Sample records for growth cone motility

  1. How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?

    PubMed

    Gasperini, Robert J; Pavez, Macarena; Thompson, Adrian C; Mitchell, Camilla B; Hardy, Holly; Young, Kaylene M; Chilton, John K; Foa, Lisa

    2017-10-01

    The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. The SH2/SH3 adaptor protein dock interacts with the Ste20-like kinase misshapen in controlling growth cone motility.

    PubMed

    Ruan, W; Pang, P; Rao, Y

    1999-11-01

    Recent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals.

  3. Neuronal Cell Cultures from Aplysia for High-Resolution Imaging of Growth Cones

    PubMed Central

    Lee, Aih Cheun; Decourt, Boris; Suter, Daniel

    2008-01-01

    Neuronal growth cones are the highly motile structures at the tip of axons that can detect guidance cues in the environment and transduce this information into directional movement towards the appropriate target cell. To fully understand how guidance information is transmitted from the cell surface to the underlying dynamic cytoskeletal networks, one needs a model system suitable for live cell imaging of protein dynamics at high temporal and spatial resolution. Typical vertebrate growth cones are too small to quantitatively analyze F-actin and microtubule dynamics. Neurons from the sea hare Aplysia californica are 5-10 times larger than vertebrate neurons, can easily be kept at room temperature and are very robust cells for micromanipulation and biophysical measurements. Their growth cones have very defined cytoplasmic regions and a well-described cytoskeletal system. The neuronal cell bodies can be microinjected with a variety of probes for studying growth cone motility and guidance. In the present protocol we demonstrate a procedure for dissection of the abdominal ganglion, culture of bag cell neurons and setting up an imaging chamber for live cell imaging of growth cones. PMID:19066568

  4. Domain requirements for the Dock adapter protein in growth- cone signaling

    PubMed Central

    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons. PMID:9482841

  5. Domain requirements for the Dock adapter protein in growth- cone signaling.

    PubMed

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  6. Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane.

    PubMed

    Vitriol, Eric A; Zheng, James Q

    2012-03-22

    Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of the neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to reach their targets. Research in the past two decades has also gained significant insight into the ways in which growth cones translate extracellular signals into directional migration. This review aims to examine new progress toward understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically, we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Oxygen radicals elicit paralysis and collapse of spinal cord neuron growth cones upon exposure to proinflammatory cytokines.

    PubMed

    Kuhn, Thomas B

    2014-01-01

    A persistent inflammatory and oxidative stress is a hallmark of most chronic CNS pathologies (Alzheimer's (ALS)) as well as the aging CNS orchestrated by the proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β). Loss of the integrity and plasticity of neuronal morphology and connectivity comprises an early step in neuronal degeneration and ultimate decline of cognitive function. We examined in vitro whether TNFα or IL-1β impaired morphology and motility of growth cones in spinal cord neuron cultures. TNFα and IL-1β paralyzed growth cone motility and induced growth cone collapse in a dose-dependent manner reflected by complete attenuation of neurite outgrowth. Scavenging reactive oxygen species (ROS) or inhibiting NADPH oxidase activity rescued loss of neuronal motility and morphology. TNFα and IL-1β provoked rapid, NOX-mediated generation of ROS in advancing growth cones, which preceded paralysis of motility and collapse of morphology. Increases in ROS intermediates were accompanied by an aberrant, nonproductive reorganization of actin filaments. These findings suggest that NADPH oxidase serves as a pivotal source of oxidative stress in neurons and together with disruption of actin filament reorganization contributes to the progressive degeneration of neuronal morphology in the diseased or aging CNS.

  8. Growth Cone Biomechanics in Peripheral and Central Nervous System Neurons

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey; Koch, Daniel; Rosoff, Will; Geller, Herbert

    2012-02-01

    The growth cone, a highly motile structure at the tip of an axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth-cone mediated guidance. We have investigated neurite outgrowth, traction forces and cytoskeletal substrate coupling on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that the biomechanics of DRG neurons are dramatically different from hippocampal, with DRG neurons displaying relatively large, steady traction forces and maximal outgrowth and forces on substrates of intermediate stiffness, while hippocampal neurons display weak, intermittent forces and limited dependence of outgrowth and forces on substrate stiffness. DRG growth cones have slower rates of retrograde actin flow and higher density of localized paxillin (a protein associated with substrate adhesion complexes) compared to hippocampal neurons, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate coupling in DRG growth cones.

  9. Liner collection cone and pH effects on postthaw motility, staining, and acrosomes of bovine spermatozoa.

    PubMed

    Smith, J F; Merilan, C P

    1991-04-01

    Sixteen ejaculates were collected, four each from four bulls, using artificial vaginas with polyethylene or rubber liner collection cones in a crossover design experiment. The ejaculates were diluted with egg yolk-citrate extender at pH 6.4 or 7.2, cooled, glycerolated, equilibrated, packaged in .5-ml French straws, frozen in nitrogen vapor, and stored in liquid nitrogen. Thirty frozen straws from each ejaculate were thawed rapidly (46.5 degrees C for 12 s), pooled, and then incubated at 46.5 degrees C for periodic evaluation of progressive motility, differential staining, and acrosome morphology under thermal stress conditions. The postthaw motility of spermatozoa and percentage of unstained cells were higher both when collected in polyethylene than in rubber and when extended at pH 7.2 vs. 6.4, but no interaction was found between liner collection cone composition and pII for postthaw motility. Retention of spermatozoan motility during incubation under thermal stress was greater for cells collected in polyethylene, but not different due to pH. Neither pH nor composition of liner collection cone had an effect on postthaw acrosomal scores, but the time required for a 50% increase in severely damaged acrosomes was greater for spermatozoa collected in polyethylene than in rubber liner collection cones.

  10. Drosophila Growth Cones Advance by Forward Translocation of the Neuronal Cytoskeletal Meshwork In Vivo

    PubMed Central

    Roossien, Douglas H.; Lamoureux, Phillip; Van Vactor, David; Miller, Kyle E.

    2013-01-01

    In vitro studies conducted in Aplysia and chick sensory neurons indicate that in addition to microtubule assembly, long microtubules in the C-domain of the growth cone move forward as a coherent bundle during axonal elongation. Nonetheless, whether this mode of microtubule translocation contributes to growth cone motility in vivo is unknown. To address this question, we turned to the model system Drosophila. Using docked mitochondria as fiduciary markers for the translocation of long microtubules, we first examined motion along the axon to test if the pattern of axonal elongation is conserved between Drosophila and other species in vitro. When Drosophila neurons were cultured on Drosophila extracellular matrix proteins collected from the Drosophila Kc167 cell line, docked mitochondria moved in a pattern indicative of bulk microtubule translocation, similar to that observed in chick sensory neurons grown on laminin. To investigate whether the C-domain is stationary or advances in vivo, we tracked the movement of mitochondria during elongation of the aCC motor neuron in stage 16 Drosophila embryos. We found docked mitochondria moved forward along the axon shaft and in the growth cone C-domain. This work confirms that the physical mechanism of growth cone advance is similar between Drosophila and vertebrate neurons and suggests forward translocation of the microtubule meshwork in the axon underlies the advance of the growth cone C-domain in vivo. These results highlight the need for incorporating en masse microtubule translocation, in addition to assembly, into models of axonal elongation. PMID:24244629

  11. Protein Kinase C Activation Promotes Microtubule Advance in Neuronal Growth Cones by Increasing Average Microtubule Growth Lifetimes

    PubMed Central

    Kabir, Nurul; Schaefer, Andrew W.; Nakhost, Arash; Sossin, Wayne S.; Forscher, Paul

    2001-01-01

    We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects. Significantly, MT advance occurred despite continued retrograde F-actin flow—a process that normally inhibits MT advance. Polymer assembly was necessary for PKC-mediated MT advance since it was highly sensitive to a range of antagonists at concentrations that specifically interfere with microtubule dynamics. Biochemical evidence is presented that PKC activation promotes formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics and translocation using the fluorescent speckle microscopy microtubule marking technique indicates PKC activation results in a nearly twofold increase in the typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and twofold decrease in rescue and catastrophe frequencies, respectively. No significant effects on instantaneous microtubule growth, shortening, or sliding rates (in either anterograde or retrograde directions) were observed. MTs also spent a greater percentage of time undergoing retrograde transport after PKC activation, despite overall MT advance. These results suggest that regulation of MT assembly by PKC may be an important factor in determining neurite outgrowth and regrowth rates and may play a role in other cellular processes dependent on directed MT advance. PMID:11238458

  12. Retrograde degeneration of neurite membrane structural integrity of nerve growth cones following in vitro exposure to mercury.

    PubMed

    Leong, C C; Syed, N I; Lorscheider, F L

    2001-03-26

    Inhalation of mercury vapor (Hg0) inhibits binding of GTP to rat brain tubulin, thereby inhibiting tubulin polymerization into microtubules. A similar molecular lesion has also been observed in 80% of brains from patients with Alzheimer disease (AD) compared to age-matched controls. However the precise site and mode of action of Hg ions remain illusive. Therefore, the present study examined whether Hg ions could affect membrane dynamics of neurite growth cone morphology and behavior. Since tubulin is a highly conserved cytoskeletal protein in both vertebrates and invertebrates, we hypothesized that growth cones from animal species could be highly susceptible to Hg ions. To test this possibility, the identified, large Pedal A (PeA) neurons from the central ring ganglia of the snail Lymnoea stagnalis were cultured for 48 h in 2 ml brain conditioned medium (CM). Following neurite outgrowth, metal chloride solution (2 microl) of Hg, Al, Pb, Cd, or Mn (10(-7) M) was pressure applied directly onto individual growth cones. Time-lapse images with inverted microscopy were acquired prior to, during, and after the metal ion exposure. We demonstrate that Hg ions markedly disrupted membrane structure and linear growth rates of imaged neurites in 77% of all nerve growth cones. When growth cones were stained with antibodies specific for both tubulin and actin, it was the tubulin/microtubule structure that disintegrated following Hg exposure. Moreover, some denuded neurites were also observed to form neurofibrillary aggregates. In contrast, growth cone exposure to other metal ions did not effect growth cone morphology, nor was their motility rate compromised. To determine the growth suppressive effects of Hg ions on neuronal sprouting, cells were cultured either in the presence or absence of Hg ions. We found that in the presence of Hg ions, neuronal somata failed to sprout, whereas other metalic ions did not effect growth patterns of cultured PeA cells. We conclude that this

  13. Substrate Deformation Predicts Neuronal Growth Cone Advance

    PubMed Central

    Athamneh, Ahmad I.M.; Cartagena-Rivera, Alexander X.; Raman, Arvind; Suter, Daniel M.

    2015-01-01

    Although pulling forces have been observed in axonal growth for several decades, their underlying mechanisms, absolute magnitudes, and exact roles are not well understood. In this study, using two different experimental approaches, we quantified retrograde traction force in Aplysia californica neuronal growth cones as they develop over time in response to a new adhesion substrate. In the first approach, we developed a novel method, to our knowledge, for measuring traction forces using an atomic force microscope (AFM) with a cantilever that was modified with an Aplysia cell adhesion molecule (apCAM)-coated microbead. In the second approach, we used force-calibrated glass microneedles coated with apCAM ligands to guide growth cone advance. The traction force exerted by the growth cone was measured by monitoring the microneedle deflection using an optical microscope. Both approaches showed that Aplysia growth cones can develop traction forces in the 100–102 nN range during adhesion-mediated advance. Moreover, our results suggest that the level of traction force is directly correlated to the stiffness of the microneedle, which is consistent with a reinforcement mechanism previously observed in other cell types. Interestingly, the absolute level of traction force did not correlate with growth cone advance toward the adhesion site, but the amount of microneedle deflection did. In cases of adhesion-mediated growth cone advance, the mean needle deflection was 1.05 ± 0.07 μm. By contrast, the mean deflection was significantly lower (0.48 ± 0.06 μm) when the growth cones did not advance. Our data support a hypothesis that adhesion complexes, which can undergo micron-scale elastic deformation, regulate the coupling between the retrogradely flowing actin cytoskeleton and apCAM substrates, stimulating growth cone advance if sufficiently abundant. PMID:26445437

  14. Growth cones are actively influenced by substrate-bound adhesion molecules.

    PubMed

    Burden-Gulley, S M; Payne, H R; Lemmon, V

    1995-06-01

    As axons advance to appropriate target tissues during development, their growth cones encounter a variety of cell adhesion molecules (CAMs) and extracellular matrix molecules (ECM molecules). Purified CAMs and ECM molecules influence neurite outgrowth in vitro and are thought to have a similar function in vivo. For example, when retinal ganglion cell (RGC) neurons are grown on different CAM and ECM molecule substrates in vitro, their growth cones display distinctive morphologies (Payne et al., 1992). Similarly, RGC growth cones in vivo have distinctive shapes at different points in the pathway from the eye to the tectum, suggesting the presence of localized cues that determine growth cone behaviors such as pathway selection at choice points. In this report, time-lapse video microscopy was utilized to examine dynamic transformations of RGC growth cones as they progressed from L1/8D9, N-cadherin, or laminin onto a different substrate. Contact made by the leading edge of a growth cone with a new substrate resulted in a rapid and dramatic alteration in growth cone morphology. In some cases, the changes encompassed the entire growth cone including those regions not in direct contact with the new substrate. In addition, the growth cones displayed a variety of behavioral responses that were dependent upon the order of substrate contact. These studies demonstrate that growth cones are actively affected by the substrate, and suggest that abrupt changes in the molecular composition of the growth cone environment are influential during axonal pathfinding.

  15. Filopodial dynamics and growth cone stabilization in Drosophila visual circuit development

    PubMed Central

    Özel, Mehmet Neset; Langen, Marion; Hassan, Bassem A; Hiesinger, P Robin

    2015-01-01

    Filopodial dynamics are thought to control growth cone guidance, but the types and roles of growth cone dynamics underlying neural circuit assembly in a living brain are largely unknown. To address this issue, we have developed long-term, continuous, fast and high-resolution imaging of growth cone dynamics from axon growth to synapse formation in cultured Drosophila brains. Using R7 photoreceptor neurons as a model we show that >90% of the growth cone filopodia exhibit fast, stochastic dynamics that persist despite ongoing stepwise layer formation. Correspondingly, R7 growth cones stabilize early and change their final position by passive dislocation. N-Cadherin controls both fast filopodial dynamics and growth cone stabilization. Surprisingly, loss of N-Cadherin causes no primary targeting defects, but destabilizes R7 growth cones to jump between correct and incorrect layers. Hence, growth cone dynamics can influence wiring specificity without a direct role in target recognition and implement simple rules during circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.10721.001 PMID:26512889

  16. Syndecan promotes axon regeneration by stabilizing growth cone migration

    PubMed Central

    Edwards, Tyson J.; Hammarlund, Marc

    2014-01-01

    SUMMARY Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS) proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: 1) a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains, and 2) a novel intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a novel regulator of a critical choke point in nervous system repair. PMID:25001284

  17. Syndecan promotes axon regeneration by stabilizing growth cone migration.

    PubMed

    Edwards, Tyson J; Hammarlund, Marc

    2014-07-10

    Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS) proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1) a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2) an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Kinematics of Cone-In-Cone Growth, with Implications for Timing and Formation Mechanism

    NASA Astrophysics Data System (ADS)

    Hooker, J. N.; Cartwright, J. A.

    2015-12-01

    Cone-in-cone is an enigmatic structure. Similar to many fibrous calcite veins, cone-in-cone is generally formed of calcite and present in bedding-parallel vein-like accumulations within fine-grained rocks. Unlike most fibrous veins, cone-in-cone contains conical inclusions of host-rock material, creating nested, parallel cones throughout. A long-debated aspect of cone-in-cone structures is whether the calcite precipitated with its conical form (primary cone-in-cone), or whether the cones formed afterwards (secondary cone-in-cone). Trace dolomite within a calcite cone-in-cone structure from the Cretaceous of Jordan supports the primary hypothesis. The host sediment is a siliceous mud containing abundant rhombohedral dolomite grains. Dolomite rhombohedra are also distributed throughout the cone-in-cone. The rhombohedra within the cones are randomly oriented yet locally have dolomite overgrowths having boundaries that are aligned with calcite fibers. Evidence that dolomite co-precipitated with calcite, and did not replace calcite, includes (i) preferential downward extension of dolomite overgrowths, in the presumed growth-direction of the cone-in-cone, and (ii) planar, vertical borders between dolomite crystals and calcite fibers. Because dolomite overgrows host-sediment rhombohedra and forms fibers within the cones, it follows that the host-sediment was included within the growing cone-in-cone as the calcite precipitated, and not afterward. The host-sediment was not injected into the cone-in-cone along fractures, as the secondary-origin hypothesis suggests. This finding implies that cone-in-cone in general does not form over multiple stages, and thus has greater potential to preserve the chemical signature of its original precipitation. Because cone-in-cone likely forms before complete lithification of the host, and because the calcite displaces the host material against gravity, this chemical signature can preserve information about early overpressures in fine

  19. ERM proteins regulate growth cone responses to Sema3A.

    PubMed

    Mintz, C David; Carcea, Ioana; McNickle, Daniel G; Dickson, Tracey C; Ge, Yongchao; Salton, Stephen R J; Benson, Deanna L

    2008-10-01

    Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue Semaphorin 3A (Sema3A). We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1, and its coreceptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A.

  20. Microtubule behavior in the growth cones of living neurons during axon elongation

    PubMed Central

    1991-01-01

    To understand how microtubules are generated in the growth cone, we have imaged fluorescently tagged microtubules in living frog embryonic neurons. The neurons were labeled by injecting rhodamine-labeled tubulin into the fertilized egg and explanting the neurons from the neural tube. Microtubules extend deep into the growth cone periphery and adopt three characteristic distributions: (a) dispersed and splayed throughout much of the growth cone; (b) looped and apparently contorted by compression; and (c) bundled into tight arrays. These distributions interconvert on a time scale of several minutes and these interconversions are correlated with the behavior of the growth cone. We observed microtubule growth and shrinkage in growth cones, but are unable to determine their contribution to net assembly. However, translocation of polymer form the axon appears to be a major mechanism of generating new polymer in the growth cone, while bundling of microtubules in the growth cone appears to be the critical step in generating new axon. Neurons that were about to turn spontaneously generated microtubules in the future direction of growth, suggesting that orientation of microtubules might be an important early step in neuronal pathfinding. PMID:1918145

  1. Lipoprotein Uptake by Neuronal Growth Cones in Vitro

    NASA Astrophysics Data System (ADS)

    Ignatius, Michael J.; Shooter, Eric M.; Pitas, Robert E.; Mahley, Robert W.

    1987-05-01

    Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.

  2. Batchwise growth of silica cone patterns via self-assembly of aligned nanowires.

    PubMed

    Luo, Shudong; Zhou, Weiya; Chu, Weiguo; Shen, Jun; Zhang, Zengxing; Liu, Lifeng; Liu, Dongfang; Xiang, Yanjuan; Ma, Wenjun; Xie, Sishen

    2007-03-01

    Silica-cone patterns self-assembled from well-aligned nanowires are synthesized using gallium droplets as the catalyst and silicon wafers as the silicon source. The cones form a triangular pattern array radially on almost the whole surface of the molten Ga ball. Detailed field-emission scanning electron microscopy (SEM) analysis shows that the cone-pattern pieces frequently slide off and are detached from the molten Ga ball surface, which leads to the exposure of the catalyst surface and the growth of a new batch of silicon oxide nanowires as well as the cone patterns. The processes of growth and detachment alternate, giving rise to the formation of a volcano-like or a flower-like structure with bulk-quantity pieces of cone patterns piled up around the Ga ball. Consequently, the cone-patterned layer grows batch by batch until the reaction is terminated. Different to the conventional metal-catalyzed growth model, the batch-by-batch growth of the triangular cone patterns proceeds on the molten Ga balls via alternate growth on and detachment from the catalyst surface of the patterns; the Ga droplet can be used continuously and circularly as an effective catalyst for the growth of amorphous SiO(x) nanowires during the whole growth period. The intriguing batchwise growth phenomena may enrich our understanding of the vapour-liquid-solid (VLS) growth mechanism for the catalyst growth of nanowires or other nanostructures and may offer a different way of self-assembling novel silica nanostructures.

  3. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

    PubMed Central

    Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

    2011-01-01

    Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

  4. Neuronal growth cones respond to laser-induced axonal damage

    PubMed Central

    Wu, Tao; Mohanty, Samarendra; Gomez-Godinez, Veronica; Shi, Linda Z.; Liaw, Lih-Huei; Miotke, Jill; Meyer, Ronald L.; Berns, Michael W.

    2012-01-01

    Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single goldfish axons in vitro. The axons underwent a localized decrease in thickness (‘thinning’) within seconds. Analysis by fluorescence and transmission electron microscopy indicated that there was no gross rupture of the cell membrane. Mitochondrial transport along the axonal cytoskeleton immediately stopped at the damage site, but recovered over several minutes. Within seconds of damage nearby growth cones extended filopodia towards the injury and were often observed to contact the damaged site. Turning of the growth cone towards the injured axon also was observed. Repair of the laser-induced damage was evidenced by recovery of the axon thickness as well as restoration of mitochondrial movement. We describe a new process of growth cone response to damaged axons. This has been possible through the interface of optics (laser subcellular surgery), fluorescence and electron microscopy, and a goldfish retinal ganglion cell culture model. PMID:21831892

  5. Variability and Reliabiltiy in Axon Growth Cone Navigation Decision Making

    NASA Astrophysics Data System (ADS)

    Garnelo, Marta; Ricoult, Sébastien G.; Juncker, David; Kennedy, Timothy E.; Faisal, Aldo A.

    2015-03-01

    The nervous system's wiring is a result of axon growth cones navigating through specific molecular environments during development. In order to reach their target, growth cones need to make decisions under uncertainty as they are faced with stochastic sensory information and probabilistic movements. The overall system therefore exhibits features of whole organisms (perception, decision making, action) in the subset of a single cell. We aim to characterise growth cone navigation in defined nano-dot guidance cue environments, by using the tools of computational neuroscience to conduct ``molecular psychophysics.'' We start with a generative model of growth cone behaviour and we 1. characterise sensory and internal sources of noise contributing to behavioural variables, by combining knowledge of the underlying stochastic dynamics in cue sensing and the growth of the cytoskeleton. This enables us to 2. produce bottom-up lower limit estimates of behavioural response reliability and visualise it as probability distributions over axon growth trajectories. Given this information we can match our in silico model's ``psychometric'' decision curves with empirical data. Finally we use a Monte-Carlo approach to predict response distributions of axon trajectories from our model.

  6. Ultrastructural networks in growth cones and neurites of cultured central nervous system neurons.

    PubMed Central

    Tsui, H C; Ris, H; Klein, W L

    1983-01-01

    We have examined growth cones and neurites of cultured central nervous system neurons by high-voltage electron microscopy. Embryonic chicken retina cells were cultured on polylysine-treated and Formvar-coated gold grids for 2-6 days, fixed, and critical point dried. Growth cones and neurites were examined as unembedded whole mounts. Three-dimensional images from stereo-pair electron micrographs of these regions showed a high degree of ultrastructural articulation, with distinct, non-tapering filaments (5-9 nm in diameter) joining both cytoskeletal and membranous components. In the central regions of growth cones, interconnected structures included microtubules, large membranous sacs (up to 400 nm), and irregular vesicles (25-75 nm). A denser filamentous network was prevalent at the edges of growth cones. This network, which frequently adjoined the surface membrane, linked vesicles of uniform size (35-40 nm). Such vesicles often were seen densely packed in growth cone protrusions that were about the size of small synaptic boutons. Prevalent structural interconnections within growth cones conceivably could play a logistic role in specific membrane assembly, intracellular transport, endocytosis, and secretion. Because such processes are not unique to growth cones, the extensive linkages we have observed may have implications for cytoplasmic structure in general. Images PMID:6577454

  7. Ultrastructural networks in growth cones and neurites of cultured central nervous system neurons.

    PubMed

    Tsui, H C; Ris, H; Klein, W L

    1983-09-01

    We have examined growth cones and neurites of cultured central nervous system neurons by high-voltage electron microscopy. Embryonic chicken retina cells were cultured on polylysine-treated and Formvar-coated gold grids for 2-6 days, fixed, and critical point dried. Growth cones and neurites were examined as unembedded whole mounts. Three-dimensional images from stereo-pair electron micrographs of these regions showed a high degree of ultrastructural articulation, with distinct, non-tapering filaments (5-9 nm in diameter) joining both cytoskeletal and membranous components. In the central regions of growth cones, interconnected structures included microtubules, large membranous sacs (up to 400 nm), and irregular vesicles (25-75 nm). A denser filamentous network was prevalent at the edges of growth cones. This network, which frequently adjoined the surface membrane, linked vesicles of uniform size (35-40 nm). Such vesicles often were seen densely packed in growth cone protrusions that were about the size of small synaptic boutons. Prevalent structural interconnections within growth cones conceivably could play a logistic role in specific membrane assembly, intracellular transport, endocytosis, and secretion. Because such processes are not unique to growth cones, the extensive linkages we have observed may have implications for cytoplasmic structure in general.

  8. Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

    PubMed Central

    Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla

    2013-01-01

    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549

  9. Colony Expansion of Socially Motile Myxococcus xanthus Cells Is Driven by Growth, Motility, and Exopolysaccharide Production

    PubMed Central

    Patra, Pintu; Kissoon, Kimberley; Cornejo, Isabel; Kaplan, Heidi B.; Igoshin, Oleg A.

    2016-01-01

    Myxococcus xanthus, a model organism for studies of multicellular behavior in bacteria, moves exclusively on solid surfaces using two distinct but coordinated motility mechanisms. One of these, social (S) motility is powered by the extension and retraction of type IV pili and requires the presence of exopolysaccharides (EPS) produced by neighboring cells. As a result, S motility requires close cell-to-cell proximity and isolated cells do not translocate. Previous studies measuring S motility by observing the colony expansion of cells deposited on agar have shown that the expansion rate increases with initial cell density, but the biophysical mechanisms involved remain largely unknown. To understand the dynamics of S motility-driven colony expansion, we developed a reaction-diffusion model describing the effects of cell density, EPS deposition and nutrient exposure on the expansion rate. Our results show that at steady state the population expands as a traveling wave with a speed determined by the interplay of cell motility and growth, a well-known characteristic of Fisher’s equation. The model explains the density-dependence of the colony expansion by demonstrating the presence of a lag phase–a transient period of very slow expansion with a duration dependent on the initial cell density. We propose that at a low initial density, more time is required for the cells to accumulate enough EPS to activate S-motility resulting in a longer lag period. Furthermore, our model makes the novel prediction that following the lag phase the population expands at a constant rate independent of the cell density. These predictions were confirmed by S motility experiments capturing long-term expansion dynamics. PMID:27362260

  10. Colony Expansion of Socially Motile Myxococcus xanthus Cells Is Driven by Growth, Motility, and Exopolysaccharide Production.

    PubMed

    Patra, Pintu; Kissoon, Kimberley; Cornejo, Isabel; Kaplan, Heidi B; Igoshin, Oleg A

    2016-06-01

    Myxococcus xanthus, a model organism for studies of multicellular behavior in bacteria, moves exclusively on solid surfaces using two distinct but coordinated motility mechanisms. One of these, social (S) motility is powered by the extension and retraction of type IV pili and requires the presence of exopolysaccharides (EPS) produced by neighboring cells. As a result, S motility requires close cell-to-cell proximity and isolated cells do not translocate. Previous studies measuring S motility by observing the colony expansion of cells deposited on agar have shown that the expansion rate increases with initial cell density, but the biophysical mechanisms involved remain largely unknown. To understand the dynamics of S motility-driven colony expansion, we developed a reaction-diffusion model describing the effects of cell density, EPS deposition and nutrient exposure on the expansion rate. Our results show that at steady state the population expands as a traveling wave with a speed determined by the interplay of cell motility and growth, a well-known characteristic of Fisher's equation. The model explains the density-dependence of the colony expansion by demonstrating the presence of a lag phase-a transient period of very slow expansion with a duration dependent on the initial cell density. We propose that at a low initial density, more time is required for the cells to accumulate enough EPS to activate S-motility resulting in a longer lag period. Furthermore, our model makes the novel prediction that following the lag phase the population expands at a constant rate independent of the cell density. These predictions were confirmed by S motility experiments capturing long-term expansion dynamics.

  11. Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

    PubMed

    Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

    2010-01-01

    The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

  12. Sedimentary Biosignatures of Social Organization in Cone-Forming Filamentous Bacteria

    NASA Astrophysics Data System (ADS)

    Tice, M. M.; Gong, J.; Zeng, Z.; Sneed, J.; Wehner, M.; Sparks, D. W.

    2013-12-01

    Conical mats consisting of centimeter-scale steep-sided cones growing above flat basal films form some of the most distinctive fossil microbial communities in the geologic record. Cones have been hypothesized to form by the initially random motion of filamentous bacteria into small tangled clumps followed by the phototactic motion of the same bacteria up resulting slopes. More recent models of cone development suggest that they form in response to growth in stagnant fluids where diffusion limits exchange of nutrients and wastes with the environment. Determining the biological and environmental factors that promote cone formation will be important for interpreting the geological record of fossil mats and stromatolites, on Earth and potentially on Mars. Here we report the results of new experiments demonstrating complex social organization of cone-forming communities and a novel biosignature of the growth of such communities on sandy sediments, as well as detection of that biosignature in 3.2 Ga fossil mats of the Moodies Group (Barberton greenstone belt, South Africa). In order to investigate the processes involved in cone formation, we grew cultures of a filamentous cyanobacterium originally isolated from tufted cones in Yellowstone National Park, Montana, U.S.A. (Leptolyngbya sp. Y-WT-2000 Cl 1). During early mat development, filaments coat sand grain surfaces and aggregate into ~100-μm-long tufts, or mutually aligned bundles of filaments. Tufts are highly motile, bridging sand grains and merging to form larger tufts. After 10-14 days of growth, tufts aggregate during the early morning into centers composed of many tufts that wave vertically and along the sand surface. Centers move across the sediment surface during the middle of the day and merge along bridging tufts. These bridges transmit force to the underlying sediment and are capable of rolling sand grains. At this stage, mats are composed of small mobile centers that disperse along streams of co

  13. Filopodial adhesion does not predict growth cone steering events in vivo.

    PubMed

    Isbister, C M; O'Connor, T P

    1999-04-01

    Migration of growth cones is in part mediated by adhesive interactions between filopodia and the extracellular environment, transmitting forces and signals necessary for pathfinding. To elucidate the role of substrate adhesivity in growth cone pathfinding, we developed an in vivo assay for measuring filopodial-substrate adhesivity using the well-characterized Ti pioneer neuron pathway of the embryonic grasshopper limb. Using time-lapse imaging and a combination of rhodamine-phalloidin injections and DiI labeling, we demonstrate that the filopodial retraction rate after treatment with cytochalasin D or elastase reflects the degree of filopodial-substrate adhesivity. Measurements of filopodial retraction rates along regions of known differing substrate adhesivities confirmed the use of this assay to examine filopodial-substrate adhesion during in vivo pathfinding events. We analyzed 359 filopodia from 22 Ti growth cones and found that there is no difference between the retraction rates of filopodia extending toward the correct target (on-axis) and filopodia extending away from the correct target (off-axis). These results indicate on-axis and off-axis filopodia have similar substrate adherence. Interestingly, we observed a 300% increase in the extension rates of on-axis filopodia during Ti growth cone turning events. Therefore, in addition to providing filopodia with important guidance information, regional cues are capable of modulating the filopodial extension rate. The homogeneity in filopodial retraction rates, even among these turning growth cones in which differential adhesivity might be expected to be greatest, strongly establishes that differential adhesion does not govern Ti pioneer neuron migration rate or pathfinding. We propose that the presence of local differences in receptor-mediated second messenger cascades and the resulting assembly of force-generating machinery may underlie the ability of filopodial contacts to regulate growth cone steering in vivo.

  14. Multi-phasic bi-directional chemotactic responses of the growth cone

    PubMed Central

    Naoki, Honda; Nishiyama, Makoto; Togashi, Kazunobu; Igarashi, Yasunobu; Hong, Kyonsoo; Ishii, Shin

    2016-01-01

    The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca2+ level, which was then experimentally confirmed by growth cone turning assays and Ca2+ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone. PMID:27808115

  15. Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion.

    PubMed

    Togashi, Kazunobu; von Schimmelmann, Melanie J; Nishiyama, Makoto; Lim, Chae-Seok; Yoshida, Norihiro; Yun, Bokyoung; Molday, Robert S; Goshima, Yoshio; Hong, Kyonsoo

    2008-06-12

    Cyclic nucleotide-gated channels (CNGCs) transduce external signals required for sensory processes, e.g., photoreception, olfaction, and taste. Nerve growth cone guidance by diffusible attractive and repulsive molecules is regulated by differential growth cone Ca2+ signaling. However, the Ca2+-conducting ion channels that transduce guidance molecule signals are largely unknown. We show that rod-type CNGC-like channels function in the repulsion of cultured Xenopus spinal neuron growth cones by Sema3A, which triggers the production of the cGMP that activates the Xenopus CNGA1 (xCNGA1) subunit-containing channels in interneurons. Downregulation of xCNGA1 or overexpression of a mutant xCNGA1 incapable of binding cGMP abolished CNG currents and converted growth cone repulsion to attraction in response to Sema3A. We also show that Ca2+ entry through xCNGCs is required to mediate the repulsive Sema3A signal. These studies extend our knowledge of the function of CNGCs by demonstrating their requirement for signal transduction in growth cone guidance.

  16. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

    PubMed

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-03-17

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

  17. Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

    PubMed Central

    Ko, Hyo Rim; Kwon, Il-Sun; Hwang, Inwoo; Jin, Eun-Ju; Shin, Joo-Ho; Brennan-Minnella, Angela M; Swanson, Raymond; Cho, Sung-Woo; Lee, Kyung-Hoon; Ahn, Jee-Yin

    2016-01-01

    Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration. DOI: http://dx.doi.org/10.7554/eLife.20799.001 PMID:27938661

  18. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

    PubMed Central

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-01-01

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017

  19. Effect of HSP27 on Human Breast Tumor Cell Growth and Motility

    DTIC Science & Technology

    1999-08-01

    the small stress protein, HSP27 , on growth and motility characteristics of normal and tumor-derived human mammary cell lines. We hypothesized that...cells overexpressing HSP27 would show increased motility, altered chemotactic properties, increased resistance to heat killing and to certain drugs...Donna has prepared and studied 19 clonal MDA23 1 breast tumor cell lines that overexpress human HSP27 , and determined that, while heat resistance is

  20. Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

    PubMed Central

    Fuentes, Federico

    2009-01-01

    PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. PMID:19158394

  1. Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology.

    PubMed

    Matsuo, Naoki; Terao, Mami; Nabeshima, Yo-ichi; Hoshino, Mikio

    2003-09-01

    Rho family GTPases are suggested to be pivotal for growth cone behavior, but regulation of their activities in response to environmental cues remains elusive. Here, we describe roles of STEF and Tiam1, guanine nucleotide exchange factors for Rac1, in neurite growth and growth cone remodeling. We reveal that, in primary hippocampal neurons, STEF/Tiam1 are localized within growth cones and essential for formation of growth cone lamellipodia, eventually contributing to neurite growth. Furthermore, experiments using a dominant-negative form demonstrate that STEF/Tiam1 mediate extracellular laminin signals to activate Rac1, promoting neurite growth in N1E-115 neuroblastoma cells. STEF/Tiam1 are revealed to mediate Cdc42 signal to activate Rac1 during lamellipodial formation. We also show that RhoA inhibits the STEF/Tiam1-Rac1 pathway. These data are used to propose a model that extracellular and intracellular information is integrated by STEF/Tiam1 to modulate the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior.

  2. Effect of HSP27 on Human Breast Tumor Cell Growth and Motility.

    DTIC Science & Technology

    1997-09-01

    the small heat shock protein, Hsp27 , on growth and motility characteristics of human mammary tumor cell lines. Since Hsp27 regulates actin...microfilament dynamics, we hypothesize that cells expressing high levels of Hsp27 will show increased motility and altered chemotactic properties, in addition to...significantly elevated levels of Hsp27 has proven to be daunting. Down regulation of Hsp27 levels in MCF7 cells using antisense technology has also

  3. VEGF Triggers the Activation of Cofilin and the Arp2/3 Complex within the Growth Cone

    PubMed Central

    Schlau, Matthias; Terheyden-Keighley, Daniel; Theis, Verena; Mannherz, Hans Georg; Theiss, Carsten

    2018-01-01

    A crucial neuronal structure for the development and regeneration of neuronal networks is the axonal growth cone. Affected by different guidance cues, it grows in a predetermined direction to reach its final destination. One of those cues is the vascular endothelial growth factor (VEGF), which was identified as a positive effector for growth cone movement. These positive effects are mainly mediated by a reorganization of the actin network. This study shows that VEGF triggers a tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton within chicken dorsal root ganglia (DRG). Live cell imaging after microinjection of GFP (green fluorescent protein)-cofilin and RFP (red fluorescent protein)-LifeAct revealed that both labeled proteins rapidly redistributed within growth cones, and showed a congruent distribution pattern after VEGF supplementation. Disruption of signaling upstream of cofilin via blocking LIM-kinase (LIMK) activity resulted in growth cones displaying regressive growth behavior. Microinjection of GFP-p16b (a subunit of the Arp2/3 complex) and RFP-LifeAct revealed that both proteins redistributed into lamellipodia of the growth cone within minutes after VEGF stimulation. Disruption of the signaling to the Arp2/3 complex in the presence of VEGF by inhibition of N-WASP (neuronal Wiskott–Aldrich–Scott protein) caused retraction of growth cones. Hence, cofilin and the Arp2/3 complex appear to be downstream effector proteins of VEGF signaling to the actin cytoskeleton of DRG growth cones. Our data suggest that VEGF simultaneously affects different pathways for signaling to the actin cytoskeleton, since activation of cofilin occurs via inhibition of LIMK, whereas activation of Arp2/3 is achieved by stimulation of N-WASP. PMID:29382077

  4. Accumulation of actin in subsets of pioneer growth cone filopodia in response to neural and epithelial guidance cues in situ

    PubMed Central

    1993-01-01

    Directed outgrowth of neural processes must involve transmission of signals from the tips of filopodia to the central region of the growth cone. Here, we report on the distribution and dynamics of one possible element in this process, actin, in live growth cones which are reorienting in response to in situ guidance cues. In grasshopper embryonic limbs, pioneer growth cones respond to at least three types of guidance cues: a limb axis cue, intermediate target cells, and a circumferential band of epithelial cells. With time-lapse imaging of intracellularly injected rhodamine-phalloidin and rhodamine-actin, we monitored the distribution of actin during growth cone responses to these cues. In distal limb regions, accumulation of actin in filopodia and growth cone branches accompanies continued growth, while reduction of actin accompanies withdrawal. Where growth cones are reorienting to intermediate target cells, or along the circumferential epithelial band, actin selectively accumulates in the proximal regions of those filopodia that have contacted target cells or are extending along the band. Actin accumulations can be retrogradely transported along filopodia, and can extend into the central region of the growth cone. These results suggest that regulation and translocation of actin may be a significant element in growth cone steering. PMID:8227150

  5. Dynamic behaviors of growth cones extending in the corpus callosum of living cortical brain slices observed with video microscopy.

