagating front into sand ripples under regular waves.

    PubMed

    Lebunetel-Levaslot, J; Jarno-Druaux, A; Ezersky, A B; Marin, F

    2010-09-01

    The results of an experimental study of pattern formation on sandy bottom under the action of regular harmonic surface waves are reported. It is found that two modes of pattern formation occur: sand ripples form uniformly on the whole bottom or from localized nucleation sites. In the second regime, the ripples appear in isolated regions (patches) increasing in size, and front propagation speed is measured. A simple dynamical model based on the Ginzburg-Landau equation is proposed to explain the characteristics of patches. PMID:21230122

  4. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons.

    PubMed

    Murayama, Chiaki; Watanabe, Shimpei; Nakamura, Motokazu; Norimoto, Hisayoshi

    2015-01-01

    Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation. PMID:26287150

  5. Simulating spin dynamics in organic solids under heteronuclear decoupling.

    PubMed

    Frantsuzov, Ilya; Ernst, Matthias; Brown, Steven P; Hodgkinson, Paul

    2015-09-01

    Although considerable progress has been made in simulating the dynamics of multiple coupled nuclear spins, predicting the evolution of nuclear magnetisation in the presence of radio-frequency decoupling remains challenging. We use exact numerical simulations of the spin dynamics under simultaneous magic-angle spinning and RF decoupling to determine the extent to which numerical simulations can be used to predict the experimental performance of heteronuclear decoupling for the CW, TPPM and XiX sequences, using the methylene group of glycine as a model system. The signal decay times are shown to be strongly dependent on the largest spin order simulated. Unexpectedly large differences are observed between the dynamics with and without spin echoes. Qualitative trends are well reproduced by modestly sized spin system simulations, and the effects of finite spin-system size can, in favourable cases, be mitigated by extrapolation. Quantitative prediction of the behaviour in complex parameter spaces is found, however, to be very challenging, suggesting that there are significant limits to the role of numerical simulations in RF decoupling problems, even when specialist techniques, such as state-space restriction, are used. PMID:26073419

  6. Dynamics of dendritic polymers in the bulk and under confinement

    SciTech Connect

    Chrissopoulou, K.; Fotiadou, S.; Androulaki, K.; Anastasiadis, S. H.; Tanis, I.; Karatasos, K.; Prevosto, D.; Labardi, M.; Frick, B.

    2014-05-15

    The structure and dynamics of a hyperbranched polyesteramide (Hybrane® S 1200) polymer and its nanocomposites with natural montmorillonite (Na{sup +}-MMT) are investigated by XRD, DSC, QENS, DS and Molecular Dynamics (MD) simulation. In bulk, the energy-resolved elastically scattered intensity from the polymer exhibits two relaxation steps, one attributed to sub-T{sub g} motions and one observed at temperatures above the glass transition, T{sub g}. The QENS spectra measured over the complete temperature range are consistent with the elastic measurements and can be correlated to the results emerging from the detailed description afforded by the atomistic simulations, which predict the existence of three relaxation processes. Moreover, dielectric spectroscopy shows the sub- T{sub g} beta process as well as the segmental relaxation. For the nanocomposites, XRD reveals an intercalated structure for all hybrids with distinct interlayer distances due to polymer chains residing within the galleries of the Na{sup +}-MMT. The polymer chains confined within the galleries show similarities in the behavior with that of the polymer in the bulk for temperatures below the bulk polymer T{sub g}, whereas they exhibit frozen dynamics under confinement at temperatures higher than that.

  7. Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch

    PubMed Central

    Yang, Huaxiao; Schmidt, Lucas P.; Wang, Zhonghai; Yang, Xiaoqi; Shao, Yonghong; Borg, Thomas K.; Markwald, Roger; Runyan, Raymond; Gao, Bruce Z.

    2016-01-01

    An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live-cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy. PMID:26861590

  8. Stock price dynamics and option valuations under volatility feedback effect

    NASA Astrophysics Data System (ADS)

    Kanniainen, Juho; Piché, Robert

    2013-02-01

    According to the volatility feedback effect, an unexpected increase in squared volatility leads to an immediate decline in the price-dividend ratio. In this paper, we consider the properties of stock price dynamics and option valuations under the volatility feedback effect by modeling the joint dynamics of stock price, dividends, and volatility in continuous time. Most importantly, our model predicts the negative effect of an increase in squared return volatility on the value of deep-in-the-money call options and, furthermore, attempts to explain the volatility puzzle. We theoretically demonstrate a mechanism by which the market price of diffusion return risk, or an equity risk-premium, affects option prices and empirically illustrate how to identify that mechanism using forward-looking information on option contracts. Our theoretical and empirical results support the relevance of the volatility feedback effect. Overall, the results indicate that the prevailing practice of ignoring the time-varying dividend yield in option pricing can lead to oversimplification of the stock market dynamics.

  9. Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch.

    PubMed

    Yang, Huaxiao; Schmidt, Lucas P; Wang, Zhonghai; Yang, Xiaoqi; Shao, Yonghong; Borg, Thomas K; Markwald, Roger; Runyan, Raymond; Gao, Bruce Z

    2016-01-01

    An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live-cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy. PMID:26861590

  10. Dynamics of a polyelectrolyte under a constant electric field

    NASA Astrophysics Data System (ADS)

    Park, Pyeong Jun

    2015-11-01

    We perform a molecular dynamics simulation of a polyelectrolyte in a viscous fluid under an external electric field to study the dynamics of gel-free electrophoresis. To incorporate the hydrodynamic effects, we employ a coarse-grained description of water by using multiparticle collision dynamics. We use a screened Coulomb interaction among the monomers and explicit monovalent counterions to model the electrostatic interactions in an ionic solution. The mobility of the polyelectrolyte µ is obtained as a function of the molecular weight N, the electric field strength E,and the Debye screening length of the solvent λ. The mobility is found to be independent of N for large N and to exhibit a maximum at a certain N for a large λ, which are in agreement with experimental results. The dependence of µ on E is also examined and discussed by considering the effects of an electric field on counterion condensation. The dependence of µ on λ shows a discrepancy between our simulation and experiments, which implies that the added salts not only screen out the Coulomb interaction but also participate in the counterion condensation significantly.

  11. HAWT dynamic stall response asymmetries under yawed flow conditions

    NASA Astrophysics Data System (ADS)

    Schreck, S.; Robinson, M.; Hand, M.; Simms, D.

    2000-10-01

    Horizontal axis wind turbines can experience significant time-varying aerodynamic loads, potentially causing adverse effects on structures, mechanical components and power production. As designers attempt lighter and more flexible wind energy machines, greater accuracy and robustness will become even more critical in future aerodynamics models. Aerodynamics modelling advances, in turn, will rely on more thorough comprehension of the three-dimensional, unsteady, vortical flows that dominate wind turbine blade aerodynamics under high-load conditions. To experimentally characterize these flows, turbine blade surface pressures were acquired at multiple span locations via the NREL Phase IV Unsteady Aerodynamics Experiment. Surface pressures and associated normal force histories were used to characterize dynamic stall vortex kinematics and normal force amplification. Dynamic stall vortices and normal force amplification were confirmed to occur in response to angle-of-attack excursions above the static stall threshold. Stall vortices occupied approximately one-half of the blade span and persisted for nearly one-fourth of the blade rotation cycle. Stall vortex convection varied along the blade, resulting in dramatic deformation of the vortex. Presence and deformation of the dynamic stall vortex produced corresponding amplification of normal forces. Analyses revealed consistent alterations to vortex kinematics in response to changes in reduced frequency, span location and yaw error. Finally, vortex structures and kinematics not previously documented for wind turbine blades were isolated. Published in 2000 by John Wiley & Sons, Ltd.

  12. Dynamic properties of elastomer cartridge specimens under a rotating load

    NASA Technical Reports Server (NTRS)

    Darlow, M. S.; Smalley, A. J.; Cunningham, R. E.

    1979-01-01

    This paper presents the results of a program of analysis and test to determine the dynamic properties of elastomer cartridges operating under a rotating load. These measured properties were compared to predictions based on results of unidirectional tests with the same elastomer material. The test method for the dynamic stiffness and damping measurements was essentially the same as the Base Excitation Resonant Mass Method. The primary difference is that the exciting force used for these most recent tests was exerted by rotating unbalance in a rotational test rig rather than a shake table. The specimens tested were: two rectangular cross-section, continuous ring cartridges of different cross-section and three cylindrical button cartridges of different button thickness. Tests were performed for strains from about 0.0001 to about 0.01 (double amplitude). Material properties and prediction equations determined from reciprocating tests were used to make numerical predictions of stiffness, damping, and loss coefficient for the test elements, with encouraging results. Strain was shown to be an important parameter in determining these dynamic properties, particularly damping and loss coefficient.

  13. Deterministic nature of the underlying dynamics of surface wind fluctuations

    NASA Astrophysics Data System (ADS)

    Sreelekshmi, R. C.; Asokan, K.; Satheesh Kumar, K.

    2012-10-01

    Modelling the fluctuations of the Earth's surface wind has a significant role in understanding the dynamics of atmosphere besides its impact on various fields ranging from agriculture to structural engineering. Most of the studies on the modelling and prediction of wind speed and power reported in the literature are based on statistical methods or the probabilistic distribution of the wind speed data. In this paper we investigate the suitability of a deterministic model to represent the wind speed fluctuations by employing tools of nonlinear dynamics. We have carried out a detailed nonlinear time series analysis of the daily mean wind speed data measured at Thiruvananthapuram (8.483° N,76.950° E) from 2000 to 2010. The results of the analysis strongly suggest that the underlying dynamics is deterministic, low-dimensional and chaotic suggesting the possibility of accurate short-term prediction. As most of the chaotic systems are confined to laboratories, this is another example of a naturally occurring time series showing chaotic behaviour.

  14. Rupture of a biomembrane under dynamic surface tension

    NASA Astrophysics Data System (ADS)

    Bicout, D. J.; Kats, E.

    2012-03-01

    How long will a fluid membrane vesicle stressed with a steady ramp of micropipette last before rupture? Or conversely, how high should the surface tension be to rupture such a membrane? To answer these challenging questions we developed a theoretical framework that allows for the description and reproduction of dynamic tension spectroscopy (DTS) observations. The kinetics of the membrane rupture under ramps of surface tension is described as a succession of an initial pore formation followed by the Brownian process of the pore radius crossing the time-dependent energy barrier. We present the formalism and a derive (formal) analytical expression of the survival probability describing the fate of the membrane under DTS conditions. Using numerical simulations for the membrane prepared in an initial state with a given distribution of times for pore nucleation, we study the membrane lifetime (or inverse of rupture rate) and distribution of membrane surface tension at rupture as a function of membrane characteristics like pore nucleation rate, the energy barrier to failure, and tension loading rate. It is found that simulations reproduce the main features of DTS experiments, particularly the pore nucleation and pore-size diffusion-controlled limits of membrane rupture dynamics. This approach can be adapted and applied to processes of permeation and pore opening in membranes (electroporation, membrane disruption by antimicrobial peptides, vesicle fusion).

  15. Three dimensional dynamics of rotating structures under mixed boundary conditions

    NASA Astrophysics Data System (ADS)

    Bediz, Bekir; Romero, L. A.; Ozdoganlar, O. Burak

    2015-12-01

    This paper presents the spectral-Tchebychev (ST) technique for solution of three dimensional (3D) dynamics of rotating structures. In particular, structures that exhibit coupled dynamic response require a 3D modeling approach to capture their dynamic behavior. Rotational motions further complicate this behavior, inducing coriolis, centrifugal softening, and (nonlinear) stress-stiffening effects. Therefore, a 3D solution approach is needed to accurately capture the rotational dynamics. The presented 3D-ST technique provides a fast-converging and precise solution approach for rotational dynamics of structures with complex geometries and mixed boundary conditions. Specifically, unlike finite elements techniques, the presented technique uses a series expansion approach considering distributed-parameter system equations: The integral boundary value problem for rotating structures is discretized using the spectral-Tchebychev approach. To simplify the domain of the structures, cross-sectional and rotational transformations are applied to problems with curved cross-section and pretwisted geometry. The nonlinear terms included in the integral boundary value problem are linearized around an equilibrium solution using the quasi-static method. As a result, mass, damping, and stiffness matrices, as well as a forcing vector, are obtained for a given rotating structure. Several case studies are then performed to demonstrate the application and effectiveness of the 3D-ST solution. For each problem, the natural frequencies and modes shapes from the 3D-ST solution are compared to those from the literature (when available) and to those from a commercial finite elements software. The case studies include rotating/spinning parallelepipeds under free and mixed boundary conditions, and a cantilevered pretwisted beam (i.e., rotating blade) with an airfoil geometry rotating on a hub. It is seen that the natural frequencies and mode shapes from the 3D-ST technique differ from those from the

  16. Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins

    PubMed Central

    Koh, Sehwon; Kim, Namsoo; Yin, Henry H.; Harris, Ian R.; Dejneka, Nadine S.