    PubMed

    Halloran, M C; Kalil, K

    1994-04-01

    During development, axons of the mammalian corpus callosum must navigate across the midline to establish connections with corresponding targets in the contralateral cerebral cortex. To gain insight into how growth cones of callosal axons respond to putative guidance cues along this CNS pathway, we have used time-lapse video microscopy to observe dynamic behaviors of individual callosal growth cones extending in living brain slices from neonatal hamster sensorimotor cortex. Crystals of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) were inserted into the cortex in vivo to label small populations of callosal axons and their growth cones. Subsequently, 400 microns brain slices that included the injection site, the corpus callosum, and the target cortex were placed in culture and viewed under low-light-level conditions with a silicon-intensified target (SIT) camera. Time-lapse video observations revealed striking differences in growth cone behaviors in different regions of the callosal pathway. In the tract, which is defined as the region of the callosal pathway from the injection site to the corresponding target cortex, growth cones advanced rapidly, displaying continual lamellipodial shape changes and filopodial exploration. Forward advance was sometimes interrupted by brief pauses or retraction. Growth cones in the target cortex had almost uniform compact shapes that were consistently smaller than those in the tract. In cortex, axons adhered to straight radial trajectories and their growth cones extended at only half the speed of those in the tract. Growth cones in subtarget regions of the callosum beneath cortical targets displayed complex behaviors characterized by long pauses, extension of transitory branches, and repeated cycles of collapse, withdrawal, and resurgence. Video observations suggested that extension of axons into cortical targets could occur by interstitial branching from callosal axons rather than by

  6. Growth and field emission properties of tubular carbon cones.

    PubMed

    Li, J J; Wang, Q; Gu, C Z

    2007-09-01

    New forms of tubular carbon cone (TCC) were grown on gold wires by hot-filament chemical vapor deposition (HFCVD). They have a long-cone-shaped appearance with a herringbone hollow interior, surrounded by helical sheets of graphite that are coiled around it. It is considered that TCC formation results because the size of the catalyst particle located in the top of the TCC decreases continuously during growth, due to etching effects in the CVD plasma, reflecting competition between the growth and etching processes in the plasma. In addition, field emission measurements show that TCCs have a very low-threshold field of 0.27 V/microm, and that a stable macroscopic emitting current density of 1 mA/cm2 can be obtained at only 0.5 V/microm. TCCs have good field emission properties, compared to other forms of carbon field emitter, and may be good candidates for use in field emission display devices.

  7. Modulation of keratinocyte motility. Correlation with production of extracellular matrix molecules in response to growth promoting and antiproliferative factors.

    PubMed Central

    Nickoloff, B. J.; Mitra, R. S.; Riser, B. L.; Dixit, V. M.; Varani, J.

    1988-01-01

    Normal human epidermal keratinocytes (KC) grown under conditions that maintain the undifferentiated state are highly motile. Migration of these cells as measured in two different assays (migration out of an agarose drop explant, and into micropore filters in a modified Boyden chamber), is stimulated by fibronectin (FN) and to a lesser extent by thrombospondin (TSP). In contrast, laminin (LN) inhibits KC migration. Cultivation of the cells for 1 day under conditions that induce differentiation (ie, in the presence of 1.4 mM Ca2+) suppresses KC motility. A number of soluble growth modulating polypeptide factors also influence KC migration. Transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) stimulate KC motility. These factors simultaneously induce KC production of FN and a significant portion of the stimulated motility can be inhibited with antibodies to FN. EGF and somatomedin-C (SM-C), but not TGF-beta, also stimulate TSP production while EGF and SM-C (but not TGF-beta) induce KC proliferation. In contrast to these factors, interferon-gamma (INF-gamma) inhibits KC production of both FN and TSP and concomitantly inhibits both motility and proliferation. These data suggest that KC properties essential for normal wound healing (ie, motility and proliferation) are regulated by both extracellular matrix molecules and soluble peptide factors. Finally, these effects of various growth promoting and antiproliferative factors on KCs may, in part, be mediated through alteration in the endogenous production of extracellular matrix molecules by KCs. Images Figure 2 PMID:2458044

  8. Dietary n-3 fatty acid restriction during gestation in rats: neuronal cell body and growth-cone fatty acids.

    PubMed

    Auestad, N; Innis, S M

    2000-01-01

    Growth cones are membrane-rich structures found at the distal end of growing axons and are the predecessors of the synaptic membranes of nerve endings. This study examined whether n-3 fatty acid restriction during gestation in rats alters the composition of growth cone and neuronal cell body membrane fatty acids in newborns. Female rats were fed a standard control diet containing soy oil (8% of fatty acids as 18:3n-3 by wt) or a semisynthetic n-3 fatty acid-deficient diet with safflower oil (0.3% of fatty acids as 18:3n-3 by wt) throughout normal pregnancy. Experiments were conducted on postnatal day 2 to minimize the potential for contamination from synaptic membranes and glial cells. Dietary n-3 fatty acid restriction resulted in lower docosahexaenoic acid (DHA) concentrations and a corresponding higher docosapentaenoic acid concentration in neuronal growth cones, but had no effects on neuronal cell body fatty acid concentrations. These studies suggest that accretion of DHA in growth cones, but not neuronal cell bodies, is affected by n-3 fatty acid restriction during gestation. Differences in other fatty acids or components between the semisynthetic and the standard diet, however, could have been involved in the effects on growth-cone DHA content. The results also provide evidence to suggest that the addition of new membrane fatty acids to neurons during development occurs along the shaft of the axon or at the growth cone, rather than originating at the cell body.

  9. Regulated release of serotonin from axonal growth cones isolated from the fetal rat brain.

    PubMed

    Mercado, R; Floran, B; Hernandez, J

    1998-01-01

    In the present work we propose an hypothetical model related to a molecular recognizing system for serotonin in isolated growth cone particles. This model is supported by previous results from our laboratory plus new ones which show that growth cones release serotonin tonically and such release can be stimulated by potassium in a calcium-dependent manner. The present results, together with other author's data, suggest a physiological basis for the putative role of serotonin as a trophic factor during nervous system development.

  10. Cone production, seed dispersal, germination in...old-growth redwood cut and uncut stands

    Treesearch

    Kenneth N. Boe

    1968-01-01

    Records of 5 and 6 years' cone crops in old-growth redwood (Sequoia sempervirens [D. Don Endl.] stands in northern California were studied for silvical facts. They show that (a) the principal trees in both cut and uncut stands bore fair to good cone crops for 5 consecutive years, (b) maximum seed dispersal of both total and sound seed occurred in winter, (c)...

  11. 2D motility tracking of Pseudomonas putida KT2440 in growth phases using video microscopy

    PubMed Central

    Davis, Michael L.; Mounteer, Leslie C.; Stevens, Lindsey K.; Miller, Charles D.; Zhou, Anhong

    2011-01-01

    Pseudomonas putida KT2440 is a gram negative motile soil bacterium important in bioremediation and biotechnology. Thus, it is important to understand its motility characteristics as individuals and in populations. Population characteristics were determined using a modified Gompertz model. Video microscopy and imaging software were utilized to analyze two dimensional (2D) bacteria movement tracks to quantify individual bacteria behavior. It was determined that inoculum density increased the lag time as seeding densities decreased, and that the maximum specific growth rate decreased as seeding densities increased. Average bacterial velocity remained relatively similar throughout exponential growth phase (~20.9 µm/sec), while maximum velocities peak early in exponential growth phase at a velocity of 51.2 µm/sec. Pseudomonas putida KT2440 also favor smaller turn angles indicating they often continue in the same direction after a change in flagella rotation throughout the exponential growth phase. PMID:21334971

  12. Bioconvective patterns, synchrony, and survival. [in light-limited growth model of motile algae culture

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1990-01-01

    With and without bioconvective pattern formation, a theoretical model predicts growth in light-limited cultures of motile algae. At the critical density for pattern formation, the resulting doubly exponential population curves show an inflection. Such growth corresponds quantitatively to experiments in mechanically unstirred cultures. This attaches survival value to synchronized pattern formation.

  13. Novel inhibitory action of tunicamycin homologues suggests a role for dynamic protein fatty acylation in growth cone-mediated neurite extension

    PubMed Central

    1994-01-01

    In neuronal growth cones, the advancing tips of elongating axons and dendrites, specific protein substrates appear to undergo cycles of posttranslational modification by covalent attachment and removal of long-chain fatty acids. We show here that ongoing fatty acylation can be inhibited selectively by long-chain homologues of the antibiotic tunicamycin, a known inhibitor of N-linked glycosylation. Tunicamycin directly inhibits transfer of palmitate to protein in a cell-free system, indicating that tunicamycin inhibition of protein palmitoylation reflects an action of the drug separate from its previously established effects on glycosylation. Tunicamycin treatment of differentiated PC12 cells or dissociated rat sensory neurons, under conditions in which protein palmitoylation is inhibited, produces a prompt cessation of neurite elongation and induces a collapse of neuronal growth cones. These growth cone responses are rapidly reversed by washout of the antibiotic, even in the absence of protein synthesis, or by addition of serum. Two additional lines of evidence suggest that the effects of tunicamycin on growth cones arise from its ability to inhibit protein long-chain acylation, rather than its previously established effects on protein glycosylation and synthesis. (a) The abilities of different tunicamycin homologues to induce growth cone collapse very systematically with the length of the fatty acyl side- chain of tunicamycin, in a manner predicted and observed for the inhibition of protein palmitoylation. Homologues with fatty acyl moieties shorter than palmitic acid (16 hydrocarbons), including potent inhibitors of glycosylation, are poor inhibitors of growth cone function. (b) The tunicamycin-induced impairment of growth cone function can be reversed by the addition of excess exogenous fatty acid, which reverses the inhibition of protein palmitoylation but has no effect on the inhibition of protein glycosylation. These results suggest an important role for

  14. Thinning and fertilizing red pine to increase growth and cone production.

    Treesearch

    John H. Cooley

    1970-01-01

    Cone production and growth were increased more by heavy thinning than by fertilizing in 53- and 55-year-old natural red pine stands growing on medium sites, and in a 20-year-old plantation on a good site.

  15. 2D motility tracking of Pseudomonas putida KT2440 in growth phases using video microscopy.

    PubMed

    Davis, Michael L; Mounteer, Leslie C; Stevens, Lindsey K; Miller, Charles D; Zhou, Anhong

    2011-05-01

    Pseudomonas putida KT2440 is a gram negative motile soil bacterium important in bioremediation and biotechnology. Thus, it is important to understand its motility characteristics as individuals and in populations. Population characteristics were determined using a modified Gompertz model. Video microscopy and imaging software were utilized to analyze two dimensional (2D) bacteria movement tracks to quantify individual bacteria behavior. It was determined that inoculum density increased the lag time as seeding densities decreased, and that the maximum specific growth rate decreased as seeding densities increased. Average bacterial velocity remained relatively similar throughout the exponential growth phase (~20.9 μm/s), while maximum velocities peak early in the exponential growth phase at a velocity of 51.2 μm/s. P. putida KT2440 also favors smaller turn angles indicating that they often continue in the same direction after a change in flagella rotation throughout the exponential growth phase. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Differential Expression of Virulence Genes and Motility in Ralstonia (Pseudomonas) solanacearum during Exponential Growth.

    PubMed

    Clough, S J; Flavier, A B; Schell, M A; Denny, T P

    1997-03-01

    A complex network regulates virulence in Ralstonia solanacearum (formerly Pseudomonas solanacearum); central to this system is PhcA, a LysR-type transcriptional regulator. We report here that two PhcA-regulated virulence factors, endoglucanase (Egl) and acidic exopolysaccharide I (EPS I), and motility are expressed differentially during exponential growth in batch cultures. Tests with strains carrying lacZ fusions in a wild-type genetic background revealed that expression (on a per-cell basis) of phcA was constant but expression of egl and epsB increased 20- to 50-fold during multiplication from 1 x 10(sup7) to 5 x 10(sup8) CFU/ml. Expression of xpsR, an intermediate regulator downstream of PhcA in the regulatory cascade for eps expression, was similar to that of epsB and egl. Motility track photography revealed that all strains were essentially nonmotile at 10(sup6) CFU/ml. As cell density increased, 30 to 50% of wild-type cells were motile between 10(sup7) and 10(sup8) CFU/ml, but this population was again nonmotile at 10(sup9) CFU/ml. In contrast, about 60% of the cells of phcB and phcA mutants remained motile at 10(sup9) CFU/ml. Expression of phcB, which is not positively regulated by PhcA, was the inverse of epsB, egl, and xpsR (i.e., it decreased 20-fold at high cell density). PhcB is essential for production of an extracellular factor, tentatively identified as 3-hydroxypalmitic acid methyl ester (3-OH PAME), that might act as an exponential-phase signal to activate motility or expression of virulence genes. However, growth of the lacZ fusion strains in medium containing excess 3-OH PAME did not result in motility or expression of virulence genes at dramatically lower cell densities, suggesting that 3-OH PAME is not the only factor controlling these traits.

  17. Arginyltransferase ATE1 is targeted to the neuronal growth cones and regulates neurite outgrowth during brain development.

    PubMed

    Wang, Junling; Pavlyk, Iuliia; Vedula, Pavan; Sterling, Stephanie; Leu, N Adrian; Dong, Dawei W; Kashina, Anna

    2017-10-01

    Arginylation is an emerging protein modification mediated by arginyltransferase ATE1, shown to regulate embryogenesis and actin cytoskeleton, however its functions in different physiological systems are not well understood. Here we analyzed the role of ATE1 in brain development and neuronal growth by producing a conditional mouse knockout with Ate1 deletion in the nervous system driven by Nestin promoter (Nes-Ate1 mice). These mice were weaker than wild type, resulting in low postnatal survival rates, and had abnormalities in the brain that suggested defects in neuronal migration. Cultured Ate1 knockout neurons showed a reduction in the neurite outgrowth and the levels of doublecortin and F-actin in the growth cones. In wild type, ATE1 prominently localized to the growth cones, in addition to the cell bodies. Examination of the Ate1 mRNA sequence reveals the existence of putative zipcode-binding sequences involved in mRNA targeting to the cell periphery and local translation at the growth cones. Fluorescence in situ hybridization showed that Ate1 mRNA localized to the tips of the growth cones, likely due to zipcode-mediated targeting, and this localization coincided with spots of localization of arginylated β-actin, which disappeared in the presence of protein synthesis inhibitors. We propose that zipcode-mediated co-targeting of Ate1 and β-actin mRNA leads to localized co-translational arginylation of β-actin that drives the growth cone migration and neurite outgrowth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis

    PubMed Central

    Abe, Kouki; Katsuno, Hiroko; Toriyama, Michinori; Baba, Kentarou; Mori, Tomoyuki; Hakoshima, Toshio; Kanemura, Yonehiro; Watanabe, Rikiya; Inagaki, Naoyuki

    2018-01-01

    Chemical cues presented on the adhesive substrate direct cell migration, a process termed haptotaxis. To migrate, cells must generate traction forces upon the substrate. However, how cells probe substrate-bound cues and generate directional forces for migration remains unclear. Here, we show that the cell adhesion molecule (CAM) L1-CAM is involved in laminin-induced haptotaxis of axonal growth cones. L1-CAM underwent grip and slip on the substrate. The ratio of the grip state was higher on laminin than on the control substrate polylysine; this was accompanied by an increase in the traction force upon laminin. Our data suggest that the directional force for laminin-induced growth cone haptotaxis is generated by the grip and slip of L1-CAM on the substrates, which occur asymmetrically under the growth cone. This mechanism is distinct from the conventional cell signaling models for directional cell migration. We further show that this mechanism is disrupted in a human patient with L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia. PMID:29483251

  19. Comparison of the force exerted by hippocampal and DRG growth cones.

    PubMed

    Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

    2013-01-01

    Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties.

  20. Comparison of the Force Exerted by Hippocampal and DRG Growth Cones

    PubMed Central

    Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

    2013-01-01

    Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm2 and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties. PMID:23991169

  1. Sperm cryopreservation affects postthaw motility, but not embryogenesis or larval growth in the Brazilian fish Brycon insignis (Characiformes).

    PubMed

    Viveiros, A T M; Isaú, Z A; Caneppele, D; Leal, M C

    2012-09-01

    Sperm cryopreservation is an important method for preserving genetic information and facilitating artificial reproduction. The objective was to investigate whether the cryopreservation process affects postthaw sperm motility, embryogenesis, and larval growth in the fish Brycon insignis. Sperm was diluted in methyl glycol and Beltsville Thawing solution, frozen in a nitrogen vapor vessel (dry shipper) and stored in liquid nitrogen. Half of the samples were evaluated both subjectively (% of motile sperm and motility quality score-arbitrary grading system from 0 [no movement] to 5 [rapidly swimming sperm]) and in a computer-assisted sperm analyzer (CASA; percentage of motile sperm and velocity). The other half was used for fertilization and the evaluation of embryogenesis (cleavage and gastrula stages), hatching rate, percentage of larvae with normal development and larval growth up to 112 days posthatching (dph). Fresh sperm was analyzed subjectively (percentage of motile sperm and motility quality score) and used as the control. In the subjective analysis, sperm motility significantly decreased from 100% motile sperm and quality score of 5 in fresh sperm to 54% motile sperm and quality score of 3 after thawing. Under computer-assisted sperm analyzer evaluation, postthaw sperm had 67% motile sperm, 122 μm/sec of curvilinear velocity, 87 μm/sec of straight-line velocity and 103 μm/sec of average path velocity. There were no significant differences between progenies (pooled data) for the percentage of viable embryos in cleavage (62%) or gastrula stages (24%) or in the hatching rate (24%), percentage of normal hatched larvae (93%), larval body weight (39.8 g), or standard length (12.7 cm) at 112 days posthatching. Based on these findings, cryopreserved sperm can be used as a tool to restore the population of endangered species, such as B. insignis, as well as for aquaculture purposes, without any concern regarding quality of the offspring. Copyright © 2012 Elsevier

  2. Rac regulates vascular endothelial growth factor stimulated motility.

    PubMed

    Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

    2001-01-01

    During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent

  3. How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.

    PubMed

    Sidebotham, Ramon L; Worku, Mulugeta L; Karim, Q Najma; Dhir, Nirmal K; Baron, J Hugh

    2003-04-01

    Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment. Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach. H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8. Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.

  4. The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

    PubMed

    Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

    2007-01-01

    The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

  5. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  6. The role of collapsing and cone rafting on eruption style changes and final cone morphology: Los Morados scoria cone, Mendoza, Argentina

    NASA Astrophysics Data System (ADS)

    Németh, Karoly; Risso, Corina; Nullo, Francisco; Kereszturi, Gabor

    2011-06-01

    Payún Matru Volcanic Field is a Quaternary monogenetic volcanic field that hosts scoria cones with perfect to breached morphologies. Los Morados complex is a group of at least four closely spaced scoria cones (Los Morados main cone and the older Cones A, B, and C). Los Morados main cone was formed by a long lived eruption of months to years. After an initial Hawaiian-style stage, the eruption changed to a normal Strombolian, conebuilding style, forming a cone over 150 metres high on a northward dipping (˜4°) surface. An initial cone gradually grew until a lava flow breached the cone's base and rafted an estimated 10% of the total volume. A sudden sector collapse initiated a dramatic decompression in the upper part of the feeding conduit and triggered violent a Strombolian style eruptive stage. Subsequently, the eruption became more stable, and changed to a regular Strombolian style that partially rebuilt the cone. A likely increase in magma flux coupled with the gradual growth of a new cone caused another lava flow outbreak at the structurally weakened earlier breach site. For a second time, the unstable flank of the cone was rafted, triggering a second violent Strombolian eruptive stage which was followed by a Hawaiian style lava fountain stage. The lava fountaining was accompanied by a steady outpour of voluminous lava emission accompanied by constant rafting of the cone flank, preventing the healing of the cone. Santa Maria is another scoria cone built on a nearly flat pre-eruption surface. Despite this it went through similar stages as Los Morados main cone, but probably not in as dramatic a manner as Los Morados. In contrast to these examples of large breached cones, volumetrically smaller cones, associated to less extensive lava flows, were able to heal raft/collapse events, due to the smaller magma output and flux rates. Our evidence shows that scoria cone growth is a complex process, and is a consequence of the magma internal parameters (e.g. volatile

  7. The discovery of the growth cone and its influence on the study of axon guidance

    PubMed Central

    Tamariz, Elisa; Varela-Echavarría, Alfredo

    2015-01-01

    For over a century, there has been a great deal of interest in understanding how neural connectivity is established during development and regeneration. Interest in the latter arises from the possibility that knowledge of this process can be used to re-establish lost connections after lesion or neurodegeneration. At the end of the XIX century, Santiago Ramón y Cajal discovered that the distal tip of growing axons contained a structure that he called the growth cone. He proposed that this structure enabled the axon’s oriented growth in response to attractants, now known as chemotropic molecules. He further proposed that the physical properties of the surrounding tissues could influence the growth cone and the direction of growth. This seminal discovery afforded a plausible explanation for directed axonal growth and has led to the discovery of axon guidance mechanisms that include diffusible attractants and repellants and guidance cues anchored to cell membranes or extracellular matrix. In this review the major events in the development of this field are discussed. PMID:26029056

  8. Birefringence imaging directly reveals architectural dynamics of filamentous actin in living growth cones.

    PubMed

    Katoh, K; Hammar, K; Smith, P J; Oldenbourg, R

    1999-01-01

    We have investigated the dynamic behavior of cytoskeletal fine structure in the lamellipodium of nerve growth cones using a new type of polarized light microscope (the Pol-Scope). Pol-Scope images display with exquisite resolution and definition birefringent fine structures, such as filaments and membranes, without having to treat the cell with exogenous dyes or fluorescent labels. Furthermore, the measured birefringence of protein fibers in the thin lamellipodial region can be interpreted in terms of the number of filaments in the bundles. We confirmed that birefringent fibers are actin-based using conventional fluorescence-labeling methods. By recording movies of time-lapsed Pol-Scope images, we analyzed the creation and dynamic composition of radial fibers, filopodia, and intrapodia in advancing growth cones. The strictly quantitative information available in time-lapsed Pol-Scope images confirms previously deduced behavior and provides new insight into the architectural dynamics of filamentous actin.

  9. The growth and erosion of cinder cones in Guatemala and El Salvador: Models and statistics

    NASA Astrophysics Data System (ADS)

    Bemis, Karen; Walker, Jim; Borgia, Andrea; Turrin, Brent; Neri, Marco; Swisher, Carl, III

    2011-04-01

    Morphologic data for 147 cinder cones in southern Guatemala and western El Salvador are compared with data from the San Francisco volcanic field, Arizona (USA), Cima volcanic field, California (USA), Michoácan-Guanajuato volcanic field, Mexico, and the Lamongan volcanic field, East Java. The Guatemala cones have an average height of 110 +/- 50 m, an average basal diameter of 660 +/- 230 m and an average top diameter of 180 +/- 150 m. The general morphology of these cones can be described by their average cone angle of slope (24 +/- 7), average height-to-radius ratio (0.33 +/- 0.09) and their flatness (0.24 +/- 0.18). Although the mean values for the Guatemalan cones are similar to those for other volcanic fields (e.g., San Francisco volcanic field, Arizona; Cima volcanic field, California; Michoácan-Guanajuato volcanic field, Mexico; and Lamongan volcanic field, East Java), the range of morphologies encompasses almost all of those observed worldwide for cinder cones. Three new 40Ar/ 39Ar age dates are combined with 19 previously published dates for cones in Guatemala and El Salvador. There is no indication that the morphologies of these cones have changed over the last 500-1000 ka. Furthermore, a re-analysis of published data for other volcanic fields suggests that only in the Cima volcanic field (of those studied) is there clear evidence of degradation with age. Preliminary results of a numerical model of cinder cone growth are used to show that the range of morphologies observed in the Guatemalan cinder cones could all be primary, that is, due to processes occurring at the time of eruption.

  10. The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones.

    PubMed

    Chernyshova, Yana; Leshchyns'ka, Iryna; Hsu, Shu-Chan; Schachner, Melitta; Sytnyk, Vladimir

    2011-03-09

    The exocyst complex is an essential regulator of polarized exocytosis involved in morphogenesis of neurons. We show that this complex binds to the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes FGF receptor-mediated phosphorylation of two tyrosine residues in the sec8 subunit of the exocyst complex and is required for efficient recruitment of the exocyst complex to growth cones. NCAM at the surface of growth cones induces Ca(2+)-dependent vesicle exocytosis, which is blocked by an inhibitor of L-type voltage-dependent Ca(2+) channels and tetanus toxin. Preferential exocytosis in growth cones underlying neurite outgrowth is inhibited in NCAM-deficient neurons as well as in neurons transfected with phosphorylation-deficient sec8 and dominant-negative peptides derived from the intracellular domain of NCAM. Thus, we reveal a novel role for a cell adhesion molecule in that it regulates addition of the new membrane to the cell surface of growth cones in developing neurons.

  11. Corneal Sulfated Glycosaminoglycans and Their Effects on Trigeminal Nerve Growth Cone Behavior In Vitro: Roles for ECM in Cornea Innervation

    PubMed Central

    Schwend, Tyler; Deaton, Ryan J.; Zhang, Yuntao; Caterson, Bruce; Conrad, Gary W.

    2012-01-01

    Purpose. Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM–GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation. Methods. Immunostaining using antineuron-specific-β-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy. Effects of purified GAGs on trigeminal nerve growth cone behavior were tested using in vitro neuronal explant cultures. Results. At E9 to E10, nerves exiting the pericorneal nerve ring grew as tight fascicles, advancing straight toward the corneal stroma. In contrast, upon entering the stroma, nerves bifurcated repeatedly as they extended anteriorly toward the epithelium. KS was localized in the path of trigeminal nerves, whereas DS and CSA/C–rich areas were avoided by growth cones. When E10 trigeminal neurons were cultured on different substrates comprised of purified GAG molecules, their neurite growth cone behavior varied depending on GAG type, concentration, and mode of presentation (immobilized versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited neurite growth to varying degrees. Neurites traversing lower, permissive concentrations of immobilized DS and CSA/C displayed increased fasciculation and decreased branching, whereas KS caused decreased fasciculation and increased branching. Enzymatic digestion of sulfated GAGs canceled their effects on trigeminal neurons. Conclusions. Data herein suggest that GAGs may direct the movement of trigeminal nerve growth cones innervating the cornea. PMID:23132805

  12. Responses of growth cones to changes in osmolality of the surrounding medium.

    PubMed

    Bray, D; Money, N P; Harold, F M; Bamburg, J R

    1991-04-01

    The possible involvement of osmotically generated hydrostatic pressure in driving actin-rich extensions of the cell surface was examined using cultures of chick neurons. Estimation of the excess internal osmotic pressure of chick neural tissue by vapor pressure deficit osmometry, and of the excess internal hydrostatic pressure in cultured chick neurons using a calibrated pressure pipette, gave upper limits of 10 mosM and 0.1 atmosphere (1 atmosphere = 101325 Pa), respectively. Increases in the osmolality of the medium surrounding cultured neurons by addition of sucrose, mannitol or polyethylene glycol by amounts that should eliminate any internal pressure not only failed to arrest the growth of filopodia but caused them to increase in length up to twofold in 3-5 min. Lamellipodia remained unchanged following hyperosmotic shifts of 20 mosM, but higher levels caused a small decrease in area. Reduction of osmolality by the addition of water to the culture fluid down to 50% of its normal value failed to show any detectable change in either filopodial length or lamellipodia area. These observations argue against an osmotic mechanism for growth cone extension and show that the growth of filopodia, in particular, is unlikely to be driven by osmotically generated hydrostatic pressure. In contrast to the short-term effects on growth cone morphology, the slower elongation of the neuritic cylinder showed a consistent osmotic response. Growth rates were reduced following addition of osmolytes and increased in rate (as much as sixfold) following addition of water to the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Calpain-Mediated Proteolysis of Talin and FAK Regulates Adhesion Dynamics Necessary for Axon Guidance

    PubMed Central

    Kerstein, Patrick C.; Patel, Kevin M.

    2017-01-01

    Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca2+) is an essential signal for axon guidance that mediates opposing effects on growth cone motility. The diverse effects of Ca2+ arise from the precise localization of Ca2+ signals into microdomains containing specific Ca2+ effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca2+ signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain. However, how calpain regulates growth cone motility remains unclear. Here, we identify the adhesion proteins talin and focal adhesion kinase (FAK) as proteolytic targets of calpain in Xenopus laevis spinal cord neurons both in vivo and in vitro. Inhibition of calpain increases the localization of endogenous adhesion signaling to growth cone filopodia. Using live cell microscopy and specific calpain-resistant point-mutants of talin (L432G) and FAK (V744G), we find that calpain inhibits paxillin-based adhesion assembly through cleavage of talin and FAK, and adhesion disassembly through cleavage of FAK. Blocking calpain cleavage of talin and FAK inhibits repulsive turning from focal uncaging of Ca2+ within filopodia. In addition, blocking calpain cleavage of talin and FAK in vivo promotes Rohon–Beard peripheral axon extension into the skin. These data demonstrate that filopodial Ca2+ signals regulate axon outgrowth and guidance through calpain regulation of adhesion dynamics through specific cleavage of talin and FAK. SIGNIFICANCE STATEMENT The proper formation of neuronal networks requires accurate guidance of axons and dendrites during development by motile structures known as growth cones. Understanding the intracellular signaling mechanisms that govern growth cone motility will clarify how the nervous system develops and regenerates, and may

  14. Mechanosensitivity in axon growth and guidance

    NASA Astrophysics Data System (ADS)

    Urbach, Jeff

    2013-03-01

    In the developing nervous system, axons respond to a diverse array of cues to generate the intricate connection network required for proper function. The growth cone, a highly motile structure at the tip of a growing axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth cone behavior. We have investigated axon outgrowth and force generation on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that force generation and stiffness-dependent outgrowth are strongly dependent on cell type. We also observe very different internal dynamics and substrate coupling in the two populations, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate engagement in the peripheral nervous system neurons. We will discuss the biological origins of these differences, and recent analyses of the dynamic aspects of growth cone force generation and the implications for the role of mechanosensitivity in axon guidance. In collaboration with D. Koch, W. Rosoff, and H. M. Geller. Supported by NINDS grant 1R01NS064250-01 (J.S.U.) and the NHLBI Intramural Research Program (H.M.G.).

  15. Whisker/Cone growth on the thermal control surfaces experiment no. S0069

    NASA Technical Reports Server (NTRS)

    Zwiener, James M.; Coston, James E., Jr.; Miller, Edgar R.; Mell, Richard J.; Wilkes, Donald R.

    1995-01-01

    An unusual surface 'growth' was found during scanning electron microscope (SEM) investigations of the Thermal Control Surface Experiment (TCSE) S0069 front thermal cover. This 'growth' is similar to the cone type whisker growth phenomena as studied by G. K. Wehner beginning in the 1960's. Extensive analysis has identified the most probable composition of the whiskers to be a silicate type glass. Sources of the growth material are outgassing products from the experiment and orbital atomic oxygen, which occurs naturally at the orbital altitudes of the LDEF mission in the form of neutral atomic oxygen. The highly ordered symmetry and directionality of the whiskers are attributed to the long term (5.8 year) stable flight orientation of the LDEF.

  16. Lactobacilli Antagonize the Growth, Motility, and Adherence of Brachyspira pilosicoli: a Potential Intervention against Avian Intestinal Spirochetosis ▿

    PubMed Central

    Mappley, Luke J.; Tchórzewska, Monika A.; Cooley, William A.; Woodward, Martin J.; La Ragione, Roberto M.

    2011-01-01

    Avian intestinal spirochetosis (AIS) results from the colonization of the ceca and colorectum of poultry by pathogenic Brachyspira species. The number of cases of AIS has increased since the 2006 European Union ban on the use of antibiotic growth promoters, which, together with emerging antimicrobial resistance in Brachyspira, has driven renewed interest in alternative intervention strategies. Probiotics have been reported as protecting livestock against infection with common enteric pathogens, and here we investigate which aspects of the biology of Brachyspira they antagonize in order to identify possible interventions against AIS. The cell-free supernatants (CFS) of two Lactobacillus strains, Lactobacillus reuteri LM1 and Lactobacillus salivarius LM2, suppressed the growth of Brachyspira pilosicoli B2904 in a pH-dependent manner. In in vitro adherence and invasion assays with HT29-16E three-dimensional (3D) cells and in a novel avian cecal in vitro organ culture (IVOC) model, the adherence and invasion of B. pilosicoli in epithelial cells were reduced significantly by the presence of lactobacilli (P < 0.001). In addition, live and heat-inactivated lactobacilli inhibited the motility of B. pilosicoli, and electron microscopic observations indicated that contact between the lactobacilli and Brachyspira was crucial in inhibiting both adherence and motility. These data suggest that motility is essential for B. pilosicoli to adhere to and invade the gut epithelium and that any interference of motility may be a useful tool for the development of control strategies. PMID:21666022

  17. Further characterization of [3H]gamma-aminobutyric acid release from isolated neuronal growth cones: role of intracellular Ca2+ stores.

    PubMed

    Lockerbie, R O; Gordon-Weeks, P R

    1986-04-01

    We have recently shown that growth cones isolated from neonatal rat forebrain possess uptake and release mechanisms for the neurotransmitter gamma-aminobutyric acid. About half of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones is dependent on extracellular Ca2+. The remaining component of the [3H]gamma-aminobutyric acid release is unaffected by removal of extracellular Ca2+ and is resistant to blockade by the voltage-sensitive Ca2+-channel blocker methoxyverapamil. In the present series of experiments we have used caffeine to assess the possible role of intracellular stores of Ca2+ in supporting that component of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones that is independent of extracellular Ca2+. We have chosen caffeine because of its well established effect of releasing Ca2+ from smooth endoplasmic reticulum in muscle. We found that caffeine can release [3H]gamma-aminobutyric acid from isolated growth cones. This effect persists in Ca2+-free medium, in the presence of methoxyverapamil and in the absence of Na+. Furthermore, isobutylmethylxanthine could not substitute for caffeine suggesting that the caffeine effect is not due to phosphodiesterase inhibition and the subsequent rise in intracellular cyclic nucleotides. A combination of the mitochondrial poisons, Antimycin A and sodium azide had no effect on the release of [3H]gamma-aminobutyric acid induced either by caffeine or by high K+. We conclude that caffeine causes the release of Ca2+ from a non-mitochondrial store within the growth cone and that this Ca2+ store supports that component of the K+-induced release of [3H]gamma-aminobutyric acid that is independent of extracellular Ca2+.

  18. Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep; Kulkarni, Rahul; Sen, Shamik

    2016-06-01

    Tumors consist of multiple cell sub-populations including cancer stem cells (CSCs), transiently amplifying cells and terminally differentiated cells (TDCs), with the CSC fraction dictating the aggressiveness of the tumor and drug sensitivity. In epithelial cancers, tumor growth is influenced greatly by properties of the extracellular matrix (ECM), with cancer progression associated with an increase in ECM density. However, the extent to which increased ECM confinement induced by an increase in ECM density influences tumor growth and post treatment relapse dynamics remains incompletely understood. In this study, we use a cellular automata-based discrete modeling approach to study the collective influence of ECM density, cell motility and ECM proteolysis on tumor growth, tumor heterogeneity, and tumor relapse after drug treatment. We show that while increased confinement suppresses tumor growth and the spatial scattering of CSCs, this effect can be reversed when cells become more motile and proteolytically active. Our results further suggest that, in addition to the absolute number of CSCs, their spatial positioning also plays an important role in driving tumor growth. In a nutshell, our study suggests that, in confined environments, cell motility and ECM proteolysis are two key factors that regulate tumor growth and tumor relapse dynamics by altering the number and spatial distribution of CSCs.

  19. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease

    PubMed Central

    Lewis, Wesley R.; Malarkey, Erik B.; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C.; Porath, Jonathan D.; Birket, Susan E.; Saunier, Sophie; Antignac, Corinne; Leigh, Margaret W.; Zariwala, Maimoona A.; Drummond, Iain A.; Parant, John M.; Hildebrandt, Friedhelm; Yoder, Bradley K.

    2016-01-01

    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or ‘primary’ cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants

  20. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    PubMed

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

    2016-07-01

    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in

  1. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    PubMed Central

    2014-01-01

    Background KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. Methods We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. Results KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Conclusions Our findings indicate that KIAA1199 may play an important role in breast

  2. Vertical microbial community variability of carbonate-based cones may provide insight into ancient conical stromatolite formation

    NASA Astrophysics Data System (ADS)

    Bradley, James; Daille, Leslie; Trivedi, Christopher; Bojanowski, Caitlin; Nunn, Heather; Stamps, Blake; Johnson, Hope; Stevenson, Bradley; Berelson, Will; Corsetti, Frank; Spear, John

    2016-04-01

    Stromatolite morphogenesis is poorly understood, and the process by which microbial mats become mineralized is a primary question in microbialite formation. Ancient conical stromatolites are primarily carbonate-based whereas the few modern analogues in hot springs are either non-mineralized or mineralized by silica. A team from the 2015 International GeoBiology Course investigated carbonate-rich microbial cones from near Little Hot Creek (LHC), Long Valley Caldera, California, to investigate how conical stromatolites might form in a hot spring carbonate system. The cones rise up from a layered microbial mat on the east side of a 45° C pool with very low flow that is super-saturated with respect to CaCO3. Cone structures are 8-30 mm in height, are rigid and do not deform when removed from the pool. Morphological characterization through environmental scanning electronic microscopy revealed that the cone structure is maintained by a matrix of intertwining microbial filaments around carbonate grains. This matrix gives rise to cone-filaments that are arranged vertically or horizontally, and provides further stability to the cone. Preliminary 16S rRNA gene analysis indicated variability of community composition between different vertical levels of the cone. The cone tip had comparatively greater abundance of filamentous cyanobacteria including Leptolingbya, Phormidium and Isosphaera and fewer heterotrophs (e.g. Chloroflexi) compared to the cone bottom. This supports the hypothesis that cone formation may depend on the differential abundance of the microbial community and their potential functional roles. Metagenomic analyses of the cones revealed potential genes related to chemotaxis and motility. Specifically, a genomic bin identified as a member of the genus Isosphaera contained an hmp chemotaxis operon implicated in gliding motility in the cyanobacterium Nostoc punctiforme. Isosphaera is a Planctomycete shown to have phototactic capabilities, and may play a role in

  3. Vertical Microbial Community Variability of Carbonate-based Cones may Provide Insight into Formation in the Rock Record

    NASA Astrophysics Data System (ADS)

    Trivedi, C.; Bojanowski, C.; Daille, L. K.; Bradley, J.; Johnson, H.; Stamps, B. W.; Stevenson, B. S.; Berelson, W.; Corsetti, F. A.; Spear, J. R.

    2015-12-01

    Stromatolite morphogenesis is poorly understood, and the process by which microbial mats become mineralized is a primary question in microbialite formation. Ancient conical stromatolites are primarily carbonate-based whereas the few modern analogues in hot springs are either non-mineralized or mineralized by silica. A team from the 2015 International GeoBiology Course investigated carbonate-rich microbial cones from near Little Hot Creek (LHC), Long Valley Caldera, California, to investigate how conical stromatolites might form in a hot spring carbonate system. The cones are up to 3 cm tall and are found in a calm, ~45° C pool near LHC that is 4 times super-saturated with respect to CaCO3. The cones rise from a flat, layered microbial mat at the edge of the pool. Scanning electron microscopy revealed filamentous bacteria associated with calcite crystals within the cone tips. Preliminary 16S rRNA gene analysis indicated variability of community composition between different vertical levels of the cone. The cone tip had comparatively greater abundance of filamentous cyanobacteria (Leptolyngbya and Phormidium) and fewer heterotrophs (e.g. Chloroflexi) compared to the cone bottom. This supports the hypothesis that cone formation may depend on the differential abundance of the microbial community and their potential functional roles. Metagenomic analyses of the cones revealed potential genes related to chemotaxis and motility. Specifically, a genomic bin identified as a member of the genus Isosphaera contained an hmp chemotaxis operon implicated in gliding motility in the cyanobacterium Nostoc punctiforme [1]. Isosphaera is a Planctomycete shown to have phototactic capabilities [2], and may play a role in conjunction with cyanobacteria in the vertical formation of the cones. This analysis of actively growing cones indicates a complex interplay of geochemistry and microbiology that form structures which can serve as models for processes that occurred in the past and are

  4. Novel mechanisms power bacterial gliding motility.

    PubMed

    Nan, Beiyan; Zusman, David R

    2016-07-01

    For many bacteria, motility is essential for survival, growth, virulence, biofilm formation and intra/interspecies interactions. Since natural environments differ, bacteria have evolved remarkable motility systems to adapt, including swimming in aqueous media, and swarming, twitching and gliding on solid and semi-solid surfaces. Although tremendous advances have been achieved in understanding swimming and swarming motilities powered by flagella, and twitching motility powered by Type IV pili, little is known about gliding motility. Bacterial gliders are a heterogeneous group containing diverse bacteria that utilize surface motilities that do not depend on traditional flagella or pili, but are powered by mechanisms that are less well understood. Recently, advances in our understanding of the molecular machineries for several gliding bacteria revealed the roles of modified ion channels, secretion systems and unique machinery for surface movements. These novel mechanisms provide rich source materials for studying the function and evolution of complex microbial nanomachines. In this review, we summarize recent findings made on the gliding mechanisms of the myxobacteria, flavobacteria and mycoplasmas. © 2016 John Wiley & Sons Ltd.

  5. A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues.

    PubMed

    Joanne Wang, C; Li, Xiong; Lin, Benjamin; Shim, Sangwoo; Ming, Guo-Li; Levchenko, Andre

    2008-02-01

    Neuronal growth cones contain sophisticated molecular machinery precisely regulating their migration in response to complex combinatorial gradients of diverse external cues. The details of this regulation are still largely unknown, in part due to limitations of the currently available experimental techniques. Microfluidic devices have been shown to be capable of generating complex, stable and precisely controlled chemical gradients, but their use in studying growth cone migration has been limited in part due to the effects of shear stress. Here we describe a microfluidics-based turning-assay chip designed to overcome this issue. In addition to generating precise gradients of soluble guidance cues, the chip can also fabricate complex composite gradients of diffusible and surface-bound guidance cues that mimic the conditions the growth cones realistically counter in vivo. Applying this assay to Xenopus embryonic spinal neurons, we demonstrate that the presence of a surface-bound laminin gradient can finely tune the polarity of growth cone responses (repulsion or attraction) to gradients of brain-derived neurotrophic factor (BDNF), with the guidance outcome dependent on the mean BDNF concentration. The flexibility inherent in this assay holds significant potential for refinement of our understanding of nervous system development and regeneration, and can be extended to elucidate other cellular processes involving chemotaxis of shear sensitive cells.

  6. Generation of the membrane potential and its impact on the motility, ATP production and growth in Campylobacter jejuni

    USDA-ARS?s Scientific Manuscript database

    The generation of an electrical membrane potential (''), the major constituent of the proton motive force (pmf) is crucial for the ATP synthesis, bacterial growth and motility. The pmf drives the rotation of flagella and is vital for the microaerophilic human pathogen Campylobacter jejuni to coloniz...

  7. Automated laser guidance of neuronal growth cones using a spatial light modulator.

    PubMed

    Carnegie, David J; Cizmár, Tomás; Baumgartl, Jörg; Gunn-Moore, Frank J; Dholakia, Kishan

    2009-11-01

    The growth cone of a developing neuron can be guided using a focused infra-red (IR) laser beam [1]. In previous setups this process has required a significant amount of user intervention to adjust continuously the laser beam to guide the growing neuron. Previously, a system using an acousto-optical deflector (AOD) has been developed to steer the beam [2]. However, to enhance the controllability of this system, here we demonstrate the use of a computer controlled spatial light modulator (SLM) to steer and manipulate the shape of a laser beam for use in guided neuronal growth. This new experimental setup paves the way to enable a comprehensive investigation into beam shaping effects on neuronal growth and we show neuronal growth initiated by a Bessel light mode. This is a robust platform to explore the biochemistry of this novel phenomenon. (c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  8. L1CAM stimulates glioma cell motility and proliferation through the fibroblast growth factor receptor.

    PubMed

    Mohanan, Vishnu; Temburni, Murali K; Kappes, John C; Galileo, Deni S

    2013-04-01

    The L1CAM cell adhesion/recognition molecule (L1, CD171) and fibroblast growth factor receptor (FGFR) both are expressed by human high-grade glioma cells, but their potential actions in controlling cell behavior have not been linked. L1 actions in cancer cells have been attributed mainly to integrin receptors, and we demonstrated previously that L1-stimulated glioma cell migration correlates with integrin expression, increased focal adhesion kinase activation and focal complex turnover. Our analyses of datasets revealed FGFR is overexpressed in glioma regardless of grade, while ADAM10 metalloprotease expression increases with glioma grade. Here, we used dominant-negative and short hairpin RNA approaches to inhibit the activation of FGFR1 and expression of L1, respectively. An L1 peptide that inhibits L1-FGFR interaction and PD173074, a chemical inhibitor of FGFR1 activity, also were used to elucidate the involvement of L1-FGFR interactions on glioma cell behavior. Time-lapse cell motility studies and flow cytometry cell cycle analyses showed that L1 operates to increase glioma cell motility and proliferation through FGFR activation. Shutdown of both L1 expression and FGFR activity in glioma cells resulted in a complete termination of cell migration in vitro. These studies show for the first time that soluble L1 ectodomain (L1LE) acts on glioma cells through FGFRs, and that FGFRs are used by glioma cells for increasing motility as well as proliferation in response to activation by L1LE ligand. Thus, effective treatment of high-grade glioma may require simultaneous targeting of L1, FGFRs, and integrin receptors, which would reduce glioma cell motility as well as proliferation.

  9. Dissecting Nck/Dock signaling pathways in Drosophila visual system.

    PubMed

    Rao, Yong

    2005-01-01

    The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

  10. Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

    PubMed Central

    2005-01-01

    The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility. PMID:15951852

  11. Automated measurement of cell motility and proliferation

    PubMed Central

    Bahnson, Alfred; Athanassiou, Charalambos; Koebler, Douglas; Qian, Lei; Shun, Tongying; Shields, Donna; Yu, Hui; Wang, Hong; Goff, Julie; Cheng, Tao; Houck, Raymond; Cowsert, Lex

    2005-01-01

    Background Time-lapse microscopic imaging provides a powerful approach for following changes in cell phenotype over time. Visible responses of whole cells can yield insight into functional changes that underlie physiological processes in health and disease. For example, features of cell motility accompany molecular changes that are central to the immune response, to carcinogenesis and metastasis, to wound healing and tissue regeneration, and to the myriad developmental processes that generate an organism. Previously reported image processing methods for motility analysis required custom viewing devices and manual interactions that may introduce bias, that slow throughput, and that constrain the scope of experiments in terms of the number of treatment variables, time period of observation, replication and statistical options. Here we describe a fully automated system in which images are acquired 24/7 from 384 well plates and are automatically processed to yield high-content motility and morphological data. Results We have applied this technology to study the effects of different extracellular matrix compounds on human osteoblast-like cell lines to explore functional changes that may underlie processes involved in bone formation and maintenance. We show dose-response and kinetic data for induction of increased motility by laminin and collagen type I without significant effects on growth rate. Differential motility response was evident within 4 hours of plating cells; long-term responses differed depending upon cell type and surface coating. Average velocities were increased approximately 0.1 um/min by ten-fold increases in laminin coating concentration in some cases. Comparison with manual tracking demonstrated the accuracy of the automated method and highlighted the comparative imprecision of human tracking for analysis of cell motility data. Quality statistics are reported that associate with stage noise, interference by non-cell objects, and uncertainty in the

  12. Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression, Functionality and Involvement in Motility Regulation.

    PubMed

    Saucedo, Lucía; Buffa, Gabriela N; Rosso, Marina; Guillardoy, Tomás; Góngora, Adrian; Munuce, María J; Vazquez-Levin, Mónica H; Marín-Briggiler, Clara

    2015-01-01

    Fibroblast growth factors receptors (FGFRs) have been widely characterized in somatic cells, but there is scarce evidence of their expression and function in mammalian gametes. The objective of the present study was to evaluate the expression of FGFRs in human male germ cells, to determine sperm FGFR activation by the FGF2 ligand and their participation in the regulation of sperm motility. The expression of FGFR1, 2, 3 and 4 mRNAs and proteins in human testis and localization of these receptors in germ cells of the seminiferous epithelium was demonstrated. In ejaculated sperm, FGFRs were localized to the acrosomal region and flagellum. Sperm exposure to FGF2 caused an increase in flagellar FGFR phosphorylation and activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB or Akt) signaling pathways. Incubation with FGF2 led to a significant increase in the percentage of total and progressive sperm motility, as well as in sperm kinematics. All responses were prevented by sperm preincubation with BGJ398, a specific inhibitor of FGFR tyrosine kinase activity. In addition to confirming the expression of FGFRs in germ cells of the human testis, our study describes for the first time the presence, localization and functionality of human sperm FGFRs, and provides evidence of the beneficial effect of FGF2 upon sperm motility.

  13. Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression, Functionality and Involvement in Motility Regulation

    PubMed Central

    Saucedo, Lucía; Buffa, Gabriela N.; Rosso, Marina; Guillardoy, Tomás; Góngora, Adrian; Munuce, María J.

    2015-01-01

    Fibroblast growth factors receptors (FGFRs) have been widely characterized in somatic cells, but there is scarce evidence of their expression and function in mammalian gametes. The objective of the present study was to evaluate the expression of FGFRs in human male germ cells, to determine sperm FGFR activation by the FGF2 ligand and their participation in the regulation of sperm motility. The expression of FGFR1, 2, 3 and 4 mRNAs and proteins in human testis and localization of these receptors in germ cells of the seminiferous epithelium was demonstrated. In ejaculated sperm, FGFRs were localized to the acrosomal region and flagellum. Sperm exposure to FGF2 caused an increase in flagellar FGFR phosphorylation and activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB or Akt) signaling pathways. Incubation with FGF2 led to a significant increase in the percentage of total and progressive sperm motility, as well as in sperm kinematics. All responses were prevented by sperm preincubation with BGJ398, a specific inhibitor of FGFR tyrosine kinase activity. In addition to confirming the expression of FGFRs in germ cells of the human testis, our study describes for the first time the presence, localization and functionality of human sperm FGFRs, and provides evidence of the beneficial effect of FGF2 upon sperm motility. PMID:25970615

  14. Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth

    PubMed Central

    Moretti, Francesca; Rolando, Chiara; Winker, Moritz; Ivanek, Robert; Rodriguez, Javier; Von Kriegsheim, Alex; Taylor, Verdon; Bustin, Michael

    2015-01-01

    Neurons exploit local mRNA translation and retrograde transport of transcription factors to regulate gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high-mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuron-like cells and of hippocampal neurons, where it has the potential to be translated, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth, while HMGN5 overexpression induces neurite outgrowth and chromatin decompaction; these effects are dependent on growth cone localization of Hmgn5 mRNA. We suggest that the localization and local translation of transcripts coding for epigenetic factors couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus. PMID:25825524

  15. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.

    PubMed

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M; Esguerra, Camila V; Blust, Ronny; Darras, Veerle M; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  16. Deiodinase Knockdown during Early Zebrafish Development Affects Growth, Development, Energy Metabolism, Motility and Phototransduction

    PubMed Central

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M.; Esguerra, Camila V.; Blust, Ronny; Darras, Veerle M.; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  17. Cone calorimeter evaluation of wood products

    Treesearch

    Robert H. White; Mark A. Dietenberger

    2004-01-01

    The Forest Products Laboratory uses the cone calorimeter for the initial evaluation of the flammability of untreated and fire retardant treated wood products. The results of various studies are reviewed using a model presented at the 12th Annual BBC Conference on Flame Retardancy. The model uses data from the cone calorimeter to provide measures of fire growth...

  18. Whiskers, cones and pyramids created in sputtering by ion bombardment

    NASA Technical Reports Server (NTRS)

    Wehner, G. K.

    1979-01-01

    A thorough study of the role which foreign atoms play in cone formation during sputtering of metals revealed many experimental facts. Two types of cone formation were distinquished, deposit cones and seed cones. Twenty-six combinations of metals for seed cone formation were tested. The sputtering yield variations with composition for combinations which form seed cones were measured. It was demonstrated that whisker growth becomes a common occurrence when low melting point material is sputter deposited on a hot nonsputtered high melting point electrode.

  19. Effect of tannic and gallic acids alone or in combination with carbenicillin or tetracycline on Chromobacterium violaceum CV026 growth, motility, and biofilm formation.

    PubMed

    Dusane, Devendra H; O'May, Che; Tufenkji, Nathalie

    2015-07-01

    Chromobacterium violaceum is an opportunistic pathogen that causes infections that are difficult to treat. The goal of this research was to evaluate the effect of selected tannins (tannic acid (TA) and gallic acid (GA)) on bacterial growth, motility, antibiotic (carbenicillin, tetracycline) susceptibility, and biofilm formation. Both tannins, particularly TA, impaired bacterial growth levels and swimming motilities at sub-minimum inhibitory concentrations (sub-MICs). In combination with tannins, antibiotics showed increased MICs, suggesting that tannins interfered with antibacterial activity. Sub-MICs of tetracycline or TA alone enhanced biofilm formation of C. violaceum; however, in combination, these compounds inhibited biofilm formation. In contrast, carbenicillin at sub-MICs was effective in inhibiting C. violaceum biofilm formation; however, in combination with lower concentrations of TA or GA, biofilms were enhanced. These results provide insights into the effects of tannins on C. violaceum growth and their varying interaction with antibiotics used to target C. violaceum infections.

  20. Selective area growth of N-polar GaN nanorods by plasma-assisted MBE on micro-cone-patterned c-sapphire substrates

    NASA Astrophysics Data System (ADS)

    Jmerik, V. N.; Kuznetsova, N. V.; Nechaev, D. V.; Shubina, T. V.; Kirilenko, D. A.; Troshkov, S. I.; Davydov, V. Yu.; Smirnov, A. N.; Ivanov, S. V.

    2017-11-01

    The site-controlled selective area growth of N-polar GaN nanorods (NR) was developed by plasma-assisted MBE (PA MBE) on micro-cone-patterned sapphire substrates (μ-CPSS) by using a two-stage growth process. A GaN nucleation layer grown by migration enhanced epitaxy provides the best selectivity for nucleation of NRs on the apexes of 3.5-μm-diameter cones, whereas the subsequent growth of 1-μm-high NRs with a constant diameter of about 100 nm proceeds by standard high-temperature PA MBE at nitrogen-rich conditions. These results are explained by anisotropy of the surface energy for GaN of different polarity and crystal orientation. The InGaN single quantum wells inserted in the GaN NRs grown on the μ-CPSS demonstrate photoluminescence at 510 nm with a spatially periodic variation of its intensity with a period of ∼6 μm equal to that of the substrate patterning profile.

  1. Preparation, Imaging, and Quantification of Bacterial Surface Motility Assays

    PubMed Central

    Morales-Soto, Nydia; Anyan, Morgen E.; Mattingly, Anne E.; Madukoma, Chinedu S.; Harvey, Cameron W.; Alber, Mark; Déziel, Eric; Kearns, Daniel B.; Shrout, Joshua D.

    2015-01-01

    Bacterial surface motility, such as swarming, is commonly examined in the laboratory using plate assays that necessitate specific concentrations of agar and sometimes inclusion of specific nutrients in the growth medium. The preparation of such explicit media and surface growth conditions serves to provide the favorable conditions that allow not just bacterial growth but coordinated motility of bacteria over these surfaces within thin liquid films. Reproducibility of swarm plate and other surface motility plate assays can be a major challenge. Especially for more “temperate swarmers” that exhibit motility only within agar ranges of 0.4%-0.8% (wt/vol), minor changes in protocol or laboratory environment can greatly influence swarm assay results. “Wettability”, or water content at the liquid-solid-air interface of these plate assays, is often a key variable to be controlled. An additional challenge in assessing swarming is how to quantify observed differences between any two (or more) experiments. Here we detail a versatile two-phase protocol to prepare and image swarm assays. We include guidelines to circumvent the challenges commonly associated with swarm assay media preparation and quantification of data from these assays. We specifically demonstrate our method using bacteria that express fluorescent or bioluminescent genetic reporters like green fluorescent protein (GFP), luciferase (lux operon), or cellular stains to enable time-lapse optical imaging. We further demonstrate the ability of our method to track competing swarming species in the same experiment. PMID:25938934

  2. Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

    PubMed Central

    Akin, Orkun; Zipursky, S Lawrence

    2016-01-01

    Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them. DOI: http://dx.doi.org/10.7554/eLife.20762.001 PMID:27743477

  3. Potential anthelmintic: D-psicose inhibits motility, growth and reproductive maturity of L1 larvae of Caenorhabditis elegans.

    PubMed

    Sato, Masashi; Kurose, Hiroyuki; Yamasaki, Toru; Izumori, Ken

    2008-04-01

    No anthelmintic sugars have yet been identified. Eight ketohexose stereoisomers (D- and L-forms of psicose, fructose, tagatose and sorbose), along with D-galactose and D-glucose, were examined for potency against L1 stage Caenorhabditis elegans fed Escherichia coli. Of the sugars, D-psicose specifically inhibited the motility, growth and reproductive maturity of the L1 stage. D-Psicose probably interferes with the nematode nutrition. The present results suggest that D-psicose, one of the rare sugars, is a potential anthelmintic.

  4. A Nutrient-Tunable Bistable Switch Controls Motility in Salmonella enterica Serovar Typhimurium

    PubMed Central

    Koirala, Santosh; Mears, Patrick; Sim, Martin; Golding, Ido; Chemla, Yann R.; Aldridge, Phillip D.

    2014-01-01

    ABSTRACT Many bacteria are motile only when nutrients are scarce. In contrast, Salmonella enterica serovar Typhimurium is motile only when nutrients are plentiful, suggesting that this bacterium uses motility for purposes other than foraging, most likely for host colonization. In this study, we investigated how nutrients affect motility in S. enterica and found that they tune the fraction of motile cells. In particular, we observed coexisting populations of motile and nonmotile cells, with the distribution being determined by the concentration of nutrients in the growth medium. Interestingly, S. enterica responds not to a single nutrient but apparently to a complex mixture of them. Using a combination of experimentation and mathematical modeling, we investigated the mechanism governing this behavior and found that it results from two antagonizing regulatory proteins, FliZ and YdiV. We also found that a positive feedback loop involving the alternate sigma factor FliA is required, although its role appears solely to amplify FliZ expression. We further demonstrate that the response is bistable: that is, genetically identical cells can exhibit different phenotypes under identical growth conditions. Together, these results uncover a new facet of the regulation of the flagellar genes in S. enterica and further demonstrate how bacteria employ phenotypic diversity as a general mechanism for adapting to change in their environment. PMID:25161191

  5. Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

    NASA Astrophysics Data System (ADS)

    Geum, Dongil T.; Kim, Beum Jun; Chang, Audrey E.; Hall, Matthew S.; Wu, Mingming

    2016-01-01

    The receptor of epidermal growth factor (EGFR) critically regulates tumor cell invasion and is a potent therapeutic target for treatment of many types of cancers, including carcinomas and glioblastomas. It is known that EGF regulates cell motility when tumor cells are embedded within a 3D biomatrix. However, roles of EGF in modulating tumor cell motility phenotype are largely unknown. In this article, we report that EGF promotes a mesenchymal over an amoeboid motility phenotype using a malignant breast tumor cell line, MDA-MB-231, embedded within a 3D collagen matrix. Amoeboid cells are rounded in shape, while mesenchymal cells are elongated, and their migrations are governed by a distinctly different set of biomolecules. Using single cell tracking analysis, we also show that EGF promotes cell dissemination through a significant increase in cell persistence along with a moderate increase of speed. The increase of persistence is correlated with the increase of the percentage of the mesenchymal cells within the population. Our work reveals a novel role of microenvironmental cue, EGF, in modulating heterogeneity and plasticity of tumor cell motility phenotype. In addition, it suggests a potential visual cue for diagnosing invasive states of breast cancer cells. This work can be easily extended beyond breast cancer cells.

  6. Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation

    PubMed Central

    Feltrin, Daniel; Fusco, Ludovico; Witte, Harald; Moretti, Francesca; Martin, Katrin; Letzelter, Michel; Fluri, Erika; Scheiffele, Peter; Pertz, Olivier

    2012-01-01

    Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. PMID:23226105

  7. About GI Motility

    MedlinePlus

    ... eNewsletter Sidebar × MOBILE MENU About Us Learn About GI Motility Digestive Tract Disorders of the Esophagus Disorders ... Floor Motility Testing Personal Stories Contact Search About GI Motility Twitter Facebook YouTube Search Search ... About Us ...

  8. Cone biopsy

    MedlinePlus

    ... grade cone biopsy; High-grade cone biopsy; Carcinoma in situ-cone biopsy; CIS - cone biopsy; ASCUS - cone biopsy; ... marked dysplasia CIN III -- severe dysplasia to carcinoma in situ Abnormal results may also be due to cervical ...

  9. The Salmonella enterica serovar Typhimurium QseB Response Regulator Negatively Regulates Bacterial Motility and Swine Colonization in the Absence of the QseC Sensor Kinase

    USDA-ARS?s Scientific Manuscript database

    Salmonella enterica serovar Typhimurium (S. Typhimurium) responds to the catecholamine, norepinephrine by increasing bacterial growth and enhancing motility. In this study, iron with or without the siderophore, ferrioxamine E also enhanced bacterial motility. Iron-enhanced motility was growth-rate ...

  10. A molecular recognizing system of serotonin in rat fetal axonal growth cones: uptake and high affinity binding.

    PubMed

    Mercado, R; Hernández, J

    1992-09-18

    Axonal growth cone particles (AGCP) isolated from prenatal and postnatal rat brain had different high-affinity 5-HT uptake characteristics. In postnatal AGCP the uptake behaves as in the adult rat brain, while in the prenatal AGCP the uptake characteristics seem to be in a transitional stage. Also in prenatal AGCP we observed specific, high-affinity 5-HT binding sites. These results support the idea of an important role for 5-HT during axogenesis.

  11. Emergence of HGF/SF-Induced Coordinated Cellular Motility

    PubMed Central

    Zaritsky, Assaf; Natan, Sari; Ben-Jacob, Eshel; Tsarfaty, Ilan

    2012-01-01

    Collective cell migration plays a major role in embryonic morphogenesis, tissue remodeling, wound repair and cancer invasion. Despite many decades of extensive investigations, only few analytical tools have been developed to enhance the biological understanding of this important phenomenon. Here we present a novel quantitative approach to analyze long term kinetics of bright field time-lapse wound healing. Fully-automated spatiotemporal measures and visualization of cells' motility and implicit morphology were proven to be sound, repetitive and highly informative compared to single-cell tracking analysis. We study cellular collective migration induced by tyrosine kinase-growth factor signaling (Met-Hepatocyte Growth Factor/Scatter Factor (HGF/SF)). Our quantitative approach is applied to demonstrate that collective migration of the adenocarcinoma cell lines is characterized by simple morpho-kinetics. HGF/SF induces complex morpho-kinetic coordinated collective migration: cells at the front move faster and are more spread than those further away from the wound edge. As the wound heals, distant cells gradually accelerate and enhance spread and elongation –resembling the epithelial to mesenchymal transition (EMT), and then the cells become more spread and maintain higher velocity than cells located closer to the wound. Finally, upon wound closure, front cells halt, shrink and round up (resembling mesenchymal to epithelial transition (MET) phenotype) while distant cells undergo the same process gradually. Met inhibition experiments further validate that Met signaling dramatically alters the morpho-kinetic dynamics of the healing wound. Machine-learning classification was applied to demonstrate the generalization of our findings, revealing even subtle changes in motility patterns induced by Met-inhibition. It is concluded that activation of Met-signaling induces an elaborated model in which cells lead a coordinated increased motility along with gradual differentiation

  12. Actin-based motility propelled by molecular motors

    NASA Astrophysics Data System (ADS)

    Upadyayula, Sai Pramod; Rangarajan, Murali

    2012-09-01

    Actin-based motility of Listeria monocytogenes propelled by filament end-tracking molecular motors has been simulated. Such systems may act as potential nanoscale actuators and shuttles useful in sorting and sensing biomolecules. Filaments are modeled as three-dimensional elastic springs distributed on one end of the capsule and persistently attached to the motile bacterial surface through an end-tracking motor complex. Filament distribution is random, and monomer concentration decreases linearly as a function of position on the bacterial surface. Filament growth rate increases with monomer concentration but decreases with the extent of compression. The growing filaments exert push-pull forces on the bacterial surface. In addition to forces, torques arise due to two factors—distribution of motors on the bacterial surface, and coupling of torsion upon growth due to the right-handed helicity of F-actin—causing the motile object to undergo simultaneous translation and rotation. The trajectory of the bacterium is simulated by performing a force and torque balance on the bacterium. All simulations use a fixed value of torsion. Simulations show strong alignment of the filaments and the long axis of the bacterium along the direction of motion. In the absence of torsion, the bacterial surface essentially moves along the direction of the long axis. When a small amount of the torsion is applied to the bacterial surface, the bacterium is seen to move in right-handed helical trajectories, consistent with experimental observations.

  13. Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure.

    PubMed

    Syal, Kirtimaan; Maiti, Krishnagopal; Naresh, Kottari; Avaji, Prakash Gouda; Chatterji, Dipankar; Jayaraman, Narayanaswamy

    2016-10-01

    Mycobacterium has evolved distinct cell wall and strategies such as biofilm formation, which helps it to survive in hostile conditions. We have reported previously that arabinofuranoside containing glycolipids exhibit inhibition activities against the above functions of the mycobacterial species M. smegmatis. In search for activities mediated by oligosaccharide glycolipids, we report herein the inhibitory activities of a linear and a branched pentasaccharides having arabinan and mannan moieties. In the presence of the pentasaccharide glycolipids, a significant reduction in mycobacterial growth is observed, concomitant with reductions in sliding motility and colonization through biofilm formation, at the optimal glycolipid concentrations of 50-100 μg mL(-1). Especially the biofilm coat is ruptured by ~80-85 % in the presence of glycolipids. Pentasaccharides alone without the lipidic chain show only a weak effect. The glycolipids are non-toxic, as evaluated through their effect on RBCs. Analysis of the mycolic acid profile of glycolipid treated biofilm shows that α- and epoxy mycolic acids are downregulated significantly, in comparison to glycolipid untreated biofilms. Lipidomics profile analysis through mass spectrometry further reveals profound downregulation of phosphatidylinositol mannosides, acylatedphosphoglycerols and mycolic acid family, namely, keto-, alpha- and methoxymycolic acids.

  14. Control of actin-based motility through localized actin binding

    PubMed Central

    Banigan, Edward J.; Lee, Kun-Chun; Liu, Andrea J.

    2014-01-01

    A wide variety of cell biological and biomimetic systems use actin polymerization to drive motility. It has been suggested that an object such as a bacterium can propel itself by self-assembling a high concentration of actin behind it if it is repelled by actin. However, it is also known that it is essential for the moving object to bind actin. Therefore, a key question is how the actin tail can propel an object when it both binds and repels the object. We present a physically consistent Brownian dynamics model for actin-based motility that includes the minimal components of the dendritic nucleation model and allows for both attractive and repulsive interactions between actin and a moveable disk. We find that the concentration gradient of filamentous actin generated by polymerization is sufficient to propel the object, even with moderately strong binding interactions. Additionally, actin binding can act as a biophysical cap, and may directly control motility through modulation of network growth. Overall, this mechanism is robust in that it can drive motility against a load up to a stall pressure that depends on the Young’s modulus of the actin network and can explain several aspects of actin-based motility. PMID:24225232

  15. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

    PubMed

    Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

    1996-05-31

    Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

  16. Motor-driven intracellular transport powers bacterial gliding motility.

    PubMed

    Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W; Mignot, Tâm

    2011-05-03

    Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility.

  17. Motor-driven intracellular transport powers bacterial gliding motility

    PubMed Central

    Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W.; Mignot, Tâm

    2011-01-01

    Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility. PMID:21482768

  18. The swarming motility of Pseudomonas aeruginosa is blocked by cranberry proanthocyanidins and other tannin-containing materials.

    PubMed

    O'May, Che; Tufenkji, Nathalie

    2011-05-01

    Bacterial motility plays a key role in the colonization of surfaces by bacteria and the subsequent formation of resistant communities of bacteria called biofilms. Derivatives of cranberry fruit, predominantly condensed tannins called proanthocyanidins (PACs) have been reported to interfere with bacterial adhesion, but the effects of PACs and other tannins on bacterial motilities remain largely unknown. In this study, we investigated whether cranberry PAC (CPAC) and the hydrolyzable tannin in pomegranate (PG; punicalagin) affected the levels of motilities exhibited by the bacterium Pseudomonas aeruginosa. This bacterium utilizes flagellum-mediated swimming motility to approach a surface, attaches, and then further spreads via the surface-associated motilities designated swarming and twitching, mediated by multiple flagella and type IV pili, respectively. Under the conditions tested, both CPAC and PG completely blocked swarming motility but did not block swimming or twitching motilities. Other cranberry-containing materials and extracts of green tea (also rich in tannins) were also able to block or impair swarming motility. Moreover, swarming bacteria were repelled by filter paper discs impregnated with many tannin-containing materials. Growth experiments demonstrated that the majority of these compounds did not impair bacterial growth. When CPAC- or PG-containing medium was supplemented with surfactant (rhamnolipid), swarming motility was partially restored, suggesting that the effective tannins are in part acting by a rhamnolipid-related mechanism. Further support for this theory was provided by demonstrating that the agar surrounding tannin-induced nonswarming bacteria was considerably less hydrophilic than the agar area surrounding swarming bacteria. This is the first study to show that natural compounds containing tannins are able to block P. aeruginosa swarming motility and that swarming bacteria are repelled by such compounds.

  19. The Swarming Motility of Pseudomonas aeruginosa Is Blocked by Cranberry Proanthocyanidins and Other Tannin-Containing Materials▿

    PubMed Central

    O'May, Che; Tufenkji, Nathalie

    2011-01-01

    Bacterial motility plays a key role in the colonization of surfaces by bacteria and the subsequent formation of resistant communities of bacteria called biofilms. Derivatives of cranberry fruit, predominantly condensed tannins called proanthocyanidins (PACs) have been reported to interfere with bacterial adhesion, but the effects of PACs and other tannins on bacterial motilities remain largely unknown. In this study, we investigated whether cranberry PAC (CPAC) and the hydrolyzable tannin in pomegranate (PG; punicalagin) affected the levels of motilities exhibited by the bacterium Pseudomonas aeruginosa. This bacterium utilizes flagellum-mediated swimming motility to approach a surface, attaches, and then further spreads via the surface-associated motilities designated swarming and twitching, mediated by multiple flagella and type IV pili, respectively. Under the conditions tested, both CPAC and PG completely blocked swarming motility but did not block swimming or twitching motilities. Other cranberry-containing materials and extracts of green tea (also rich in tannins) were also able to block or impair swarming motility. Moreover, swarming bacteria were repelled by filter paper discs impregnated with many tannin-containing materials. Growth experiments demonstrated that the majority of these compounds did not impair bacterial growth. When CPAC- or PG-containing medium was supplemented with surfactant (rhamnolipid), swarming motility was partially restored, suggesting that the effective tannins are in part acting by a rhamnolipid-related mechanism. Further support for this theory was provided by demonstrating that the agar surrounding tannin-induced nonswarming bacteria was considerably less hydrophilic than the agar area surrounding swarming bacteria. This is the first study to show that natural compounds containing tannins are able to block P. aeruginosa swarming motility and that swarming bacteria are repelled by such compounds. PMID:21378043

  20. Learn About GI Motility

    MedlinePlus

    ... eNewsletter Sidebar × MOBILE MENU About Us Learn About GI Motility Digestive Tract Disorders of the Esophagus Disorders ... Floor Motility Testing Personal Stories Contact Search About GI Motility Twitter Facebook YouTube Search Search ... About Us ...

  1. Recurrent abnormalities in conifer cones and the evolutionary origins of flower-like structures.

    PubMed

    Rudall, Paula J; Hilton, Jason; Vergara-Silva, Francisco; Bateman, Richard M

    2011-03-01

    Conifer cones are reproductive structures that are typically of restricted growth and either exclusively pollen-bearing (male) or exclusively ovule-bearing (female). Here, we review two common spontaneous developmental abnormalities of conifer cones: proliferated cones, in which the apex grows vegetatively, and bisexual cones, which possess both male and female structures. Emerging developmental genetic data, combined with evidence from comparative morphology, ontogeny and palaeobotany, provide new insights into the evolution of both cones and flowers, and prompt novel strategies for understanding seed-plant evolution. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Antagonistic Effects of BACE1 and APH1B-γ-Secretase Control Axonal Guidance by Regulating Growth Cone Collapse.

    PubMed

    Barão, Soraia; Gärtner, Annette; Leyva-Díaz, Eduardo; Demyanenko, Galina; Munck, Sebastian; Vanhoutvin, Tine; Zhou, Lujia; Schachner, Melitta; López-Bendito, Guillermina; Maness, Patricia F; De Strooper, Bart

    2015-09-01

    ΒACE1 is the major drug target for Alzheimer's disease, but we know surprisingly little about its normal function in the CNS. Here, we show that this protease is critically involved in semaphorin 3A (Sema3A)-mediated axonal guidance processes in thalamic and hippocampal neurons. An active membrane-bound proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This fragment relays the Sema3A signal via ezrin-radixin-moesin (ERM) proteins to the neuronal cytoskeleton. APH1B-γ-secretase-mediated degradation of this fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the next axonal guidance cue. Thus, we reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. Our data also suggest that BACE1 and γ-secretase inhibition have physiologically opposite effects in this process, supporting the idea that combination therapy might attenuate some of the side effects associated with these drugs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors.

    PubMed

    Cornish, Elisa E; Natoli, Riccardo C; Hendrickson, Anita; Provis, Jan M

    2004-01-08

    Relatively little is known of the expression and distribution of FGF receptors (FGFR) in the primate retina. We investigated expression of FGFRs in developing and adult Macaca monkey retina, paying particular attention to the cone rich, macular region. One fetal human retina was used for diagnostic PCR using primers designed for FGFR1, FGFR2, FGFR3, FGFR4, and FGFR like-protein 1 (FGFrl1) and for probe design to FGFR3, FGFR4, and FGFrl1. Rat cDNA was used to synthesize probes for FGFR1 and FGFR2 with 90% and 93% homology to human, respectively. Paraffin sections of retina from macaque fetuses sacrificed at fetal days (Fd) 64, 73, 85, 105, 115, 120, and 165, and postnatal ages 2.5 and 11 years were used to detect FGF receptors by immunohistochemistry and in situ hybridization. PCR showed each of the FGF receptors are expressed in fetal human retina. In situ hybridization indicated that mRNA for each receptor is expressed in all retinal cell layers during development, but most intensely in the ganglion cell layer (GCL). FGFR2 mRNA is reduced in the adult inner (INL) and outer (ONL) nuclear layers, while FGFrl1 mRNA is virtually absent from the adult ONL. FGFR4 mRNA is particularly intense in fetal and adult cone photoreceptors. Immunoreactivity to FGFR1-FGFR4 was detected in the interphotoreceptor matrix in what appeared to be RPE microvilli associated with developing photoreceptor outer segments, and generally is high in the GCL and low in the INL. Different patterns of FGFR3 and FGFR4 immunoreactivities in the outer plexiform layer (OPL) suggest localization of FGFR3 to horizontal cell processes, with FGFR4 being expressed by both horizontal and bipolar cell processes. FGFR1, FGFR3, and FGFR4 immunoreactivities are present in the inner segments and somata of adult cones. The pedicles of developing and adult cones are FGFR1 and FGFR3 immunoreactive, and the basal, synaptic region is FGFR4 immunoreactive. FGFR4 labels cones almost in their entirety from early in

  4. Using experimental evolution to explore natural patterns between bacterial motility and resistance to bacteriophages

    PubMed Central

    Koskella, Britt; Taylor, Tiffany B; Bates, Jennifer; Buckling, Angus

    2011-01-01

    Resistance of bacteria to phages may be gained by alteration of surface proteins to which phages bind, a mechanism that is likely to be costly as these molecules typically have critical functions such as movement or nutrient uptake. To address this potential trade-off, we combine a systematic study of natural bacteria and phage populations with an experimental evolution approach. We compare motility, growth rate and susceptibility to local phages for 80 bacteria isolated from horse chestnut leaves and, contrary to expectation, find no negative association between resistance to phages and bacterial motility or growth rate. However, because correlational patterns (and their absence) are open to numerous interpretations, we test for any causal association between resistance to phages and bacterial motility using experimental evolution of a subset of bacteria in both the presence and absence of naturally associated phages. Again, we find no clear link between the acquisition of resistance and bacterial motility, suggesting that for these natural bacterial populations, phage-mediated selection is unlikely to shape bacterial motility, a key fitness trait for many bacteria in the phyllosphere. The agreement between the observed natural pattern and the experimental evolution results presented here demonstrates the power of this combined approach for testing evolutionary trade-offs. PMID:21509046

  5. Controllable synthesis and optical properties of novel ZnO cone arrays via vapor transport at low temperature.

    PubMed

    Han, Xinhai; Wang, Guanzhong; Jie, Jiansheng; Choy, Wallace C H; Luo, Yi; Yuk, T I; Hou, J G

    2005-02-24

    Novel ZnO cone arrays with controllable morphologies have been synthesized on silicon (100) substrates by thermal evaporation of metal Zn powder at a low temperature of 570 degrees C without a metal catalyst. Clear structure evolutions were observed using scanning electron microscopy: well-aligned ZnO nanocones, double-cones with growing head cones attached by stem cones, and cones with straight hexagonal pillar were obtained as the distance between the source and the substrates was increased. X-ray diffraction shows that all cone arrays grow along the c-axis. Raman and photoluminescence spectra reveal that the optical properties of the buffer layer between the ZnO cone arrays and the silicon substrates are better than those of the ZnO cone arrays due to high concentration of Zn in the heads of the ZnO cone arrays and higher growth temperature of the buffer layer. The growth of ZnO arrays reveals that the cone arrays are synthesized through a self-catalyzed vapor-liquid-solid (VLS) process.