    2015-01-01

    Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degeneration, but the underlying therapeutic mechanisms are unknown. Because synaptic dysfunction, synapse loss, degeneration of neuronal processes, and neuronal death are hallmarks of neurological diseases and retinal degenerations, we tested whether hUTCs contribute to tissue repair and regeneration by stimulating synapse formation, neurite outgrowth, and neuronal survival. To do so, we used a purified rat retinal ganglion cell culture system and found that hUTCs secrete factors that strongly promote excitatory synaptic connectivity and enhance neuronal survival. Additionally, we demonstrated that hUTCs support neurite outgrowth under normal culture conditions and in the presence of the growth-inhibitory proteins chondroitin sulfate proteoglycan, myelin basic protein, or Nogo-A (reticulon 4). Furthermore, through biochemical fractionation and pharmacology, we identified the major hUTC-secreted synaptogenic factors as the thrombospondin family proteins (TSPs), TSP1, TSP2, and TSP4. Silencing TSP expression in hUTCs, using small RNA interference, eliminated both the synaptogenic function of these cells and their ability to promote neurite outgrowth. However, the majority of the prosurvival functions of hUTC-conditioned media was spared after TSP knockdown, indicating that hUTCs secrete additional neurotrophic factors. Together, our findings demonstrate that hUTCs affect multiple aspects of neuronal health and connectivity through secreted factors, and each of these paracrine effects may individually contribute to the therapeutic function of these cells. SIGNIFICANCE STATEMENT Human umbilical tissue-derived cells (hUTC) are currently under clinical investigation for the treatment of geographic atrophy secondary to age-related macular

  17. Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations

    PubMed Central

    Khalili-Araghi, Fatemeh; Ziervogel, Brigitte; Gumbart, James C.

    2013-01-01

    A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solvent representation. The method, which consists of introducing a nonperiodic energy step acting on the ionic species at the edge of the simulation cell, is first tested with illustrative applications to a simple membrane slab model and a phospholipid membrane bilayer. The nonperiodic energy-step method is then used to calculate the reversal potential of the bacterial porin OmpF, a large cation-specific β-barrel channel, by simulating the I-V curve under an asymmetric 10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is found to be in excellent agreement with the values of 26–27 mV measured from lipid bilayer experiments, thereby demonstrating that the method allows realistic simulations of nonequilibrium membrane transport with quantitative accuracy. As a final example, the pore domain of Kv1.2, a highly selective voltage-activated K+ channel, is simulated in a lipid bilayer under conditions that recreate, for the first time, the physiological K+ and Na+ concentration gradients and the electrostatic potential difference of living cells. PMID:24081985

  18. Material dynamics under extreme conditions of pressure and strain rate

    SciTech Connect

    Remington, B A; Allen, P; Bringa, E; Hawreliak, J; Ho, D; Lorenz, K T; Lorenzana, H; Meyers, M A; Pollaine, S W; Rosolankova, K; Sadik, B; Schneider, M S; Swift, D; Wark, J; Yaakobi, B

    2005-09-06

    Solid state experiments at extreme pressures (10-100 GPa) and strain rates ({approx}10{sup 6}-10{sup 8}s{sup -1}) are being developed on high-energy laser facilities, and offer the possibility for exploring new regimes of materials science. These extreme solid-state conditions can be accessed with either shock loading or with a quasi-isentropic ramped pressure drive. Velocity interferometer measurements establish the high pressure conditions. Constitutive models for solid-state strength under these conditions are tested by comparing 2D continuum simulations with experiments measuring perturbation growth due to the Rayleigh-Taylor instability in solid-state samples. Lattice compression, phase, and temperature are deduced from extended x-ray absorption fine structure (EXAFS) measurements, from which the shock-induced {alpha}-{omega} phase transition in Ti and the {alpha}-{var_epsilon} phase transition in Fe are inferred to occur on sub-nanosec time scales. Time resolved lattice response and phase can also be measured with dynamic x-ray diffraction measurements, where the elastic-plastic (1D-3D) lattice relaxation in shocked Cu is shown to occur promptly (< 1 ns). Subsequent large-scale molecular dynamics (MD) simulations elucidate the microscopic dynamics that underlie the 3D lattice relaxation. Deformation mechanisms are identified by examining the residual microstructure in recovered samples. The slip-twinning threshold in single-crystal Cu shocked along the [001] direction is shown to occur at shock strengths of {approx}20 GPa, whereas the corresponding transition for Cu shocked along the [134] direction occurs at higher shock strengths. This slip-twinning threshold also depends on the stacking fault energy (SFE), being lower for low SFE materials. Designs have been developed for achieving much higher pressures, P > 1000 GPa, in the solid state on the National Ignition Facility (NIF) laser.

  19. A technique for measuring dynamic friction coefficient under impact loading

    NASA Astrophysics Data System (ADS)

    Lin, Y. L.; Qin, J. G.; Chen, R.; Zhao, P. D.; Lu, F. Y.

    2014-09-01

    We develop a novel setup based on the split Hopkinson pressure bar technique to test the dynamic friction coefficient under impact loading. In the setup, the major improvement is that the end of the incident bar near the specimen is wedge-shaped, which results in a combined compressive and shear loading applied to the specimen. In fact, the shear loading is caused by the interfacial friction between specimen and bars. Therefore, when the two loading force histories are measured, the friction coefficient histories can be calculated without any assumptions and theoretical derivations. The geometry of the friction pairs is simple, and can be either cuboid or cylindrical. Regarding the measurements, two quartz transducers are used to directly record the force histories, and an optical apparatus is designed to test the interfacial slip movement. By using the setup, the dynamic friction coefficient of PTFE/aluminum 7075 friction pairs was tested. The time resolved dynamic friction coefficient and slip movement histories were achieved. The results show that the friction coefficient changes during the loading process, the average data of the relatively stable flat plateau section of the friction coefficient curves is 0.137, the maximum normal pressure is 52 MPa, the maximum relative slip velocity is 1.5 m/s, and the acceleration is 8400 m2/s. Furthermore, the friction test was simulated using an explicit FEM code LS-DYNA. The simulation results showed that the constant pressure and slip velocity can both be obtained with a wide flat plateau incident pulse. For some special friction pairs, normal pressure up to a few hundred MPa, interfacial slip velocities up to 10 m/s, and slip movement up to centimeter-level can be expected.

  20. A technique for measuring dynamic friction coefficient under impact loading.

    PubMed

    Lin, Y L; Qin, J G; Chen, R; Zhao, P D; Lu, F Y

    2014-09-01

    We develop a novel setup based on the split Hopkinson pressure bar technique to test the dynamic friction coefficient under impact loading. In the setup, the major improvement is that the end of the incident bar near the specimen is wedge-shaped, which results in a combined compressive and shear loading applied to the specimen. In fact, the shear loading is caused by the interfacial friction between specimen and bars. Therefore, when the two loading force histories are measured, the friction coefficient histories can be calculated without any assumptions and theoretical derivations. The geometry of the friction pairs is simple, and can be either cuboid or cylindrical. Regarding the measurements, two quartz transducers are used to directly record the force histories, and an optical apparatus is designed to test the interfacial slip movement. By using the setup, the dynamic friction coefficient of PTFE/aluminum 7075 friction pairs was tested. The time resolved dynamic friction coefficient and slip movement histories were achieved. The results show that the friction coefficient changes during the loading process, the average data of the relatively stable flat plateau section of the friction coefficient curves is 0.137, the maximum normal pressure is 52 MPa, the maximum relative slip velocity is 1.5 m/s, and the acceleration is 8400 m(2)/s. Furthermore, the friction test was simulated using an explicit FEM code LS-DYNA. The simulation results showed that the constant pressure and slip velocity can both be obtained with a wide flat plateau incident pulse. For some special friction pairs, normal pressure up to a few hundred MPa, interfacial slip velocities up to 10 m/s, and slip movement up to centimeter-level can be expected. PMID:25273746

  1. Dynamic properties of structural transition in iron under uniaxial compression.

    PubMed

    Shao, J L; Duan, S Q; He, A M; Qin, C S; Wang, P

    2009-06-17

    By using molecular dynamics simulations, we have successfully simulated the bcc [Formula: see text] hcp structural transition in single-crystal iron under isothermal compression along the [001] direction. The results reveal a distinct softening of C(33) and a hardening of C(31) (or C(32)) prior to the transition and an over-relaxation of the stress after transition. Above the critical stress the morphology evolution of structural transition is analyzed, which can be divided into four stages: hcp homogeneously nucleated, columnar grains formed, nuclei competed and merged, and a laminar structure formed along {110} planes. Besides, our simulations demonstrate that in mixed phases the hcp phase has negative shear stress and the potential of the hcp phase is higher than the bcc phase, and the shear stress of the system keeps a linear decrease with hcp mass fraction. The effect of temperature on the structural transition is also discussed. PMID:21693955

  2. The dynamic behaviour of postbuckled composite plates under acoustic excitation

    NASA Technical Reports Server (NTRS)

    Ng, C. F.; White, R. G.

    1988-01-01

    The Rayleigh-Ritz method was used to find the postbuckling static displacement pattern of a composite plane (CFRP) under uniaxial in-plane compression of uniform edge-shortening. The resonance frequencies and mode shapes at various postbuckled states are then evaluated by eigenvalue analysis of the dynamical matrix equation consisting of up-dated tangential stiffness matrix at corresponding static configuration. The theoretical results are compared with experimental results obtained in 16-layered CFRP laminate of aspect ratio 1.5. The resonance frequencies and mode shapes obtained are used to interpret the multimodal and nonlinear strain responses to high level of acoustic excitation. The dominance of second-mode contribution and softening-spring behavior are found in the strain response of postbuckled plates.

  3. Dynamic Group Diffie-Hellman Key Exchange under standard assumptions

    SciTech Connect

    Bresson, Emmanuel; Chevassut, Olivier; Pointcheval, David

    2002-02-14

    Authenticated Diffie-Hellman key exchange allows two principals communicating over a public network, and each holding public-private keys, to agree on a shared secret value. In this paper we study the natural extension of this cryptographic problem to a group of principals. We begin from existing formal security models and refine them to incorporate major missing details (e.g., strong-corruption and concurrent sessions). Within this model we define the execution of a protocol for authenticated dynamic group Diffie-Hellman and show that it is provably secure under the decisional Diffie-Hellman assumption. Our security result holds in the standard model and thus provides better security guarantees than previously published results in the random oracle model.

  4. Dynamic response of a riser under excitation of internal waves

    NASA Astrophysics Data System (ADS)

    Lou, Min; Yu, Chenglong; Chen, Peng

    2015-12-01

    In this paper, the dynamic response of a marine riser under excitation of internal waves is studied. With the linear approximation, the governing equation of internal waves is given. Based on the rigid-lid boundary condition assumption, the equation is solved by Thompson-Haskell method. Thus the velocity field of internal waves is obtained by the continuity equation. Combined with the modified Morison formula, using finite element method, the motion equation of riser is solved in time domain with Newmark-β method. The computation programs are compiled to solve the differential equations in time domain. Then we get the numerical results, including riser displacement and transfiguration. It is observed that the internal wave will result in circular shear flow, and the first two modes have a dominant effect on dynamic response of the marine riser. In the high mode, the response diminishes rapidly. In different modes of internal waves, the deformation of riser has different shapes, and the location of maximum displacement shifts. Studies on wave parameters indicate that the wave amplitude plays a considerable role in response displacement of riser, while the wave frequency contributes little. Nevertheless, the internal waves of high wave frequency will lead to a high-frequency oscillation of riser; it possibly gives rise to fatigue crack extension and partial fatigue failure.

  5. Void collapse under distributed dynamic loading near material interfaces

    NASA Astrophysics Data System (ADS)

    Shpuntova, Galina; Austin, Joanna

    2012-11-01

    Collapsing voids cause significant damage in diverse applications from biomedicine to underwater propulsion to explosives. While shock-induced void collapse has been studied extensively, less attention has been devoted to stress wave loading, which will occur instead if there are mechanisms for wave attenuation or if the impact velocity is relatively low. A set of dynamic experiments was carried out in a model experimental setup to investigate the effect of acoustic heterogeneities in the surrounding medium on void collapse. Two tissue-surrogate polymer materials of varying acoustic properties were used to create flowfield geometries involving a boundary and a void. A stress wave, generated by projectile impact, triggered void collapse in the gelatinous polymer medium. When the length scales of features in the flow field were on the same order of magnitude as the stress wave length scale, the presence of the boundary was found to affect the void collapse process relative to collapse in the absence of a boundary. This effect was quantified for a range of geometries and impact conditions using a two-color, single-frame particle image velocimetry technique. Research supported by NSF Award #0954769, ``CAREER: Dynamics and damage of void collapse in biological materials under stress wave loading'' with Prof. Henning Winter as Program Manager.