  6. Motility Disorders in Children.

    PubMed

    Nurko, Samuel

    2017-06-01

    Gastrointestinal motility disorders in the pediatric population are common and can range from benign processes to more serious disorders. Performing and interpreting motility evaluations in children present unique challenges. There are primary motility disorders but abnormal motility may be secondary due to other disease processes. Diagnostic studies include radiographic scintigraphic and manometry studies. Although recent advances in the genetics, biology, and technical aspects are having an important impact and have allowed for a better understanding of the pathophysiology and therapy for gastrointestinal motility disorders in children, further research is needed to be done to have better understanding of the pathophysiology and for better therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling

    PubMed Central

    Hu, Zu-Quan; Xue, Hui; Long, Jin-Hua; Wang, Yun; Jia, Yi; Qiu, Wei; Zhou, Jing; Wen, Zong-Yao; Yao, Wei-Juan; Zeng, Zhu

    2016-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors. PMID:27809226

  8. In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor.

    PubMed

    Badie, B; Schartner, J; Klaver, J; Vorpahl, J

    1999-05-01

    Considered as immune effector cells of the central nervous system, microglia represent a major component of the inflammatory cells found in malignant gliomas. Although their role in brain tumor biology is unclear, accumulation of microglia in malignant brain tumors may be mediated through active secretion of cytokines by glioma cells. Because hepatocyte growth factor/scatter factor (HGF/SF) has been shown to modulate glioma motility through an autocrine mechanism, and because microglia have been reported to express the HGF/SF receptor Met, we hypothesized that microglia recruitment by gliomas may also occur through the secretion of HGF/SF. The effect of glioma cells in augmenting BV-2 murine microglia motility was studied by using an in vitro Boyden chamber migration assay. To determine the chemokines involved in microglia migration, neutralizing monoclonal antibodies against monocyte chemotactic protein-1 and HGF/SF were tested. Immunoblotting was used to check for the expression of HGF/SF by glioma cells, and the expression of Met by BV-2 cells was examined by flow cytometry. BV-2 migration was noted within 7 hours of incubation with both human (U251 MG and U373 MG) and murine (GL261) glioma cell lines. This migration corresponded to HGF/SF secretion by glioma cells and was completely inhibited by neutralizing monoclonal antibody against HGF/SF, but not monocyte chemotactic protein-1. Exposure of BV-2 cells to recombinant HGF/SF, but not monocyte chemotactic protein-1, resulted in their migration and down-regulation of Met in a dose-dependent fashion. HGF/SF, which plays a role in glioma motility and mitogenesis, may also act as a chemokine for microglia and may be responsible for the microglia infiltration in malignant gliomas. This active recruitment of microglia may play an important role in glioma biology.

  9. Surface Topography Hinders Bacterial Surface Motility.

    PubMed

    Chang, Yow-Ren; Weeks, Eric R; Ducker, William A

    2018-03-21

    We demonstrate that the surface motility of the bacterium, Pseudomonas aeruginosa, is hindered by a crystalline hemispherical topography with wavelength in the range of 2-8 μm. The motility was determined by the analysis of time-lapse microscopy images of cells in a flowing growth medium maintained at 37 °C. The net displacement of bacteria over 5 min is much lower on surfaces containing 2-8 μm hemispheres than on flat topography, but displacement on the 1 μm hemispheres is not lower. That is, there is a threshold between 1 and 2 μm for response to the topography. Cells on the 4 μm hemispheres were more likely to travel parallel to the local crystal axis than in other directions. Cells on the 8 μm topography were less likely to travel across the crowns of the hemispheres and were also more likely to make 30°-50° turns than on flat surfaces. These results show that surface topography can act as a significant barrier to surface motility and may therefore hinder surface exploration by bacteria. Because surface exploration can be a part of the process whereby bacteria form colonies and seek nutrients, these results help to elucidate the mechanism by which surface topography hinders biofilm formation.

  10. Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions.

    PubMed

    Atabey, N; Gao, Y; Yao, Z J; Breckenridge, D; Soon, L; Soriano, J V; Burke, T R; Bottaro, D P

    2001-04-27

    Hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets during development, homeostasis and tissue regeneration. Inappropriate HGF signaling occurs in several human cancers, and the ability of HGF to initiate a program of protease production, cell dissociation, and motility has been shown to promote cellular invasion and is strongly linked to tumor metastasis. Upon HGF binding, several tyrosines within the intracellular domain of its receptor, c-Met, become phosphorylated and mediate the binding of effector proteins, such as Grb2. Grb2 binding through its SH2 domain is thought to link c-Met with downstream mediators of cell proliferation, shape change, and motility. We analyzed the effects of Grb2 SH2 domain antagonists on HGF signaling and observed potent blockade of cell motility, matrix invasion, and branching morphogenesis, with ED(50) values of 30 nm or less, but only modest inhibition of mitogenesis. These compounds are 1000-10,000-fold more potent anti-motility agents than any previously characterized Grb2 SH2 domain antagonists. Our results suggest that SH2 domain-mediated c-Met-Grb2 interaction contributes primarily to the motogenic and morphogenic responses to HGF, and that these compounds may have therapeutic application as anti-metastatic agents for tumors where the HGF signaling pathway is active.

  11. Using Computer Simulations to Model Scoria Cone Growth

    NASA Astrophysics Data System (ADS)

    Bemis, K. G.; Mehta, R. D.

    2016-12-01

    Scoria cones form from the accumulation of scoria delivered by either bursting lava bubbles (Strombolian style eruptions) or the gas thrust of an eruption column (Hawaiian to sub-Plinian style eruption). In this study, we focus on connecting the distribution of scoria delivery to the eventual cone shape rather than the specifics of the mechanism of delivery. For simplicity, we choose to model ballistic paths, that follow the scoria from ejection from crater to landing on the surface and then avalanching down slope. The first stage corresponds to Strombolian-like bursts of the bubble. The second stage only occurs if the angle of repose is greater than 30 degrees. After this condition is met, the scoria particles grain flow downwards until a stable slope is formed. These two stages of the volcanic eruption repeat themselves in the number of phases. We hypothesize that the horizontal travel distance of the ballistic paths, and as a result the width of the volcano, is primarily dependent of the velocity of the particles bursting from the bubble in the crater. Other parameters that may affect the shape of cinder cones are air resistance on ballistic paths, ranges in particle size, ballistic ejection angles, and the total number of particles. Ejection velocity, ejection angle, particle size and air resistance control the delivery distribution of scoria; a similar distribution of scoria can be obtained by sedimentation from columns and the controlling parameters of such (gas thrust velocity, particle density, etc.) can be related to the ballistic delivery in terms of eruption energy and particle characteristics. We present a series of numerical experiments that test our hypotheses by varying different parameters one or more at a time in sets each designed to test a specific hypothesis. Volcano width increases as ejection velocity, ejection angle (measured from surface), or the total number of scoria particles increases. Ongoing investigations seek the controls on crater

  12. Identification and Characterization of a Gene stp17 Located on the Linear Plasmid pBSSB1 as an Enhanced Gene of Growth and Motility in Salmonella enterica Serovar Typhi

    PubMed Central

    Zhang, Haifang; Zhu, Yunxia; Xie, Xiaofang; Wang, Min; Du, Hong; Xu, Shungao; Zhang, Ying; Gong, Mingyu; Ni, Bin; Xu, Huaxi; Huang, Xinxiang

    2016-01-01

    The linear plasmid pBSSB1 mediates the flagellar phase variation in H:z66 positive Salmonella enterica serovar Typhi (S. Typhi). The gene named stp17 (S. Typhi plasmid number 17 gene) is located on pBSSB1 and encodes the protein STP17. The expression pattern at the protein-level and function of STP17 remains unknown. In this study, the recombinant protein STP17His6 was expressed, purified and used to prepare the polyclonal anti-STP17 antibody. We detected protein-level expression of stp17 in S. Typhi and further investigated the protein expression characteristics of stp17 in different growth phases by western blot analysis. The effects of STP17 on bacterial growth and motility were analyzed. In addition, the structure of STP17 was predicted and the active site of STP17 was identified by site-directed mutagenesis. The results showed that STP17 was expressed stably in the wild type strain of S. Typhi. STP17 expression at the protein level peaks when cultures reach an OD600 value of 1.2. The growth rate and motility of the Δstp17 strain were significantly decreased compared with the wild type strain (P < 0.05) and this phenotype was restored in the stp17 complementary strain. Moreover, the growth rate and motility of the stp17 over-expression strain was greater than the wild type strain. STP17 contains nine Helix segments, six Stand segments and some Coil segments in the secondary structural level. The top-ranked 3-D structure of STP17 predicted by I-TASSER contains a putative ATPase domain and the amino acid residues of GLY16, GLY19, LYS20, ASN133, LYS157, and LYS158 may be the active site residues of STP17. Finally, STP17 was able to catalyze the ATP to ADP reaction, suggesting that STP17 may be an ATPase. To our knowledge, this is the first report describing the protein expression characteristics of STP17 in S. Typhi, showing that STP17 promotes bacterial growth and motility, which may be associated with its potential ATPase activity. PMID:27761429

  13. A Novel Action of the Proton Pump Inhibitor Rabeprazole and Its Thioether Derivative against the Motility of Helicobacter pylori

    PubMed Central

    Tsutsui, Nanako; Taneike, Ikue; Ohara, Tatsuki; Goshi, Satoshi; Kojio, Seiichi; Iwakura, Nobuhiro; Matsumaru, Hiroyuki; Wakisaka-Saito, Noriko; Zhang, Hui-Min; Yamamoto, Tatsuo

    2000-01-01

    The motility of Helicobacter pylori was maximum at 37°C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of H. pylori. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 μg/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H2 blockers or anti-H. pylori agents. The motilities of Campylobacter jejuni and C. coli—but not those of Vibrio cholerae O1 and O139, Vibrio parahaemolyticus, Salmonella enterica serovar Typhimurium, and Proteus mirabilis—were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth. PMID:11036024

  14. The Interplay between Signaling and Metabolism in Breast Cancer Cell Motility and Metastasis

    NASA Astrophysics Data System (ADS)

    Tsarfaty, Ilan

    2013-03-01

    The initiation and growth of tumor metastases require tumor cells go through a transition between collective-to-individual cell migration. Understanding the molecular, cellular and physical mechanisms of these different migration modes is limited. We focus on the tumor cell migration induced by Hepatocyte Growth Factor / Scatter Factor (HGF/SF) - Met-signaling, a master regulator of cell motility in normal and malignant processes. Met has been implicated in tumorigenesis and metastasis and several Met targeting agents have been introduced into the clinic, and are currently in all phases of clinical trials Our analysis demonstrates that Met signaling dramatically alter the morpho-kinetic dynamics of collective migration of tumor cells. It induce a ``wave'' of increasing velocities that propagates back from the leading edge, increases cells' orientation and cooperation capabilities. In parallel Met signaling induces amoeboid cell motility that increased cell individuality. The decision making regarding the motility mode is dependent on the extent of activation of unique signal and metabolic cues. We present a combination of molecular imaging, conceptual and modeling framework for the analysis and assessment of the collective mesenchymal to epithelial versus amoeboid motility. Combined together our analysis can contribute to the understanding of metastasis and personalizing anti Met targeted therapy.

  15. Insulinlike growth factor I improves yak (Bos grunniens) spermatozoa motility and the oocyte cleavage rate by modulating the expression of Bax and Bcl-2.

    PubMed

    Pan, Yangyang; Cui, Yan; Baloch, Abdul Rasheed; Fan, Jiangfeng; He, Junfeng; Li, Guyue; Zheng, Hongfei; Zhang, Yifu; Lv, Peng; Yu, Sijiu

    2015-09-15

    The aim of our present study was to examine the effects of insulinlike growth factor 1 (IGF-1) on yak sperm motility during in vitro capacitation and the relationship between the effects of IGF-1 on yak sperm motility and apoptosis was evaluated. Frozen-thawed yak spermatozoa were incubated at 38 °C for 1 hour in Tyrode's bicarbonate-buffered medium for sperm culture (Sp-TALP) with different concentrations (0, 50, 100, and 200 ng/mL) of IGF-1. In every treatment, the sperm motility was measured by a computer-assisted sperm analyzer system. The fertilizing ability of spermatozoa was evaluated on the basis of oocyte cleavage rate after insemination. The expression of Bax and Bcl-2 was examined by real-time polymerase chain reaction and Western blot for the messenger RNA and protein levels. It is interesting to note that IGF-1 improved yak spermatozoa motility and the cleavage rate of oocytes; these improvements were highest in the 100 ng/mL IGF-1 group, followed by the 200 ng/mL and 50 ng/mL groups, with the lowest improvements in motility and cleavage rates in groups without IGF-1. The expression level of Bax was downregulated by IGF-1, whereas Bcl-2 was upregulated. Both messenger RNA and Bax proteins were lowest in groups with 100 ng/mL IGF-1, where the Bcl-2 was the highest. Bax expression in the groups with IGF-1 was lower than that in the group without IGF-1, and Bcl-2 expression was higher in groups with IGF-1 than that in the group without IGF-1. In conclusion, this research reports that improvements in yak spermatozoa motility and the oocyte cleavage rate after the addition of IGF-I may be a result of the reduction of spermatozoa apoptosis rates by modulating the expression of Bax and Bcl-2. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of transforming growth factor-beta1 on cell motility, collagen gel contraction, myofibroblastic differentiation, and extracellular matrix expression of human adipose-derived stem cell.

    PubMed

    Kakudo, Natsuko; Kushida, Satoshi; Suzuki, Kenji; Ogura, Tsunetaka; Notodihardjo, Priscilla Valentin; Hara, Tomoya; Kusumoto, Kenji

    2012-12-01

    Human adipose-derived stem cells (ASCs) are adult pluripotent stem cells, and their usefulness in plastic surgery has garnered attention in recent years. Although, there have been expectations that ASCs might function in wound repair and regeneration, no studies to date have examined the role of ASCs in the mechanism that promotes wound-healing. Transforming growth factor-beta1 (TGF-β1) is a strong candidate cytokine for the triggering of mesenchymal stem cell migration, construction of extracellular matrices, and differentiation of ASCs into myofibroblasts. Cell proliferation, motility, and differentiation, as well as extracellular matrix production, play an important role in wound-healing. We have evaluated the capacity of ASCs to proliferate and their potential to differentiate into phenotypic myofibroblasts, as well as their cell motility and collagen gel contraction ability, when cultured with TGF-β1. Cell motility was analyzed using a wound-healing assay. ASCs that differentiated into myofibroblasts expressed the gene for alpha-smooth muscle actin, and its protein expression was detected immunohistochemically. The extracellular matrix expression in ASCs was evaluated using real-time RT-PCR. Based on the results, we conclude that human ASCs have the potential for cell motility, extracellular matrix gene expression, gel contraction, and differentiation into myofibroblasts and, therefore, may play an important role in the wound-healing process.

  17. Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

    PubMed

    Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

    2016-03-30

    Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization

  18. Axon growth regulation by a bistable molecular switch.

    PubMed

    Padmanabhan, Pranesh; Goodhill, Geoffrey J

    2018-04-25

    For the brain to function properly, its neurons must make the right connections during neural development. A key aspect of this process is the tight regulation of axon growth as axons navigate towards their targets. Neuronal growth cones at the tips of developing axons switch between growth and paused states during axonal pathfinding, and this switching behaviour determines the heterogeneous axon growth rates observed during brain development. The mechanisms controlling this switching behaviour, however, remain largely unknown. Here, using mathematical modelling, we predict that the molecular interaction network involved in axon growth can exhibit bistability, with one state representing a fast-growing growth cone state and the other a paused growth cone state. Owing to stochastic effects, even in an unchanging environment, model growth cones reversibly switch between growth and paused states. Our model further predicts that environmental signals could regulate axon growth rate by controlling the rates of switching between the two states. Our study presents a new conceptual understanding of growth cone switching behaviour, and suggests that axon guidance may be controlled by both cell-extrinsic factors and cell-intrinsic growth regulatory mechanisms. © 2018 The Author(s).

  19. The Developmental Process of the Growing Motile Ciliary Tip Region.

    PubMed

    Reynolds, Matthew J; Phetruen, Tanaporn; Fisher, Rebecca L; Chen, Ke; Pentecost, Brian T; Gomez, George; Ounjai, Puey; Sui, Haixin

    2018-05-22

    Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis. Our results demonstrated that the distal tip region of motile cilia exhibit progressive morphological changes as cilia develop. This developmental process is time-dependent and continues after growing cilia reach their full lengths. The structural analysis of growing ciliary tips revealed that B-tubules of axonemal microtubule doublets terminate far away from the tip end, which is led by the flagellar tip complex (FTC), demonstrating that the FTC might not directly mediate the fast turnover of intraflagellar transport (IFT).

  20. The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.

    PubMed

    Chávez-Güitrón, L E; Morales-Montor, J; Muñoz-Guzmán, M A; Nava-Castro, K E; Ramírez-Álvarez, H; Moreno-Méndoza, N A; Hernández-Cervantes, R; Alba-Hurtado, F

    2016-07-15

    The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. RON kinase isoforms demonstrate variable cell motility in normal cells.

    PubMed

    Greenbaum, Alissa; Rajput, Ashwani; Wan, Guanghua

    2016-09-01

    Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility. Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants. RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03). RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis.

  2. Measuring Borrelia burgdorferi Motility and Chemotaxis.

    PubMed

    Zhang, Kai; Li, Chunhao

    2018-01-01

    Swimming plate, cell motion tracking, and capillary tube assays are very useful tools to quantitatively measure bacterial motility and chemotaxis. These methods were modified and applied to study Borrelia burgdorferi motility and chemotaxis. By using these methods, numerous motility and chemotaxis mutants have been characterized and several chemoattractants were identified. With the assistance of these tools, the role of motility and chemotaxis in the pathogenicity of B. burgdorferi has been established. In addition, these tools also facilitate the study of motility and chemotaxis in other spirochetes.

  3. ZnO twin-cones: synthesis, photoluminescence, and catalytic decomposition of ammonium perchlorate.

    PubMed

    Sun, Xuefei; Qiu, Xiaoqing; Li, Liping; Li, Guangshe

    2008-05-19

    ZnO twin-cones, a new member to the ZnO family, were prepared directly by a solvothermal method using a mixed solution of zinc nitrate and ethanol. The reaction and growth mechanisms of ZnO twin-cones were investigated by X-ray diffraction, UV-visible spectra, infrared and ion trap mass spectra, and transmission electron microscopy. All as-prepared ZnO cones consisted of tiny single crystals with lengths of several micrometers. With prolonging of the reaction time from 1.5 h to 7 days, the twin-cone shape did not change at all, while the lattice parameters increased slightly and the emission peak of photoluminescence shifted from the green region to the near orange region. ZnO twin-cones are also explored as an additive to promote the thermal decomposition of ammonium perchlorate. The variations of photoluminescence spectra and catalytic roles in ammonium perchlorate decomposition were discussed in terms of the defect structure of ZnO twin-cones.

  4. Primary Esophageal Motility Disorders: Beyond Achalasia.

    PubMed

    Schlottmann, Francisco; Patti, Marco G

    2017-06-30

    The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders. The Chicago classification introduced new manometric parameters and better defined esophageal motility disorders. Motility disorders beyond achalasia with the current classification are: esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility) and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). The aim of this study was to review the current diagnosis and management of esophageal motility disorders other than achalasia.

  5. Primary Esophageal Motility Disorders: Beyond Achalasia

    PubMed Central

    Schlottmann, Francisco; Patti, Marco G.

    2017-01-01

    The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders. The Chicago classification introduced new manometric parameters and better defined esophageal motility disorders. Motility disorders beyond achalasia with the current classification are: esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility) and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). The aim of this study was to review the current diagnosis and management of esophageal motility disorders other than achalasia. PMID:28665309

  6. Mathematical models of cell motility.

    PubMed

    Flaherty, Brendan; McGarry, J P; McHugh, P E

    2007-01-01

    Cell motility is an essential biological action in the creation, operation and maintenance of our bodies. Developing mathematical models elucidating cell motility will greatly advance our understanding of this fundamental biological process. With accurate models it is possible to explore many permutations of the same event and concisely investigate their outcome. While great advancements have been made in experimental studies of cell motility, it now has somewhat fallen on mathematical models to taking a leading role in future developments. The obvious reason for this is the complexity of cell motility. Employing the processing power of today's computers will give researches the ability to run complex biophysical and biochemical scenarios, without the inherent difficulty and time associated with in vitro investigations. Before any great advancement can be made, the basics of cell motility will have to be well-defined. Without this, complicated mathematical models will be hindered by their inherent conjecture. This review will look at current mathematical investigations of cell motility, explore the reasoning behind such work and conclude with how best to advance this interesting and challenging research area.

  7. Tubular graphite cones.

    PubMed

    Zhang, Guangyu; Jiang, Xin; Wang, Enge

    2003-04-18

    We report the synthesis of tubular graphite cones using a chemical vapor deposition method. The cones have nanometer-sized tips, micrometer-sized roots, and hollow interiors with a diameter ranging from about 2 to several tens of nanometers. The cones are composed of cylindrical graphite sheets; a continuous shortening of the graphite layers from the interior to the exterior makes them cone-shaped. All of the tubular graphite cones have a faceted morphology. The constituent graphite sheets have identical chiralities of a zigzag type across the entire diameter, imparting structural control to tubular-based carbon structures. The tubular graphite cones have potential for use as tips for scanning probe microscopy, but with greater rigidity and easier mounting than currently used carbon nanotubes.

  8. Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations.

    PubMed

    Gardner, J C; Michaelides, M; Hardcastle, A J

    2016-05-25

    X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.

  9. Mechanism of Actin-Based Motility

    NASA Astrophysics Data System (ADS)

    Pantaloni, Dominique; Le Clainche, Christophe; Carlier, Marie-France

    2001-05-01

    Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, which undergo actin-based propulsion, are acknowledged models of the leading edge of lamellipodia. Actin-based motility of the bacteria or of functionalized microspheres can be reconstituted in vitro from only five pure proteins. Movement results from the regulated site-directed treadmilling of actin filaments, consistent with observations of actin dynamics in living motile cells and with the biochemical properties of the components of the synthetic motility medium.

  10. Motility versus fluctuations in mixtures of self-motile and passive agents.

    PubMed

    Hinz, Denis F; Panchenko, Alexander; Kim, Tae-Yeon; Fried, Eliot

    2014-12-07

    Many biological systems consist of self-motile and passive agents both of which contribute to overall functionality. However, little is known about the properties of such mixtures. Here we formulate a model for mixtures of self-motile and passive agents and show that the model gives rise to three different dynamical phases: a disordered mesoturbulent phase, a polar flocking phase, and a vortical phase characterized by large-scale counter rotating vortices. We use numerical simulations to construct a phase diagram and compare the statistical properties of the different phases with observed features of self-motile bacterial suspensions. Our findings afford specific insights regarding the interaction of microorganisms and passive particles and provide novel strategic guidance for efficient technological realizations of artificial active matter.

  11. Efficacy of chemical sterilization and storage conditions of gutta-percha cones.

    PubMed

    da Motta, P G; de Figueiredo, C B; Maltos, S M; Nicoli, J R; Ribeiro Sobrinho, A P; Maltos, K L; Carvalhais, H P

    2001-09-01

    The objective of the present study was to assess the efficacy of 2.5% sodium hypochlorite and 2.2% glutaraldehyde ('Cidex') as sterilizing agents for gutta-percha cones. The efficacy of storage of gutta-percha cones in the presence or absence of paraformaldehyde was also evaluated. Gutta-percha cones artificially contaminated with a suspension of Bacillus stearothermophilus (ATCC/7953) were treated with either 2.2% glutaraldehyde for 10, 15, 30 and 60 min and 10 and 12 h, or 2.5% sodium hypochlorite for 5, 10 and 15 min. The cones were then incubated in thioglycollate medium for the determination of microbial growth. In parallel, additional sterile gutta-percha cones were stored in sealed containers with or without paraformaldehyde tablets for 30 days. The containers were opened 30 min a day and exposed to the environment of a functioning dental clinic. Twelve cones were removed weekly from the containers to determine whether contamination had occurred. The results showed that 2.5% sodium hypochlorite was effective after 5, 10 and 15 min, whereas 10 and 12 h contact with 2.2% glutaraldehyde was necessary to obtain sterilization. There was no contamination of the gutta-percha cones when stored with or without paraformaldehyde. Sodium hypochlorite (2.5%) and 2.2% glutaraldehyde ('Cidex') proved to be effective as sterilizing agents for gutta-percha cones, with sodium hypochlorite requiring shorter periods of use. No difference was observed between the two methods of cone storage.

  12. Deployable micro-traps to sequester motile bacteria

    NASA Astrophysics Data System (ADS)

    di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

    2017-04-01

    The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.

  13. Deployable micro-traps to sequester motile bacteria

    PubMed Central

    Di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

    2017-01-01

    The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria. PMID:28378786

  14. Deployable micro-traps to sequester motile bacteria.

    PubMed

    Di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

    2017-04-05

    The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.

  15. Motile and non-motile sperm diagnostic manipulation using optoelectronic tweezers.

    PubMed

    Ohta, Aaron T; Garcia, Maurice; Valley, Justin K; Banie, Lia; Hsu, Hsan-Yin; Jamshidi, Arash; Neale, Steven L; Lue, Tom; Wu, Ming C

    2010-12-07

    Optoelectronic tweezers was used to manipulate human spermatozoa to determine whether their response to OET predicts sperm viability among non-motile sperm. We review the electro-physical basis for how live and dead human spermatozoa respond to OET. The maximal velocity that non-motile spermatozoa could be induced to move by attraction or repulsion to a moving OET field was measured. Viable sperm are attracted to OET fields and can be induced to move at an average maximal velocity of 8.8 ± 4.2 µm s(-1), while non-viable sperm are repelled to OET, and are induced to move at an average maximal velocity of -0.8 ± 1.0 µm s(-1). Manipulation of the sperm using OET does not appear to result in increased DNA fragmentation, making this a potential method by which to identify viable non-motile sperm for assisted reproductive technologies.

  16. Coupled effects of chemotaxis and growth on traveling bacterial waves.

    PubMed

    Yan, Zhifeng; Bouwer, Edward J; Hilpert, Markus

    2014-08-01

    Traveling bacterial waves are capable of improving contaminant remediation in the subsurface. It is fairly well understood how bacterial chemotaxis and growth separately affect the formation and propagation of such waves. However, their interaction is not well understood. We therefore perform a modeling study to investigate the coupled effects of chemotaxis and growth on bacterial migration, and examine their effects on contaminant remediation. We study the waves by using different initial electron acceptor concentrations for different bacteria and substrate systems. Three types of traveling waves can occur: a chemotactic wave due to the biased movement of chemotactic bacteria resulting from metabolism-generated substrate concentration gradients; a growth/decay/motility wave due to a dynamic equilibrium between bacterial growth, decay and random motility; and an integrated wave due to the interaction between bacterial chemotaxis and growth. Chemotaxis hardly enhances the bacterial propagation if it is too weak to form a chemotactic wave or its wave speed is less than half of the growth/decay/motility wave speed. However, chemotaxis significantly accelerates bacterial propagation once its wave speed exceeds the growth/decay/motility wave speed. When convection occurs, it speeds up the growth/decay/motility wave but slows down or even eliminates the chemotactic wave due to the dispersion. Bacterial survival proves particularly important for bacterial propagation. Therefore we develop a conceptual model to estimate the speed of growth/decay/motility waves. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

    NASA Astrophysics Data System (ADS)

    Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

    2012-01-01

    Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

  18. Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

    PubMed

    Marcos, S; Tornow, R P; Elsner, A E; Navarro, R

    1997-07-01

    Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

  19. 21 CFR 876.1725 - Gastrointestinal motility monitoring system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastrointestinal motility monitoring system. 876... Gastrointestinal motility monitoring system. (a) Identification. A gastrointestinal motility monitoring system is a... esophageal motility monitor and tube, the gastrointestinal motility (electrical) system, and certain...

  20. 21 CFR 876.1725 - Gastrointestinal motility monitoring system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gastrointestinal motility monitoring system. 876... Gastrointestinal motility monitoring system. (a) Identification. A gastrointestinal motility monitoring system is a... esophageal motility monitor and tube, the gastrointestinal motility (electrical) system, and certain...

  1. A Cyanobacterium Capable of Swimming Motility

    NASA Astrophysics Data System (ADS)

    Waterbury, John B.; Willey, Joanne M.; Franks, Diana G.; Valois, Frederica W.; Watson, Stanley W.

    1985-10-01

    A novel cyanobacterium capable of swimming motility wass isolated in pure culture from several locations in the Atlantic Ocean. It is a small unicellular form, assignable to the genus Synechococcus, that is capable of swimming through liquids at speeds of 25 micrometers per second. Light microscopy revealed that the motile cells display many features characteristic of bacterial flagellar motility. However, electron microscopy failed to reveal flagella and shearing did not arrest motility, indicating that the cyanobacterium may be propelled by a novel mechanism.

  2. Matriptase is required for the active form of hepatocyte growth factor induced Met, focal adhesion kinase and protein kinase B activation on neural stem/progenitor cell motility.

    PubMed

    Fang, Jung-Da; Lee, Sheau-Ling

    2014-07-01

    Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k-Akt signaling which then leads to FAK activation. This signaling pathway ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of recombinant protein of MTP protease domain or transfected with the full-length wild-type but not the protease-defected MTP restored HGF-responsive events in NS/P cells. In addition to functioning as HGF activator, our data revealed novel function of MTP on HGF-stimulated c-Met signaling activation. Copyright © 2014. Published by Elsevier B.V.

  3. Ecophysiological variables influencing Aleppo pine seed and cone production: a review.

    PubMed

    Ayari, Abdelaziz; Khouja, Mohamed Larbi

    2014-04-01

    The most interesting factors associated with seed and cone production of Aleppo pine were largely reviewed to identify broad patterns and potential effectiveness of reforestation efforts and planning. Aleppo pine cone production and seed yields are relatively variable, with differences between spatial and temporal influences. These differences are considered, mainly between (i) year, (ii) stand characteristics and (iii) individual tree measurements. Annual variability among populations was recorded for cone production per tree, based on influencing factors such as genetic characteristics, wetness, nutrient availability, insect pests and disease. In addition, some factors may affect Aleppo pine tree growth directly but may be affecting seed and cone production indirectly. Therefore, reduced stand density results in less competition among Aleppo pine trees and accompanying understory flora, which subsequently increases the stem diameter and other tree dimensions, including seed production. This review suggests that reforestation planning, particularly thinning, will result in improved tree morphology that will increase Aleppo pine seed and cone crops. Wildfire intensity and stand conditions such as light and soil nutrient status are also examined.

  4. Electromagnetic cyclotron-loss-cone instability associated with weakly relativistic electrons

    NASA Technical Reports Server (NTRS)

    Wong, H. K.; Wu, C. S.; Ke, F. J.; Schneider, R. S.; Ziebell, L. F.

    1982-01-01

    The amplification of fast extraordinary mode waves at frequencies very close to the electron cyclotron frequency, due to the presence of a population of energetic electrons with a loss-cone type distribution, is studied. Low-energy background electrons are included in the analysis. Two types of loss-cone distribution functions are considered, and it is found that the maximum growth rates for both distribution functions are of the same order of magnitude. When the thermal effects of the energetic electrons are included in the dispersion equation, the real frequencies of the waves are lower than those obtained by using the cold plasma approximation. This effect tends to enhance the growth rate. An idealized case including a parallel electric field such that the distribution function of the trapped energetic electrons is modified is also considered. It is assumed that the parallel electric field can remove the low-energy background electrons away from the source region of radiation. Both these effects increase the growth rate.

  5. Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.

    PubMed

    Deming, Janise D; Pak, Joseph S; Brown, Bruce M; Kim, Moon K; Aung, Moe H; Eom, Yun Sung; Shin, Jung-A; Lee, Eun-Jin; Pardue, Machelle T; Craft, Cheryl Mae

    2015-08-01

    Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice. When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy.

  6. Cone arrestin confers cone vision of high temporal resolution in zebrafish larvae.

    PubMed

    Renninger, Sabine L; Gesemann, Matthias; Neuhauss, Stephan C F

    2011-02-01

    Vision of high temporal resolution depends on careful regulation of photoresponse kinetics, beginning with the lifetime of activated photopigment. The activity of rhodopsin is quenched by high-affinity binding of arrestin to photoexcited phosphorylated photopigment, which effectively terminates the visual transduction cascade. This regulation mechanism is well established for rod photoreceptors, yet its role for cone vision is still controversial. In this study we therefore analyzed arrestin function in the cone-dominated vision of larval zebrafish. For both rod (arrS ) and cone (arr3 ) arrestin we isolated two paralogs, each expressed in the respective subset of photoreceptors. Labeling with paralog-specific antibodies revealed subfunctionalized expression of Arr3a in M- and L-cones, and Arr3b in S- and UV-cones. The inactivation of arr3a by morpholino knockdown technology resulted in a severe delay in photoresponse recovery which, under bright light conditions, was rate-limiting. Comparison to opsin phosphorylation-deficient animals confirmed the role of cone arrestin in late cone response recovery. Arr3a activity partially overlapped with the function of the cone-specific kinase Grk7a involved in initial response recovery. Behavioral measurements further revealed Arr3a deficiency to be sufficient to reduce temporal contrast sensitivity, providing evidence for the importance of arrestin in cone vision of high temporal resolution. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. Hydrodynamic effects on microcapillary motility and chemotaxis assays of Methylosinus trichosporium OB3b.

    PubMed Central

    Shonnard, D R; Taylor, R T; Tompson, A; Knapp, R B

    1992-01-01

    A study of the random motility and chemotaxis of Methylosinus trichosporium OB3b was conducted by using Palleroni-chamber microcapillary assay procedures. Under the growth conditions employed, this methanotroph was observed qualitatively with a microscope to be either slightly motile or essentially nonmotile. However, the cells did not not respond in the microcapillary assays in the manner expected for nonmotile Brownian particles. As a consequence, several hydrodynamic effects on these Palleroni microcapillary assays were uncovered. In the random-motility microcapillary assay, nondiffusive cell accumulations occurred that were strongly dependent upon cell concentration. An apparent minimal random-motility coefficient (mu) for this bacterial cell of 1.0 x 10(-7) cm2/s was estimated from microcapillary assays. A simple alternative spectrophotometric assay, based upon gravitational settling, was developed and shown to be an improvement over the Palleroni microcapillary motility assay for M. trichosporium OB3b in that it yielded a more-accurate threefold-lower random-motility coefficient. In addition, it provided a calculation of the gravitational-settling velocity. In the chemotaxis microcapillary assay, the apparent chemotactic responses were strongest for the highest test-chemical concentrations in the microcapillaries, were correlated with microcapillary fluid density, and were strongly dependent upon the microcapillary volume. A simple method to establish the maximal concentration of a chemical that can be tested and to quantify any contributions of abiotic convection is described. Investigators should be aware of the potential problems due to density-driven convection when using these commonly employed microcapillary assays for studying cells which have low motilities. PMID:1444383

  8. Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health

    PubMed Central

    Deming, Janise D.; Pak, Joseph S.; Brown, Bruce M.; Kim, Moon K.; Aung, Moe H.; Eom, Yun Sung; Shin, Jung-a; Lee, Eun-Jin; Pardue, Machelle T.; Craft, Cheryl Mae

    2015-01-01

    Purpose Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. Methods A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4−/−) compared with age-matched control, wild-type mice. Results When 2-month-old Arr4−/− mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4−/− mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4−/− mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Conclusions Our study demonstrates that Arr4−/− mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy. PMID:26284544

  9. Thermo-Regulation of Genes Mediating Motility and Plant Interactions in Pseudomonas syringae

    PubMed Central

    Hockett, Kevin L.; Burch, Adrien Y.; Lindow, Steven E.

    2013-01-01

    Pseudomonas syringae is an important phyllosphere colonist that utilizes flagellum-mediated motility both as a means to explore leaf surfaces, as well as to invade into leaf interiors, where it survives as a pathogen. We found that multiple forms of flagellum-mediated motility are thermo-suppressed, including swarming and swimming motility. Suppression of swarming motility occurs between 28° and 30°C, which coincides with the optimal growth temperature of P. syringae. Both fliC (encoding flagellin) and syfA (encoding a non-ribosomal peptide synthetase involved in syringafactin biosynthesis) were suppressed with increasing temperature. RNA-seq revealed 1440 genes of the P. syringae genome are temperature sensitive in expression. Genes involved in polysaccharide synthesis and regulation, phage and IS elements, type VI secretion, chemosensing and chemotaxis, translation, flagellar synthesis and motility, and phytotoxin synthesis and transport were generally repressed at 30°C, while genes involved in transcriptional regulation, quaternary ammonium compound metabolism and transport, chaperone/heat shock proteins, and hypothetical genes were generally induced at 30°C. Deletion of flgM, a key regulator in the transition from class III to class IV gene expression, led to elevated and constitutive expression of fliC regardless of temperature, but did not affect thermo-regulation of syfA. This work highlights the importance of temperature in the biology of P. syringae, as many genes encoding traits important for plant-microbe interactions were thermo-regulated. PMID:23527276

  10. Distribution and specificity of S-cone ("blue cone") signals in subcortical visual pathways.

    PubMed

    Martin, Paul R; Lee, Barry B

    2014-03-01

    We review here the distribution of S-cone signals and properties of S-cone recipient receptive fields in subcortical pathways. Nearly everything we know about S-cone signals in the subcortical visual system comes from the study of visual systems in cats and primates (monkeys); in this review, we concentrate on results from macaque and marmoset monkeys. We discuss segregation of S-cone recipient (blue-on and blue-off) receptive fields in the dorsal lateral geniculate nucleus and describe their receptive field properties. We treat in some detail the question of detecting weak S-cone signals as an introduction for newcomers to the field. Finally, we briefly consider the question on how S-cone signals are distributed among nongeniculate targets.