  6. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    PubMed

    Reddy, Radhika C; Amodei, Rebecka; Estill, Charles T; Stormshak, Fred; Meaker, Mary; Roselli, Charles E

    2015-01-01

    Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA) and cerebral cortex (CTX) of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM) for 3 days significantly (P < 0.05) increased both total neurite outgrowth (35%) and soma size (8%) in the HPOA and outgrowth (21%) and number of branch points (33%) in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain. PMID:26053052

  7. Sustainable infrastructure system modeling under uncertainties and dynamics

    NASA Astrophysics Data System (ADS)

    Huang, Yongxi

    Infrastructure systems support human activities in transportation, communication, water use, and energy supply. The dissertation research focuses on critical transportation infrastructure and renewable energy infrastructure systems. The goal of the research efforts is to improve the sustainability of the infrastructure systems, with an emphasis on economic viability, system reliability and robustness, and environmental impacts. The research efforts in critical transportation infrastructure concern the development of strategic robust resource allocation strategies in an uncertain decision-making environment, considering both uncertain service availability and accessibility. The study explores the performances of different modeling approaches (i.e., deterministic, stochastic programming, and robust optimization) to reflect various risk preferences. The models are evaluated in a case study of Singapore and results demonstrate that stochastic modeling methods in general offers more robust allocation strategies compared to deterministic approaches in achieving high coverage to critical infrastructures under risks. This general modeling framework can be applied to other emergency service applications, such as, locating medical emergency services. The development of renewable energy infrastructure system development aims to answer the following key research questions: (1) is the renewable energy an economically viable solution? (2) what are the energy distribution and infrastructure system requirements to support such energy supply systems in hedging against potential risks? (3) how does the energy system adapt the dynamics from evolving technology and societal needs in the transition into a renewable energy based society? The study of Renewable Energy System Planning with Risk Management incorporates risk management into its strategic planning of the supply chains. The physical design and operational management are integrated as a whole in seeking mitigations against the

  8. Bringing social standards into project evaluation under dynamic uncertainty.

    PubMed

    Knudsen, Odin K; Scandizzo, Pasquale L

    2005-04-01

    Society often sets social standards that define thresholds of damage to society or the environment above which compensation must be paid to the state or other parties. In this article, we analyze the interdependence between the use of social standards and investment evaluation under dynamic uncertainty where a negative externality above a threshold established by society requires an assessment and payment of damages. Under uncertainty, the party considering implementing a project or new technology must not only assess when the project is economically efficient to implement but when to abandon a project that could potentially exceed the social standard. Using real-option theory and simple models, we demonstrate how such a social standard can be integrated into cost-benefit analysis through the use of a development option and a liability option coupled with a damage function. Uncertainty, in fact, implies that both parties interpret the social standard as a target for safety rather than an inflexible barrier that cannot be overcome. The larger is the uncertainty, in fact, the greater will be the tolerance for damages in excess of the social standard from both parties. PMID:15876217

  9. Bubble dynamics under acoustic excitation with multiple frequencies

    NASA Astrophysics Data System (ADS)

    Zhang, Y. N.; Zhang, Y. N.; Li, S. C.

    2015-01-01

    Because of its magnificent mechanical and chemical effects, acoustic cavitation plays an important role in a broad range of biomedical, chemical and mechanical engineering problems. Particularly, irradiation of the multiple frequency acoustic wave could enhance the effects of cavitation. The advantages of employment of multi-frequency ultrasonic field include decreasing the cavitation thresholds, promoting cavitation nuclei generation, increasing the mass transfer and improving energy efficiency. Therefore, multi-frequency ultrasonic systems are employed in a variety of applications, e.g., to enhance the intensity of sonoluminenscence, to increase efficiency of sonochemical reaction, to improve the accuracy of ultrasound imaging and the efficiency of tissue ablation. Compared to single-frequency systems, a lot of new features of bubble dynamics exist in multi-frequency systems, such as special properties of oscillating bubbles, unique resonances in the bubble response curves, and unusual chaotic behaviours. In present paper, the underlying mechanisms of the cavitation effects under multi-frequency acoustical excitation are also briefly introduced.

  10. Comminution of Ceramic Materials Under High-Shear Dynamic Compaction

    NASA Astrophysics Data System (ADS)

    Homel, Michael; Loiseau, Jason; Higgins, Andrew; Herbold, Eric; Hogan, Jamie

    The post-failure ``granular flow'' response of high-strength lightweight ceramics has important implications on the materials' effectiveness for ballistic protection. We study the dynamic compaction and shear flow of ceramic fragments and powders using computational and experimental analysis of a collapsing thick-walled cylinder geometry. Using newly developed tools for mesoscale simulation of brittle materials, we study the effect of fracture, comminution, shear-enhanced dilatation, and frictional contact on the continuum compaction response. Simulations are directly validated through particle Doppler velocimetry measurements at the inner surface of the cylindrical powder bed. We characterize the size distribution and morphologies of the initial and compacted material fragments to both validate the computational model and to elucidate the dominant failure processes. A portion of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. Lawrence Livermore National Security, LLC. LLNL-ABS-678862.

  11. Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

    PubMed Central

    2015-01-01

    Actin dynamics is fundamental for neurite development; monomer depolymerization from pointed ends is rate-limiting in actin treadmilling. Tropomodulins (Tmod) make up a family of actin pointed end-capping proteins. Of the four known isoforms, Tmod1–Tmod3 are expressed in brain cells. We investigated the role of Tmod’s C-terminal (LRR) domain in the formation of neurite-like processes by overexpressing Tmod1 and Tmod2 with deleted or mutated LRR domains in PC12 cells, a model system used to study neuritogenesis. Tmod1 overexpression results in a normal quantity and a normal length of processes, while Tmod2 overexpression reduces both measures. The Tmod2 overexpression phenotype is mimicked by overexpression of Tmod1 with the LRR domain removed or with three point mutations in the LRR domain that disrupt exposed clusters of conserved residues. Removal of Tmod2’s LRR domain does not significantly alter the outgrowth of neurite-like processes compared to that of Tmod2. Overexpression of chimeras with the N-terminal and C-terminal domains switched between Tmod1 and Tmod2 reinforces the idea that Tmod1’s LRR domain counteracts the reductive effect of the Tmod N-terminal domain upon formation of processes while Tmod2’s LRR domain does not. We suggest that the TM-dependent actin capping ability of both Tmods inhibits the formation of processes, but in Tmod1, this inhibition can be controlled via its LRR domain. Circular dichroism, limited proteolysis, and molecular dynamics demonstrate structural differences in the C-terminal region of the LRR domains of Tmod1, Tmod2, and the Tmod1 mutant. PMID:24746171

  12. Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants.

    PubMed

    Krug, Anne K; Balmer, Nina V; Matt, Florian; Schönenberger, Felix; Merhof, Dorit; Leist, Marcel

    2013-12-01

    Organ-specific in vitro toxicity assays are often highly sensitive, but they lack specificity. We evaluated here examples of assay features that can affect test specificity, and some general procedures are suggested on how positive hits in complex biological assays may be defined. Differentiating human LUHMES cells were used as potential model for developmental neurotoxicity testing. Forty candidate toxicants were screened, and several hits were obtained and confirmed. Although the cells had a definitive neuronal phenotype, the use of a general cell death endpoint in these cultures did not allow specific identification of neurotoxicants. As alternative approach, neurite growth was measured as an organ-specific functional endpoint. We found that neurite extension of developing LUHMES was specifically inhibited by diverse compounds such as colchicine, vincristine, narciclasine, rotenone, cycloheximide, or diquat. These compounds reduced neurite growth at concentrations that did not compromise cell viability, and neurite growth was affected more potently than the integrity of developed neurites of mature neurons. A ratio of the EC50 values of neurite growth inhibition and cell death of >4 provided a robust classifier for compounds associated with a developmental neurotoxic hazard. Screening of unspecific toxicants in the test system always yielded ratios <4. The assay identified also compounds that accelerated neurite growth, such as the rho kinase pathway modifiers blebbistatin or thiazovivin. The negative effects of colchicine or rotenone were completely inhibited by a rho kinase inhibitor. In summary, we suggest that assays using functional endpoints (neurite growth) can specifically identify and characterize (developmental) neurotoxicants. PMID:23670202

  13. Nanomaterials under extreme environments: A study of structural and dynamic properties using reactive molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Shekhar, Adarsh

    Nanotechnology is becoming increasingly important with the continuing advances in experimental techniques. As researchers around the world are trying to expand the current understanding of the behavior of materials at the atomistic scale, the limited resolution of equipment, both in terms of time and space, act as roadblocks to a comprehensive study. Numerical methods, in general and molecular dynamics, in particular act as able compliment to the experiments in our quest for understanding material behavior. In this research work, large scale molecular dynamics simulations to gain insight into the mechano-chemical behavior under extreme conditions of a variety of systems with many real world applications. The body of this work is divided into three parts, each covering a particular system: 1) Aggregates of aluminum nanoparticles are good solid fuel due to high flame propagation rates. Multi-million atom molecular dynamics simulations reveal the mechanism underlying higher reaction rate in a chain of aluminum nanoparticles as compared to an isolated nanoparticle. This is due to the penetration of hot atoms from reacting nanoparticles to an adjacent, unreacted nanoparticle, which brings in external heat and initiates exothermic oxidation reactions. 2) Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near amorphous silica. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The pit contains a large number of silanol groups and its volume is found to be directly proportional to the volume of the nanobubble. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. 3) The structure and dynamics of water confined in

  14. Interface dynamics under nonequilibrium conditions: from a self-propelled droplet to dynamic pattern evolution.

    PubMed

    Chen, Y-J; Yoshikawa, K

    2011-04-01

    In this article, we describe the instability of a contact line under nonequilibrium conditions mainly based on the results of our recent studies. Two experimental examples are presented: the self-propelled motion of a liquid droplet and spontaneous dynamic pattern formation. For the self-propelled motion of a droplet, we introduce an experiment in which a droplet of aniline sitting on an aqueous layer moves spontaneously at an air-water interface. The spontaneous symmetry breaking of Marangoni-driven spreading causes regular motion. In a circular Petri dish, the droplet exhibits either beeline motion or circular motion. On the other hand, we show the emergence of a dynamic labyrinthine pattern caused by dewetting of a metastable thin film from the air-water interface. The contact line between the organic phase and the aqueous phase forms a unique spatio-temporal pattern characterized as a dynamic labyrinth. Motion of the contact line is controlled by diffusion processes. We propose a theoretical model to interpret essential aspects of the observed dynamic behavior. PMID:21509663

  15. Relaxation dynamics of lysozyme in solution under pressure: Combining molecular dynamics simulations and quasielastic neutron scattering

    NASA Astrophysics Data System (ADS)

    Calandrini, V.; Hamon, V.; Hinsen, K.; Calligari, P.; Bellissent-Funel, M.-C.; Kneller, G. R.

    2008-04-01

    This paper presents a study of the influence of non-denaturing hydrostatic pressure on the relaxation dynamics of lysozyme in solution, which combines molecular dynamics simulations and quasielastic neutron scattering experiments. We compare results obtained at ambient pressure and at 3 kbar. Experiments have been performed at pD 4.6 and at a protein concentration of 60 mg/ml. For both pressures we checked the monodispersity of the protein solution by small angle neutron scattering. To interpret the simulation results and the experimental data, we adopt the fractional Ornstein-Uhlenbeck process as a model for the internal relaxation dynamics of the protein. On the experimental side, global protein motions are accounted for by the model of free translational diffusion, neglecting the much slower rotational diffusion. We find that the protein dynamics in the observed time window from about 1 to 100 ps is slowed down under pressure, while its fractal characteristics is preserved, and that the amplitudes of the motions are reduced by about 20%. The slowing down of the relaxation is reduced with increasing q-values, where more localized motions are seen.

  16. Dynamics of transitions between capillary stable states under weightlessness

    NASA Astrophysics Data System (ADS)

    Srikanth, Praveen

    The study of two phase systems with one of the phases obstructing the other is of importance in a lot of fields. Liquid droplets in airways and air bubbles in the blood stream both fall under this category of problems. Helium bubbles in hydrazine fuel lines of satellites also have been found to cause frequent thruster shutdown and also seriously affect spacecraft control. Studies have been carried out until now to look at static equilibrium topologies and stability of such two phase systems in straight, bent and laterally compressed capillaries. In this investigation we look at the dynamics of the transitions between the stable topologies identified for a straight cylindrical capillary. The break up of the interface could adversely affect system performance. OpenFOAM is used to compute transitions from a stable droplet to a plug or the reverse by suitably adding or removing the obstructing phase through inlet patches on the wall of the cylinder. The main parameters presented are the non-dimensional energy, non-dimensional transition times, non-dimensional transition volumes and the general dynamics of the transitions itself. Before computing transitions the static equilibrium topologies computed by OpenFOAM are compared with those predicted by Surface Evolver and are found to be within acceptable deviations. The grid dependence of these transitions has also been studied. Transitions are computed for contact angles in the range of 10° to 170°. Different modes of transitions are observed depending on the contact angle of the case for both the types of transitions. The transition volumes are compared to the volume of existence limits for the corresponding initial topology at a particular contact angle for both the transitions.

  17. A Farnesyltransferase Acts to Inhibit Ectopic Neurite Formation in C. elegans

    PubMed Central

    Carr, David; Sanchez-Alvarez, Leticia; Imai, Janice H.; Slatculescu, Cristina; Noblett, Nathaniel; Mao, Lei; Beese, Lorena; Colavita, Antonio

    2016-01-01

    Genetic pathways that regulate nascent neurite formation play a critical role in neuronal morphogenesis. The core planar cell polarity components VANG-1/Van Gogh and PRKL-1/Prickle are involved in blocking inappropriate neurite formation in a subset of motor neurons in C. elegans. A genetic screen for mutants that display supernumerary neurites was performed to identify additional factors involved in this process. This screen identified mutations in fntb-1, the β subunit of farnesyltransferase. We show that fntb-1 is expressed in neurons and acts cell-autonomously to regulate neurite formation. Prickle proteins are known to be post-translationally modified by farnesylation at their C-terminal CAAX motifs. We show that PRKL-1 can be recruited to the plasma membrane in both a CAAX-dependent and CAAX-independent manner but that PRKL-1 can only inhibit neurite formation in a CAAX-dependent manner. PMID:27300162

  18. Growth, collapse, and stalling in a mechanical model for neurite motility

    NASA Astrophysics Data System (ADS)

    Recho, Pierre; Jerusalem, Antoine; Goriely, Alain

    2016-03-01

    Neurites, the long cellular protrusions that form the routes of the neuronal network, are capable of actively extending during early morphogenesis or regenerating after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical traction or compression balance of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

  19. The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model

    PubMed Central

    Li, Tong; Braunstein, Kerstin E.; Zhang, Juhong; Lau, Ashley; Sibener, Leslie; Deeble, Christopher; Wong, Philip C.

    2016-01-01

    A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau. PMID:27373369

  20. A three-dimensional image processing program for accurate, rapid, and semi-automated segmentation of neuronal somata with dense neurite outgrowth

    PubMed Central

    Ross, James D.; Cullen, D. Kacy; Harris, James P.; LaPlaca, Michelle C.; DeWeerth, Stephen P.

    2015-01-01

    Three-dimensional (3-D) image analysis techniques provide a powerful means to rapidly and accurately assess complex morphological and functional interactions between neural cells. Current software-based identification methods of neural cells generally fall into two applications: (1) segmentation of cell nuclei in high-density constructs or (2) tracing of cell neurites in single cell investigations. We have developed novel methodologies to permit the systematic identification of populations of neuronal somata possessing rich morphological detail and dense neurite arborization throughout thick tissue or 3-D in vitro constructs. The image analysis incorporates several novel automated features for the discrimination of neurites and somata by initially classifying features in 2-D and merging these classifications into 3-D objects; the 3-D reconstructions automatically identify and adjust for over and under segmentation errors. Additionally, the platform provides for software-assisted error corrections to further minimize error. These features attain very accurate cell boundary identifications to handle a wide range of morphological complexities. We validated these tools using confocal z-stacks from thick 3-D neural constructs where neuronal somata had varying degrees of neurite arborization and complexity, achieving an accuracy of ≥95%. We demonstrated the robustness of these algorithms in a more complex arena through the automated segmentation of neural cells in ex vivo brain slices. These novel methods surpass previous techniques by improving the robustness and accuracy by: (1) the ability to process neurites and somata, (2) bidirectional segmentation correction, and (3) validation via software-assisted user input. This 3-D image analysis platform provides valuable tools for the unbiased analysis of neural tissue or tissue surrogates within a 3-D context, appropriate for the study of multi-dimensional cell-cell and cell-extracellular matrix interactions. PMID

  1. Influence of cAMP and protein kinase A on neurite length from spiral ganglion neurons

    PubMed Central

    Xu, Ningyong; Engbers, Jonathan; Khaja, Sobia; Xu, Linjing; Clark, J. Jason; Hansen, Marlan R.

    2011-01-01

    Regrowth of peripheral spiral ganglion neuron (SGN) fibers is a primary objective in efforts to improve cochlear implant outcomes and to potentially reinnervate regenerated hair cells. Cyclic adenosine monophosphate (cAMP) regulates neurite growth and guidance via activation of protein kinase A (PKA) and Exchange Protein directly Activated by Cylic AMP (Epac). Here we explored the effects of cAMP signaling on SGN neurite length in vitro. We find that the cAMP analog, cpt-cAMP, exerts a biphasic effect on neurite length; increasing length at lower concentrations and reducing length at higher concentrations. This biphasic response occurs in cultures plated on laminin, fibronectin, or tenascin C suggesting that it is not substrate dependent. cpt-cAMP also reduces SGN neurite branching. The Epac-specific agonist, 8-pCPT-2’-O-Me-cAMP, does not alter SGN neurite length. Constitutively active PKA isoforms strongly inhibit SGN neurite length similar to higher levels of cAMP. Chronic membrane depolarization activates PKA in SGNs and also inhibits SGN neurite length. However, inhibition of PKA fails to rescue neurite length in depolarized cultures implying that activation of PKA is not necessary for the inhibition of SGN neurite length by chronic depolarization. Expression of constitutively active phosphatidylinositol 3-kinase, but not c-Jun N-terminal kinase, isoforms partially rescues SGN neurite length in the presence of activated PKA. Taken together, these results suggest that activation of cAMP/PKA represents a potential strategy to enhance SGN fiber elongation following deafness; however such therapies will likely require careful titration so as to simultaneously promote rather than inhibit nerve fiber regeneration. PMID:22154930

  2. Coastal-zone biogeochemical dynamics under global warming

    SciTech Connect

    Mackenzie, F.T.; Ver, L.M.; Lerman, A.

    2000-03-01

    The coastal zone, consisting of the continental shelves to a depth of 200 meters, including bays, lagoons, estuaries, and near-shore banks, is an environment that is strongly affected by its biogeochemical and physical interactions with reservoirs in the adjacent domains of land, atmosphere, open ocean, and marine sediments. Because the coastal zone is smaller in volume and area coverage relative to the open ocean, it traditionally has been studied as an integral part of the global oceans. In this paper, the authors show by numerical modeling that it is important to consider the coastal zone as an entity separate from the open ocean in any assessment of future Earth-system response under human perturbation. Model analyses for the early part of the 21st century suggest that the coastal zone plays a significant modifying role in the biogeochemical dynamics of the carbon cycle and the nutrient cycles coupled to it. This role is manifested in changes in primary production, storage, and/or export of organic matter, its remineralization, and calcium carbonate precipitation--all of which determine the state of the coastal zone with respect to exchange of CO{sub 2} with the atmosphere. Under a scenario of future reduced or complete cessation of the thermohaline circulation (THC) of the global oceans, coastal waters become an important sink for atmospheric CO{sub 2}, as opposed to the conditions in the past and present, when coastal waters are believed to be a source of CO{sub 2} to the atmosphere. Profound changes in coastal-zone primary productivity underscore the important role of phosphorus as a limiting nutrient. In addition, calculations indicate that the saturation state of coastal waters with respect to carbonate minerals will decline by {approximately}15% by the year 2030. Any future slowdown in the THC of the oceans will increase slightly the rate of decline in saturation state.

  3. Performance of HEPA filters under hot dynamic conditions

    SciTech Connect

    Frankum, D.P.; Costigan, G.

    1995-02-01

    Accidents in nuclear facilities involving fires may have implications upon the ventilation systems where high efficiency particulate air (HEPA) filters are used to minimise the airborne release of radioactive or toxic particles. The Filter Development Section at Harwell Laboratory has been investigating the effect of temperature on the performance of HEPA filters under hot dynamic conditions[{sub 1}] for a number of years. The test rig is capable of delivering air flows of 10001/s (at ambient conditions) at temperatures up to 500{degrees}C, where measurements of the penetration and pressure drop across the filter are obtained. This paper reports the experiments on different constructions of HEPA filters; rectangular and circular. The filters were tested at an air temperature of 200{degrees}C for up to 48 hours at the rated airflow to assess their performance. The penetration measurements for rectangular filters were observed to be below 0.021% after prolonged operation. In a number of cases, holes appeared along the pleat creases of circular filters although the penetration remained below 1%. The sealing gasket for these filters was noted to deform with temperature, permitting a leakage path. A prototype high strength circular filter was evaluated at temperatures of up to 400{degrees}C with a penetration less than 0.65%.

  4. Dynamic behavior of thermionic dispenser cathodes under ion bombardment

    NASA Astrophysics Data System (ADS)

    Cortenraad, R.; van der Gon, A. W. Denier; Brongersma, H. H.; Gärtner, G.; Raasch, D.; Manenschijn, A.

    2001-04-01

    We have investigated the surface coverage and electron emission of thermionic dispenser cathodes during 3 keV Ar+ ion bombardment, thereby simulating the bombardment of the cathodes by residual gases that takes place in cathode-ray tubes as used in television sets. During the ion bombardment at the operating temperature of 1030 °C, a dynamic equilibrium is established between the sputter removal and resupply mechanisms of the Ba and O atoms that form the dipole layer on the cathode substrate. We demonstrated that the performance of the cathodes under ion bombardment is governed by the O removal and resupply rates. It was found that the Ba resupply rate is almost an order of magnitude higher than the O resupply rate, but that the Ba can only be present on the surface bound to O atoms. Therefore, the Ba/O ratio is approximately equal to unity during the ion bombardment. Based on the investigations of the removal and resupply processes, we proposed a model that accurately describes the surface coverage and electron emission during the ion bombardment, including the dependence of the ion flux and cathode temperature.

  5. Analyzing freeway traffic under congestion: Traffic dynamics approach

    SciTech Connect

    Nam, D.H.; Drew, D.R.

    1998-05-01

    This paper presents an analysis of freeway traffic flows under congestion based on the principle of traffic dynamics, using the example of recurring congestion. Queuing and discharging mechanisms are analyzed using the fundamental concept of conservation of vehicles. These analysis results are applied for reviewing the two conventional macroscopic analysis tools, deterministic queuing analysis and shock-wave analysis. Comparative study results have demonstrated that (1) the two methods are fundamentally different from the traffic modeling point of view; (2) deterministic queuing analysis always underestimates the overall magnitude of delays compared to shock-wave analysis; and (3) the area between the demand and the capacity curves in a queuing diagram is analytically equivalent to total vehicle-hours of travel in congestion as opposed to the widely accepted total vehicle-hours of delay. The study results imply that the guidelines of the 1994 Highway Capacity Manual may result in the underestimation of congestion-related statistics. For the purposes of illustration and verification, a numerical example problem is provided.

  6. Stress relaxation in vanadium under shock and shockless dynamic compression

    SciTech Connect

    Kanel, G. I.; Razorenov, S. V.; Garkushin, G. V.; Savinykh, A. S.; Zaretsky, E. B.

    2015-07-28

    Evolutions of elastic-plastic waves have been recorded in three series of plate impact experiments with annealed vanadium samples under conditions of shockless and combined ramp and shock dynamic compression. The shaping of incident wave profiles was realized using intermediate base plates made of different silicate glasses through which the compression waves were entered into the samples. Measurements of the free surface velocity histories revealed an apparent growth of the Hugoniot elastic limit with decreasing average rate of compression. The growth was explained by “freezing” of the elastic precursor decay in the area of interaction of the incident and reflected waves. A set of obtained data show that the current value of the Hugoniot elastic limit and plastic strain rate is rather associated with the rate of the elastic precursor decay than with the local rate of compression. The study has revealed the contributions of dislocation multiplications in elastic waves. It has been shown that independently of the compression history the material arrives at the minimum point between the elastic and plastic waves with the same density of mobile dislocations.