  11. Effects of Motility and Adsorption Rate Coefficient on Transport of Bacteria through Saturated Porous Media

    PubMed Central

    Camper, Anne K.; Hayes, Jason T.; Sturman, Paul J.; Jones, Warren L.; Cunningham, Alfred B.

    1993-01-01

    Three strains of Pseudomonas fluorescens with different motility rates and adsorption rate coefficients were injected into porous-medium reactors packed with l-mm-diameter glass spheres. Cell breakthrough, time to peak concentration, tailing, and cell recovery were measured at three interstitial pore velocities (higher than, lower than, and much lower than the maximal bacterial motility rate). All experiments were done with distilled water to reduce the effects of growth and chemotaxis. Contrary to expectations, motility did not result in either early breakthrough or early time to peak concentration at flow velocities below the motility rate. Bacterial size exclusion effects were shown to affect breakthrough curve shape at the very low flow velocity, but no such effect was seen at the higher flow velocity. The tendency of bacteria to adsorb to porous-medium surfaces, as measured by adsorption rate coefficients, profoundly influenced transport characteristics. Cell recoveries were shown to be correlated with the ratio of advective to adsorptive transport in the reactors. Adsorption rate coefficients were found to be better predictors of microbial transport phenomena than individual characteristics, such as size, motility, or porous-medium hydrodynamics. PMID:16349075

  12. Detection and Genomic Characterization of Motility in Lactobacillus curvatus: Confirmation of Motility in a Species outside the Lactobacillus salivarius Clade

    PubMed Central

    Cousin, Fabien J.; Lynch, Shónagh M.; Harris, Hugh M. B.; McCann, Angela; Lynch, Denise B.; Neville, B. Anne; Irisawa, Tomohiro; Okada, Sanae; Endo, Akihito

    2014-01-01

    Lactobacillus is the largest genus within the lactic acid bacteria (LAB), with almost 180 species currently identified. Motility has been reported for at least 13 Lactobacillus species, all belonging to the Lactobacillus salivarius clade. Motility in lactobacilli is poorly characterized. It probably confers competitive advantages, such as superior nutrient acquisition and niche colonization, but it could also play an important role in innate immune system activation through flagellin–Toll-like receptor 5 (TLR5) interaction. We now report strong evidence of motility in a species outside the L. salivarius clade, Lactobacillus curvatus (strain NRIC 0822). The motility of L. curvatus NRIC 0822 was revealed by phase-contrast microscopy and soft-agar motility assays. Strain NRIC 0822 was motile at temperatures between 15°C and 37°C, with a range of different carbohydrates, and under varying atmospheric conditions. We sequenced the L. curvatus NRIC 0822 genome, which revealed that the motility genes are organized in a single operon and that the products are very similar (>98.5% amino acid similarity over >11,000 amino acids) to those encoded by the motility operon of Lactobacillus acidipiscis KCTC 13900 (shown for the first time to be motile also). Moreover, the presence of a large number of mobile genetic elements within and flanking the motility operon of L. curvatus suggests recent horizontal transfer between members of two distinct Lactobacillus clades: L. acidipiscis in the L. salivarius clade and L. curvatus in the L. sakei clade. This study provides novel phenotypic, genetic, and phylogenetic insights into flagellum-mediated motility in lactobacilli. PMID:25501479

  13. Detection and genomic characterization of motility in Lactobacillus curvatus: confirmation of motility in a species outside the Lactobacillus salivarius clade.

    PubMed

    Cousin, Fabien J; Lynch, Shónagh M; Harris, Hugh M B; McCann, Angela; Lynch, Denise B; Neville, B Anne; Irisawa, Tomohiro; Okada, Sanae; Endo, Akihito; O'Toole, Paul W

    2015-02-01

    Lactobacillus is the largest genus within the lactic acid bacteria (LAB), with almost 180 species currently identified. Motility has been reported for at least 13 Lactobacillus species, all belonging to the Lactobacillus salivarius clade. Motility in lactobacilli is poorly characterized. It probably confers competitive advantages, such as superior nutrient acquisition and niche colonization, but it could also play an important role in innate immune system activation through flagellin–Toll-like receptor 5 (TLR5) interaction. We now report strong evidence of motility in a species outside the L. salivarius clade, Lactobacillus curvatus (strain NRIC0822). The motility of L. curvatus NRIC 0822 was revealed by phase-contrast microscopy and soft-agar motility assays. Strain NRIC 0822 was motile at temperatures between 15 °C and 37 °C, with a range of different carbohydrates, and under varying atmospheric conditions. We sequenced the L. curvatus NRIC 0822 genome, which revealed that the motility genes are organized in a single operon and that the products are very similar (>98.5% amino acid similarity over >11,000 amino acids) to those encoded by the motility operon of Lactobacillus acidipiscis KCTC 13900 (shown for the first time to be motile also). Moreover, the presence of a large number of mobile genetic elements within and flanking the motility operon of L. curvatus suggests recent horizontal transfer between members of two distinct Lactobacillus clades: L. acidipiscis in the L. salivarius clade and L. curvatus inthe L. sakei clade. This study provides novel phenotypic, genetic, and phylogenetic insights into flagellum-mediated motility in lactobacilli.

  14. Berkeley Lighting Cone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lask, Kathleen; Gadgil, Ashok

    A lighting cone is a simple metal cone placed on the fuel bed of a stove during ignition to act as a chimney, increasing the draft through the fuel bed. Many stoves tend to be difficult to light due to poor draft through the fuel bed, so lighting cones are used in various parts of the world as an inexpensive accessory to help with ignition.

  15. Symmetry breaking in actin gels - Implications for cellular motility

    NASA Astrophysics Data System (ADS)

    John, Karin; Peyla, Philippe; Misbah, Chaouqi

    2007-03-01

    The physical origin of cell motility is not fully understood. Recently minimal model systems have shown, that polymerizing actin itself can produce a motile force, without the help of motor proteins. Pathogens like Shigella or Listeria use actin to propel themselves forward in their host cell. The same process can be mimicked with polystyrene beads covered with the activating protein ActA, which reside in a solution containing actin monomers. ActA induces the growth of an actin gel at the bead surface. Initially the gel grows symmetrically around the bead until a critical size is reached. Subsequently one observes a symmetry breaking and the gel starts to grow asymmetrically around the bead developing a tail of actin at one side. This symmetry breaking is accompanied by a directed movement of the bead, with the actin tail trailing behind the bead. Force generation relies on the combination of two properties: growth and elasticity of the actin gel. We study this phenomenon theoretically within the framework of a linear elasticity theory and linear flux-force relationships for the evolution of an elastic gel around a hard sphere. Conditions for a parity symmetry breaking are identified analytically and illustrated numerically with the help of a phasefield model.

  16. Sperm Motility in Flow

    NASA Astrophysics Data System (ADS)

    Guasto, Jeffrey; Juarez, Gabriel; Stocker, Roman

    2012-11-01

    A wide variety of plants and animals reproduce sexually by releasing motile sperm that seek out a conspecific egg, for example in the reproductive tract for mammals or in the water column for externally fertilizing organisms. Sperm are aided in their quest by chemical cues, but must also contend with hydrodynamic forces, resulting from laminar flows in reproductive tracts or turbulence in aquatic habitats. To understand how velocity gradients affect motility, we subjected swimming sperm to a range of highly-controlled straining flows using a cross-flow microfluidic device. The motion of the cell body and flagellum were captured through high-speed video microscopy. The effects of flow on swimming are twofold. For moderate velocity gradients, flow simply advects and reorients cells, quenching their ability to cross streamlines. For high velocity gradients, fluid stresses hinder the internal bending of the flagellum, directly inhibiting motility. The transition between the two regimes is governed by the Sperm number, which compares the external viscous stresses with the internal elastic stresses. Ultimately, unraveling the role of flow in sperm motility will lead to a better understanding of population dynamics among aquatic organisms and infertility problems in humans.

  17. Cone Heads

    ERIC Educational Resources Information Center

    Coy, Mary

    2005-01-01

    The author, a middle school art teacher, describes a sculpture project lesson involving Cone Heads (sculptures made from cardboard cones). Discussion of caricatures with exaggerated facial features and interesting profiles helped students understand that the more expressive the face, the better. This project took approximately four to five…

  18. Asian motility studies in irritable bowel syndrome.

    PubMed

    Lee, Oh Young

    2010-04-01

    Altered motility remains one of the important pathophysiologic factors in patients with irritable bowel syndrome (IBS) who commonly complain of abdominal pain and stool changes such as diarrhea and constipation. The prevalence of IBS has increased among Asian populations these days. Gastrointestinal (GI) physiology may vary between Asian and Western populations because of differences in diets, socio-cultural backgrounds, and genetic factors. The characteristics and differences of GI dysmotility in Asian IBS patients were reviewed. MEDLINE search work was performed including following terms, 'IBS,' 'motility,' 'transit time,' 'esophageal motility,' 'gastric motility,' 'small intestinal motility,' 'colonic motility,' 'anorectal function,' and 'gallbladder motility' and over 100 articles were categorized under 'esophagus,' 'stomach,' 'small intestine,' 'colon,' 'anorectum,' 'gallbladder,' 'transit,' 'motor pattern,' and 'effect of stressors.' Delayed gastric emptying, slow tansit in constipation predominant IBS patients, rapid transit in diarrhea predominant IBS patients, accelerated motility responses to various stressors such as meals, mental stress, or corticotrophin releasing hormones, and altered rectal compliance and altered rectal accomodation were reported in many Asian studies regarding IBS. Many conflicting results were found among these studies and there are still controversies to conclude these as unique features of Asian IBS patients. Multinational and multicenter studies are needed to be performed vigorously in order to elaborate characteristics as well as differences of altered motililty in Asian patients with IBS.

  19. Cellular Motility--Experiments on Contractile and Motile Mechanisms in the Slime Mould, Physarum Polycephalum

    ERIC Educational Resources Information Center

    Holmes, R. P.; Stewart, P. R.

    1977-01-01

    Actin and myosin have now been demonstrated to be important constituents of many eukaryotic cells. Their role is primarily that of a contractile system underlying all aspects of cellular motility. Described here is a simple experimental system to demonstrate quantitatively aspects of motility and its regulation in a slime mold. (Author/MA)

  20. Social Motility in African Trypanosomes

    PubMed Central

    McLelland, Bryce T.; Hill, Kent L.

    2010-01-01

    African trypanosomes are devastating human and animal pathogens that cause significant human mortality and limit economic development in sub-Saharan Africa. Studies of trypanosome biology generally consider these protozoan parasites as individual cells in suspension cultures or in animal models of infection. Here we report that the procyclic form of the African trypanosome Trypanosoma brucei engages in social behavior when cultivated on semisolid agarose surfaces. This behavior is characterized by trypanosomes assembling into multicellular communities that engage in polarized migrations across the agarose surface and cooperate to divert their movements in response to external signals. These cooperative movements are flagellum-mediated, since they do not occur in trypanin knockdown parasites that lack normal flagellum motility. We term this behavior social motility based on features shared with social motility and other types of surface-induced social behavior in bacteria. Social motility represents a novel and unexpected aspect of trypanosome biology and offers new paradigms for considering host-parasite interactions. PMID:20126443

  1. Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

    PubMed Central

    Todeschini, Adriane Regina; Dos Santos, Jose Nilson; Handa, Kazuko; Hakomori, Sen-itiroh

    2008-01-01

    Ganglioside GM2 complexed with tetraspanin CD82 in glycosynaptic microdomain of HCV29 and other epithelial cells inhibits hepatocyte growth factor-induced cMet tyrosine kinase. In addition, adhesion of HCV29 cells to extracellular matrix proteins also activates cMet kinase through “cross-talk” of integrins with cMet, leading to inhibition of cell motility and growth. Present studies indicate that cell motility and growth are greatly influenced by expression of GM2, GM3, or GM2/GM3 complexes, which affect cMet kinase activity of various types of cells, based on the following series of observations: (i) Cells expressing CD82, cultured with GM2 and GM3 cocoated on silica nanospheres, displayed stronger and more consistent motility inhibition than those cultured with GM2 or GM3 alone or with other glycosphingolipids. (ii) GM2-GM3, in the presence of Ca2+ form a heterodimer, as evidenced by electrospray ionization (ESI) mass spectrometry and by specific reactivity with mAb 8E11, directed to GM2/GM3 dimer structure. (iii) Cells expressing cMet and CD82 were characterized by enhanced motility associated with HGF-induced cMet activation. Both cMet and motility were strongly inhibited by culturing cells with GM2/GM3 dimer coated on nanospheres. (iv) Adhesion of HCV29 or YTS-1/CD82 cells to laminin-5-coated plate activated cMet kinase in the absence of HGF, whereas GM2/GM3 dimer inhibited adhesion-induced cMet kinase activity and inhibited cell motility. (v) Inhibited cell motility as in i, iii, and iv was restored to normal level by addition of mAb 8E11, which blocks interaction of GM2/GM3 dimer with CD82. Signaling through Src and MAP kinases is activated or inhibited in close association with cMet kinase, in response to GM2/GM3 dimer interaction with CD82. Thus, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway. PMID:18272501

  2. Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway.

    PubMed

    Todeschini, Adriane Regina; Dos Santos, Jose Nilson; Handa, Kazuko; Hakomori, Sen-itiroh

    2008-02-12

    Ganglioside GM2 complexed with tetraspanin CD82 in glycosynaptic microdomain of HCV29 and other epithelial cells inhibits hepatocyte growth factor-induced cMet tyrosine kinase. In addition, adhesion of HCV29 cells to extracellular matrix proteins also activates cMet kinase through "cross-talk" of integrins with cMet, leading to inhibition of cell motility and growth. Present studies indicate that cell motility and growth are greatly influenced by expression of GM2, GM3, or GM2/GM3 complexes, which affect cMet kinase activity of various types of cells, based on the following series of observations: (i) Cells expressing CD82, cultured with GM2 and GM3 cocoated on silica nanospheres, displayed stronger and more consistent motility inhibition than those cultured with GM2 or GM3 alone or with other glycosphingolipids. (ii) GM2-GM3, in the presence of Ca2+ form a heterodimer, as evidenced by electrospray ionization (ESI) mass spectrometry and by specific reactivity with mAb 8E11, directed to GM2/GM3 dimer structure. (iii) Cells expressing cMet and CD82 were characterized by enhanced motility associated with HGF-induced cMet activation. Both cMet and motility were strongly inhibited by culturing cells with GM2/GM3 dimer coated on nanospheres. (iv) Adhesion of HCV29 or YTS-1/CD82 cells to laminin-5-coated plate activated cMet kinase in the absence of HGF, whereas GM2/GM3 dimer inhibited adhesion-induced cMet kinase activity and inhibited cell motility. (v) Inhibited cell motility as in i, iii, and iv was restored to normal level by addition of mAb 8E11, which blocks interaction of GM2/GM3 dimer with CD82. Signaling through Src and MAP kinases is activated or inhibited in close association with cMet kinase, in response to GM2/GM3 dimer interaction with CD82. Thus, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway.

  3. Nonlinear Dirac cones

    NASA Astrophysics Data System (ADS)

    Bomantara, Raditya Weda; Zhao, Wenlei; Zhou, Longwen; Gong, Jiangbin

    2017-09-01

    Physics arising from two-dimensional (2D) Dirac cones has been a topic of great theoretical and experimental interest to studies of gapless topological phases and to simulations of relativistic systems. Such 2D Dirac cones are often characterized by a π Berry phase and are destroyed by a perturbative mass term. By considering mean-field nonlinearity in a minimal two-band Chern insulator model, we obtain a different type of Dirac cone that is robust to local perturbations without symmetry restrictions. Due to a different pseudospin texture, the Berry phase of the Dirac cone is no longer quantized in π , and can be continuously tuned as an order parameter. Furthermore, in an Aharonov-Bohm (AB) interference setup to detect such Dirac cones, the adiabatic AB phase is found to be π both theoretically and computationally, offering an observable topological invariant and a fascinating example where the Berry phase and AB phase are fundamentally different. We hence discover a nonlinearity-induced quantum phase transition from a known topological insulating phase to an unusual gapless topological phase.

  4. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed Central

    Zhang, J; Loew, L M; Davidson, R M

    1996-01-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells. PMID:8913589

  5. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed

    Zhang, J; Loew, L M; Davidson, R M

    1996-11-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells.

  6. How actin network dynamics control the onset of actin-based motility

    PubMed Central

    Kawska, Agnieszka; Carvalho, Kévin; Manzi, John; Boujemaa-Paterski, Rajaa; Blanchoin, Laurent; Martiel, Jean-Louis; Sykes, Cécile

    2012-01-01

    Cells use their dynamic actin network to control their mechanics and motility. These networks are made of branched actin filaments generated by the Arp2/3 complex. Here we study under which conditions the microscopic organization of branched actin networks builds up a sufficient stress to trigger sustained motility. In our experimental setup, dynamic actin networks or “gels” are grown on a hard bead in a controlled minimal protein system containing actin monomers, profilin, the Arp2/3 complex and capping protein. We vary protein concentrations and follow experimentally and through simulations the shape and mechanical properties of the actin gel growing around beads. Actin gel morphology is controlled by elementary steps including “primer” contact, growth of the network, entanglement, mechanical interaction and force production. We show that varying the biochemical orchestration of these steps can lead to the loss of network cohesion and the lack of effective force production. We propose a predictive phase diagram of actin gel fate as a function of protein concentrations. This work unveils how, in growing actin networks, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and governs force buildup and cell motility. PMID:22908255

  7. Exopolysaccharide-Independent Social Motility of Myxococcus xanthus

    PubMed Central

    Hu, Wei; Hossain, Muhaiminu; Lux, Renate; Wang, Jing; Yang, Zhe; Li, Yuezhong; Shi, Wenyuan

    2011-01-01

    Social motility (S motility), the coordinated movement of large cell groups on agar surfaces, of Myxococcus xanthus requires type IV pili (TFP) and exopolysaccharides (EPS). Previous models proposed that this behavior, which only occurred within cell groups, requires cycles of TFP extension and retraction triggered by the close interaction of TFP with EPS. However, the curious observation that M. xanthus can perform TFP-dependent motility at a single-cell level when placed onto polystyrene surfaces in a highly viscous medium containing 1% methylcellulose indicated that “S motility” is not limited to group movements. In an apparent further challenge of the previous findings for S motility, mutants defective in EPS production were found to perform TFP-dependent motility on polystyrene surface in methylcellulose-containing medium. By exploring the interactions between pilin and surface materials, we found that the binding of TFP onto polystyrene surfaces eliminated the requirement for EPS in EPS- cells and thus enabled TFP-dependent motility on a single cell level. However, the presence of a general anchoring surface in a viscous environment could not substitute for the role of cell surface EPS in group movement. Furthermore, EPS was found to serve as a self-produced anchoring substrate that can be shed onto surfaces to enable cells to conduct TFP-dependent motility regardless of surface properties. These results suggested that in certain environments, such as in methylcellulose solution, the cells could bypass the need for EPS to anchor their TPF and conduct single-cell S motility to promote exploratory movement of colonies over new specific surfaces. PMID:21245931

  8. Motility Determinants in WASP Family ProteinsD⃞

    PubMed Central

    Yarar, Defne; D'Alessio, Joseph A.; Jeng, Robert L.; Welch, Matthew D.

    2002-01-01

    In response to upstream signals, proteins in the Wiskott-Aldrich Syndrome protein (WASP) family regulate actin nucleation via the Arp2/3 complex. Despite intensive study of the function of WASP family proteins in nucleation, it is not yet understood how their distinct structural organization contributes to actin-based motility. Herein, we analyzed the activities of WASP and Scar1 truncation derivatives by using a bead-based motility assay. The minimal region of WASP sufficient to direct movement was the C-terminal WCA fragment, whereas the corresponding region of Scar1 was insufficient. In addition, the proline-rich regions of WASP and Scar1 and the Ena/VASP homology 1 (EVH1) domain of WASP independently enhanced motility rates. The contributions of these regions to motility could not be accounted for by their direct effects on actin nucleation with the Arp2/3 complex, suggesting that they stimulate motility by recruiting additional factors. We have identified profilin as one such factor. WASP- and Scar1-coated bead motility rates were significantly reduced by depletion of profilin and VASP and could be more efficiently rescued by a combination of VASP and wild-type profilin than by VASP and a mutant profilin that cannot bind proline-rich sequences. Moreover, motility of WASP WCA beads was not affected by the depletion or addback of VASP and profilin. Our results suggest that recruitment of factors, including profilin, by the proline-rich regions of WASP and Scar1 and the EVH1 domain of WASP stimulates cellular actin-based motility. PMID:12429845

  9. Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme

    PubMed Central

    Raman, Fabio; Scribner, Elizabeth; Saut, Olivier; Wenger, Cornelia; Colin, Thierry; Fathallah-Shaykh, Hassan M.

    2016-01-01

    Glioblastoma multiforme is a malignant brain tumor with poor prognosis and high morbidity due to its invasiveness. Hypoxia-driven motility and concentration-driven motility are two mechanisms of glioblastoma multiforme invasion in the brain. The use of anti-angiogenic drugs has uncovered new progression patterns of glioblastoma multiforme associated with significant differences in overall survival. Here, we apply a mathematical model of glioblastoma multiforme growth and invasion in humans and design computational trials using agents that target angiogenesis, tumor replication rates, or motility. The findings link highly-dispersive, moderately-dispersive, and hypoxia-driven tumors to the patterns observed in glioblastoma multiforme treated by anti-angiogenesis, consisting of progression by Expanding FLAIR, Expanding FLAIR + Necrosis, and Expanding Necrosis, respectively. Furthermore, replication rate-reducing strategies (e.g. Tumor Treating Fields) appear to be effective in highly-dispersive and moderately-dispersive tumors but not in hypoxia-driven tumors. The latter may respond to motility-reducing agents. In a population computational trial, with all three phenotypes, a correlation was observed between the efficacy of the rate-reducing agent and the prolongation of overall survival times. This research highlights the potential applications of computational trials and supports new hypotheses on glioblastoma multiforme phenotypes and treatment options. PMID:26756205

  10. Comparison of orbital prosthesis motility following enucleation or evisceration with sclerotomy with or without a motility coupling post in dogs.

    PubMed

    Yi, Na Young; Park, Shin Ae; Jeong, Man Bok; Kim, Won Tae; Kim, Se Eun; Kim, Ji Youn; Chae, Je Min; Jang, Kyoung Jin; Seong, Je Kyung; Seo, Kang Moon

    2009-01-01

    To evaluate motility of silicone orbital implants and corneoscleral prostheses, with and without use of a motility coupling post (MCP) in dogs. Eighteen mixed-breed dogs. The motility of an orbital silicone implant and corneoscleral prosthesis after enucleation (n = 6), evisceration (n = 6), or use of a MCP with evisceration (n = 6) in dogs were compared. One eye from each dog had surgery whereas the opposite eye was used as a control. Clinical evaluations were performed three times a week. Histopathology of the orbital tissues was performed 8 and 12 weeks after surgery. Implant motility in dogs with evisceration (vertical movement [VM] 8.04 +/- 2.13; horizontal movement [HM] 11 +/- 3.05) and evisceration with MCP (VM 9.61 +/- 1.59); HM was significantly greater than the enucleation group (VM 0.51 +/- 0.5; HM 1.22 +/- 0.68) (P < 0.01). Prosthetic motility in dogs with evisceration with MCP was significantly greater than in dogs with evisceration; dogs with evisceration had significantly greater motility than dogs with enucleation (P < 0.01). No postoperative complications were observed in any of the groups. No significant abnormalities were noted on histopathology. MCP placement in silicone orbital implants significantly enhanced the prosthetic motility in dogs. This study supports the use of MCP in silicone orbital implants to enhance corneoscleral prosthesis motility and cosmetics in dogs.

  11. Cell Guidance on Nanogratings: A Computational Model of the Interplay between PC12 Growth Cones and Nanostructures

    PubMed Central

    Tonazzini, Ilaria; Cecchini, Marco; Micera, Silvestro

    2013-01-01

    Background Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites. Methodology/Principal Findings A synergistic procedure was used to study the mechanism of alignment of PC12 neurites with respect to the main direction of nanogratings. Finite Element simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation. After modelling all adhesions under non-spread growth cone and filopodial protrusions, the values of local stress maxima resulted from the length of filopodia. Since the stress was assumed to be the main triggering cause leading to the increase and stabilization of filopodia, the position of the local maxima was directly related to the orientation of neurites. An analytic closed form equation was then written to quantitatively assess the average ridge width needed to achieve a given neuritic alignment (R2 = 0.96), and the alignment course, when the ridge depth varied (R2 = 0.97). A computational framework was implemented within an improved free Java environment (CX3D) and in silico simulations were carried out to reproduce and predict biological experiments. No significant differences were found between biological experiments and in silico simulations (alignment, p = 0.3571; tortuosity, p = 0.2236) with a standard level of confidence (95%). Conclusions/Significance A mechanism involved in filopodial sensing of nanogratings is proposed and modelled through a synergistic use of FE models, theoretical equations and in silico simulations. This approach shows the importance of the neuritic terminal geometry, and the key role of the distribution of the adhesion constraints for the cell/substrate coupling process. Finally, the effects of the geometry of nanogratings were

  12. Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

    PubMed

    Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

    2013-01-01

    A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

  13. Val66Met Polymorphism of BDNF Alters Prodomain Structure to Induce Neuronal Growth Cone Retraction

    PubMed Central

    Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V.; Will, Nathan E.; Irmady, Krithi; Lee, Francis S.; Hempstead, Barbara L.; Bracken, Clay

    2013-01-01

    A common single-nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This single-nucleotide polymorphism is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75NTR and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand which modulates neuronal morphology. PMID:24048383

  14. Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod Dystrophy.

    PubMed

    Oishi, Akio; Oishi, Maho; Ogino, Ken; Morooka, Satoshi; Yoshimura, Nagahisa

    2016-01-01

    Retinitis pigmentosa and cone/cone-rod dystrophy are inherited retinal diseases characterized by the progressive loss of rod and/or cone photoreceptors. To evaluate the status of rod/cone photoreceptors and visual function, visual acuity and visual field tests, electroretinogram, and optical coherence tomography are typically used. In addition to these examinations, fundus autofluorescence (FAF) has recently garnered attention. FAF visualizes the intrinsic fluorescent material in the retina, which is mainly lipofuscin contained within the retinal pigment epithelium. While conventional devices offer limited viewing angles in FAF, the recently developed Optos machine enables recording of wide-field FAF. With wide-field analysis, an association between abnormal FAF areas and visual function was demonstrated in retinitis pigmentosa and cone-rod dystrophy. In addition, the presence of "patchy" hypoautofluorescent areas was found to be correlated with symptom duration. Although physicians should be cautious when interpreting wide-field FAF results because the peripheral parts of the image are magnified significantly, this examination method provides previously unavailable information.

  15. Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

    PubMed Central

    Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

    2012-01-01

    In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the

  16. DRG axon elongation and growth cone collapse rate induced by Sema3A are differently dependent on NGF concentration.

    PubMed

    Kaselis, Andrius; Treinys, Rimantas; Vosyliūtė, Rūta; Šatkauskas, Saulius

    2014-03-01

    Regeneration of embryonic and adult dorsal root ganglion (DRG) sensory axons is highly impeded when they encounter neuronal growth cone-collapsing factor semaphorin3A (Sema3A). On the other hand, increasing evidence shows that DRG axon's regeneration can be stimulated by nerve growth factor (NGF). In this study, we aimed to evaluate whether increased NGF concentrations can counterweight Sema3A-induced inhibitory responses in 15-day-old mouse embryo (E15) DRG axons. The DRG explants were grown in Neurobasal-based medium with different NGF concentrations ranging from 0 to 100 ng/mL and then treated with Sema3A at constant 10 ng/mL concentration. To evaluate interplay between NGF and Sema3A number of DRG axons, axon outgrowth distance and collapse rate were measured. We found that the increased NGF concentrations abolish Sema3A-induced inhibitory effect on axon outgrowth, while they have no effect on Sema3A-induced collapse rate.

  17. Computational approaches to substrate-based cell motility

    DOE PAGES

    Ziebert, Falko; Aranson, Igor S.

    2016-07-15

    Substrate-based crawling motility of eukaryotic cells is essential for many biological functions, both in developing and mature organisms. Motility dysfunctions are involved in several life-threatening pathologies such as cancer and metastasis. Motile cells are also a natural realization of active, self-propelled ‘particles’, a popular research topic in nonequilibrium physics. Finally, from the materials perspective, assemblies of motile cells and evolving tissues constitute a class of adaptive self-healing materials that respond to the topography, elasticity, and surface chemistry of the environment and react to external stimuli. Although a comprehensive understanding of substrate-based cell motility remains elusive, progress has been achieved recentlymore » in its modeling on the whole cell level. Furthermore we survey the most recent advances in computational approaches to cell movement and demonstrate how these models improve our understanding of complex self-organized systems such as living cells.« less

  18. Self-organized cell motility

    NASA Astrophysics Data System (ADS)

    Du, Xinxin; Doubrovinski, Konstantin

    2011-03-01

    Cell migration plays a key role in a wide range of biological phenomena, such as morphogenesis, chemotaxis, and wound healing. Cell locomotion relies on the cytoskeleton, a meshwork of filamentous proteins, intrinsically out of thermodynamic equilibrium and cross-linked by molecular motors, proteins that turn chemical energy into mechanical work. In the course of locomotion, cells remain polarized, i.e. they retain a single direction of motion in the absence of external cues. Traditionally, polarization has been attributed to intracellular signaling. However, recent experiments show that polarization may be a consequence of self-organized cytoskeletal dynamics. Our aim is to elucidate the mechanisms by which persistent unidirectional locomotion may arise through simple mechanical interactions of the cytoskeletal proteins. To this end, we develop a simple physical description of cytoskeletal dynamics. We find that the proposed description accounts for a range of phenomena associated with cell motility, including spontaneous polarization, persistent unidirectional motion, and the co-existence of motile and non-motile states.

  19. Control of Human Endometrial Stromal Cell Motility by PDGF-BB, HB-EGF and Trophoblast-Secreted Factors

    PubMed Central

    Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H. E.; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S.; Bamberger, Ana-Maria; Gellersen, Birgit

    2013-01-01

    Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of

  20. Cones in Supersonic Flow

    NASA Technical Reports Server (NTRS)

    Hantzsche, W.; Wendt, H.

    1947-01-01

    In the case of cones in axially symmetric flow of supersonic velocity, adiabatic compression takes place between shock wave and surface of the cone. Interpolation curves betwen shock polars and the surface are therefore necessary for the complete understanding of this type of flow. They are given in the present report by graphical-numerical integration of the differential equation for all cone angles and airspeeds.

  1. Motility modes of the parasite Trypanosoma brucei

    NASA Astrophysics Data System (ADS)

    Temel, Fatma Zeynep; Qu, Zijie; McAllaster, Michael; de Graffenried, Christopher; Breuer, Kenneth

    2015-11-01

    The parasitic single-celled protozoan Trypanosoma brucei causes African Sleeping Sickness, which is a fatal disease in humans and animals that threatens more than 60 million people in 36 African countries. Cell motility plays a critical role in the developmental phases and dissemination of the parasite. Unlike many other motile cells such as bacteria Escherichia coli or Caulobacter crescentus, the flagellum of T. brucei is attached along the length of its awl-like body, producing a unique mode of motility that is not fully understood or characterized. Here, we report on the motility of T. brucei, which swims using its single flagellum employing both rotating and undulating propulsion modes. We tracked cells in real-time in three dimensions using fluorescent microscopy. Data obtained from experiments using both short-term tracking within the field of view and long-term tracking using a tracking microscope were analyzed. Motility modes and swimming speed were analyzed as functions of cell size, rotation rate and undulation pattern. Research supported by NSF.

  2. Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow

    PubMed Central

    Yang, Qing; Zhang, Xiao-Feng; Pollard, Thomas D.

    2012-01-01

    The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility. PMID:22711700

  3. Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

    PubMed

    Dörken, Veit Martin; Rudall, Paula J

    2018-01-01

    Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

  4. Surface Orientation Affects the Direction of Cone Growth by Leptolyngbya sp. Strain C1, a Likely Architect of Coniform Structures Octopus Spring (Yellowstone National Park)

    PubMed Central

    Reyes, Kristina; Gonzalez, Nicolas I.; Stewart, Joshua; Ospino, Frank; Nguyen, Dickie; Cho, David T.; Ghahremani, Nahal; Spear, John R.

    2013-01-01

    Laminated, microbially produced stromatolites within the rock record provide some of the earliest evidence for life on Earth. The chemical, physical, and biological factors that lead to the initiation of these organosedimentary structures and shape their morphology are unclear. Modern coniform structures with morphological features similar to stromatolites are found on the surface of cyanobacterial/microbial mats. They display a vertical element of growth, can have lamination, can be lithified, and observably grow with time. To begin to understand the microbial processes and interactions required for cone formation, we determined the phylogenetic composition of the microbial community of a coniform structure from a cyanobacterial mat at Octopus Spring, Yellowstone National Park, and reconstituted coniform structures in vitro. The 16S rRNA clone library from the coniform structure was dominated by Leptolyngbya sp. Other cyanobacteria and heterotrophic bacteria were present in much lower abundance. The same Leptolyngbya sp. identified in the clone library was also enriched in the laboratory and could produce cones in vitro. When coniform structures were cultivated in the laboratory, the initial incubation conditions were found to influence coniform morphology. In addition, both the angle of illumination and the orientation of the surface affected the angle of cone formation demonstrating how external factors can influence coniform, and likely, stromatolite morphology. PMID:23241986

  5. 21 CFR 876.1725 - Gastrointestinal motility monitoring system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastrointestinal motility monitoring system. 876... Gastrointestinal motility monitoring system. (a) Identification. A gastrointestinal motility monitoring system is a device used to measure peristalic activity or pressure in the stomach or esophagus by means of a probe...

  6. Characterizing motility dynamics in human RPE cells

    NASA Astrophysics Data System (ADS)

    Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu; Miller, Donald T.

    2017-02-01

    Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, however, are often compromised in ageing and ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, but while in vivo biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. Recently we addressed this problem by using organelle motility as a novel contrast agent to enhance the RPE cell in conjunction with 3D resolution of adaptive optics-optical coherence tomography (AO-OCT) to section the RPE layer. In this study, we expand on the central novelty of our method - organelle motility - by characterizing the dynamics of the motility in individual RPE cells, important because of its direct link to RPE physiology. To do this, AO-OCT videos of the same retinal patch were acquired at approximately 1 min intervals or less, time stamped, and registered in 3D with sub-cellular accuracy. Motility was quantified by an exponential decay time constant, the time for motility to decorrelate the speckle field across an RPE cell. In two normal subjects, we found the decay time constant to be just 3 seconds, thus indicating rapid motility in normal RPE cells.

  7. Laser range profile of cones

    NASA Astrophysics Data System (ADS)

    Zhou, Wenzhen; Gong, Yanjun; Wang, Mingjun; Gong, Lei

    2016-10-01

    technology. Laser one-dimensional range profile can reflect the characteristics of the target shape and surface material. These techniques were motivated by applications of laser radar to target discrimination in ballistic missile defense. The radar equation of pulse laser about cone is given in this paper. This paper demonstrates the analytical model of laser one-dimensional range profile of cone based on the radar equation of the pulse laser. Simulations results of laser one-dimensional range profiles of some cones are given. Laser one-dimensional range profiles of cone, whose surface material with diffuse lambertian reflectance, is given in this paper. Laser one-dimensional range profiles of cone, whose surface mater with diffuse materials whose retroreflectance can be modeled closely with an exponential term that decays with increasing incidence angles, is given in this paper. Laser one-dimensional range profiles of different pulse width of cone is given in this paper. The influences of surface material, pulse width, attitude on the one-dimensional range are analyzed. The laser two-dimensional range profile is two-dimensional scattering imaging of pulse laser of target. The two-dimensional range profile of roughness target can provide range resolved information. An analytical model of two-dimensional laser range profile of cone is proposed. The simulations of two-dimensional laser range profiles of some cones are given. Laser two-dimensional range profiles of cone, whose surface mater with diffuse lambertian reflectance, is given in this paper. Laser two-dimensional range profiles of cone, whose surface mater with diffuse materials whose retroreflectance can be modeled closely with an exponential term that decays with increasing incidence angles, is given in this paper. The influence of pulse width, surface material on laser two-dimensional range profile is analyzed. Laser one-dimensional range profile and laser two-dimensional range profile are called as laser

  8. [Thyroid-intestinal motility interactions summary].