  7. Molecular dynamics simulation of VN thin films under indentation

    NASA Astrophysics Data System (ADS)

    Fu, Tao; Peng, Xianghe; Huang, Cheng; Yin, Deqiang; Li, Qibin; Wang, Zhongchang

    2015-12-01

    We investigated with molecular dynamics simulation the mechanical responses of VN (0 0 1) thin films subjected to indentation with a diamond columnar indenter. We calculated the generalized stacking-fault energies as a function of the displacement in the rbond2 1 1 0lbond2 directions on the {0 0 1}, {1 1 0}, and {1 1 1} planes, and analyzed systematically the microstructures and their evolution during the indentation with the centro-symmetry parameters and the slices of the VN films. We found the slips on {1 1 0}rbond2 1 1 0lbond2 of the VN film under indentation at the initial stage. With the increase of indentation depth, slips are also activated on {1 1 1}rbond2 1 1 0lbond2 and {1 0 0}rbond2 0 1 1lbond2 systems. We further found that the slip system is determined by the stacking-fault energy rather than the layer spacing. The indentations with other different parameters were also performed, and the results further prove the validity of the conclusion.

  8. Behavior of sodium borosilicate glasses under compression using molecular dynamics

    SciTech Connect

    Kilymis, D. A.; Ispas, S.; Delaye, J.-M.

    2015-09-07

    We have performed classical molecular dynamics simulations in order to study the changes under compression in the local and medium range structural properties of three sodium borosilicate glasses with varying sodium content. These glasses have been isostatically compressed up to 20 GPa and then decompressed in order to analyze the different mechanisms that affect densification, alongside with the permanent modifications of the structure after a full compression/decompression cycle. The results show that the atomic packing is the prominent characteristic that governs the amount of densification in the glass, as well as the setup of the permanent densification. During compression, the bulk modulus increases linearly up to approximately 15 GPa and more rapidly for higher pressures, a behavior which is reflected on the rate of increase of the average coordination for B and Na. Radial distribution functions at different pressures during the cycle help to quantify the amount of distortions in the elementary structural units, with a pronounced shortening of the Na–Na and Na–O bond lengths during compression. A subsequent decomposition of the glassy matrix into elementary Voronoi volumes verifies the high compressibility of Na-rich regions.

  9. Skyrmion dynamics in chiral ferromagnets under spin-transfer torque

    NASA Astrophysics Data System (ADS)

    Komineas, Stavros; Papanicolaou, Nikos

    2015-11-01

    We study the dynamics of skyrmions under spin-transfer torque in Dzyaloshinskii-Moriya materials with easy-axis anisotropy. In particular, we study the motion of a topological skyrmion with skyrmion number Q =1 and a nontopological skyrmionium with Q =0 using their linear momentum, virial relations, and numerical simulations. The nontopological Q =0 skyrmionium is accelerated in the direction of the current flow and it either reaches a steady state with constant velocity, or it is elongated to infinity. The steady-state velocity is given by a balance between current and dissipation and has an upper limit. In contrast, the topological Q =1 skyrmion converges to a steady state with constant velocity at an angle to the current flow. When the spin current stops the Q =1 skyrmion is spontaneously pinned, whereas the Q =0 skyrmionium continues propagation. Exact solutions for the propagating skyrmionium are identified as solutions of equations given numerically in a previous work. Further exact results for propagating skyrmions are given in the case of the pure exchange model. The traveling solutions provide arguments that a spin-polarized current will cause rigid motion of a skyrmion or a skyrmionium.

  10. Buckling of circular cylindrical shells under dynamically applied axial loads

    NASA Technical Reports Server (NTRS)

    Tulk, J. D.

    1972-01-01

    A theoretical and experimental study was made of the buckling characteristics of perfect and imperfect circular cylindrical shells subjected to dynamic axial loading. Experimental data included dynamic buckling loads (124 data points), high speed photographs of buckling mode shapes and observations of the dynamic stability of shells subjected to rapidly applied sub-critical loads. A mathematical model was developed to describe the dynamic behavior of perfect and imperfect shells. This model was based on the Donnell-Von Karman compatibility and equilibrium equations and had a wall deflection function incorporating five separate modes of deflection. Close agreement between theory and experiment was found for both dynamic buckling strength and buckling mode shapes.

  11. C dynamics in Amazonian podzols under climate change

    NASA Astrophysics Data System (ADS)

    Nunan, Naoise; Soro, Andre; Potard, Kevin; Pouteau, Valerie; Montes, Celia; Melphi, Adolpho; Lucas, Yves; Chenu, Claire

    2016-04-01

    It has recently been shown that the C stocks in Amazonian podzols are very large. They are much larger than was previously thought, particularly in the Bh horizon, which has been estimated to contain in excess of 13Pg C for Amazonia alone. It is predicted that the changes in regional climate will result in a drier soil water regime which may affect the C dynamics in these soils that are usually saturated. In order to determine the vulnerability to change of the organic C contained in the Amazonian podzols, a series of incubation experiments were established in which the effects of a number of different factors on microbial decomposition were measured. The direct effect of drier soil water regimes was tested by incubating undisturbed cores from the Bh horizon at a range of matric potentials (saturation to wilting point). Contrary to what is usually found in soils, no significant difference in mineralisation was found among matric potentials, suggesting that other factors control microbial mineralisation of this organic C. The effect of nitrogen additions, of anaerobic conditions and of the addition labile C substrate were also tested on undisturbed cores of the Bh horizon of the podzols. Samples incubated under aerobic conditions produced 3 times more CO2 than samples incubated under anaerobic conditions, whilst samples incubated under aerobic conditions with the addition of N mineralised 6.7 times more CO2 than the anaerobic samples. The addition of labile C did not have a significant effect on C mineralisation, i.e. there was no priming effect. The combined addition of labile C and mineral N did not stimulate C mineralisation more than N additions alone. By extrapolating the differences obtained here to the whole of the Amazonian podzols, it is estimated that changes in conditions which result in an increase in O2 and in N (i.e. changes in vegetation due to increases in dry periods with the establishment of a savanna for example) in the soil will cause the release

  12. Microfluidic Generation of Haptotactic Gradients through 3D Collagen Gels for Enhanced Neurite Growth

    PubMed Central

    Sundararaghavan, Harini G.; Masand, Shirley N.

    2011-01-01

    Abstract We adapted a microfluidic system used previously to generate durotactic gradients of stiffness in a 3D collagen gel, to produce haptotactic gradients of adhesive ligands through the collagen gel. Oligopeptide sequences that included bioactive peptide sequences from laminin, YIGSR, or IKVAV, were grafted separately onto type I collagen using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Solutions of peptide-grafted collagen and untreated collagen were then used as source and sink input solutions, respectively, in an H-shaped microfluidic network fabricated using traditional soft lithography. One-dimensional gradients of the peptide-grafted collagen solution were generated in the channel that connected the source and sink channels, and these gradients became immobilized upon self-assembly of the collagen into a 3D fibrillar gel. The slope and average concentration of the gradients were adjusted by changing the concentration of the source solutions and by changing the length of the cross-channel. A separate, underlying channel in the microfluidic construct allowed the introduction of a chick embryo dorsal root ganglion into the network. Neurites from these explants grew significantly longer up steep gradients of YIGSR, but shallow gradients of IKVAV in comparison to untreated collagen controls. When these two gradients were presented in combination, the bias in growth acceleration was the largest and most consistent. No differences were observed in the number of neurites choosing to grow up or down the gradients in any condition. These results suggest that the incorporation of distinct gradients of multiple bioactive ligands can improve directional acceleration of regenerating axons. PMID:21473683

  13. Design improvement and dynamic finite element analysis of novel ITI dental implant under dynamic chewing loads.

    PubMed

    Cheng, Yung-Chang; Lin, Deng-Huei; Jiang, Cho-Pei; Lee, Shyh-Yuan

    2015-01-01

    The main aim of this article was to introduce the application of a uniform design for experimental methods to drop the micromotion of a novel ITI dental implant model under the dynamic loads. Combining the characteristics of the traditional ITI and Nano-Tite implants, a new implant with concave holes has been constructed. Compared to the traditional ITI dental implant model, the micromotion of the new dental implant model was significantly reduced by explicit dynamic finite element analysis. From uniform design of experiments, the dynamic finite element analysis method was applied to caluculated the maximum micromotion of the full model. Finally, the chief design in all the experiment simulations which cause the minimum micromotion is picked as the advanced model of the design. Related to the original design, which was associated with a micromotion of 45.11 μm, the micromotion of the improved version was 31.37 μm, for an improvement rate of 30.5%. PMID:26406049

  14. Evolution of specialization under non-equilibrium population dynamics.

    PubMed

    Nurmi, Tuomas; Parvinen, Kalle

    2013-03-21

    We analyze the evolution of specialization in resource utilization in a mechanistically underpinned discrete-time model using the adaptive dynamics approach. We assume two nutritionally equivalent resources that in the absence of consumers grow sigmoidally towards a resource-specific carrying capacity. The consumers use resources according to the law of mass-action with rates involving trade-off. The resulting discrete-time model for the consumer population has over-compensatory dynamics. We illuminate the way non-equilibrium population dynamics affect the evolutionary dynamics of the resource consumption rates, and show that evolution to the trimorphic coexistence of a generalist and two specialists is possible due to asynchronous non-equilibrium population dynamics of the specialists. In addition, various forms of cyclic evolutionary dynamics are possible. Furthermore, evolutionary suicide may occur even without Allee effects and demographic stochasticity. PMID:23306058

  15. Examining Hyporheic Dynamics Under Fluctuating Stream Stage Conditions

    NASA Astrophysics Data System (ADS)

    Dudley-Southern, M. J.; Binley, A. M.; Pates, J.; Wynn, P.

    2013-12-01

    Gaining river systems that are connected to groundwaters with increasing nitrate levels are at risk from increased nitrate loading. The consequences of greater nitrate transfer to surface waters are uncertain, but attenuation of nitrate waters at the groundwater -surface water interface may help to reduce the ecological impact on receiving surface waters. The majority of studies of groundwater-surface water interactions have focussed on low flow conditions. Some studies have revealed evidence of biogeochemical reactions occurring at a greater depth in the subsurface than could be supported by mixing between surface water and groundwater under low flow conditions. We believe that, under particular geomorphological settings, short-lived changes in groundwater flow pathways may lead to transformations of the extent of hyporheic flow, and thus potentially impact on biogeochemical cycling at this interface. Here we focus on the influence of changes in stream stage, during storm events, on the extent of the hyporheic zone. It is hypothesised that when there is a large sudden change in surface water level, ambient groundwater gradients can undergo a transient reversal, leading to temporary downwelling of surface water which alters the physical and biogeochemical conditions in the subsurface. Physically, downwelling surface water increases the residence time of water within the subsurface by impeding the movement of upwelling groundwater. Biogeochemically, downwelling surface water supplies, for example, dissolved organic carbon to the subsurface, potentially supporting favourable redox conditions for nutrient transformations. To evaluate this concept, the dynamics of groundwater-surface water interactions are being examined at an instrumented gaining reach of the River Leith, Cumbria, UK. Experimental evidence is being gathered by continuously logged hydraulic head data, electrical geophysics and temperature profiles. These data are supported by repeat spot sampling

  16. Pn anisotropic tomography and dynamics under eastern Tibetan plateau

    NASA Astrophysics Data System (ADS)

    Lei, Jianshe; Li, Yuan; Xie, Furen; Teng, Jiwen; Zhang, Guangwei; Sun, Changqing; Zha, Xiaohui

    2014-03-01

    We present a new anisotropic tomographic model of the uppermost mantle around eastern Tibet using Pn traveltime data from a newly deployed temporary seismic array and recent observation bulletins of Chinese provincial networks. Our results are generally consistent with previous results but provide new insights into the dynamics of Tibetan plateau. Prominent high-velocity (high-V) anomalies are visible under Alashan block and Qaidam and Sichuan basins, which clearly outline their tectonic margins. A distinct high-V zone representing the double-sided subduction of Indo-Eurasian plates is imaged from Lhasa block to the south of Qaidam basin. A pronounced low-velocity (low-V) zone is observed from Songpan-Ganzi block to southern Chuan-Dian diamond block, suggesting the existence of hot material upwelling there. Crustal strong earthquakes frequently occurred around high-V anomalies or transition zones from high-V to low-V anomalies, suggesting that these earthquakes could be related to lateral heterogeneities in the mantle. The Pn fast direction approximately rotates around Eastern Himalayan Syntaxis, and it is tangential to the margins of Sichuan basin, suggesting that the mantle material flow of Tibetan plateau may have affected east China. In the Yunnan region to the south of 26°N, the Pn fast direction is different from SKS splitting results, indicating that the mantle lithosphere could be mechanically decoupled at certain depth below the uppermost mantle, which might be attributable to the subduction of Indian (or Burma) slab. Although the correlation between anisotropy and velocity is complicated, anisotropy strength could be associated with the pattern of velocity anomalies in the region.

  17. Transcriptome dynamics of Pseudomonas putida KT2440 under water stress.

    PubMed

    Gülez, Gamze; Dechesne, Arnaud; Workman, Christopher T; Smets, Barth F

    2012-02-01

    Water deprivation can be a major stressor to microbial life in surface and subsurface soil. In unsaturated soils, the matric potential (Ψ(m)) is often the main component of the water potential, which measures the thermodynamic availability of water. A low matric potential usually translates into water forming thin liquid films in the soil pores. Little is known of how bacteria respond to such conditions, where, in addition to facing water deprivation that might impair their metabolism, they have to adapt their dispersal strategy as swimming motility may be compromised. Using the pressurized porous surface model (PPSM), which allows creation of thin liquid films by controlling Ψ(m), we examined the transcriptome dynamics of Pseudomonas putida KT2440. We identified the differentially expressed genes in cells exposed to a mild matric stress (-0.4 MPa) for 4, 24, or 72 h. The major response was detected at 4 h before gradually disappearing. Upregulation of alginate genes was notable in this early response. Flagellar genes were not downregulated, and the microarray data even suggested increasing expression as the stress prolonged. Moreover, we tested the effect of polyethylene glycol 8000 (PEG 8000), a nonpermeating solute often used to simulate Ψ(m), on the gene expression profile and detected a different profile than that observed by directly imposing Ψ(m). This study is the first transcriptome profiling of KT2440 under directly controlled Ψ(m) and also the first to show the difference in gene expression profiles between a PEG 8000-simulated and a directly controlled Ψ(m). PMID:22138988

  18. Dynamics of non-Brownian fiber suspensions under periodic shear.

    PubMed

    Franceschini, Alexandre; Filippidi, Emmanouela; Guazzelli, Elisabeth; Pine, David J

    2014-09-21

    We report experiments studying the dynamics of dense non-Brownian fiber suspensions subjected to periodic oscillatory shear. We find that periodic shear initially causes fibers to collide and to undergo irreversible diffusion. As time progresses, the fibers tend to orient in the vorticity direction while the number of collisions decreases. Ultimately, the system goes to one of two steady states: an absorbing steady state, where collisions cease and the fibers undergo reversible trajectories; an active state, where fibers continue to collide causing them to diffuse and undergo irreversible trajectories. Collisions between fibers can be characterized by an effective volume fraction Φ with a critical volume fraction Φc that separates absorbing from active (diffusing) steady states. The effective volume fraction Φ depends on the mean fiber orientation and thus decreases in time as fibers progressively orient under periodic shear. In the limit that the temporal evolution of Φ is slow compared to the activity relaxation time τ, all the data for all strain amplitudes and all concentrations can be scaled onto a single master curve with a functional dependence well-described by t(-β/ν)R(e(-t)R), where tR is the rescaled time. As Φ → Φc, τ diverges. Therefore, for experiments in which Φ(t) starts above Φc but goes to a steady state below Φc, departures from scaling are observed for Φ very near Φc. The critical exponents are measured to be β = 0.84 ± 0.04 and ν = 1.1 ± 0.1, which is consistent with the Manna universality class for directed percolation. PMID:25068577

  19. FGF-2 deficiency causes dysregulation of Arhgef6 and downstream targets in the cerebral cortex accompanied by altered neurite outgrowth and dendritic spine morphology.

    PubMed

    Baum, Philip; Vogt, Miriam A; Gass, Peter; Unsicker, Klaus; von Bohlen Und Halbach, Oliver

    2016-05-01

    Fibroblast growth factor 2 (FGF-2) is an abundant growth factor in the brain and exerts multiple functions on neural cells ranging from cell division, cell fate determination to differentiation. However, many details of the molecular mechanisms underlying the diverse functions of FGF-2 are poorly understood. In a comparative microarray analysis of motor sensory cortex (MSC) tissue of adult knockout (FGF-2(-/-)) and control (FGF-2(+/+)) mice, we found a substantial number of regulated genes, which are implicated in cytoskeletal machinery dynamics. Specifically, we found a prominent downregulation of Arhgef6. Arhgef6 mRNA was significantly reduced in the FGF-2(-/-) cortex, and Arhgef6 protein virtually absent, while RhoA protein levels were massively increased and Cdc42 protein levels were reduced. Since Arhgef6 is localized to dendritic spines, we next analyzed dendritic spines of adult FGF2(-/-) and control mouse cortices. Spine densities were significantly increased, whereas mean length of spines on dendrites of layer V of MSC neurons in adult FGF-2(-/-) mice was significantly decreased as compared to respective controls. Furthermore, neurite length in dissociated cortical cultures from E18 FGF-2(-/-) mice was significantly reduced at DIV7 as compared to wildtype neurons. Despite the fact that altered neuronal morphology and alterations in dendritic spines were observed, FGF-2(-/-) mice behave relatively unsuspicious in several behavioral tasks. However, FGF-2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test. PMID:26970009

  20. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.

    PubMed

    Corcoran, Jonathan; So, Po-Lin; Barber, Robert D; Vincent, Karen J; Mazarakis, Nicholas D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Maden, Malcolm

    2002-10-01

    Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use. PMID:12235288

  1. Neurite outgrowth at the interface of 2D and 3D growth environments

    NASA Astrophysics Data System (ADS)

    Kofron, Celinda M.; Fong, Vivian J.; Hoffman-Kim, Diane

    2009-02-01

    Growing neurons navigate complex environments, but in vitro systems for studying neuronal growth typically limit the cues to flat surfaces or a single type of cue, thereby limiting the resulting growth. Here we examined the growth of neurons presented with two-dimensional (2D) substrate-bound cues when these cues were presented in conjunction with a more complex three-dimensional (3D) architecture. Dorsal root ganglia (DRG) explants were cultured at the interface between a collagen I matrix and a glass coverslip. Laminin (LN) or chondroitin sulfate proteoglycans (CSPG) were uniformly coated on the surface of the glass coverslip or patterned in 50 µm tracks by microcontact printing. Quantitative analysis of neurite outgrowth with a novel grid system at multiple depths in the gel revealed several interesting trends. Most of the neurites extended at the surface of the gel when LN was presented whereas more neurites extended into the gel when CSPG was presented. Patterning of cues did not affect neurite density or depth of growth. However, neurite outgrowth near the surface of the gel aligned with LN patterns, and these extensions were significantly longer than neurites extended in other cultures. In interface cultures, DRG growth patterns varied with the type of cue where neurite density was higher in cultures presenting LN than in cultures presenting CSPG. These results represent an important step toward understanding how neurons integrate local structural and chemical cues to make net growth decisions.

  2. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells.

    PubMed

    Isoda, H; Shinmoto, H; Matsumura, M; Nakahara, T

    1999-09-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF). However, MEL-A induced one or two long neurites from the cell body, while NGF induced many neurites. In addition, MEL-A-induced differentiation was transient, and after 48 h, percentage of cells with neurites started to decrease in contrast to neurons induced by NGF, which occurred in a time-dependent manner. MEL-A could induce neurite outgrowth after treatment of PC12 cells with an anti-NGF receptor antibody that obstructed NGF action. These results indicate that MEL-A and NGF induce differentiation of PC12 cells through different mechanisms. PMID:19003137

  3. 15d-prostaglandin J2 enhancement of nerve growth factor-induced neurite outgrowth is blocked by the chemoattractant receptor- homologous molecule expressed on T-helper type 2 cells (CRTH2) antagonist CAY10471 in PC12 cells.

    PubMed

    Hatanaka, Michiyoshi; Shibata, Norihiro; Shintani, Norihito; Haba, Ryota; Hayata, Atsuko; Hashimoto, Hitoshi; Baba, Akemichi

    2010-01-01

    The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2 )(DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action. PMID:20424389

  4. Single Polymer Dynamics under Large Amplitude Oscillatory Extensional (LAOE) Flow

    NASA Astrophysics Data System (ADS)

    Zhou, Yuecheng; Schroeder, Charles M.

    Over the past two decades, advances in fluorescence imaging and particle manipulation have enabled the direct observation of single polymer dynamics in model flows such as shear flow and planar extensional flow. The vast majority of single polymer studies, however, has focused on chain dynamics using simple transient step forcing functions. In order to study single polymer dynamics in non-idealized model flows, there is a clear need to implement more complicated transient flow forcing functions. In bulk rheology, large amplitude oscillatory shear (LAOS) was widely used to study the linear and nonlinear viscoelasticity of materials, but not yet been applied to molecular rheology. In this work, we directly probe single polymer dynamics using oscillatory extensional flow in precisely controlled microfluidic devices. We are able to generate large and small amplitude sinusoidal oscillatory extensional flow in a cross-slot microfluidic device while imaging the conformational dynamics of a single polymer trapped at the stagnation point. In this flow, polymer chains are stretched, squeezed, and rotated between extensional/compressional axes in a highly dynamic and transient manner. Using this technique, we studied the dynamics and coil-stretch transition of a single λ-DNA as a function of the Weissenberg number (Wi) and Deborah number (De). Moreover, we use Brownian dynamics simulation to map a wide range of Pipkin space for polymers from linear steady-state conditions to non-linear unsteady-states. Our results reveal a critical Wi at the coil-stretch transition that is function of the De in LAOE flow. Department of Materials Science and Engineering.

  5. Examining Hyporheic Dynamics Under Fluctuating Stream Stage Conditions

    NASA Astrophysics Data System (ADS)

    Dudley-Southern, Marina; Binley, Andrew; Pates, Jackie; Wynn, Peter

    2014-05-01

    Gaining river systems that are connected to groundwaters with increasing nitrate levels are at risk from increased nitrate loading. The consequences of greater nitrate transfer to surface waters are uncertain, but attenuation of nitrate waters at the groundwater -surface water interface may help to reduce the ecological impact on receiving surface waters. The majority of studies of groundwater-surface water interactions have focussed on low flow conditions. Some studies have revealed evidence of biogeochemical reactions occurring at a greater depth in the subsurface than could be supported by mixing between surface water and groundwater under low flow conditions. We believe that, under particular geomorphological settings, short-lived changes in groundwater flow pathways may lead to transformations of the extent of hyporheic flow, and thus potentially impact on biogeochemical cycling at this interface. Here we focus on the influence of changes in stream stage, during storm events, on the extent of the hyporheic zone. It is hypothesised that when there is a large sudden change in surface water level, ambient groundwater gradients can undergo a transient reversal, leading to temporary downwelling of surface water which alters the physical and biogeochemical conditions in the subsurface. Physically, downwelling surface water increases the residence time of water within the subsurface by impeding the movement of upwelling groundwater. Biogeochemically, downwelling surface water supplies, for example, dissolved organic carbon to the subsurface, potentially supporting favourable redox conditions for nutrient transformations. To evaluate this concept, the dynamics of groundwater-surface water interactions are being examined at an instrumented gaining reach of the River Leith, Cumbria, UK. Experimental evidence is being gathered by continuously logged hydraulic head data, electrical geophysics and temperature profiles. These data are supported by repeat spot sampling

  6. Pseudo generators for under-resolved molecular dynamics

    NASA Astrophysics Data System (ADS)

    Bittracher, A.; Hartmann, C.; Junge, O.; Koltai, P.

    2015-09-01

    Many features of a molecule which are of physical interest (e.g. molecular conformations, reaction rates) are described in terms of its dynamics in configuration space. This article deals with the projection of molecular dynamics in phase space onto configuration space. Specifically, we study the situation that the phase space dynamics is governed by a stochastic Langevin equation and study its relation with the configurational Smoluchowski equation in the three different scaling regimes: Firstly, the Smoluchowski equations in non-Cartesian geometries are derived from the overdamped limit of the Langevin equation. Secondly, transfer operator methods are used to describe the metastable behaviour of the system at hand, and an explicit small-time asymptotics is derived on which the Smoluchowski equation turns out to govern the dynamics of the position coordinate (without any assumptions on the damping). By using an adequate reduction technique, these considerations are then extended to one-dimensional reaction coordinates. Thirdly, we sketch three different approaches to approximate the metastable dynamics based on time-local information only.