    PubMed

    Pustorino, S; Foti, M; Calipari, G; Pustorino, E; Ferraro, R; Guerrisi, O; Germanotta, G

    2004-12-01

    Thyroid diseases may be related to gastrointestinal motility symptoms. Such symptoms can vary in degree and, sometimes, are the only clue of a thyroid disease or, at least, the first. The mechanism by which the thyroid hormones can influence gastrointestinal motility, even if not still completely elucidated, can be found in a synergism between a direct effect of the thyronins and an indirect effect mediated by cathecolamines on the muscle cell receptors. Neck discomfort and dysphagia are common findings in patients with thyroid diseases. Hyper- and hypothyroidism can impair esophageal motility, modifying pharyngo-esophageal structure and/or muscular function and interacting with the neuro-humoral regulation of the esophageal peristalsis. Oesophageal motility alterations, observed in patients affected by small non-toxic goiter, are less understandable. At the gastro-duodenal level, basic and postprandial electric rhythm alterations have been observed in hyperthyroid patients, often associated with delayed gastric emptying, too. In such patients, the autonomous nervous system dysfunction may even modify the neuro-hormonal mutual regulation (vagal influence decrease) of the gastro-duodenal myoelectric activity. Hypothyroidism may cause a delay of the gastric emptying too, but such pattern may also be related to an associated autoimmune disease or to an independent chronic modification of the gastric mucosa. Diarrhoea and malabsorption are common findings together with hyperthyroidism, whereas constipation is frequently observed in hypothyroidism. The clinically most demanding situation is certainly the secondary chronic intestinal pseudo-obstruction syndrome, which involves the bowel in most cases, but may also show up by means of a mega-small bowel or a mega-duodenum, or even all of the above. In conclusion it may be stated that: 1) thyroid diseases may be related to symptoms due to digestive motility dysfunction. 2) Any segment of the gastrointestinal trait may be

  9. Actin-based motility allows Listeria monocytogenes to avoid autophagy in the macrophage cytosol.

    PubMed

    Cheng, Mandy I; Chen, Chen; Engström, Patrik; Portnoy, Daniel A; Mitchell, Gabriel

    2018-05-03

    Listeria monocytogenes grows in the host cytosol and uses the surface protein ActA to promote actin polymerisation and mediate actin-based motility. ActA, along with two secreted bacterial phospholipases C, also mediates avoidance from autophagy, a degradative process that targets intracellular microbes. Although it is known that ActA prevents autophagic recognition of L. monocytogenes in epithelial cells by masking the bacterial surface with host factors, the relative roles of actin polymerisation and actin-based motility in autophagy avoidance are unclear in macrophages. Using pharmacological inhibition of actin polymerisation and a collection of actA mutants, we found that actin polymerisation prevented the colocalisation of L. monocytogenes with polyubiquitin, the autophagy receptor p62, and the autophagy protein LC3 during macrophage infection. In addition, the ability of L. monocytogenes to stimulate actin polymerisation promoted autophagy avoidance and growth in macrophages in the absence of phospholipases C. Time-lapse microscopy using green fluorescent protein-LC3 macrophages and a probe for filamentous actin showed that bacteria undergoing actin-based motility moved away from LC3-positive membranes. Collectively, these results suggested that although actin polymerisation protects the bacterial surface from autophagic recognition, actin-based motility allows escape of L. monocytogenes from autophagic membranes in the macrophage cytosol. © 2018 John Wiley & Sons Ltd.

  10. Membrane tension and cytoskeleton organization in cell motility.

    PubMed

    Sens, Pierre; Plastino, Julie

    2015-07-15

    Cell membrane shape changes are important for many aspects of normal biological function, such as tissue development, wound healing and cell division and motility. Various disease states are associated with deregulation of how cells move and change shape, including notably tumor initiation and cancer cell metastasis. Cell motility is powered, in large part, by the controlled assembly and disassembly of the actin cytoskeleton. Much of this dynamic happens in close proximity to the plasma membrane due to the fact that actin assembly factors are membrane-bound, and thus actin filaments are generally oriented such that their growth occurs against or near the membrane. For a long time, the membrane was viewed as a relatively passive scaffold for signaling. However, results from the last five years show that this is not the whole picture, and that the dynamics of the actin cytoskeleton are intimately linked to the mechanics of the cell membrane. In this review, we summarize recent findings concerning the role of plasma membrane mechanics in cell cytoskeleton dynamics and architecture, showing that the cell membrane is not just an envelope or a barrier for actin assembly, but is a master regulator controlling cytoskeleton dynamics and cell polarity.

  11. Chemokinetic motility responses of the cyanobacterium oscillatoria terebriformis

    NASA Technical Reports Server (NTRS)

    Richardson, Laurie L.; Castenholz, Richard W.

    1989-01-01

    Oscillatoria terebriformis, a gliding, filamentous, thermophilic cyanobacterium, exhibited an inhibition of gliding motility upon exposure to fructose. The observed response was transient, and the duration of nonmotility was directly proportional to the concentration of fructose. Upon resumption of motility, the rate of motility was also inversely proportional to the concentration of fructose. Sulfide caused a similar response. The effect of sulfide was specific and not due to either anoxia or negative redox potential. Exposure to glucose, acetate, lactate, or mat interstitial water did not elicit any motility response.

  12. Measurement of anal pressure and motility.

    PubMed Central

    Hancock, B D

    1976-01-01

    A fine open perfused system and a closed balloon system for the measurement of anal pressure and motility have been compared. Measurements were made in 40 normal subjects and 84 patients with haemorrhoids. The rate of perfusion had a marked effect on the recorded pressure and motility details. The motility pattern was seen most clearly with the balloon probe and the pressure recorded was reproducible and easy to measure, making this a convenient method for recording activity of the internal anal sphincter. Anal motility in normal subjects was characterised by slow pressure waves (10-20/min). The frequency was fastest in the distal anal canal and this frequency gradient may represent a normal mechanism to keep the anal canal empty. Ultra slow pressure waves (0-6-1-9/min) were seen in 42% of patients with haemorrhoids and 5% of normal subjects and arose from a synchronous contraction of the whole internal sphincter. Images Fig. 1 PMID:976803

  13. Geometric convex cone volume analysis

    NASA Astrophysics Data System (ADS)

    Li, Hsiao-Chi; Chang, Chein-I.

    2016-05-01

    Convexity is a major concept used to design and develop endmember finding algorithms (EFAs). For abundance unconstrained techniques, Pixel Purity Index (PPI) and Automatic Target Generation Process (ATGP) which use Orthogonal Projection (OP) as a criterion, are commonly used method. For abundance partially constrained techniques, Convex Cone Analysis is generally preferred which makes use of convex cones to impose Abundance Non-negativity Constraint (ANC). For abundance fully constrained N-FINDR and Simplex Growing Algorithm (SGA) are most popular methods which use simplex volume as a criterion to impose ANC and Abundance Sum-to-one Constraint (ASC). This paper analyze an issue encountered in volume calculation with a hyperplane introduced to illustrate an idea of bounded convex cone. Geometric Convex Cone Volume Analysis (GCCVA) projects the boundary vectors of a convex cone orthogonally on a hyperplane to reduce the effect of background signatures and a geometric volume approach is applied to address the issue arose from calculating volume and further improve the performance of convex cone-based EFAs.

  14. Oligomerization-Dependent Regulation of Motility and Morphogenesis by the Collagen Xviii Nc1/Endostatin Domain

    PubMed Central

    Kuo, Calvin J.; LaMontagne, Kenneth R.; Garcia-Cardeña, Guillermo; Ackley, Brian D.; Kalman, Daniel; Park, Susan; Christofferson, Rolf; Kamihara, Junne; Ding, Yuan-Hua; Lo, Kin-Ming; Gillies, Stephen; Folkman, Judah; Mulligan, Richard C.; Javaherian, Kashi

    2001-01-01

    Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase–stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis. PMID:11257123

  15. Cone Quasi-Concave Multi-Objective Programming Theory and Dominance Cone Constructions.

    DTIC Science & Technology

    1988-08-01

    generalized cone concavity and nondominated solutions for later use in our development. We also derive some properties of generalized cone concavity. A set S...A-quasiconcave on S" if g(.x 1+(1-X)x 2)-Min{g(x0), g(x 2)) e IntA forallxl*x 2 E SandX e (0,1), where (in ( gi (x’), gi (x2)) Min [g (0i), g (x2 ) - 1...will lead to elimination of the points of J3 by using the dominance cone W3 . Associated with W3 , only the points of J1 and J2 are nondominated, and

  16. Biochemical properties of Na+/K(+)-ATPase in axonal growth cone particles isolated from fetal rat brain.

    PubMed

    Mercado, R; Hernández, J

    1994-08-01

    Axonal growth cones (AGC) isolated from fetal rat brain have an important specific activity of N+/K(+)-ATPase. Kinetic assays of the enzyme in AGC showed that Km values for ATP or K+ are similar to those reported for the adult brain enzyme. For Na+ the affinity (Km) was lower. Vmax for the three substrates was several times lower in AGC as compared to the adult value. We also observed two apparent inhibition constants of Na+/K(+)-ATPase by ouabain, one of low affinity, possibly corresponding to the alpha 1 isoform and another of high affinity which is different to that described for the alpha 2 isoform of the enzyme. These results support an important role for the sodium pump in the maintainance of volume and cationic balance in neuronal differentiating structures. The functional differences observed also suggest that the enzymatic complex of Na+/K(+)-ATPase in AGC is in a transitional state towards the adult configuration.

  17. TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance

    PubMed Central

    Bearce, Elizabeth A.; Erdogan, Burcu; Lowery, Laura Anne

    2015-01-01

    The growth cone is a dynamic cytoskeletal vehicle, which drives the end of a developing axon. It serves to interpret and navigate through the complex landscape and guidance cues of the early nervous system. The growth cone’s distinctive cytoskeletal organization offers a fascinating platform to study how extracellular cues can be translated into mechanical outgrowth and turning behaviors. While many studies of cell motility highlight the importance of actin networks in signaling, adhesion, and propulsion, both seminal and emerging works in the field have highlighted a unique and necessary role for microtubules (MTs) in growth cone navigation. Here, we focus on the role of singular pioneer MTs, which extend into the growth cone periphery and are regulated by a diverse family of microtubule plus-end tracking proteins (+TIPs). These +TIPs accumulate at the dynamic ends of MTs, where they are well-positioned to encounter and respond to key signaling events downstream of guidance receptors, catalyzing immediate changes in microtubule stability and actin cross-talk, that facilitate both axonal outgrowth and turning events. PMID:26175669

  18. Uncovering the Mystery of Gliding Motility in the Myxobacteria

    PubMed Central

    Nan, Beiyan; Zusman, David R.

    2012-01-01

    Bacterial gliding motility is the smooth movement of cells on solid surfaces unaided by flagella or pili. Many diverse groups of bacteria exhibit gliding, but the mechanism of gliding motility has remained a mystery since it was first observed more than a century ago. Recent studies on the motility of Myxococcus xanthus, a soil myxobacterium, suggest a likely mechanism for gliding in this organism. About forty M. xanthus genes were shown to be involved in gliding motility, and some of their protein products were labeled and localized within cells. These studies suggest that gliding motility in M. xanthus involves large multiprotein structural complexes, regulatory proteins, and cytoskeletal filaments. In this review, we summarize recent experiments that provide the basis for this emerging view of M. xanthus motility. We also discuss alternative models for gliding. PMID:21910630

  19. Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

    PubMed

    Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

    1999-03-15

    We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

  20. Transverse loop colostomy and colonic motility.

    PubMed

    Pucciani, F; Ringressi, M N; Maltinti, G; Bechi, P

    2014-11-01

    The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

  1. Pattern-formation mechanisms in motility mutants of Myxococcus xanthus

    PubMed Central

    Starruß, Jörn; Peruani, Fernando; Jakovljevic, Vladimir; Søgaard-Andersen, Lotte; Deutsch, Andreas; Bär, Markus

    2012-01-01

    Formation of spatial patterns of cells is a recurring theme in biology and often depends on regulated cell motility. Motility of the rod-shaped cells of the bacterium Myxococcus xanthus depends on two motility machineries, type IV pili (giving rise to S-motility) and the gliding motility apparatus (giving rise to A-motility). Cell motility is regulated by occasional reversals. Moving M. xanthus cells can organize into spreading colonies or spore-filled fruiting bodies, depending on their nutritional status. To ultimately understand these two pattern-formation processes and the contributions by the two motility machineries, as well as the cell reversal machinery, we analyse spatial self-organization in three M. xanthus strains: (i) a mutant that moves unidirectionally without reversing by the A-motility system only, (ii) a unidirectional mutant that is also equipped with the S-motility system, and (iii) the wild-type that, in addition to the two motility systems, occasionally reverses its direction of movement. The mutant moving by means of the A-engine illustrates that collective motion in the form of large moving clusters can arise in gliding bacteria owing to steric interactions of the rod-shaped cells, without the need of invoking any biochemical signal regulation. The two-engine strain mutant reveals that the same phenomenon emerges when both motility systems are present, and as long as cells exhibit unidirectional motion only. From the study of these two strains, we conclude that unidirectional cell motion induces the formation of large moving clusters at low and intermediate densities, while it results in vortex formation at very high densities. These findings are consistent with what is known from self-propelled rod models, which strongly suggests that the combined effect of self-propulsion and volume exclusion interactions is the pattern-formation mechanism leading to the observed phenomena. On the other hand, we learn that when cells occasionally reverse

  2. Guiding neuronal growth with light

    PubMed Central

    Ehrlicher, A.; Betz, T.; Stuhrmann, B.; Koch, D.; Milner, V.; Raizen, M. G.; Käs, J.

    2002-01-01

    Control over neuronal growth is a fundamental objective in neuroscience, cell biology, developmental biology, biophysics, and biomedicine and is particularly important for the formation of neural circuits in vitro, as well as nerve regeneration in vivo [Zeck, G. & Fromherz, P. (2001) Proc. Natl. Acad. Sci. USA 98, 10457–10462]. We have shown experimentally that we can use weak optical forces to guide the direction taken by the leading edge, or growth cone, of a nerve cell. In actively extending growth cones, a laser spot is placed in front of a specific area of the nerve's leading edge, enhancing growth into the beam focus and resulting in guided neuronal turns as well as enhanced growth. The power of our laser is chosen so that the resulting gradient forces are sufficiently powerful to bias the actin polymerization-driven lamellipodia extension, but too weak to hold and move the growth cone. We are therefore using light to control a natural biological process, in sharp contrast to the established technique of optical tweezers [Ashkin, A. (1970) Phys. Rev. Lett. 24, 156–159; Ashkin, A. & Dziedzic, J. M. (1987) Science 235, 1517–1520], which uses large optical forces to manipulate entire structures. Our results therefore open an avenue to controlling neuronal growth in vitro and in vivo with a simple, noncontact technique. PMID:12456879

  3. Rod- and cone-driven responses in mice expressing human L-cone pigment

    PubMed Central

    Atorf, Jenny; Neitz, Maureen; Neitz, Jay

    2015-01-01

    The mouse is commonly used for studying retinal processing, primarily because it is amenable to genetic manipulation. To accurately study photoreceptor driven signals in the healthy and diseased retina, it is of great importance to isolate the responses of single photoreceptor types. This is not easily achieved in mice because of the strong overlap of rod and M-cone absorption spectra (i.e., maxima at 498 and 508 nm, respectively). With a newly developed mouse model (Opn1lwLIAIS) expressing a variant of the human L-cone pigment (561 nm) instead of the mouse M-opsin, the absorption spectra are substantially separated, allowing retinal physiology to be studied using silent substitution stimuli. Unlike conventional chromatic isolation methods, this spectral compensation approach can isolate single photoreceptor subtypes without changing the retinal adaptation. We measured flicker electroretinograms in these mutants under ketamine-xylazine sedation with double silent substitution (silent S-cone and either rod or M/L-cones) and obtained robust responses for both rods and (L-)cones. Small signals were yielded in wild-type mice, whereas heterozygotes exhibited responses that were generally intermediate to both. Fundamental response amplitudes and phase behaviors (as a function of temporal frequency) in all genotypes were largely similar. Surprisingly, isolated (L-)cone and rod response properties in the mutant strain were alike. Thus the LIAIS mouse warrants a more comprehensive in vivo assessment of photoreceptor subtype-specific physiology, because it overcomes the hindrance of overlapping spectral sensitivities present in the normal mouse. PMID:26245314

  4. Exact-solution for cone-plate viscometry

    NASA Astrophysics Data System (ADS)

    Giacomin, A. J.; Gilbert, P. H.

    2017-11-01

    The viscosity of a Newtonian fluid is often measured by confining the fluid to the gap between a rotating cone that is perpendicular to a fixed disk. We call this experiment cone-plate viscometry. When the cone angle approaches π/2 , the viscometer gap is called narrow. The shear stress in the fluid, throughout a narrow gap, hardly departs from the shear stress exerted on the plate, and we thus call cone-plate flow nearly homogeneous. In this paper, we derive an exact solution for this slight heterogeneity, and from this, we derive the correction factors for the shear rate on the cone and plate, for the torque, and thus, for the measured Newtonian viscosity. These factors thus allow the cone-plate viscometer to be used more accurately, and with cone-angles well below π/2 . We find cone-plate flow field heterogeneity to be far slighter than previously thought. We next use our exact solution for the velocity to arrive at the exact solution for the temperature rise, due to viscous dissipation, in cone-plate flow subject to isothermal boundaries. Since Newtonian viscosity is a strong function of temperature, we expect our new exact solution for the temperature rise be useful to those measuring Newtonian viscosity, and especially so, to those using wide gaps. We include two worked examples to teach practitioners how to use our main results.

  5. Boundary-layer instability & transition on a flared cone in a Mach 6 quiet wind tunnel

    NASA Astrophysics Data System (ADS)

    Hofferth, Jerrod; Saric, William

    2011-11-01

    Measurements of boundary-layer transition location and instability growth on a sharp-tipped 5°-half-angle flared cone were conducted in a low-disturbance Mach 6 wind tunnel at a freestream unit Reynolds number of 10 × 106/m. Under quiet flow at these conditions, the boundary layer becomes transitional near the base of the cone, where significant second-mode instability growth is evident. Transition location is determined using an array of embedded thermocouples, and instability development is observed in mean and fluctuating mass flux data using hotwire anemometry. The present work seeks to reproduce and build upon previous experiments which used the same test article and similar diagnostics in the facility's former installation at NASA Langley. Together with comprehensive measurements of the freestream disturbance environment, these baseline cone data characterize the facility's performance relative to that in its previous installation. In addition, the current campaign establishes experimental readiness for future research, which will study the effects of periodic surface roughness and controlled-input disturbances. AFOSR/NASA National Center for Hypersonic Research in Laminar-Turbulent Transition; Grant FA9550-09-1-0341.

  6. Toward the reconstitution of synthetic cell motility

    PubMed Central

    Siton-Mendelson, Orit; Bernheim-Groswasser, Anne

    2016-01-01

    ABSTRACT Cellular motility is a fundamental process essential for embryonic development, wound healing, immune responses, and tissues development. Cells are mostly moving by crawling on external, or inside, substrates which can differ in their surface composition, geometry, and dimensionality. Cells can adopt different migration phenotypes, e.g., bleb-based and protrusion-based, depending on myosin contractility, surface adhesion, and cell confinement. In the few past decades, research on cell motility has focused on uncovering the major molecular players and their order of events. Despite major progresses, our ability to infer on the collective behavior from the molecular properties remains a major challenge, especially because cell migration integrates numerous chemical and mechanical processes that are coupled via feedbacks that span over large range of time and length scales. For this reason, reconstituted model systems were developed. These systems allow for full control of the molecular constituents and various system parameters, thereby providing insight into their individual roles and functions. In this review we describe the various reconstituted model systems that were developed in the past decades. Because of the multiple steps involved in cell motility and the complexity of the overall process, most of the model systems focus on very specific aspects of the individual steps of cell motility. Here we describe the main advancement in cell motility reconstitution and discuss the main challenges toward the realization of a synthetic motile cell. PMID:27019160

  7. Media Screening for Obtaining Haematococcus pluvialis Red Motile Macrozooids Rich in Astaxanthin and Fatty Acids

    PubMed Central

    Butler, Thomas O.; McDougall, Gordon J.; Campbell, Raymond; Stanley, Michele S.; Day, John G.

    2017-01-01

    Astaxanthin from Haematococcus pluvialis is commercially produced in a two-stage process, involving green vegetative (macrozooid) and red aplanospore stages. This approach has been scaled up to an industrial process but constraints limit its commercial success and profitability, including: contamination issues, high pigment extraction costs, requirements for high light levels and photo-bleaching in the red stage. However, in addition to the aplanospore stage, this alga can produce astaxanthin in vegetative palmelloid and motile macrozooid cells. In this study, a two-stage process utilising different media in the green stage, with subsequent re-suspension in medium without nitrate was employed to optimise the formation of red motile macrozooids. Optimal growth in the green phase was obtained on cultivation under mixotrophic conditions in EG:JM media followed by re-suspension in medium without nitrate resulting in red motile macrozooids with an astaxanthin content of 2.74% (78.4% of total carotenoids) and a lipid content of 35.3% (rich in unsaturated fatty acids. It is envisaged that the red motile macrozooids could be harvested and fed as a whole-cell product directly in the animal feed and aquaculture sectors, or used as a blend of carotenoids and polyunsaturated fatty acids (PUFAs) in nutraceutical products. PMID:29278377

  8. Media Screening for Obtaining Haematococcus pluvialis Red Motile Macrozooids Rich in Astaxanthin and Fatty Acids.

    PubMed

    Butler, Thomas O; McDougall, Gordon J; Campbell, Raymond; Stanley, Michele S; Day, John G

    2017-12-26

    Astaxanthin from Haematococcus pluvialis is commercially produced in a two-stage process, involving green vegetative (macrozooid) and red aplanospore stages. This approach has been scaled up to an industrial process but constraints limit its commercial success and profitability, including: contamination issues, high pigment extraction costs, requirements for high light levels and photo-bleaching in the red stage. However, in addition to the aplanospore stage, this alga can produce astaxanthin in vegetative palmelloid and motile macrozooid cells. In this study, a two-stage process utilising different media in the green stage, with subsequent re-suspension in medium without nitrate was employed to optimise the formation of red motile macrozooids. Optimal growth in the green phase was obtained on cultivation under mixotrophic conditions in EG:JM media followed by re-suspension in medium without nitrate resulting in red motile macrozooids with an astaxanthin content of 2.74% (78.4% of total carotenoids) and a lipid content of 35.3% (rich in unsaturated fatty acids. It is envisaged that the red motile macrozooids could be harvested and fed as a whole-cell product directly in the animal feed and aquaculture sectors, or used as a blend of carotenoids and polyunsaturated fatty acids (PUFAs) in nutraceutical products.

  9. Esophageal motility in eosinophilic esophagitis.

    PubMed

    Weiss, A H; Iorio, N; Schey, R

    2015-01-01

    Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on

  10. The NLO jet vertex in the small-cone approximation for kt and cone algorithms

    NASA Astrophysics Data System (ADS)

    Colferai, D.; Niccoli, A.

    2015-04-01

    We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet "radius" R = 0 .5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

  11. Stages of rootless cone formation observed within the Raudhólar cone group, Iceland

    NASA Astrophysics Data System (ADS)

    Fitch, E. P.; Hamilton, C.; Fagents, S. A.; Thordarson, T.

    2013-12-01

    Secondary (rootless) cones form when lava interacts explosively with water contained in the substrate, and represent a largely degassed, end-member system that can elucidate mechanisms of magma-water interactions in the absence of primary degassing-induced fragmentation. Rootless cones are well documented in Iceland. The Raudhólar rootless cone group, located within the ~5200-year-old Ellidaá lava flow on the south-eastern outskirts of Reykjavík, was extensively quarried during the Second World War and now provides excellent cross-sections through the tephra sequences. Taking advantage of this exposure, we performed detailed stratigraphic, grain-size, and componentry analyses, which suggest that the energetics of rootless explosions vary substantially during cone formation. The lower unit contains the most substrate sediment and is characterized by dilute pyroclastic density current deposits. The middle unit is dominated by a succession of bed-pairs, each containing a finer-grained lower layer and coarser-grained upper layer. In the upper unit, the succession grades into a welded section that caps the cone. The abundance of substrate sediment generally decreases upwards within the cone, which suggests that the efficiency of lava-substrate mixing decreased with time. In addition, clast size generally increases upwards within the cone, implying that the fragmentation energy also decreased as the rootless eruption progressed. Both lines of evidence suggest that the explosions decreased in intensity with time, likely due to the depletion of available groundwater. However, alternating fine- and coarse-grained beds imply cycles of increased and decreased fragmentation efficiency, which we attribute to groundwater recharge and depletion during the event. Therefore, this study presents a detailed look at rootless cone formation and provides the foundation for future work on this important, yet understudied, system.

  12. Disruption of TgPHIL1 Alters Specific Parameters of Toxoplasma gondii Motility Measured in a Quantitative, Three-Dimensional Live Motility Assay

    PubMed Central

    Leung, Jacqueline M.; Rould, Mark A.; Konradt, Christoph; Hunter, Christopher A.; Ward, Gary E.

    2014-01-01

    T. gondii uses substrate-dependent gliding motility to invade cells of its hosts, egress from these cells at the end of its lytic cycle and disseminate through the host organism during infection. The ability of the parasite to move is therefore critical for its virulence. T. gondii engages in three distinct types of gliding motility on coated two-dimensional surfaces: twirling, circular gliding and helical gliding. We show here that motility in a three-dimensional Matrigel-based environment is strikingly different, in that all parasites move in irregular corkscrew-like trajectories. Methods developed for quantitative analysis of motility parameters along the smoothed trajectories demonstrate a complex but periodic pattern of motility with mean and maximum velocities of 0.58±0.07 µm/s and 2.01±0.17 µm/s, respectively. To test how a change in the parasite's crescent shape might affect trajectory parameters, we compared the motility of Δphil1 parasites, which are shorter and wider than wild type, to the corresponding parental and complemented lines. Although comparable percentages of parasites were moving for all three lines, the Δphil1 mutant exhibited significantly decreased trajectory lengths and mean and maximum velocities compared to the parental parasite line. These effects were either partially or fully restored upon complementation of the Δphil1 mutant. These results show that alterations in morphology may have a significant impact on T. gondii motility in an extracellular matrix-like environment, provide a possible explanation for the decreased fitness of Δphil1 parasites in vivo, and demonstrate the utility of the quantitative three-dimensional assay for studying parasite motility. PMID:24489670

  13. NMNAT1 variants cause cone and cone-rod dystrophy.

    PubMed

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  14. A photon-driven micromotor can direct nerve fibre growth

    NASA Astrophysics Data System (ADS)

    Wu, Tao; Nieminen, Timo A.; Mohanty, Samarendra; Miotke, Jill; Meyer, Ronald L.; Rubinsztein-Dunlop, Halina; Berns, Michael W.

    2012-01-01

    Axonal path-finding is important in the development of the nervous system, nerve repair and nerve regeneration. The behaviour of the growth cone at the tip of the growing axon determines the direction of axonal growth and migration. We have developed an optical-based system to control the direction of growth of individual axons (nerve fibres) using laser-driven spinning birefringent spheres. One or two optical traps position birefringent beads adjacent to growth cones of cultured goldfish retinal ganglion cell axons. Circularly polarized light with angular momentum causes the trapped bead to spin. This creates a localized microfluidic flow generating an estimated 0.17 pN shear force against the growth cone that turns in response to the shear. The direction of axonal growth can be precisely manipulated by changing the rotation direction and position of this optically driven micromotor. A physical model estimating the shear force density on the axon is described.

  15. Deletion of murine choline dehydrogenase results in diminished sperm motility

    PubMed Central

    Johnson, Amy R.; Craciunescu, Corneliu N.; Guo, Zhong; Teng, Ya-Wen; Thresher, Randy J.; Blusztajn, Jan K.; Zeisel, Steven H.

    2010-01-01

    Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine, an important methyl donor and organic osmolyte. We have previously identified single nucleotide polymorphisms (SNPs) in the human CHDH gene that, when present, seem to alter the activity of the CHDH enzyme. These SNPs occur frequently in humans. We created a Chdh−/− mouse to determine the functional effects of mutations that result in decreased CHDH activity. Chdh deletion did not affect fetal viability or alter growth or survival of these mice. Only one of eleven Chdh−/− males was able to reproduce. Loss of CHDH activity resulted in decreased testicular betaine and increased choline and PCho concentrations. Chdh+/+ and Chdh−/− mice produced comparable amounts of sperm; the impaired fertility was due to diminished sperm motility in the Chdh−/− males. Transmission electron microscopy revealed abnormal mitochondrial morphology in Chdh−/− sperm. ATP content, total mitochondrial dehydrogenase activity and inner mitochondrial membrane polarization were all significantly reduced in sperm from Chdh−/− animals. Mitochondrial changes were also detected in liver, kidney, heart, and testis tissues. We suggest that men who have SNPs in CHDH that decrease the activity of the CHDH enzyme could have decreased sperm motility and fertility.—Johnson, A. R., Craciunescu, C. N., Guo, Z., Teng, Y.-W., Thresher, R. J., Blusztajn, J. K., Zeisel, S. H. Deletion of murine choline dehydrogenase results in diminished sperm motility. PMID:20371614

  16. ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.

    PubMed

    Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru

    2016-03-01

    Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.

  17. S100A4 is frequently overexpressed in lung cancer cells and promotes cell growth and cell motility

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Na; Sato, Daisuke; Saiki, Yuriko

    2014-05-09

    Highlights: • We observed frequent overexpression of S100A4 in lung cancer cell lines. • Knockdown of S100A4 suppressed proliferation in lung cancer cells. • Forced expression of S100A4 accelerated cell motility in lung cancer cells. • PRDM2 was found to be one of the downstream suppressed genes of S100A4. - Abstract: S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells. However, its biological role in lung carcinogenesis is largely unknown. In thismore » study, we found that S100A4 was frequently overexpressed in lung cancer cells, irrespective of histological subtype. Then we performed knockdown and forced expression of S100A4 in lung cancer cell lines and found that specific knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer cells with S100A4-overexpression; forced expression of S100A4 accelerated cell motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1, identified as novel upregulated genes by microarray after specific knockdown of S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was significantly upregulated after S100A4-knockdown in one of two analyzed S100A4-overexpressing lung cancer cells. Our present results suggest that S100A4 plays an important role in lung carcinogenesis by means of cell proliferation and motility by a pathway similar to that in pancreatic cancer.« less

  18. The Wireless Motility Capsule: a One-Stop Shop for the Evaluation of GI Motility Disorders.

    PubMed

    Saad, Richard J

    2016-03-01

    The wireless motility and pH capsule (WMC) provides an office-based test to simultaneously assess both regional and whole gut transit. Ingestion of this non-digestible capsule capable of measuring temperature, pH, and the pressure of its immediate surroundings allows for the measurement of gastric, small bowel, and colonic transit times in an ambulatory setting. Approved by the US Food and Drug Administration for the evaluation of suspected conditions of delayed gastric emptying and the evaluation of colonic transit in chronic idiopathic constipation, WMC should be considered in suspected gastrointestinal motility disorders as it provides a single study capable of simultaneously assessing for regional, multiregional, or generalized motility disorders. Specific indications for testing with the WMC should include the evaluation of suspect cases of gastroparesis, small bowel dysmotility, and slow transit constipation, as well as symptom syndromes suggestive of a multiregional or generalized gastrointestinal transit delay.

  19. Effects of Surface Passivation on Gliding Motility Assays

    PubMed Central

    Maloney, Andy; Herskowitz, Lawrence J.; Koch, Steven J.

    2011-01-01

    In this study, we report differences in the observed gliding speed of microtubules dependent on the choice of bovine casein used as a surface passivator. We observed differences in both speed and support of microtubules in each of the assays. Whole casein, comprised of αs1, αs2, β, and κ casein, supported motility and averaged speeds of 966±7 nm/s. Alpha casein can be purchased as a combination of αs1 and αs2 and supported gliding motility and average speeds of 949±4 nm/s. Beta casein did not support motility very well and averaged speeds of 870±30 nm/s. Kappa casein supported motility very poorly and we were unable to obtain an average speed. Finally, we observed that mixing alpha, beta, and kappa casein with the proportions found in bovine whole casein supported motility and averaged speeds of 966±6 nm/s. PMID:21674032

  20. Effects of prophylactic incisional gastropexy on markers of gastric motility in dogs as determined by use of a novel wireless motility device.

    PubMed

    Gazzola, Krista M; Nelson, Laura L; Fritz, Michele C; Clancy, Michelle R; Hauptman, Joe G

    2017-01-01

    OBJECTIVE To evaluate effects of laparoscopic-assisted incisional gastropexy (LAIG) on gastric motility in dogs by use of a wireless motility device (WMD). ANIMALS 10 healthy client-owned large or giant-breed dogs. PROCEDURES 10 dogs owned by clients interested in prophylactic LAIG were enrolled. To determine effects of LAIG on gastrointestinal motility in dogs during the nonfed state, each dog was evaluated by use of a noninvasive WMD before and > 4 weeks after LAIG. All dogs underwent LAIG, with or without concurrent elective gonadectomy. Data obtained before and after LAIG were analyzed by use of proprietary software to determine the gastric emptying time, small bowel transit time, large bowel transit time, whole bowel transit time, and motility index. RESULTS No changes in variables were detected between measurements obtained before and after prophylactic LAIG. CONCLUSIONS AND CLINICAL RELEVANCE In this study, prophylactic LAIG did not have an effect on gastrointestinal motility. The WMD was tolerated well by all dogs and appeared to be a safe and effective method for evaluating gastrointestinal motility in this population of dogs.

  1. In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility

    PubMed Central

    Dayel, Mark J.; Akin, Orkun; Landeryou, Mark; Risca, Viviana; Mogilner, Alex; Mullins, R. Dyche

    2009-01-01

    Eukaryotic cells assemble viscoelastic networks of crosslinked actin filaments to control their shape, mechanical properties, and motility. One important class of actin network is nucleated by the Arp2/3 complex and drives both membrane protrusion at the leading edge of motile cells and intracellular motility of pathogens such as Listeria monocytogenes. These networks can be reconstituted in vitro from purified components to drive the motility of spherical micron-sized beads. An Elastic Gel model has been successful in explaining how these networks break symmetry, but how they produce directed motile force has been less clear. We have combined numerical simulations with in vitro experiments to reconstitute the behavior of these motile actin networks in silico using an Accumulative Particle-Spring (APS) model that builds on the Elastic Gel model, and demonstrates simple intuitive mechanisms for both symmetry breaking and sustained motility. The APS model explains observed transitions between smooth and pulsatile motion as well as subtle variations in network architecture caused by differences in geometry and conditions. Our findings also explain sideways symmetry breaking and motility of elongated beads, and show that elastic recoil, though important for symmetry breaking and pulsatile motion, is not necessary for smooth directional motility. The APS model demonstrates how a small number of viscoelastic network parameters and construction rules suffice to recapture the complex behavior of motile actin networks. The fact that the model not only mirrors our in vitro observations, but also makes novel predictions that we confirm by experiment, suggests that the model captures much of the essence of actin-based motility in this system. PMID:19771152

  2. Spirochete motility and morpholgy

    NASA Astrophysics Data System (ADS)

    Charon, Nyles

    2004-03-01

    Spirochetes have a unique structure, and as a result their motility is different from that of other bacteria. These organisms can swim in a highly viscous, gel-like medium, such as that found in connective tissue, that inhibits the motility of most other bacteria. In spirochetes, the organelles for motility, the periplasmic flagella, reside inside the cell within the periplasmic space. A given periplasmic flagellum is attached only at one end of the cell, and depending on the species, may or may not overlap in the center of the cell. The number of periplasmic flagella varies from species to species. These structures have been shown to be directly involved in motility and function by rotating within the periplasmic space (1). The present talk focuses on the spirochete that causes Lyme disease, Borrelia burgdorferi. In many bacterial species, cell shape is usually dictated by the peptidoyglycan layer of the cell wall. In the first part of the talk, results will be presented that the morphology of B. burgdorferi is the result of a complex interaction between the cell cylinder and the internal periplasmic flagella resulting in a cell with a flat-wave morphology. Backward moving, propagating waves enable these bacteria to swim and translate in a given direction. Using targeted mutagenesis, we inactivated the gene encoding the major periplasmic flagellar filament protein FlaB. The resulting flaB mutants not only were non-motile, but were rod-shaped (2). Western blot analysis indicated that flaB was no longer synthesized, and electron microscopy revealed that the mutants were completely deficient in periplasmic flagella. Our results indicate that the periplasmic flagella of B. burgdorferi have a skeletal function. These organelles dynamically interact with the rod-shaped cell cylinder to enable the cell to swim, and to confer in part its flat-wave morphology The latter part of the talk concerns the basis for asymmetrical rotation of the periplasmic flagella of B

  3. Exploratory Research on Latent Esophageal Motility Disorders in Dysphagia Patients.

    PubMed

    Kawaguchi, Shinpei; Takeuchi, Toshihisa; Inoue, Yousuke; Takahashi, Yoshiaki; Ozaki, Haruhiko; Ota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Yamashita, Hiroshi; Fukuchi, Takumi; Ashida, Kiyoshi; Higuchi, Kazuhide

    2017-01-01

    High-resolution manometry (HRM) has been applied to assess esophageal motility disorders. However, the frequency and types of motility disorders in patients with dysphagia, which are frequently seen in clinical practice, are not clear. We evaluated latent esophageal motility disorders associated with dysphagia. The study included patients without erosive esophageal mucosal damage and with dysphagia symptoms refractory to at least 8 weeks of standard-dose proton pump inhibitors. After enrolment, HRM was used to evaluate for esophageal motility disorder based on the Chicago classification. Esophageal motility disorder was found in 58 of 100 patients and was classified based on the causes: achalasia (13%), esophagogastric junction outflow obstruction (16%), distal esophageal spasms (3%), weak peristalsis (14%), frequently failed peristalsis (5%), and hypertensive peristalsis (7%). Primary esophageal motility disorder was found in approximately 50% of cases in dysphagia patients. Therefore, esophageal motility disorder is not an uncommon condition and should be sought for in order to elucidate precisely the cause of dysphagia. © 2017 S. Karger AG, Basel.

  4. Experimental Study of Second-Mode Instabilities on a 7-Degree Cone at Mach 6

    NASA Technical Reports Server (NTRS)

    Rufer, Shann J.; Berridge, Dennis C.

    2011-01-01

    Experiments have been carried out in the NASA Langley Research Center 20-Inch Mach 6 Air Tunnel to measure the second-mode boundary-layer instability on a 7deg half-angle cone using high-frequency pressure sensors. Data were obtained with both blunt and sharp nosetips installed on the cone. The second-mode wave amplitudes were observed to saturate and then begin to decrease in the Langley tunnels, indicating wave breakdown. Pressure fluctuation measurements and thermocouple data indicated the location of transition along the cone at the different conditions tested. Comparisons between the power density spectra obtained during the current test and previous data from the Langley 15-Inch Mach 6 High Temperature Tunnel and the Boeing/AFOSR Mach 6 Quiet tunnel illustrate the effect of tunnel noise on instability growth and transition.

  5. Identification of a cone bipolar cell in cat retina which has input from both rod and cone photoreceptors.

    PubMed

    Fyk-Kolodziej, Bozena; Qin, Pu; Pourcho, Roberta G

    2003-09-08

    It has been generally accepted that rod photoreceptor cells in the mammalian retina make synaptic contact with only a single population of rod bipolar cells, whereas cone photoreceptors contact a variety of cone bipolar cells. This assumption has been challenged in rodents by reports of a type of cone bipolar cell which receives input from both rods and cones. Questions remained as to whether similar pathways are present in other mammals. We have used an antiserum against the glutamate transporter GLT1-B to visualize a population of cone bipolar cells in the cat retina which make flat contacts with axon terminals of both rod and cone photoreceptor cells. These cells are identified as OFF-cone bipolar cells and correspond morphologically to type cb1 (CBa2) cone bipolar cells which are a major source of input to OFF-beta ganglion cells in the cat retina. The GLT1-B transporter was also localized to processes making flat contacts with photoreceptor terminals in rat and rabbit retinas. Examination of tissue processed for the GluR1 glutamate receptor subunit showed that cb1 cone bipolar cells, like their rodent counterparts, express this alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-selective receptor at their contacts with rod spherules. Thus, a direct excitatory pathway from rod photoreceptors to OFF-cone bipolar cells appears to be a common feature of mammalian retinas. Copyright 2003 Wiley-Liss, Inc.