  7. Dynamic Stability of Uncertain Laminated Beams Under Subtangential Loads

    NASA Technical Reports Server (NTRS)

    Goyal, Vijay K.; Kapania, Rakesh K.; Adelman, Howard (Technical Monitor); Horta, Lucas (Technical Monitor)

    2002-01-01

    Because of the inherent complexity of fiber-reinforced laminated composites, it can be challenging to manufacture composite structures according to their exact design specifications, resulting in unwanted material and geometric uncertainties. In this research, we focus on the deterministic and probabilistic stability analysis of laminated structures subject to subtangential loading, a combination of conservative and nonconservative tangential loads, using the dynamic criterion. Thus a shear-deformable laminated beam element, including warping effects, is derived to study the deterministic and probabilistic response of laminated beams. This twenty-one degrees of freedom element can be used for solving both static and dynamic problems. In the first-order shear deformable model used here we have employed a more accurate method to obtain the transverse shear correction factor. The dynamic version of the principle of virtual work for laminated composites is expressed in its nondimensional form and the element tangent stiffness and mass matrices are obtained using analytical integration The stability is studied by giving the structure a small disturbance about an equilibrium configuration, and observing if the resulting response remains small. In order to study the dynamic behavior by including uncertainties into the problem, three models were developed: Exact Monte Carlo Simulation, Sensitivity Based Monte Carlo Simulation, and Probabilistic FEA. These methods were integrated into the developed finite element analysis. Also, perturbation and sensitivity analysis have been used to study nonconservative problems, as well as to study the stability analysis, using the dynamic criterion.

  8. Dynamics of range margins for metapopulations under climate change.

    PubMed

    Anderson, B J; Akçakaya, H R; Araújo, M B; Fordham, D A; Martinez-Meyer, E; Thuiller, W; Brook, B W

    2009-04-22

    We link spatially explicit climate change predictions to a dynamic metapopulation model. Predictions of species' responses to climate change, incorporating metapopulation dynamics and elements of dispersal, allow us to explore the range margin dynamics for two lagomorphs of conservation concern. Although the lagomorphs have very different distribution patterns, shifts at the edge of the range were more pronounced than shifts in the overall metapopulation. For Romerolagus diazi (volcano rabbit), the lower elevation range limit shifted upslope by approximately 700 m. This reduced the area occupied by the metapopulation, as the mountain peak currently lacks suitable vegetation. For Lepus timidus (European mountain hare), we modelled the British metapopulation. Increasing the dispersive estimate caused the metapopulation to shift faster on the northern range margin (leading edge). By contrast, it caused the metapopulation to respond to climate change slower, rather than faster, on the southern range margin (trailing edge). The differential responses of the leading and trailing range margins and the relative sensitivity of range limits to climate change compared with that of the metapopulation centroid have important implications for where conservation monitoring should be targeted. Our study demonstrates the importance and possibility of moving from simple bioclimatic envelope models to second-generation models that incorporate both dynamic climate change and metapopulation dynamics. PMID:19324811

  9. Dynamics of range margins for metapopulations under climate change

    PubMed Central

    Anderson, B.J.; Akçakaya, H.R.; Araújo, M.B.; Fordham, D.A.; Martinez-Meyer, E.; Thuiller, W.; Brook, B.W.

    2009-01-01

    We link spatially explicit climate change predictions to a dynamic metapopulation model. Predictions of species' responses to climate change, incorporating metapopulation dynamics and elements of dispersal, allow us to explore the range margin dynamics for two lagomorphs of conservation concern. Although the lagomorphs have very different distribution patterns, shifts at the edge of the range were more pronounced than shifts in the overall metapopulation. For Romerolagus diazi (volcano rabbit), the lower elevation range limit shifted upslope by approximately 700 m. This reduced the area occupied by the metapopulation, as the mountain peak currently lacks suitable vegetation. For Lepus timidus (European mountain hare), we modelled the British metapopulation. Increasing the dispersive estimate caused the metapopulation to shift faster on the northern range margin (leading edge). By contrast, it caused the metapopulation to respond to climate change slower, rather than faster, on the southern range margin (trailing edge). The differential responses of the leading and trailing range margins and the relative sensitivity of range limits to climate change compared with that of the metapopulation centroid have important implications for where conservation monitoring should be targeted. Our study demonstrates the importance and possibility of moving from simple bioclimatic envelope models to second-generation models that incorporate both dynamic climate change and metapopulation dynamics. PMID:19324811

  10. Expression of Ndufb11 encoding the neuronal protein 15.6 during neurite outgrowth and development.

    PubMed

    Gurok, Ulf; Bork, Kaya; Nuber, Ulrike; Spörle, Ralf; Nöhring, Sabine; Horstkorte, Rüdiger

    2007-01-01

    Neurite outgrowth (e.g. axonal or dendrite outgrowth) of neurons is necessary for the development and functioning of the central nervous system. It is well accepted that the differentiation of neurons and neurite outgrowth involve alterations in gene expression. Furthermore, mitochondria play a role in different aspects of neurite outgrowth. Here we show that the expression of Ndufb11, a gene encoding the mitochondrial protein NP15.6 is decreased in the course of neuronal differentiation. NP15.6 is homologous to the bovine protein ESSS, a component of the mitochondrial complex 1. The homologous human NDUFB11 gene is localized to Xp11.3-Xp11.23, a region associated with neurogenetic disorders. The down-regulation of NP15.6 correlates with neurite outgrowth of PC12 cells induced by nerve growth factor. Furthermore, we analyzed the expression of Ndufb11 in the embryonic and adult mouse. PMID:16962385

  11. ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro

    PubMed Central

    Jia, Xu-feng; Ye, Fei; Wang, Yan-bo; Feng, Da-xiong

    2016-01-01

    Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway. PMID:27482229

  12. ANALYSIS OF THE STRUCTURE OF MAGNETIC FIELDS THAT INDUCED INHIBITION OF STIMULATED NEURITE OUTGROWTH

    EPA Science Inventory

    The important experiments showing nonlinear amplitude dependences of the neurite outgrowth in pheochromocytoma nerve cells due to ELF magnetic field exposure had been carried out in a nonuniform ac magnetic field. The nonuniformity entailed larger than expected variances in magne...

  13. Morphological assessment of neurite outgrowth in hippocampal neuron-astrocyte co-cultures.

    PubMed

    Giordano, Gennaro; Costa, Lucio G

    2012-05-01

    Neurite outgrowth is a fundamental event in brain development, as well as in regeneration of damaged neurons. Astrocytes play a major role in neuritogenesis, by expressing and releasing factors that facilitate neurite outgrowth, such as extracellular matrix proteins, and factors that can inhibit neuritogenesis, such as the chondroitin sulfate proteoglycan neurocan. In this unit we describe a noncontact co-culture system of hippocampal neurons and cortical (or hippocampal) astrocytes for measurement of neurite outgrowth. Hippocampal pyramidal neurons are plated on glass coverslips, which are inverted onto an astrocyte feeder layer, allowing exposure of neurons to astrocyte-derived factors without direct contact between these two cell types. After co-culture, neurons are stained and photographed, and processes are assessed morphologically using Metamorph software. This method allows exposing astrocytes to various agents before co-culture in order to assess how these exposures may influence the ability of astrocytes to foster neurite outgrowth. PMID:22549268

  14. Gait recognition under carrying condition: a static dynamic fusion method

    NASA Astrophysics Data System (ADS)

    Yu, Guan; Li, Chang-Tsun; Hu, Yongjian

    2012-06-01

    When an individual carries an object, such as a briefcase, conventional gait recognition algorithms based on average silhouette/Gait Energy Image (GEI) do not always perform well as the object carried may have the potential of being mistakenly regarded as a part of the human body. To solve such a problem, in this paper, instead of directly applying GEI to represent the gait information, we propose a novel dynamic feature template for classification. Based on this extracted dynamic information and some static feature templates (i.e., head part and trunk part), we cast gait recognition on the large USF (University of South Florida) database by adopting a static/dynamic fusion strategy. For the experiments involving carrying condition covariate, significant improvements are achieved when compared with other classic algorithms.

  15. Design of three-dimensional engineered protein hydrogels for tailored control of neurite growth.

    PubMed

    Lampe, Kyle J; Antaris, Alexander L; Heilshorn, Sarah C

    2013-03-01

    The design of bioactive materials allows tailored studies probing cell-biomaterial interactions, however, relatively few studies have examined the effects of ligand density and material stiffness on neurite growth in three-dimensions. Elastin-like proteins (ELPs) have been designed with modular bioactive and structural regions to enable the systematic characterization of design parameters within three-dimensional (3-D) materials. To promote neurite out-growth and better understand the effects of common biomaterial design parameters on neuronal cultures we here focused on the cell-adhesive ligand density and hydrogel stiffness as design variables for ELP hydrogels. With the inherent design freedom of engineered proteins these 3-D ELP hydrogels enabled decoupled investigations into the effects of biomechanics and biochemistry on neurite out-growth from dorsal root ganglia. Increasing the cell-adhesive RGD ligand density from 0 to 1.9×10(7)ligands μm(-3) led to a significant increase in the rate, length, and density of neurite out-growth, as quantified by a high throughput algorithm developed for dense neurite analysis. An approximately two-fold improvement in total neurite out-growth was observed in materials with the higher ligand density at all time points up to 7 days. ELP hydrogels with initial elastic moduli of 0.5, 1.5, or 2.1kPa and identical RGD ligand densities revealed that the most compliant materials led to the greatest out-growth, with some neurites extending over 1800μm by day 7. Given the ability of ELP hydrogels to efficiently promote neurite out-growth within defined and tunable 3-D microenvironments these materials may be useful in developing therapeutic nerve guides and the further study of basic neuron-biomaterial interactions. PMID:23128159

  16. Functional coordination of muscles underlying changes in behavioural dynamics.

    PubMed

    Vernooij, Carlijn A; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K; Temprado, Jean-Jacques

    2016-01-01

    The dynamical systems approach addresses Bernstein's degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts' task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts' task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system. PMID:27282349

  17. Functional coordination of muscles underlying changes in behavioural dynamics

    PubMed Central

    Vernooij, Carlijn A.; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K.; Temprado, Jean-Jacques

    2016-01-01

    The dynamical systems approach addresses Bernstein’s degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts’ task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts’ task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system. PMID:27282349

  18. Soil phosphorus dynamics under sprinkler and furrow irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Furrow irrigation detaches and transports soil particles and subsequently nutrients such as phosphorus. To reduce the risk of erosion and offsite phosphorus movement, producers can convert from furrow to sprinkler irrigation. We completed research on soil phosphorus dynamics in furrow versus sprin...

  19. MorphoNeuroNet: an automated method for dense neurite network analysis.

    PubMed

    Pani, Giuseppe; De Vos, Winnok H; Samari, Nada; de Saint-Georges, Louis; Baatout, Sarah; Van Oostveldt, Patrick; Benotmane, Mohammed Abderrafi

    2014-02-01

    High content cell-based screens are rapidly gaining popularity in the context of neuronal regeneration studies. To analyze neuronal morphology, automatic image analysis pipelines have been conceived, which accurately quantify the shape changes of neurons in cell cultures with non-dense neurite networks. However, most existing methods show poor performance for well-connected and differentiated neuronal networks, which may serve as valuable models for inter alia synaptogenesis. Here, we present a fully automated method for quantifying the morphology of neurons and the density of neurite networks, in dense neuronal cultures, which are grown for more than 10 days. MorphoNeuroNet, written as a script for ImageJ, Java based freeware, automatically determines various morphological parameters of the soma and the neurites (size, shape, starting points, and fractional occupation). The image analysis pipeline consists of a multi-tier approach in which the somas are segmented by adaptive region growing using nuclei as seeds, and the neurites are delineated by a combination of various intensity and edge detection algorithms. Quantitative comparison showed a superior performance of MorphoNeuroNet to existing analysis tools, especially for revealing subtle changes in thin neurites, which have weak fluorescence intensity compared to the rest of the network. The proposed method will help determining the effects of compounds on cultures with dense neurite networks, thereby boosting physiological relevance of cell-based assays in the context of neuronal diseases. PMID:24222510

  20. Myoblasts and myoblast-conditioned medium attract the earliest spinal neurites from frog embryos.

    PubMed Central

    McCaig, C D

    1986-01-01

    A study was made of the capacity of newly segmented somites, unsegmented mesoderm and medium conditioned by each of these tissues to attract the growth of the earliest spinal neurites from the neural tube of Xenopus laevis in tissue culture. When presented with segmented somitic myoblasts or sheets of skin, spinal neurites grew selectively towards the somitic myoblasts. Neurites were not attracted specifically to somitic myoblasts from their own rostrocaudal level. A variable proportion of myoblasts from unsegmented caudal mesoderm differentiated and elongated in co-culture with neural tube and skin. These myoblasts also attracted neural outgrowths, but only if present in sufficient numbers. An agar slab containing medium conditioned by the presence of segmented myoblasts for 1 day attracted neurite outgrowths. A source of medium conditioned by the presence of undifferentiated, unsegmented myotomal mesoderm alone did not attract neurite outgrowths. Nerve growth factor (NGF) at a range of concentrations in the agar source (500-10,000 ng/ml) did not attract the earliest neurite outgrowths. It is concluded that the earliest skeletal myoblasts from Xenopus laevis embryos may attract neural outgrowths by releasing a soluble factor. Myoblasts may have to develop to the stage of somite segmentation before secretion of such an agent begins. The release of a myoblast-derived factor so early in development may assist directed nerve growth in vivo. Images Plate 1 Plate 2 PMID:3795063

  1. Amyloid β-Protein as a Substrate Interacts with Extracellular Matrix to Promote Neurite Outgrowth

    NASA Astrophysics Data System (ADS)

    Koo, Edward H.; Park, Lisa; Selkoe, Dennis J.

    1993-05-01

    Progressive deposition of amyloid β-protein (Aβ) in brain parenchyma and blood vessels is a characteristic feature of Alzheimer disease. Recent evidence suggests that addition of solubilized synthetic Aβ to medium may produce toxic or trophic effects on cultured hippocampal neurons. Because soluble Aβ may not accumulate in significant quantities in brain, we asked whether immobilized Aβ peptide as a substrate alters neurite outgrowth from cultured rat peripheral sensory neurons. This paradigm may closely mimic the conditions in Alzheimer disease brain tissue, in which neurites contact insoluble, extracellular aggregates of β-amyloid. We detected no detrimental effects of Aβ substrate on neurite outgrowth. Rather, Aβ in combination with low doses of laminin or fibronectin enhanced neurite out-growth from these neuronal explants. Our results suggest that insoluble Aβ in the cerebral neuropil may serve as a neurite-promoting matrix, perhaps explaining the apparent regenerative response of neurites observed around amyloid plaques in Alzheimer disease. Moreover, in concert with the recent discovery of Aβ production by cultured neurons, our data suggest that Aβ plays a normal physiological role in brain by complexing with the extracellular matrix.

  2. Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha.

    PubMed

    Schmitt, Katharina R L; Boato, Francesco; Diestel, Antje; Hechler, Daniel; Kruglov, Andrei; Berger, Felix; Hendrix, Sven

    2010-07-01

    Systemic or brain-selective hypothermia is a well-established method for neuroprotection after brain trauma. There is increasing evidence that hypothermia exerts beneficial effects on the brain and may also support regenerative responses after brain damage. Here, we have investigated whether hypothermia influences neurite outgrowth in vitro via modulation of the post-injury cytokine milieu. Organotypic brain slices were incubated: deep hypothermia (2 h at 17 degrees C), rewarming (2 h up to 37 degrees C), normothermia (20 h at 37 degrees C). Neurite density and cytokine release (IL 1beta, IL-6, IL-10, and TNF-alpha) were investigated after 24 h. For functional analysis mice deficient in NT-3/NT-4 and TNF-alpha as well as the TNF-alpha inhibitor etanercept were used. Hypothermia led to a significant increase of neurite outgrowth, which was independent of neurotrophin signaling. In contrast to other cytokines investigated, TNF-alpha secretion by organotypic brain slices was significantly increased after deep hypothermia. Moreover, hypothermia-induced neurite extension was abolished after administration of the TNF-alpha inhibitor and in TNF-alpha knockout mice. We demonstrate that TNF-alpha is responsible for inducing neurite outgrowth in the context of deep hypothermia and rewarming. These data suggest that hypothermia not only exerts protective effects in the CNS but may also support neurite outgrowth as a potential mechanism of regeneration. PMID:20070303

  3. Survival and neurite growth of chick embryo spinal cord cells in serum-free culture.

    PubMed

    Tanaka, H; Obata, K

    1982-07-01

    Cell survival and neurite growth were investigated in serum-free spinal cord cell cultures on polyornithine coating (PORN). Cells were obtained from 6- or 7-day-old chick embryos. Isolated spinal cord cells required promoting factors for their survival and neurite growth. The survival-promoting factors were initially present in spinal cord cells. High density cultures, co-cultures with spinal cord explants, and spinal cord extract promoted survival of isolated spinal cord cells in MEM with no additives. Other tissue extracts (brain, liver, heart and skeletal muscle), serum, and serum-free conditioned medium (SF-CM) of muscle or glioma C6 cells also promoted survival. The active substances in the brain extract and SF-CM were shown to be protein and were separated into 3 fractions (approximately molecular weight 150,000, 70,000, 40,000) by gel filtration chromatography. Survival and neurite growth were suggested to be promoted by different factors because: (1) survival was promoted by both tissue extract and SF-CM, but neurite growth was promoted only by SF-CM; (2) the neurite growth-stimulating activity of SF-CM was lost following dialysis and heat (100 degrees C, 2 min) treatment; however, the survival-promoting activity was not. It was also suggested that spinal cord cells produce neurite growth promoting factors, but did not initially contain these factors. PMID:7104764

  4. Multiscale Analysis of Neurite Orientation and Spatial Organization in Neuronal Images.

    PubMed

    Singh, Pankaj; Negi, Pooran; Laezza, Fernanda; Papadakis, Manos; Labate, Demetrio

    2016-10-01

    The spatial organization of neurites, the thin processes (i.e., dendrites and axons) that stem from a neuron's soma, conveys structural information required for proper brain function. The alignment, direction and overall geometry of neurites in the brain are subject to continuous remodeling in response to healthy and noxious stimuli. In the developing brain, during neurogenesis or in neuroregeneration, these structural changes are indicators of the ability of neurons to establish axon-to-dendrite connections that can ultimately develop into functional synapses. Enabling a proper quantification of this structural remodeling would facilitate the identification of new phenotypic criteria to classify developmental stages and further our understanding of brain function. However, adequate algorithms to accurately and reliably quantify neurite orientation and alignment are still lacking. To fill this gap, we introduce a novel algorithm that relies on multiscale directional filters designed to measure local neurites orientation over multiple scales. This innovative approach allows us to discriminate the physical orientation of neurites from finer scale phenomena associated with local irregularities and noise. Building on this multiscale framework, we also introduce a notion of alignment score that we apply to quantify the degree of spatial organization of neurites in tissue and cultured neurons. Numerical codes were implemented in Python and released open source and freely available to the scientific community. PMID:27369547

  5. Sigma-1 Receptor Enhances Neurite Elongation of Cerebellar Granule Neurons via TrkB Signaling

    PubMed Central

    Kimura, Yuriko; Fujita, Yuki; Shibata, Kumi; Mori, Megumi; Yamashita, Toshihide

    2013-01-01

    Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various synthetic compounds including well-known psychotherapeutic drugs in the central nervous system (CNS). For that, it is considered as an alternative target for psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is known to play a role in neuroprotection and neurite elongation. These effects are suggested to be mediated by its ligand-operated molecular chaperone activity, and/or upregulation of various Ca2+ signaling. In addition, recent studies show that Sig-1R activation induces neurite outgrowth via neurotrophin signaling. Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706. Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in CGNs through Y515 phosphorylation of TrkB. PMID:24116072

  6. In vitro neurite guidance effects induced by polylysine pinstripe micropatterns with polylysine background.

    PubMed

    Joo, Sunghoon; Kang, Kyungtae; Nam, Yoonkey

    2015-08-01

    Engineered culture substrates with chemical neurite guidance cues have been used for studying the mechanism of axon pathfinding at cellular level. In this study, we designed a novel poly-l-lysine (PLL) micropattern ("pinstripe micropattern") to investigate how the same biomolecules with slightly different surface concentration can affect in vitro neuronal growth. The pinstripe micropattern was fabricated by stamping PLL on a PLL-coated glass coverslip, which resulted in denser PLL lines and a less-dense PLL background. There were two effects of the substrate on cultured primary hippocampal neuron: neurite initiation and growth cone turning. Although the whole surface was permissive for neurite outgrowth, we observed that the growth direction of neurites had a strong tendency to follow the stamped PLL line patterns with PLL background. However, the micropattern did not affect the spreading of cell body on the substrate. According to these investigations, we concluded that the PLL pinstripe pattern with PLL background, which had the step difference of polylysine concentrations, would be very useful for designing novel cell assays for the investigation of neurite guidance mechanisms, and suggested it as a new design method for controlling the direction of neurite growth on in vitro neural network. PMID:25630479

  7. Oxytocin Increases Neurite Length and Expression of Cytoskeletal Proteins Associated with Neuronal Growth.

    PubMed

    Lestanova, Z; Bacova, Z; Kiss, A; Havranek, T; Strbak, V; Bakos, J

    2016-06-01

    Neuropeptide oxytocin acts as a growth and differentiation factor; however, its effects on neurite growth are poorly understood. The aims of the present study were (1) to evaluate time effects of oxytocin on expression of nestin and MAP2; (2) to measure the effect of oxytocin on gene expression of β-actin, vimentin, cofilin, and drebrin; and (3) to measure changes in neurite length and number in response to oxytocin/oxytocin receptor antagonist L-371,257. Exposure of SH-SY5Y cells to 1 μM oxytocin resulted in a significant increase in gene expression and protein levels of nestin after 12, 24, and 48 h. Oxytocin treatment induced no changes in gene expression of MAP2; however, a decrease of protein levels was observed in all time intervals. Gene expression of β-actin, vimentin, and drebrin increased in response to oxytocin. Oxytocin induced significant elongation of neurites after 12, 24, and 48 h. No change in neurite length was observed in the presence of the combination of retinoic acid and oxytocin receptor antagonist L-371,257. Oxytocin treatment for 12 h increased the number of neurites. Overall, the present data suggest that oxytocin contributes to the regulation of expression of cytoskeletal proteins associated with growth of neuronal cones and induces neurite elongation mediated by oxytocin receptors at least in certain types of neuronal cells. PMID:26474566

  8. Control of Retinal Ganglion Cell Positioning and Neurite Growth: Combining 3D Printing with Radial Electrospun Scaffolds.

    PubMed

    Kador, Karl E; Grogan, Shawn P; Dorthé, Erik W; Venugopalan, Praseeda; Malek, Monisha F; Goldberg, Jeffrey L; D'lima, Darryl D

    2016-02-01

    Retinal ganglion cells (RGCs) are responsible for the transfer of signals from the retina to the brain. As part of the central nervous system, RGCs are unable to regenerate following injury, and implanted cells have limited capacity to orient and integrate in vivo. During development, secreted guidance molecules along with signals from extracellular matrix and the vasculature guide cell positioning, for example, around the fovea, and axon outgrowth; however, these changes are temporally regulated and are not the same in the adult. Here, we combine electrospun cell transplantation scaffolds capable of RGC neurite guidance with thermal inkjet 3D cell printing techniques capable of precise positioning of RGCs on the scaffold surface. Optimal printing parameters are developed for viability, electrophysiological function and, neurite pathfinding. Different media, commonly used to promote RGC survival and growth, were tested under varying conditions. When printed in growth media containing both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), RGCs maintained survival and normal electrophysiological function, and displayed radial axon outgrowth when printed onto electrospun scaffolds. These results demonstrate that 3D printing technology may be combined with complex electrospun surfaces in the design of future retinal models or therapies. PMID:26729061

  9. Minimum Wind Dynamic Soaring Trajectories under Boundary Layer Thickness Limits

    NASA Astrophysics Data System (ADS)

    Bousquet, Gabriel; Triantafyllou, Michael; Slotine, Jean-Jacques

    2015-11-01

    Dynamic soaring is the flight technique where a glider, either avian or manmade, extracts its propulsive energy from the non-uniformity of horizontal winds. Albatrosses have been recorded to fly an impressive 5000 km/week at no energy cost of their own. In the sharp boundary layer limit, we show that the popular image, where the glider travels in a succession of half turns, is suboptimal for travel speed, airspeed, and soaring ability. Instead, we show that the strategy that maximizes the three criteria simultaneously is a succession of infinitely small arc-circles connecting transitions between the calm and windy layers. The model is consistent with the recordings of albatross flight patterns. This lowers the required wind speed for dynamic soaring by over 50% compared to previous beliefs. In the thick boundary layer limit, energetic considerations allow us to predict a minimum wind gradient necessary for sustained soaring consistent with numerical models.

  10. Studies of TLP dynamic response under wind, waves and current

    NASA Astrophysics Data System (ADS)

    Gu, Jia-yang; Yang, Jian-min; Lv, Hai-ning

    2012-09-01

    Investigated is the coupled response of a tension leg platform (TLP) for random waves. Inferred are the mass matrix, coupling stiffness matrix, damping matrix in the vibration differential equation and external load of TLP in moving coordinating system. Infinitesimal method is applied to divide columns and pontoons into small parts. Time domain motion equation is solved by Runge-Kutta integration scheme. Jonswap spectrum is simulated in the random wave, current is simulated by linear interpolation, and NPD spectrum is applied as wind spectrum. The Monte Carlo method is used to simulate random waves and fluctuated wind. Coupling dynamic response, change of tendon tension and riser tension in different sea conditions are analyzed by power spectral density (PSD). The influence of approach angle on dynamic response of TLP and tendon tension is compared.