  6. Shatter cones: (Mis)understood?

    PubMed

    Osinski, Gordon R; Ferrière, Ludovic

    2016-08-01

    Meteorite impact craters are one of the most common geological features in the solar system. An impact event is a near-instantaneous process that releases a huge amount of energy over a very small region on a planetary surface. This results in characteristic changes in the target rocks, from vaporization and melting to solid-state effects, such as fracturing and shock metamorphism. Shatter cones are distinctive striated conical fractures that are considered unequivocal evidence of impact events. They are one of the most used and trusted shock-metamorphic effects for the recognition of meteorite impact structures. Despite this, there is still considerable debate regarding their formation. We show that shatter cones are present in several stratigraphic settings within and around impact structures. Together with the occurrence of complete and "double" cones, our observations are most consistent with shatter cone formation due to tensional stresses generated by scattering of the shock wave due to heterogeneities in the rock. On the basis of field mapping, we derive the relationship D sc = 0.4 D a, where D sc is the maximum spatial extent of in situ shatter cones, and D a is the apparent crater diameter. This provides an important, new, more accurate method to estimate the apparent diameter of eroded complex craters on Earth. We have reestimated the diameter of eight well-known impact craters as part of this study. Finally, we suggest that shatter cones may reduce the strength of the target, thus aiding crater collapse, and that their distribution in central uplifts also records the obliquity of impact.

  7. Shatter cones: (Mis)understood?

    PubMed Central

    Osinski, Gordon R.; Ferrière, Ludovic

    2016-01-01

    Meteorite impact craters are one of the most common geological features in the solar system. An impact event is a near-instantaneous process that releases a huge amount of energy over a very small region on a planetary surface. This results in characteristic changes in the target rocks, from vaporization and melting to solid-state effects, such as fracturing and shock metamorphism. Shatter cones are distinctive striated conical fractures that are considered unequivocal evidence of impact events. They are one of the most used and trusted shock-metamorphic effects for the recognition of meteorite impact structures. Despite this, there is still considerable debate regarding their formation. We show that shatter cones are present in several stratigraphic settings within and around impact structures. Together with the occurrence of complete and “double” cones, our observations are most consistent with shatter cone formation due to tensional stresses generated by scattering of the shock wave due to heterogeneities in the rock. On the basis of field mapping, we derive the relationship Dsc = 0.4 Da, where Dsc is the maximum spatial extent of in situ shatter cones, and Da is the apparent crater diameter. This provides an important, new, more accurate method to estimate the apparent diameter of eroded complex craters on Earth. We have reestimated the diameter of eight well-known impact craters as part of this study. Finally, we suggest that shatter cones may reduce the strength of the target, thus aiding crater collapse, and that their distribution in central uplifts also records the obliquity of impact. PMID:27532050

  8. Downregulation of TFPI in breast cancer cells induces tyrosine phosphorylation signaling and increases metastatic growth by stimulating cell motility

    PubMed Central

    2011-01-01

    Background Increased hemostatic activity is common in many cancer types and often causes additional complications and even death. Circumstantial evidence suggests that tissue factor pathway inhibitor-1 (TFPI) plays a role in cancer development. We recently reported that downregulation of TFPI inhibited apoptosis in a breast cancer cell line. In this study, we investigated the effects of TFPI on self-sustained growth and motility of these cells, and of another invasive breast cancer cell type (MDA-MB-231). Methods Stable cell lines with TFPI (both α and β) and only TFPIβ downregulated were created using RNA interference technology. We investigated the ability of the transduced cells to grow, when seeded at low densities, and to form colonies, along with metastatic characteristics such as adhesion, migration and invasion. Results Downregulation of TFPI was associated with increased self-sustained cell growth. An increase in cell attachment and spreading was observed to collagen type I, together with elevated levels of integrin α2. Downregulation of TFPI also stimulated migration and invasion of cells, and elevated MMP activity was involved in the increased invasion observed. Surprisingly, equivalent results were observed when TFPIβ was downregulated, revealing a novel function of this isoform in cancer metastasis. Conclusions Our results suggest an anti-metastatic effect of TFPI and may provide a novel therapeutic approach in cancer. PMID:21849050

  9. Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors

    PubMed Central

    Bruce, Kady S.; Harmening, Wolf M.; Langston, Bradley R.; Tuten, William S.; Roorda, Austin; Sincich, Lawrence C.

    2015-01-01

    Purpose To determine the light sensitivity of poorly reflective cones observed in retinas of normal subjects, and to establish a relationship between cone reflectivity and perceptual threshold. Methods Five subjects (four male, one female) with normal vision were imaged longitudinally (7–26 imaging sessions, representing 82–896 days) using adaptive optics scanning laser ophthalmoscopy (AOSLO) to monitor cone reflectance. Ten cones with unusually low reflectivity, as well as 10 normally reflective cones serving as controls, were targeted for perceptual testing. Cone-sized stimuli were delivered to the targeted cones and luminance increment thresholds were quantified. Thresholds were measured three to five times per session for each cone in the 10 pairs, all located 2.2 to 3.3° from the center of gaze. Results Compared with other cones in the same retinal area, three of 10 monitored dark cones were persistently poorly reflective, while seven occasionally manifested normal reflectance. Tested psychophysically, all 10 dark cones had thresholds comparable with those from normally reflecting cones measured concurrently (P = 0.49). The variation observed in dark cone thresholds also matched the wide variation seen in a large population (n = 56 cone pairs, six subjects) of normal cones; in the latter, no correlation was found between cone reflectivity and threshold (P = 0.0502). Conclusions Low cone reflectance cannot be used as a reliable indicator of cone sensitivity to light in normal retinas. To improve assessment of early retinal pathology, other diagnostic criteria should be employed along with imaging and cone-based microperimetry. PMID:26193919

  10. Cone and Seed Maturation of Southern Pines

    Treesearch

    James P. Barnett

    1976-01-01

    If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

  11. Directional imaging of the retinal cone mosaic

    NASA Astrophysics Data System (ADS)

    Vohnsen, Brian; Iglesias, Ignacio; Artal, Pablo

    2004-05-01

    We describe a near-IR scanning laser ophthalmoscope that allows the retinal cone mosaic to be imaged in the human eye in vivo without the use of wave-front correction techniques. The method takes advantage of the highly directional quality of cone photoreceptors that permits efficient coupling of light to individual cones and subsequent detection of most directional components of the backscattered light produced by the light-guiding effect of the cones. We discuss details of the system and describe cone-mosaic images obtained under different conditions.

  12. Persistent enhancement of bacterial motility increases tumor penetration.

    PubMed

    Thornlow, Dana N; Brackett, Emily L; Gigas, Jonathan M; Van Dessel, Nele; Forbes, Neil S

    2015-11-01

    Motile bacteria can overcome the transport limitations that hinder many cancer therapies. Active bacteria can penetrate through tissue to deliver treatment to resistant tumor regions. Bacterial therapy has had limited success, however, because this motility is heterogeneous, and within a population many individuals are non-motile. In human trials, heterogeneity led to poor dispersion and incomplete tumor colonization. To address these problems, a swarm-plate selection method was developed to increase swimming velocity. Video microscopy was used to measure the velocity distribution of selected bacteria and a microfluidic tumor-on-a-chip device was used to measure penetration through tumor cell masses. Selection on swarm plates increased average velocity fourfold, from 4.9 to 18.7 μm/s (P < 0.05) and decreased the number of non-motile individuals from 51% to 3% (P < 0.05). The selected phenotype was both robust and stable. Repeating the selection process consistently increased velocity and eliminated non-motile individuals. When selected strains were cryopreserved and subcultured for 30.1 doublings, the high-motility phenotype was preserved. In the microfluidic device, selected Salmonella penetrated deeper into cell masses than unselected controls. By 10 h after inoculation, control bacteria accumulated in the front 30% of cell masses, closest to the flow channel. In contrast, selected Salmonella accumulated in the back 30% of cell masses, farthest from the channel. Selection increased the average penetration distance from 150 to 400 μm (P < 0.05). This technique provides a simple and rapid method to generate high-motility Salmonella that has increased penetration and potential for greater tumor dispersion and clinical efficacy. © 2015 Wiley Periodicals, Inc.

  13. Elevated temperature during reproductive development affects cone traits and progeny performance in Picea glauca x engelmannii complex.

    PubMed

    Webber, Joe; Ott, Peter; Owens, John; Binder, Wolfgang

    2005-10-01

    Two temperature regimes were applied during reproductive development of seed and pollen cones of interior spruce (Picea glauca (Moench) Voss and Picea engelmannii (Parry) complex) to determine temperature effects on the adaptive traits of progeny. In Experiment 1, identical crosses were made on potted interior spruce using untreated pollen followed by exposure to a day/night temperature of 22/8 or 14/8 degrees C with a 12-h photoperiod during the stages of reproductive development from post-pollination to early embryo development. Frost hardiness and growth of progeny from seed produced in the two temperature treatments were measured over a 4-year period. Elevated temperature significantly affected both seed-cone development and the adaptive properties of the progeny. Seed cones exposed to the 22/8 degrees C treatment reached the early embryo stage in 53 days versus 92 days in the 14/8 degrees C treatment. Seed yields, cotyledon emergence and percent germination were also significantly enhanced by the 22/8 degrees C treatment. Progeny from seed produced in the higher temperature treatment showed significantly reduced spring and fall frost hardiness, but the elevated temperature treatment had no significant effects on time of bud burst, growth patterns or final heights. In Experiment 2, single ramets of the same clone were subjected to a day/night temperature of 20/8 or 10/8 degrees C during pollen cone development, starting from meiosis and ending at pollen shedding. The two populations of pollen were then crossed with untreated seed cones. Compared with pollen cones exposed to the 10/8 degrees C treatment, pollen cones exposed to the 20/8 degrees C treatment during development reached the shedding stage 2-4 weeks earlier, whereas pollen yields, in vitro viability and fertility (seed set) were significantly lower; however, the resulting progeny displayed no treatment differences in frost hardiness or growth after 1 year. Results suggest that seed orchard after

  14. The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and non-motile Pseudomonas aeruginosa.

    PubMed

    Demirdjian, Sally; Schutz, Kristin; Wargo, Matthew J; Lam, Joseph S; Berwin, Brent

    2017-12-01

    The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression. The effect of loss of O-antigen, frequently described as conversion from smooth to rough LPS, and the combined effect of loss of motility and O-antigen on phagocytic susceptibility by immune cells remain unknown. To address this, we generated genetic deletion mutants of waaL, which encodes the O-antigen ligase responsible for linking O-antigen to lipid A-core oligosaccharide, in both motile and non-motile P. aeruginosa strains. With the use of these bacterial strains we provide the first demonstration that, despite a progressive selection for P. aeruginosa with rough LPS during chronic pulmonary infections, loss of the LPS O-antigen does not confer phagocytic resistance in vitro. However, use of the waaLmotABmotCD mutant revealed that loss of motility confers resistance to phagocytosis regardless of the smooth or rough LPS phenotype. These findings reveal how the O-antigen of P. aeruginosa can influence bacterial clearance during infection and expand our current knowledge about the impact of bacterial phenotypic changes during chronic infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bright and durable field-emission source derived from frozen refractory-metal Taylor cones

    DOE PAGES

    Hirsch, Gregory

    2017-02-22

    A novel method for creating conical field-emission structures possessing unusual and desirable physical characteristics is described. This process is accomplished by solidification of electrostatically formed high-temperature Taylor cones created on the ends of laser melted refractory-metal wires. Extremely rapid freezing ensures that the resultant solid structures preserve the shape and surface smoothness of the flawless liquid Taylor-cones to a very high degree. The method also enables in situ and rapid restoration of the frozen cones to their initial pristine state after undergoing physical degradation during use. This permits maximum current to be delivered without excessive concern for any associated reductionmore » in field-emitter lifetime resulting from operation near or even above the damage threshold. In addition to the production of field emitters using polycrystalline wires as a substrate, the feasibility of producing monocrystalline frozen Taylor-cones having reproducible crystal orientation by growth on single-crystal wires was demonstrated. Finally, the development of the basic field-emission technology, progress to incorporate it into a pulsed electron gun employing laser-assisted field emission for ultrafast experiments, and some additional advances and opportunities are discussed.« less

  16. Bright and durable field-emission source derived from frozen refractory-metal Taylor cones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirsch, Gregory

    A novel method for creating conical field-emission structures possessing unusual and desirable physical characteristics is described. This process is accomplished by solidification of electrostatically formed high-temperature Taylor cones created on the ends of laser melted refractory-metal wires. Extremely rapid freezing ensures that the resultant solid structures preserve the shape and surface smoothness of the flawless liquid Taylor-cones to a very high degree. The method also enables in situ and rapid restoration of the frozen cones to their initial pristine state after undergoing physical degradation during use. This permits maximum current to be delivered without excessive concern for any associated reductionmore » in field-emitter lifetime resulting from operation near or even above the damage threshold. In addition to the production of field emitters using polycrystalline wires as a substrate, the feasibility of producing monocrystalline frozen Taylor-cones having reproducible crystal orientation by growth on single-crystal wires was demonstrated. Finally, the development of the basic field-emission technology, progress to incorporate it into a pulsed electron gun employing laser-assisted field emission for ultrafast experiments, and some additional advances and opportunities are discussed.« less

  17. WE-G-18A-03: Cone Artifacts Correction in Iterative Cone Beam CT Reconstruction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, H; Folkerts, M; Jiang, S

    Purpose: For iterative reconstruction (IR) in cone-beam CT (CBCT) imaging, data truncation along the superior-inferior (SI) direction causes severe cone artifacts in the reconstructed CBCT volume images. Not only does it reduce the effective SI coverage of the reconstructed volume, it also hinders the IR algorithm convergence. This is particular a problem for regularization based IR, where smoothing type regularization operations tend to propagate the artifacts to a large area. It is our purpose to develop a practical cone artifacts correction solution. Methods: We found it is the missing data residing in the truncated cone area that leads to inconsistencymore » between the calculated forward projections and measured projections. We overcome this problem by using FDK type reconstruction to estimate the missing data and design weighting factors to compensate the inconsistency caused by the missing data. We validate the proposed methods in our multi-GPU low-dose CBCT reconstruction system on multiple patients' datasets. Results: Compared to the FDK reconstruction with full datasets, while IR is able to reconstruct CBCT images using a subset of projection data, the severe cone artifacts degrade overall image quality. For head-neck case under a full-fan mode, 13 out of 80 slices are contaminated. It is even more severe in pelvis case under half-fan mode, where 36 out of 80 slices are affected, leading to inferior soft-tissue delineation. By applying the proposed method, the cone artifacts are effectively corrected, with a mean intensity difference decreased from ∼497 HU to ∼39HU for those contaminated slices. Conclusion: A practical and effective solution for cone artifacts correction is proposed and validated in CBCT IR algorithm. This study is supported in part by NIH (1R01CA154747-01)« less

  18. Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disorders.

    PubMed

    Hollenstein, Michael; Thwaites, Philip; Bütikofer, Simon; Heinrich, Henriette; Sauter, Matthias; Ulmer, Irina; Pohl, Daniel; Ang, Daphne; Eberli, Daniel; Schwizer, Werner; Fried, Michael; Distler, Oliver; Fox, Mark; Misselwitz, Benjamin

    2017-09-01

    The factors that determine how people eat when they are healthy or have disease have not been defined. We used high resolution manometry (HRM) to assess pharyngeal swallowing and oesophageal motility during ingestion of a solid test meal (STM) in healthy volunteers and patients with motility disorders. This study was based at University Hospital Zurich (Zürich, Switzerland). Healthy volunteers who responded to an advertisement completed HRM with ten single water swallows (SWS) in recumbent and upright positions followed by a 200 g rice STM in the upright position. Healthy volunteers were stratified for age and sex to ensure a representative population. For comparison, consecutive patients with major motility disorders on SWS and patients with dysphagia but no major motility disorders on SWS (disease controls) were selected from a database that was assembled prospectively; the rice meal data were analysed retrospectively. During STM, pharyngeal swallows were timed and oesophageal contractions were classified as representing normal motility or different types of abnormal motility in accordance with established metrics. Factors that could potentially be associated with eating speed were investigated, including age, sex, body-mass index, and presence of motility disorder. We compared diagnoses based on SWS findings, assessed with the Chicago Classification v3.0, with those based on STM findings, assessed with the Chicago Classification adapted for solids. These studies are registered with ClinicalTrials.gov, numbers NCT02407938 and NCT02397616. Between April 2, 2014, and May 13, 2015, 72 healthy volunteers were recruited and underwent HRM. Additionally, we analysed data from 54 consecutive patients with major motility disorders and 53 with dysphagia but no major motility disorders recruited between April 2, 2013, and Dec 18, 2014. We found important variations in oesophageal motility and eating speed during meal ingestion in healthy volunteers and patients. Increased

  19. Spectral characteristics of light sources for S-cone stimulation.

    PubMed

    Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

    2002-11-01

    Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

  20. Inhibition of Swarming motility of Pseudomonas aeruginosa by Methanol extracts of Alpinia officinarum Hance. and Cinnamomum tamala T. Nees and Eberm.

    PubMed

    Lakshmanan, Divya; Nanda, Jishudas; Jeevaratnam, K

    2018-06-01

    Bacterial drug resistance is a challenge in clinical settings, especially in countries like India. Hence, discovery of novel alternative therapeutics has become a necessity in the fight against drug resistance. Compounds that inhibit bacterial virulence properties form new therapeutic alternatives. Pseudomonas aeruginosa is an opportunistic, nosocomial pathogen that infects immune-compromised patients. Swarming motility is an important virulence property of Pseudomonas which aids it in reaching host cells under nutrient limiting conditions. Here, we report the screening of five plant extracts against swarming motility of P. aeruginosa and show that methanol extracts of Alpinia officinarum and Cinnamomum tamala inhibit swarming motility at 5 μg mL -1 without inhibiting its growth. These extracts did not inhibit swimming and twitching motilities indicating a mode of action specific to swarming pathway. Preliminary experiments indicated that rhamnolipid production was not affected. This study reveals the potential of the two plants in anti-virulence drug discovery.

  1. Flagellar motility of the pathogenic spirochetes

    PubMed Central

    Wolgemuth, Charles W.

    2016-01-01

    Bacterial pathogens are often classified by their toxicity and invasiveness. The invasiveness of a given bacterium is determined by how capable the bacterium is at invading a broad range of tissues in its host. Of mammalian pathogens, some of the most invasive come from a group of bacteria known as the spirochetes, which cause diseases such as syphilis, Lyme disease, relapsing fever and leptospirosis. Most of the spirochetes are characterized by their distinct shapes and unique motility. They are long, thin bacteria that can be shaped like flat-waves, helices, or have more irregular morphologies. Like many other bacteria, the spirochetes use long, helical appendages known as flagella to move; however, the spirochetes enclose their flagella in the periplasm, the narrow space between the inner and outer membranes. Rotation of the flagella in the periplasm causes the entire cell body to rotate and/or undulate. These deformations of the bacterium produce the force that drives the motility of these organisms, and it is this unique motility that likely allows these bacteria to be highly invasive in mammals. This review will describe the current state of knowledge on the motility and biophysics of these organisms and provide evidence on how this knowledge can inform our understanding of spirochetal diseases. PMID:26481969

  2. Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer

    PubMed Central

    Kim, Seok-Jun; Wang, Yuan-Guo; Lee, Hyun-Woo; Gu Kang, Hyeok; La, Sun-Hyuk; Ju Choi, Il; Irimura, Tatsuro; Ro, Jae Y.; Bresalier, Robert S.; Chun, Kyung-Hee

    2014-01-01

    Although elevated expression of neogenin-1 has been detected in human gastric cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation decreased proliferation and migration of gastric cancer cells, whereas its over-expression reversed these effects. Xenografted analyses using gastric cancer cells displayed statistically significant inhibition of tumor growth by neogenin-1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which facilitated nuclear-localization and binding on neogenin-1 promoter to drive its transcription and gastric cancer cell motility. The galectin-3-increased gastric cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the parallel expression patterns of galectin-3 and neogenin-1, as well as those of HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer patients. Taken together, high-expression of neogenin-1 promotes gastric cancer proliferation and motility and its expression is regulated by HSF-1 and galectin-3 interaction. In addition, we propose further studies for neogenin-1 and its associated pathways to provide them as a proper target for gastric cancer therapy. PMID:24930499

  3. Amniotic fluid stem cells rescue both in vitro and in vivo growth, innervation, and motility in nitrofen-exposed hypoplastic rat lungs through paracrine effects.

    PubMed

    Pederiva, F; Ghionzoli, M; Pierro, A; De Coppi, P; Tovar, J A

    2013-01-01

    Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tested the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms. Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in the presence of culture medium alone or with RA, basophils, or AFS cells. In vivo green fluorescent protein-expressing (GFP(+)) rat AFS cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds, and the frequency of bronchial contractions were assessed. Protein gene product 9.5 (PGP 9.5) and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP 9.5, and TTF-1. The levels of FGF-10, VEGFα, and TGF-β1 secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by ANOVA. In vitro, the surface, the number of terminal buds, and the bronchial peristalsis were increased in nitrofen+AFS cell explants in comparison with nitrofen-exposed lungs. While nitrofen+RA lungs were similar to nitrofen+AFS ones, basophils did not normalize these measurements. PGP 9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo, the surface, number of terminal buds, and peristalsis were similar to control after injection of AFS cells in nitrofen-exposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF-10 and VEGFα were increased in nitrofen+AFS cell explants, while the levels of TGF-β1 were similar to controls. Lung growth, bronchial motility, and innervation were decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to that observed

  4. Migration speed and directionality switch of normal epithelial cells after TGF-β1-induced EMT (tEMT) on micro-structured polydimethylsiloxane (PDMS) substrates with variations in stiffness and topographic patterning.

    PubMed

    Wu, Tsung-Hsien; Li, Chia-Hui; Tang, Ming-Jer; Liang, Jen-I; Chen, Chia-Hsin; Yeh, Ming-Long

    2013-10-01

    The epithelial to mesenchymal transition (EMT) involves several physiological and pathological phenomena and endows cells with invasive and migratory properties. However, the effects of substrate stiffness and topography on the migration of cells before or after transforming growth factor-β1 (TGF-β1)-induced EMT (tEMT) are unknown. Herein, we seed control or tEMT NMuMG cells on the 2D patterns consisted of 1 μm or 5 μm line-widths and groove or cone patterns on either 2 MPa (1.96 ± 0.48 MPa) or 4 MPa (3.70 ± 0.74 MPa) polydimethylsiloxane (PDMS) substrates. After tEMT, the increased expression of α-SMA with vinculin in focal adhesion (FA) sites led to an acceleration of tEMT cell motility. On the 2 MPa substrate, the most influenced substrate was the 1 μm, cone-patterned substrate, where the tEMT cells' motility decelerated by 0.13 μm/min (36% slower than the cells on groove pattern). However, on the 5 μm, groove-patterned substrate, where the tEMT cells demonstrated the most rapid motility relative to the control cells, with an increment of 0.18 μm/min (100%). Among the different physical cues from substrate, the cone pattern could impede the migration speed of tEMT cells. Furthermore, we recommend the groove-patterned with a 5 μm line-width substrate as a useful tool to differentiate control and tEMT cells by migration speed.

  5. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    PubMed

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  6. Possible Tuff Cones In Isidis Planitia, Mars

    NASA Astrophysics Data System (ADS)

    Seabrook, A. M.; Rothery, D. A.; Bridges, J. C.; Wright, I. P.

    The Beagle 2 lander of the ESA Mars Express mission will touch down on the martian surface in December 2003 to conduct a primarily exobiological mission. The landing site will be within Isidis Planitia, an 1100 km diameter impact basin. Isidis contains many sub-kilometre-sized cones. These can be found singly, in clusters, and in straight or arcuate chains extending many kilometres. In some areas of the basin these cones can occupy over 10% of the surface, with the most densely populated areas being in the older western half of the basin. There are few cones around the basin rim. There is also variation in the erosional state of the cones both across the basin, and within smaller areas, implying a range in time of formation for the cones. We currently favour a tuff cone origin as an explanation for these features. Tuff cones on Earth are rooted volcanic features formed at vents by the interaction between magma or magmatic heat and surface or near-surface water. Lava flows likely to be associated with at least some of the cones if they had a cinder cone (rooted eruptions at vents in a dry environment) origin are absent. This suggests the involvement of suffi- cient volatiles both to explosively fragment the erupting magma, and to cool the ejecta enough to prevent the formation of clastogenic flows. If our tuff cone interpretation is correct, this has implications for the presence, abundance and long-term persistence of sub-surface volatiles (water or carbon dioxide) on Mars. An understanding of the mechanism of formation of the Isidis cones will assist the characterisation of the basin in preparation for the landing of Beagle 2, by providing information about the history of volatiles and volcanism in the basin, and the processes that resulted in the surface we see today.

  7. Targeting tumor cell motility to prevent metastasis

    PubMed Central

    Palmer, Trenis D.; Ashby, William J.; Lewis, John D.; Zijlstra, Andries

    2011-01-01

    Mortality and morbidity in patients with solid tumors invariably results from the disruption of normal biological function caused by disseminating tumor cells. Tumor cell migration is under intense investigation as the underlying cause of cancer metastasis. The need for tumor cell motility in the progression of metastasis has been established experimentally and is supported empirically by basic and clinical research implicating a large collection of migration-related genes. However, there are few clinical interventions designed to specifically target the motility of tumor cells and adjuvant therapy to specifically prevent cancer cell dissemination is severely limited. In an attempt to define motility targets suitable for treating metastasis, we have parsed the molecular determinants of tumor cell motility into five underlying principles including cell autonomous ability, soluble communication, cell-cell adhesion, cell-matrix adhesion, and integrating these determinants of migration on molecular scaffolds. The current challenge is to implement meaningful and sustainable inhibition of metastasis by developing clinically viable disruption of molecular targets that control these fundamental capabilities. PMID:21664937

  8. Cell motility assays.

    PubMed

    Hague, Angela; Jones, Gareth E

    2008-10-01

    This report summarises practical aspects to measuring cell motility in culture. The methods described here were discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop organised by John Masters and Gareth E Jones that was held at University College London on 19th April 2007.

  9. Gliding Motility Revisited: How Do the Myxobacteria Move without Flagella?

    PubMed Central

    Mauriello, Emilia M. F.; Mignot, Tâm; Yang, Zhaomin; Zusman, David R.

    2010-01-01

    Summary: In bacteria, motility is important for a wide variety of biological functions such as virulence, fruiting body formation, and biofilm formation. While most bacteria move by using specialized appendages, usually external or periplasmic flagella, some bacteria use other mechanisms for their movements that are less well characterized. These mechanisms do not always exhibit obvious motility structures. Myxococcus xanthus is a motile bacterium that does not produce flagella but glides slowly over solid surfaces. How M. xanthus moves has remained a puzzle that has challenged microbiologists for over 50 years. Fortunately, recent advances in the analysis of motility mutants, bioinformatics, and protein localization have revealed likely mechanisms for the two M. xanthus motility systems. These results are summarized in this review. PMID:20508248

  10. Rods and cones contain antigenically distinctive S-antigens.

    PubMed

    Nork, T M; Mangini, N J; Millecchia, L L

    1993-09-01

    S-antigen (48 kDa protein or arrestin) is known to be present in rod photoreceptors. Its localization in cones is less clear with several conflicting reports among various species examined. This study employed three different anti-S-antigen antibodies (a48K, a polyclonal antiserum and two monoclonal antibodies, MAb A9-C6 and MAb 5c6.47) and examined their localization in rods and cones of human and cat retinas. To identify the respective cone types, an enzyme histochemical technique for carbonic anhydrase (CA) was employed to distinguish blue cones (CA-negative) from red or green cones (CA-positive). S-antigen localization was then examined by immunocytochemical staining of adjacent sections. In human retinas, a similar labeling pattern was seen with both a48K and MAb A9-C6, i.e., the rods and blue-sensitive cones were strongly positive, whereas the red- or green-sensitive cones showed little immunoreactivity. All human photoreceptors showed reactivity to MAb 5c6.47. In the cat retina, only CA-positive cones could be found. As in the human retina, both rods and cones of the cat were positive for MAb 5c6.47. A difference from the labeling pattern in human retina was noted for the other S-antigen antibodies; a48K labeled rods and all of the cones, whereas MAb A9-C6 reacted strongly with the rods but showed no cone staining. These results suggest that both rods and cones contain S-antigen but that they are antigenically distinctive.

  11. Increased count, motility, and total motile sperm cells collected across three consecutive ejaculations within 24 h of oocyte retrieval: implications for management of men presenting with low numbers of motile sperm for assisted reproduction.

    PubMed

    Said, Al-Hasen; Reed, Michael L

    2015-07-01

    The purpose of this study was to quantitate changes in seminal volume, sperm count, motility, qualitative forward progression, and total motile sperm cells per ejaculate, across three consecutive ejaculates collected from individuals within 24 h preceding an IVF cycle. Men presenting with oligoasthenozoospermia or asthenozoospemia attempted three ejaculates within 24 h preceding IVF. Ejaculate 1 was produced the afternoon prior to oocyte retrieval, and ejaculates 2 and 3 were produced the morning of oocyte retrieval with 2-3 h between collections. Ejaculates 1 and 2 were extended 1:1 v/v with room temperature rTYBS. Test tubes were placed into a beaker of room temperature water, then placed at 4 °C for gradual cooling. Ejaculate 3 was not extended, but pooled with ejaculates 1 and 2 and processed for intracytoplasmic sperm injection (ICSI). Out of 109 oocyte retrievals, 28 men were asked to attempt multiple consecutive ejaculations. Among this population, 25/28 (89.3 %) were successful, and 3/28 men (10.7 %) could only produce two ejaculates. Mean volumes for ejaculates 1, 2, and 3 were significantly different from each other (p < 0.01); the volume decreased for each ejaculate. Mean sperm counts, motility, qualitative forward progression, and total motile cells per ejaculate for the ejaculates1, 2, and 3 demonstrated the following: ejaculates 2 and 3 were not significantly different, but counts, motility, and total motile sperm were improved over ejaculate 1 (p < 0.01). Pooling three consecutive ejaculates within 24 h increased the numbers of available motile sperm in this population by 8-fold compared to the first ejaculate alone, facilitating avoidance of sperm cryopreservation and additional centrifugation steps that could affect sperm viability and/or function.

  12. Engineering bacterial motility towards hydrogen-peroxide.

    PubMed

    Virgile, Chelsea; Hauk, Pricila; Wu, Hsuan-Chen; Shang, Wu; Tsao, Chen-Yu; Payne, Gregory F; Bentley, William E

    2018-01-01

    Synthetic biologists construct innovative genetic/biological systems to treat environmental, energy, and health problems. Many systems employ rewired cells for non-native product synthesis, while a few have employed the rewired cells as 'smart' devices with programmable function. Building on the latter, we developed a genetic construct to control and direct bacterial motility towards hydrogen peroxide, one of the body's immune response signaling molecules. A motivation for this work is the creation of cells that can target and autonomously treat disease, the latter signaled by hydrogen peroxide release. Bacteria naturally move towards a variety of molecular cues (e.g., nutrients) in the process of chemotaxis. In this work, we engineered bacteria to recognize and move towards hydrogen peroxide, a non-native chemoattractant and potential toxin. Our system exploits oxyRS, the native oxidative stress regulon of E. coli. We first demonstrated H2O2-mediated upregulation motility regulator, CheZ. Using transwell assays, we showed a two-fold increase in net motility towards H2O2. Then, using a 2D cell tracking system, we quantified bacterial motility descriptors including velocity, % running (of tumble/run motions), and a dynamic net directionality towards the molecular cue. In CheZ mutants, we found that increased H2O2 concentration (0-200 μM) and induction time resulted in increased running speeds, ultimately reaching the native E. coli wild-type speed of ~22 μm/s with a ~45-65% ratio of running to tumbling. Finally, using a microfluidic device with stable H2O2 gradients, we characterized responses and the potential for "programmed" directionality towards H2O2 in quiescent fluids. Overall, the synthetic biology framework and tracking analysis in this work will provide a framework for investigating controlled motility of E. coli and other 'smart' probiotics for signal-directed treatment.

  13. A model for neurite growth and neuronal morphogenesis.

    PubMed

    Li, G H; Qin, C D

    1996-02-01

    A model is presented for tensile regulation of neuritic growth. It is proposed that the neurite tension can be determined by Hooke's law and determines the growth rate of neurites. The growth of a neurite is defined as the change in its unstretched length. Neuritic growth rate is assumed to increase in proportion to tension magnitude over a certain threshold [Dennerll et al., J. Cell Biol. 107: 665-674 (1988)]. The movement of branch nodes also contributes to the neuronal morphogenesis. It is supposed that the rate of a branch-node displacement is in proportion to the resultant neuritic tension exerted on this node. To deal with the growth-cone movement, it is further supposed that the environment exerts a traction force on the growth cone and the rate of growth-cone displacement is determined by the vector sum of the neuritic tension and the traction force. A group of differential equations are used to describe the model. The key point of the model is that the traction force and the neuritic tension are in opposition to generate a temporal contrast-enhancing mechanism. Results of a simulation study suggest that the model can explain some phenomena related to neuronal morphogenesis.

  14. Light-cone observables and gauge-invariance in the geodesic light-cone formalism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Scaccabarozzi, Fulvio; Yoo, Jaiyul, E-mail: fulvio@physik.uzh.ch, E-mail: jyoo@physik.uzh.ch

    The remarkable properties of the geodesic light-cone (GLC) coordinates allow analytic expressions for the light-cone observables, providing a new non-perturbative way for calculating the effects of inhomogeneities in our Universe. However, the gauge-invariance of these expressions in the GLC formalism has not been shown explicitly. Here we provide this missing part of the GLC formalism by proving the gauge-invariance of the GLC expressions for the light-cone observables, such as the observed redshift, the luminosity distance, and the physical area and volume of the observed sources. Our study provides a new insight on the properties of the GLC coordinates and itmore » complements the previous work by the GLC collaboration, leading to a comprehensive description of light propagation in the GLC representation.« less

  15. Primate Short-Wavelength Cones Share Molecular Markers with Rods

    PubMed Central

    Craft, Cheryl M.; Huang, Jing; Possin, Daniel E.; Hendrickson, Anita

    2015-01-01

    Macaca, Callithrix jacchus marmoset monkey, Pan troglodytes chim- panzee and human retinas were examined to define if short wavelength (S) cones share molecular markers with L&M cone or rod photoreceptors. S cones showed consistent differences in their immunohistochemical staining and expression levels compared to L&M cones for “rod” Arrestin1 (S-Antigen), “cone” Arrestin4, cone alpha transducin, and Calbindin. Our data verify a similar pattern of expression in these primate retinas and provide clues to the structural divergence of rods and S cones versus L&M cones, suggesting S cone retinal function is “intermediate” between them. PMID:24664680

  16. Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2

    PubMed Central

    Onishi, Keisuke

    2017-01-01

    Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes. PMID:28885142

  17. Gab2 Phosphorylation by RSK Inhibits Shp2 Recruitment and Cell Motility

    PubMed Central

    Zhang, Xiaocui; Lavoie, Genevieve; Fort, Loic; Huttlin, Edward L.; Tcherkezian, Joseph; Galan, Jacob A.; Gu, Haihua; Gygi, Steven P.; Carreno, Sebastien

    2013-01-01

    The scaffolding adapter protein Gab2 (Grb2-associated binder) participates in the signaling response evoked by various growth factors and cytokines. Gab2 is overexpressed in several human malignancies, including breast cancer, and was shown to promote mammary epithelial cell migration. The role of Gab2 in the activation of different signaling pathways is well documented, but less is known regarding the feedback mechanisms responsible for its inactivation. We now demonstrate that activation of the Ras/mitogen-activated protein kinase (MAPK) pathway promotes Gab2 phosphorylation on basic consensus motifs. More specifically, we show that RSK (p90 ribosomal S6 kinase) phosphorylates Gab2 on three conserved residues, both in vivo and in vitro. Mutation of these phosphorylation sites does not alter Gab2 binding to Grb2, but instead, we show that Gab2 phosphorylation inhibits the recruitment of the tyrosine phosphatase Shp2 in response to growth factors. Expression of an unphosphorylatable Gab2 mutant in mammary epithelial cells promotes an invasion-like phenotype and increases cell motility. Taken together, these results suggest that RSK is part of a negative-feedback loop that restricts Gab2-dependent epithelial cell motility. On the basis of the widespread role of Gab2 in receptor signaling, these findings also suggest that RSK plays a regulatory function in diverse receptor systems. PMID:23401857

  18. Deletion of murine choline dehydrogenase results in diminished sperm motility.

    PubMed

    Johnson, Amy R; Craciunescu, Corneliu N; Guo, Zhong; Teng, Ya-Wen; Thresher, Randy J; Blusztajn, Jan K; Zeisel, Steven H

    2010-08-01

    Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine, an important methyl donor and organic osmolyte. We have previously identified single nucleotide polymorphisms (SNPs) in the human CHDH gene that, when present, seem to alter the activity of the CHDH enzyme. These SNPs occur frequently in humans. We created a Chdh(-/-) mouse to determine the functional effects of mutations that result in decreased CHDH activity. Chdh deletion did not affect fetal viability or alter growth or survival of these mice. Only one of eleven Chdh(-/-) males was able to reproduce. Loss of CHDH activity resulted in decreased testicular betaine and increased choline and PCho concentrations. Chdh(+/+) and Chdh(-/-) mice produced comparable amounts of sperm; the impaired fertility was due to diminished sperm motility in the Chdh(-/-) males. Transmission electron microscopy revealed abnormal mitochondrial morphology in Chdh(-/-) sperm. ATP content, total mitochondrial dehydrogenase activity and inner mitochondrial membrane polarization were all significantly reduced in sperm from Chdh(-/-) animals. Mitochondrial changes were also detected in liver, kidney, heart, and testis tissues. We suggest that men who have SNPs in CHDH that decrease the activity of the CHDH enzyme could have decreased sperm motility and fertility.

  19. Dual energy approach for cone beam artifacts correction

    NASA Astrophysics Data System (ADS)

    Han, Chulhee; Choi, Shinkook; Lee, Changwoo; Baek, Jongduk

    2017-03-01

    Cone beam computed tomography systems generate 3D volumetric images, which provide further morphological information compared to radiography and tomosynthesis systems. However, reconstructed images by FDK algorithm contain cone beam artifacts when a cone angle is large. To reduce the cone beam artifacts, two-pass algorithm has been proposed. The two-pass algorithm considers the cone beam artifacts are mainly caused by high density materials, and proposes an effective method to estimate error images (i.e., cone beam artifacts images) by the high density materials. While this approach is simple and effective with a small cone angle (i.e., 5 - 7 degree), the correction performance is degraded as the cone angle increases. In this work, we propose a new method to reduce the cone beam artifacts using a dual energy technique. The basic idea of the proposed method is to estimate the error images generated by the high density materials more reliably. To do this, projection data of the high density materials are extracted from dual energy CT projection data using a material decomposition technique, and then reconstructed by iterative reconstruction using total-variation regularization. The reconstructed high density materials are used to estimate the error images from the original FDK images. The performance of the proposed method is compared with the two-pass algorithm using root mean square errors. The results show that the proposed method reduces the cone beam artifacts more effectively, especially with a large cone angle.

  20. Wall accumulation of bacteria with different motility patterns

    NASA Astrophysics Data System (ADS)

    Sartori, Paolo; Chiarello, Enrico; Jayaswal, Gaurav; Pierno, Matteo; Mistura, Giampaolo; Brun, Paola; Tiribocchi, Adriano; Orlandini, Enzo

    2018-02-01

    We systematically investigate the role of different swimming patterns on the concentration distribution of bacterial suspensions confined between two flat walls, by considering wild-type motility Escherichia coli and Pseudomonas aeruginosa, which perform Run and Tumble and Run and Reverse patterns, respectively. The experiments count motile bacteria at different distances from the bottom wall. In agreement with previous studies, an accumulation of motile bacteria close to the walls is observed. Different wall separations, ranging from 100 to 250 μ m , are tested. The concentration profiles result to be independent on the motility pattern and on the walls' separation. These results are confirmed by numerical simulations, based on a collection of self-propelled dumbbells-like particles interacting only through steric interactions. The good agreement with the simulations suggests that the behavior of the investigated bacterial suspensions is determined mainly by steric collisions and self-propulsion, as well as hydrodynamic interactions.

  1. Motility and peristaltic flow in maintaining microbiome populations

    NASA Astrophysics Data System (ADS)

    Mirbagheri, Seyed Amir; Fu, Henry C.

    2016-11-01

    Bacteria are an important component of the microbiome in the digestive tract, and must be able to maintain their population despite the fact that the contents of the intestines are constantly flowing towards evacuation. Many bacteria accomplish this by colonizing the surfaces of the intestines where flows diminish, but some species live in the lumen. We attempt to address whether swimming motility of these species plays an important role in maintaining bacterial population in the face of peristaltic pumping out of the intestine. Using a two-dimensional model of peristaltic flows induced by small-amplitude traveling waves we examine the Lagrangian trajectories of passive bacteria as well as motile bacteria, which are treated as Brownian particles undergoing enhanced diffusion due to the bacteria's run-and-tumble motility. We examine how the densities of growing populations of bacteria depend on the combination of motility and peristaltic flow.

  2. Wall accumulation of bacteria with different motility patterns.

    PubMed

    Sartori, Paolo; Chiarello, Enrico; Jayaswal, Gaurav; Pierno, Matteo; Mistura, Giampaolo; Brun, Paola; Tiribocchi, Adriano; Orlandini, Enzo

    2018-02-01

    We systematically investigate the role of different swimming patterns on the concentration distribution of bacterial suspensions confined between two flat walls, by considering wild-type motility Escherichia coli and Pseudomonas aeruginosa, which perform Run and Tumble and Run and Reverse patterns, respectively. The experiments count motile bacteria at different distances from the bottom wall. In agreement with previous studies, an accumulation of motile bacteria close to the walls is observed. Different wall separations, ranging from 100 to 250μm, are tested. The concentration profiles result to be independent on the motility pattern and on the walls' separation. These results are confirmed by numerical simulations, based on a collection of self-propelled dumbbells-like particles interacting only through steric interactions. The good agreement with the simulations suggests that the behavior of the investigated bacterial suspensions is determined mainly by steric collisions and self-propulsion, as well as hydrodynamic interactions.

  3. Transonic Flow Past Cone Cylinders

    NASA Technical Reports Server (NTRS)

    Solomon, George E

    1955-01-01

    Experimental results are presented for transonic flow post cone-cylinder, axially symmetric bodies. The drag coefficient and surface Mach number are studied as the free-stream Mach number is varied and, wherever possible, the experimental results are compared with theoretical predictions. Interferometric results for several typical flow configurations are shown and an example of shock-free supersonic-to-subsonic compression is experimentally demonstrated. The theoretical problem of transonic flow past finite cones is discussed briefly and an approximate solution of the axially symmetric transonic equations, valid for a semi-infinite cone, is presented.

  4. Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

    PubMed

    Patterson, Emily J; Wilk, Melissa; Langlo, Christopher S; Kasilian, Melissa; Ring, Michael; Hufnagel, Robert B; Dubis, Adam M; Tee, James J; Kalitzeos, Angelos; Gardner, Jessica C; Ahmed, Zubair M; Sisk, Robert A; Larsen, Michael; Sjoberg, Stacy; Connor, Thomas B; Dubra, Alfredo; Neitz, Jay; Hardcastle, Alison J; Neitz, Maureen; Michaelides, Michel; Carroll, Joseph

    2016-07-01

    Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

  5. Stability of drift-cyclotron loss-cone waves in H-mode plasmas

    DOE PAGES

    Farmer, W. A.; Morales, G. J.

    2016-05-24

    The drift-cyclotron loss-cone mode was first studied in mirror machines. In such devices, particles with small pitch angles are not confined, creating a hole in the velocity distribution function that is a source of free energy and leads to micro-instabilities in the cyclotron-range of frequencies. In the edge region of tokamak devices operating under H-mode conditions, ion loss also occurs. In this case, gradient drift carries ions moving opposite to the plasma current preferentially into the divertor, creating a one-sided loss cone. A simple analysis shows that for the quiescent H-mode plasmas in DIII-D the critical gradient for instability ismore » exceeded within 2 cm of the separatrix, and the maximum growth rate at the separatrix is 3×10 7 s -1.« less

  6. Microtechnologies for studying the role of mechanics in axon growth and guidance

    PubMed Central

    Kilinc, Devrim; Blasiak, Agata; Lee, Gil U.

    2015-01-01

    The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton–matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem. PMID:26283918

  7. Microtechnologies for studying the role of mechanics in axon growth and guidance.

    PubMed

    Kilinc, Devrim; Blasiak, Agata; Lee, Gil U

    2015-01-01

    The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton-matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem.

  8. Hypersonic boundary-layer transition measurements at Mach 10 on a large seven-degree cone at angle of attack

    NASA Astrophysics Data System (ADS)

    Moraru, Ciprian G.

    The ability to predict the onset of boundary-layer transition is critical for hypersonic flight vehicles. The development of prediction methods depends on a thorough comprehension of the mechanisms that cause transition. In order to improve the understanding of hypersonic boundary-layer transition, tests were conducted on a large 7° half-angle cone at Mach 10 in the Arnold Engineering Development Complex Wind Tunnel 9. Twenty-four runs were performed at varying unit Reynolds numbers and angles of attack for sharp and blunt nosetip configurations. Heat-transfer measurements were used to determine the start of transition on the cone. Increasing the unit Reynolds number caused a forward movement of transition on the sharp cone at zero angle of attack. Increasing nosetip radius delayed transition up to a radius of 12.7 mm. Larger nose radii caused the start of transition to move forward. At angles of attack up to 10°, transition was leeside forward for nose radii up to 12.7 mm and windside forward for nose radii of 25.4 mm and 50.8 mm. Second-mode instability waves were measured on the sharp cone and cones with small nose radii. At zero angle of attack, waves at a particular streamwise location on the sharp cone were in earlier stages of development as the unit Reynolds number was decreased. The same trend was observed as the nosetip radius was increased. No second-mode waves were apparent for the cones with large nosetip radii. As the angle of attack was increased, waves at a particular streamwise location on the sharp cone moved to earlier stages of growth on the windward ray and later stages of growth on the leeward ray. RMS amplitudes of second-mode waves were computed. Comparison between maximum second-mode amplitudes and edge Mach numbers showed good correlation for various nosetip radii and unit Reynolds numbers. Using the e N method, initial amplitudes were estimated and compared to freestream noise in the second-mode frequency band. Correlations indicate

  9. Dirac cones in isogonal hexagonal metallic structures

    NASA Astrophysics Data System (ADS)

    Wang, Kang

    2018-03-01

    A honeycomb hexagonal metallic lattice is equivalent to a triangular atomic one and cannot create Dirac cones in its electromagnetic wave spectrum. We study in this work the low-frequency electromagnetic band structures in isogonal hexagonal metallic lattices that are directly related to the honeycomb one and show that such structures can create Dirac cones. The band formation can be described by a tight-binding model that allows investigating, in terms of correlations between local resonance modes, the condition for the Dirac cones and the consequence of the third structure tile sustaining an extra resonance mode in the unit cell that induces band shifts and thus nonlinear deformation of the Dirac cones following the wave vectors departing from the Dirac points. We show further that, under structure deformation, the deformations of the Dirac cones result from two different correlation mechanisms, both reinforced by the lattice's metallic nature, which directly affects the resonance mode correlations. The isogonal structures provide new degrees of freedom for tuning the Dirac cones, allowing adjustment of the cone shape by modulating the structure tiles at the local scale without modifying the lattice periodicity and symmetry.

  10. Bidirectional helical motility of cytoplasmic dynein around microtubules

    PubMed Central

    Can, Sinan; Dewitt, Mark A; Yildiz, Ahmet

    2014-01-01

    Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo transport along microtubules (MTs). Dynein motility has previously been studied on surface-immobilized MTs in vitro, which constrains the motors to move in two dimensions. In this study, we explored dynein motility in three dimensions using an MT bridge assay. We found that dynein moves in a helical trajectory around the MT, demonstrating that it generates torque during cargo transport. Unlike other cytoskeletal motors that produce torque in a specific direction, dynein generates torque in either direction, resulting in bidirectional helical motility. Dynein has a net preference to move along a right-handed helical path, suggesting that the heads tend to bind to the closest tubulin binding site in the forward direction when taking sideways steps. This bidirectional helical motility may allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo transport. DOI: http://dx.doi.org/10.7554/eLife.03205.001 PMID:25069614

  11. Epidermal growth factor and tumor necrosis factor α cooperatively promote the motility of hepatocellular carcinoma cell lines via synergistic induction of fibronectin by NF-κB/p65.

    PubMed

    Liu, Zong-Cai; Ning, Fen; Wang, Hai-Fang; Chen, Dan-Yang; Cai, Yan-Na; Sheng, Hui-Ying; Lash, Gendie E; Liu, Li; Du, Jun

    2017-11-01

    The interaction between hepatocellular carcinoma (HCC) cells and their microenvironment plays a fundamental role in tumor metastasis. The HCC microenvironment is rich in epidermal growth factor (EGF) and tumor necrosis factor α (TNFα), which may cooperatively, rather than individually, interact with tumor cells to influence their biological behavior. Immunohistochemistry was performed to study the expression of EGF and TNFα in HCCs. Western blotting, immunofluorescence, qRT-PCR, wound healing scratch and invasion assay, and chromatin immunoprecipitation assays were used to study the combined roles of EGF and TNFα in the motility of HCC cells in vitro. We demonstrated that both EGF and TNFα were highly expressed in HCCs, and HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors. In vitro, EGF and TNFα cooperatively promoted the motility of HCC cells mainly via synergistic induction of an extracellular matrix glycoprotein fibronectin (FN). Mechanistically, EGF and TNFα jointly increased the nuclear translocation and PKC mediated phosphorylation of NF-κB/p65 which could bind to the -356bp to -259bp fragment of the FN promoter, leading to a markedly increased activity of the FN promoter in HCC cells. HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors. EGF and TNFα cooperatively promoted the motility of HCC cells mainly through NF-κB/p65 mediated synergistic induction of FN in vitro. These findings highlight the crosstalk between EGF and TNFα in promoting HCC, and provide potential targets for HCC prevention and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Guaifenesin and increased sperm motility: a preliminary case report.

    PubMed

    Means, Gary; Berry-Cabán, Cristóbal S; Hammermeuller, Kurt

    2010-12-20

    A review of the literature and an extensive Medline search revealed that this is the first case report of the use of guaifenesin to increase sperm motility. A 32-year-old male presented for an infertility evaluation. He reported an inability to conceive with his wife after 18 months of unprotected intercourse. A semen analysis was performed that included spermatozoa count, liquefaction, morphology, motility, viscosity and volume. Initial results of the semen analysis demonstrated low sperm count and motility. The provider offered treatment with guaifenesin 600 mg extended release tablets twice daily. Two months after guaifenesin therapy the semen analysis was repeated that demonstrated marked improvement in both total sperm count and motility. Evidence for the effectiveness of guaifenesin is almost entirely anecdotal. Given the mechanism of action of guaifenesin, it is not clear from this case why the patient demonstrated such a large improvement in both sperm count and motility. Additional studies of the effects of guaifenesin on male fertility could yield information of the medication's effect on men with normal or decreased total sperm counts.

  13. Guaifenesin and increased sperm motility: a preliminary case report

    PubMed Central

    Means, Gary; Berry-Cabán, Cristóbal S; Hammermeuller, Kurt

    2011-01-01

    Background A review of the literature and an extensive Medline search revealed that this is the first case report of the use of guaifenesin to increase sperm motility. Case A 32-year-old male presented for an infertility evaluation. He reported an inability to conceive with his wife after 18 months of unprotected intercourse. A semen analysis was performed that included spermatozoa count, liquefaction, morphology, motility, viscosity and volume. Initial results of the semen analysis demonstrated low sperm count and motility. The provider offered treatment with guaifenesin 600 mg extended release tablets twice daily. Two months after guaifenesin therapy the semen analysis was repeated that demonstrated marked improvement in both total sperm count and motility. Conclusion Evidence for the effectiveness of guaifenesin is almost entirely anecdotal. Given the mechanism of action of guaifenesin, it is not clear from this case why the patient demonstrated such a large improvement in both sperm count and motility. Additional studies of the effects of guaifenesin on male fertility could yield information of the medication’s effect on men with normal or decreased total sperm counts. PMID:21403786

  14. Mitochondrial respiratory efficiency is positively correlated with human sperm motility.

    PubMed

    Ferramosca, Alessandra; Provenzano, Sara Pinto; Coppola, Lamberto; Zara, Vincenzo

    2012-04-01

    To correlate sperm mitochondrial respiratory efficiency with variations in sperm motility and with sperm morphologic anomalies. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically-treated sperm cells. A possible relationship among sperm mitochondrial respiratory efficiency, sperm motility, and morphologic anomalies was investigated. Mitochondrial respiratory efficiency was positively correlated with sperm motility and negatively correlated with the percentage of immotile spermatozoa. Moreover, midpiece defects impaired mitochondrial functionality. Our data indicate that an increase in sperm motility requires a parallel increase in mitochondrial respiratory capacity, thereby supporting the fundamental role played by mitochondrial oxidative phosphorylation in sperm motility of normozoospermic subjects. These results are of physiopathological relevance because they suggest that disturbances of sperm mitochondrial function and of energy production could be responsible for asthenozoospermia. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency

    PubMed Central

    Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.; Kasilian, Melissa; Ring, Michael; Hufnagel, Robert B.; Dubis, Adam M.; Tee, James J.; Kalitzeos, Angelos; Gardner, Jessica C.; Ahmed, Zubair M.; Sisk, Robert A.; Larsen, Michael; Sjoberg, Stacy; Connor, Thomas B.; Dubra, Alfredo; Neitz, Jay; Hardcastle, Alison J.; Neitz, Maureen; Michaelides, Michel; Carroll, Joseph

    2016-01-01

    Purpose Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. Methods We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. Results There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. Conclusions Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus. PMID:27447086

  16. Highly efficient retinal metabolism in cones

    PubMed Central

    Miyazono, Sadaharu; Shimauchi-Matsukawa, Yoshie; Tachibanaki, Shuji; Kawamura, Satoru

    2008-01-01

    After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP+ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP+. These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods. PMID:18836074

  17. Cone-Deciphered Modes of Problem Solving Action (MPSA Cone): Alternative Perspectives on Diversified Professions.

    ERIC Educational Resources Information Center

    Lai, Su-Huei

    A conceptual framework of the modes of problem-solving action has been developed on the basis of a simple relationship cone to assist individuals in diversified professions in inquiry and implementation of theory and practice in their professional development. The conceptual framework is referred to as the Cone-Deciphered Modes of Problem Solving…

  18. The Chicago classification of motility disorders: an update.

    PubMed

    Roman, Sabine; Gyawali, C Prakash; Xiao, Yinglian; Pandolfino, John E; Kahrilas, Peter J

    2014-10-01

    The Chicago Classification defines esophageal motility disorders in high resolution manometry. This is based on individual scoring of 10 swallows performed in supine position. Disorders of esophago-gastric junction (EGJ) outflow obstruction are defined by a median integrated relaxation pressure above the limit of normal and divided into 3 achalasia subtypes and EGJ outflow obstruction. Major motility disorders (aperistalsis, distal esophageal spasm, and hypercontractile esophagus) are patterns not encountered in controls in the context of normal EGJ relaxation. Finally with the latest version of the Chicago Classification, only two minor motor disorders are considered: ineffective esophageal motility and fragmented peristalsis. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Sperm motility in fishes. (II) Effects of ions and osmolality: a review.

    PubMed

    Alavi, Sayyed Mohammad Hadi; Cosson, Jacky

    2006-01-01

    The spermatozoa of most fish species are immotile in the testis and seminal plasma. Therefore, motility is induced after the spermatozoa are released into the aqueous environment during natural reproduction or into the diluent during artificial reproduction. There are clear relationships between seminal plasma composition and osmolality and the duration of fish sperm motility. Various parameters such as ion concentrations (K+, Na+, and Ca2+), osmotic pressure, pH, temperature and dilution rate affect motility. In the present paper, we review the roles of these ions on sperm motility in Salmonidae, Cyprinidae, Acipenseridae and marine fishes, and their relationship with seminal plasma composition. Results in the literature show that: 1. K+ is a key ion controlling sperm motility in Salmonidae and Acipenseridae in combination with osmotic pressure; this control is more simple in other fish species: sperm motility is prevented when the osmotic pressure is high (Cyprinidae) or low (marine fishes) compared to that of the seminal fluid. 2. Cations (mostly divalent, such as Ca2+) are antagonistic with the inhibitory effect of K+ on sperm motility. 3. In many species, Ca2+ influx and K+ or Na+ efflux through specific ionic channels change the membrane potential and eventually lead to an increase in cAMP concentration in the cell, which constitutes the initiation signal for sperm motility in Salmonidae. 4. Media that are hyper- and hypo-osmotic relative to seminal fluid trigger sperm motility in marine and freshwater fishes, respectively. 5. The motility of fish spermatozoa is controlled through their sensitivity to osmolality and ion concentrations. This phenomenon is related to ionic channel activities in the membrane and governs the motility mechanisms of axonemes.

  20. Axon guidance molecules in vascular patterning.

    PubMed

    Adams, Ralf H; Eichmann, Anne

    2010-05-01

    Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.

  1. Light cone thermodynamics

    NASA Astrophysics Data System (ADS)

    De Lorenzo, Tommaso; Perez, Alejandro

    2018-02-01

    We show that null surfaces defined by the outgoing and infalling wave fronts emanating from and arriving at a sphere in Minkowski spacetime have thermodynamical properties that are in strict formal correspondence with those of black hole horizons in curved spacetimes. Such null surfaces, made of pieces of light cones, are bifurcate conformal Killing horizons for suitable conformally stationary observers. They can be extremal and nonextremal depending on the radius of the shining sphere. Such conformal Killing horizons have a constant light cone (conformal) temperature, given by the standard expression in terms of the generalization of surface gravity for conformal Killing horizons. Exchanges of conformally invariant energy across the horizon are described by a first law where entropy changes are given by 1 /(4 ℓp2) of the changes of a geometric quantity with the meaning of horizon area in a suitable conformal frame. These conformal horizons satisfy the zeroth to the third laws of thermodynamics in an appropriate way. In the extremal case they become light cones associated with a single event; these have vanishing temperature as well as vanishing entropy.

  2. Microscopic Analysis of Bacterial Motility at High Pressure

    PubMed Central

    Nishiyama, Masayoshi; Sowa, Yoshiyuki

    2012-01-01

    The bacterial flagellar motor is a molecular machine that converts an ion flux to the rotation of a helical flagellar filament. Counterclockwise rotation of the filaments allows them to join in a bundle and propel the cell forward. Loss of motility can be caused by environmental factors such as temperature, pH, and solvation. Hydrostatic pressure is also a physical inhibitor of bacterial motility, but the detailed mechanism of this inhibition is still unknown. Here, we developed a high-pressure microscope that enables us to acquire high-resolution microscopic images, regardless of applied pressures. We also characterized the pressure dependence of the motility of swimming Escherichia coli cells and the rotation of single flagellar motors. The fraction and speed of swimming cells decreased with increased pressure. At 80 MPa, all cells stopped swimming and simply diffused in solution. After the release of pressure, most cells immediately recovered their initial motility. Direct observation of the motility of single flagellar motors revealed that at 80 MPa, the motors generate torque that should be sufficient to join rotating filaments in a bundle. The discrepancy in the behavior of free swimming cells and individual motors could be due to the applied pressure inhibiting the formation of rotating filament bundles that can propel the cell body in an aqueous environment. PMID:22768943

  3. Mouse rods signal through gap junctions with cones

    PubMed Central

    Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

    2014-01-01

    Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod–cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod–cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001 PMID:24399457

  4. Mouse rods signal through gap junctions with cones.

    PubMed

    Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

    2014-01-01

    Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod-cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod-cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001.

  5. Motility of Colwellia psychrerythraea Strain 34H at Subzero Temperatures

    PubMed Central

    Junge, Karen; Eicken, Hajo; Deming, Jody W.

    2003-01-01

    We examined the Arctic bacterium Colwellia psychrerythraea strain 34H for motility at temperatures from −1 to −15°C by using transmitted-light microscopy in a temperature-controlled laboratory. The results, showing motility to −10°C, indicate much lower temperatures to be permissive of motility than previously reported (5°C), with implications for microbial activity in frozen environments. PMID:12839815

  6. Shape of scoria cones on Mars: Insights from numerical modeling of ballistic pathways

    NASA Astrophysics Data System (ADS)

    Brož, Petr; Čadek, Ondřej; Hauber, Ernst; Rossi, Angelo Pio

    2014-11-01

    Morphological observations of scoria cones on Mars show that their cross-sectional shapes are different from those on Earth. Due to lower gravity and atmospheric pressure on Mars, particles are spread over a larger area than on Earth. Hence, erupted volumes are typically not large enough for the flank slopes to attain the angle of repose, in contrast to Earth where this is common. The distribution of ejected material forming scoria cones on Mars, therefore, is ruled mainly by ballistic distribution and not by redistribution of flank material by avalanching after the static angle of repose is reached. As a consequence, the flank slopes of the Martian scoria cones do not reach the critical angle of repose in spite of a large volume of ejected material. Therefore, the topography of scoria cones on Mars is governed mainly by ballistic distribution of ejected particles and is not influenced by redistribution of flank material by avalanching. The growth of a scoria cone can be studied numerically by tracking the ballistic trajectories and tracing the cumulative deposition of repeatedly ejected particles. We apply this approach to a specific volcanic field, Ulysses Colles on Mars, and compare our numerical results with observations. The scoria cones in this region are not significantly affected by erosion and their morphological shape still preserves a record of physical conditions at the time of eruption. We demonstrate that the topography of these scoria cones can be rather well (with accuracy of ∼10 m) reproduced provided that the ejection velocities are a factor of ∼2 larger and the ejected particles are about ten times finer than typical on Earth, corresponding to a mean particle velocity of ∼92 m/s and a real particle size of about 4 mm. This finding is in agreement with previous theoretical works that argued for larger magma fragmentation and higher ejection velocities on Mars than on Earth due to lower gravity and different environmental conditions.

  7. Transmembrane adenylyl cyclase regulates amphibian sperm motility through Protein Kinase A activation

    PubMed Central

    O’Brien, Emma D.; Krapf, Darío; Cabada, Marcelo O.; Visconti, Pablo E.; Arranz, Silvia E.

    2014-01-01

    Sperm motility is essential for achieving fertilization. In animals with external fertilization as amphibians, spermatozoa are stored in a quiescent state in the testis. Spermiation to hypotonic fertilization media triggers activation of sperm motility. Bufo arenarum sperm are immotile in artificial seminal plasma (ASP) but acquire in situ flagellar beating upon dilution. In addition to the effect of low osmolarity on sperm motility activation, we report that diffusible factors of the egg jelly coat (EW) regulate motility patterns, switching from in situ to progressive movement. The signal transduction pathway involved in amphibian sperm motility activation is mostly unknown. In the present study, we show a correlation between motility activation triggered by low osmotic pressure and activation of protein kinase A (PKA). Moreover, this is the first study to present strong evidences that point toward a role of a transmembrane adenyl-cyclase (tmAC) in the regulation of amphibian sperm motility through PKA activation. PMID:21126515

  8. Wide-field fundus autofluorescence abnormalities and visual function in patients with cone and cone-rod dystrophies.

    PubMed

    Oishi, Maho; Oishi, Akio; Ogino, Ken; Makiyama, Yukiko; Gotoh, Norimoto; Kurimoto, Masafumi; Yoshimura, Nagahisa

    2014-05-20

    To evaluate the clinical utility of wide-field fundus autofluorescence (FAF) in patients with cone dystrophy and cone-rod dystrophy. Sixteen patients with cone dystrophy (CD) and 41 patients with cone-rod dystrophy (CRD) were recruited at one institution. The right eye of each patient was included for analysis. We obtained wide-field FAF images using a ultra-widefield retinal imaging device and measured the area of abnormal FAF. The association between the area of abnormal FAF and the results of visual acuity measurements, kinetic perimetry, and electroretinography (ERG) were investigated. The mean age of the participants was 51.4 ± 17.4 years, and the mean logarithm of the minimum angle of resolution was 1.00 ± 0.57. The area of abnormal FAF correlated with the scotoma measured by the Goldman perimetry I/4e isopter (ρ = 0.79, P < 0.001). The area also correlated with amplitudes of the rod ERG (ρ = -0.63, P < 0.001), combined ERG a-wave (ρ = -0.72, P < 0.001), combined ERG b-wave (ρ = -0.66, P < 0.001), cone ERG (ρ = -0.44, P = 0.001), and flicker ERG (ρ = -0.47, P < 0.001). The extent of abnormal FAF reflects the severity of functional impairment in patients with cone-dominant retinal dystrophies. Fundus autofluorescence measurements are useful for predicting retinal function in these patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  9. Corticotropin-releasing factor stimulates colonic motility via muscarinic receptors in the rat

    PubMed Central

    Kim, Kyung-Jo; Kim, Ki Bae; Yoon, Soon Man; Han, Joung-Ho; Chae, Hee Bok; Park, Seon Mee; Youn, Sei Jin

    2017-01-01

    AIM To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect. CONCLUSION CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility. PMID:28638222

  10. Optimization over Multi-order Cones

    DTIC Science & Technology

    2011-02-01

    Department of Mathematics Technical Report 2011-1 Optimization over multi-order cones Baha ’ M. Alzalg and K. A. Ariyawansa February 2011 Postal...Prescribed by ANSI Std Z39-18 Optimization over multi-order cones Baha M. Alzalg∗ and K. A. Ariyawansa† Abstract In this paper we propose multi-order cone...that x ∈ Qnp , and x 〈n〉 〈p〉 y to mean that x− y 〈n〉 〈p〉 0. Given 1 ≤ pi ≤ ∞ for i = 1, 2, · · · , r. Let Q 〈n1,n2,··· ,nr〉 〈p1,p2,··· ,pr〉 := Qn1p1

  11. When Do Short-Wave Cones Signal Blue or Red? A Solution Introducing the Concept of Primary and Secondary Cone Outputs

    PubMed Central

    2016-01-01

    A recent paper by Oh and Sakata investigates the “incompletely solved mystery” of how the three cone responses map onto perceived hue, and particularly the S cone’s well-known problematic contribution to blueness and redness. Citing previous workers, they argue the twentieth century traditional multistage model does not satisfactorily account for color appearance. In their experiment, increasing S cone excitation with shortening wavelength from about 480–460 nm increased perceived blueness up to the unique Blue point at 470 nm, when (a) it began decreasing and (b) redness perception began increasing. The authors asked, What mechanism can be responsible for such functions? I demonstrate a solution. First, it is shown the problem does not lie in the traditional opponent color chromatic responses yellow-blue, red-green (y-b, r-g, which accurately predict the above functions), but in the traditional multistage model of mapping cone responses to chromatic response functions. Arguably, this is due to the S cone’s hypothetically signaling both blueness and redness by the same mechanism rather than by different, independent, mechanisms. Hence a new distinction or mechanism is proposed for a more accurate model, that introduces the new terms primary and secondary cone outputs. However, this distinction requires that the cones S, M, L each directly produce one of the three spectral chromatic responses b, g, y. Such a model was recently published, based on extremely high correlation of SML cone responsivities with the three spectral (bgy) chromatic responses. This model encodes the former directly onto the latter one-to-one as cone primary outputs, whilst S and L cones have a further or secondary function where each produces one of the two spectral lobes of r chromatic response. The proposed distinction between primary and secondary cone outputs is a new concept and useful tool in detailing cone outputs to chromatic channels, and provides a solution to the above

  12. Turbulent unmixing: how marine turbulence drives patchy distributions of motile phytoplankton

    NASA Astrophysics Data System (ADS)

    Durham, William; Climent, Eric; Barry, Michael; de Lillo, Filippo; Boffetta, Guido; Cencini, Massimo; Stocker, Roman

    2013-11-01

    Centimeter-scale patchiness in the distribution of phytoplankton increases the efficacy of many important ecological interactions in the marine food web. We show that turbulent fluid motion, usually synonymous with mixing, instead triggers intense small-scale patchiness in the distribution of motile phytoplankton. We use a suite of experiments, direct numerical simulations of turbulence, and analytical tools to show that turbulent shear and acceleration directs the motility of cells towards well-defined regions of flow, increasing local cell concentrations more than ten fold. This motility-driven `unmixing' offers an explanation for why motile cells are often more patchily distributed than non-motile cells and provides a mechanistic framework to understand how turbulence, whose strength varies profoundly in marine environments, impacts ocean productivity.

  13. The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

    PubMed Central

    Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

    2016-01-01

    Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

  14. Multiple dendrochronological responses to the eruption of Cinder Cone, Lassen Volcanic National Park, California

    USGS Publications Warehouse

    Sheppard, P.R.; Ort, M.H.; Anderson, K.C.; Clynne, M.A.; May, E.M.

    2009-01-01

    Two dendrochronological properties – ring width and ring chemistry – were investigated in trees near Cinder Cone in Lassen Volcanic National Park, northeastern California, for the purpose of re-evaluating the date of its eruption. Cinder Cone is thought to have erupted in AD 1666 based on ring-width evidence, but interpreting ring-width changes alone is not straightforward because many forest disturbances can cause changes in ring width. Old Jeffrey pines growing in Cinder Cone tephra and elsewhere for control comparison were sampled. Trees growing in tephra show synchronous ring-width changes at AD 1666, but this ring-width signal could be considered ambiguous for dating the eruption because changes in ring width can be caused by other events. Trees growing in tephra also show changes in ring phosphorus, sulfur, and sodium during the late 1660s, but inter-tree variability in dendrochemical signals makes dating the eruption from ring chemistry alone difficult. The combination of dendrochemistry and ring-width signals improves confidence in dating the eruption of Cinder Cone over the analysis of just one ring-growth property. These results are similar to another case study using dendrochronology of ring width and ring chemistry at Parícutin, Michoacán, Mexico, a cinder cone that erupted beginning in 1943. In both cases, combining analysis with ring width and ring chemistry improved confidence in the dendro-dating of the eruptions.

  15. Different computer-assisted sperm analysis (CASA) systems highly influence sperm motility parameters.

    PubMed

    Boryshpolets, S; Kowalski, R K; Dietrich, G J; Dzyuba, B; Ciereszko, A

    2013-10-15

    In this study, we examined different computer-assisted sperm analysis (CASA) systems (CRISMAS, Hobson Sperm Tracker, and Image J CASA) on the exact same video recordings to evaluate the differences in sperm motility parameters related to the specific CASA used. To cover a wide range of sperm motility parameters, we chose 12-second video recordings at 25 and 50 Hz frame rates after sperm motility activation using three taxonomically distinct fish species (sterlet: Acipenser ruthenus L.; common carp: Cyprinus carpio L.; and rainbow trout: Oncorhynchus mykiss Walbaum) that are characterized by essential differences in sperm behavior during motility. Systematically higher values of velocity and beat cross frequency (BCF) were observed in video recordings obtained at 50 Hz frame frequency compared with 25 Hz for all three systems. Motility parameters were affected by the CASA and species used for analyses. Image J and CRISMAS calculated higher curvilinear velocity (VCL) values for rainbow trout and common carp at 25 Hz frequency compared with the Hobson Sperm Tracker, whereas at 50 Hz, a significant difference was observed only for rainbow trout sperm recordings. No significant difference was observed between the CASA systems for sterlet sperm motility at 25 and 50 Hz. Additional analysis of 1-second segments taken at three time points (1, 6, and 12 seconds of the recording) revealed a dramatic decrease in common carp and rainbow trout sperm speed. The motility parameters of sterlet spermatozoa did not change significantly during the 12-second motility period and should be considered as a suitable model for longer motility analyses. Our results indicated that the CASA used can affect motility results even when the same motility recordings are used. These results could be critically altered by the recording quality, time of analysis, and frame rate of camera, and could result in erroneous conclusions. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Actin-based motility of Listeria: Right-handed helical trajectories

    NASA Astrophysics Data System (ADS)

    Rangarajan, Murali

    2012-06-01

    Bacteria such as Listeria monocytogenes recruit cellular machinery to move in and between cells. Understanding the mechanism of motility, including force and torque generation and the resultant displacements, holds keys to numerous applications in medicine and biosensing. In this work, a simple back-of-the-envelope calculation is presented to illustrate that a biomechanical model of actin-based motility of a rigid surface through persistently attached filaments propelled by affinity-modulated molecular motors can produce a right-handed helical trajectory consistent with experimental observations. The implications of the mechanism to bacterial motility are discussed.

  17. Persistent growth of a young andesite lava cone: Bagana volcano, Papua New Guinea

    NASA Astrophysics Data System (ADS)

    Wadge, G.; McCormick Kilbride, B. T.; Edmonds, M.; Johnson, R. W.

    2018-05-01

    Bagana, an andesite lava cone on Bougainville Island, Papua New Guinea, is thought to be a very young central volcano. We have tested this idea by estimating the volumes of lava extruded over different time intervals (1-, 2-, 3-, 9-, 15-, 70-years) using digital elevation models (DEMs), mainly created from satellite data. Our results show that the long-term extrusion rate at Bagana, measured over years to decades, has remained at about 1.0 m3 s-1. We present models of the total edifice volume, and show that, if our measured extrusion rates are representative, the volcano could have been built in only 300 years. It could also possibly have been built at a slower rate during a longer, earlier period of growth. Six kilometres NNW of Bagana, an andesite-dacite volcano, Billy Mitchell, had a large, caldera-forming plinian eruption 437 years ago. We consider the possibility that, as a result of this eruption, the magma supply was diverted from Billy Mitchell to Bagana. It seems that Bagana is a rare example of a very youthful, polygenetic, andesite volcano. The characteristics of such a volcano, based on the example of Bagana, are: a preponderance of lava products over pyroclastic products, a high rate of lava extrusion maintained for decades, a very high rate of SO2 emission, evidence of magma batch fractionation and location in a trans-tensional setting at the end of an arc segment above a very steeply dipping and rapidly converging subduction zone.

  18. Mechanical stress as a regulator of cell motility

    NASA Astrophysics Data System (ADS)

    Putelat, T.; Recho, P.; Truskinovsky, L.

    2018-01-01

    The motility of a cell can be triggered or inhibited not only by an applied force but also by a mechanically neutral force couple. This type of loading, represented by an applied stress and commonly interpreted as either squeezing or stretching, can originate from extrinsic interaction of a cell with its neighbors. To quantify the effect of applied stresses on cell motility we use an analytically transparent one-dimensional model accounting for active myosin contraction and induced actin turnover. We show that stretching can polarize static cells and initiate cell motility while squeezing can symmetrize and arrest moving cells. We show further that sufficiently strong squeezing can lead to the loss of cell integrity. The overall behavior of the system depends on the two dimensionless parameters characterizing internal driving (chemical activity) and external loading (applied stress). We construct a phase diagram in this parameter space distinguishing between static, motile, and collapsed states. The obtained results are relevant for the mechanical understanding of contact inhibition and the epithelial-to-mesenchymal transition.

  19. Cone Storage and Seed Quality in Longleaf Pine

    Treesearch

    F.T. Bonner

    1987-01-01

    Immature cones of longleaf pine (Pinus palustris Mill.) can be stored for at least 5 weeks without adversely affecting extraction or seed quality. Cone moisture should be below 50 percent before using heat to open cones.

  20. Study of open jet wind tunnel cones

    NASA Technical Reports Server (NTRS)

    Weick, Fred E

    1927-01-01

    Tests have been made by the National Advisory Committee for Aeronautics on the air flow in an open jet wind tunnel with various sizes, shapes, and spacings of cones, and the flow studied by means of velocity and direction surveys in conjunction with flow pictures. It was found that for all combinations of cones tested the flow is essentially the same, consisting of an inner core of decreasing diameter having uniform velocity and direction, and a boundary layer of more or less turbulent air increasing in thickness with length of jet. The energy ratio of the tunnel was obtained for the different combinations of cones, and the spilling around the exit cone causing undesirable air currents in the experiment chamber was noted. An empirical formula is given for the design of cones having no appreciable spilling.

  1. Novel genes associated with enhanced motility of Escherichia coli ST131

    PubMed Central

    Kakkanat, Asha; Phan, Minh-Duy; Lo, Alvin W.; Beatson, Scott A.

    2017-01-01

    Uropathogenic Escherichia coli (UPEC) is the cause of ~75% of all urinary tract infections (UTIs) and is increasingly associated with multidrug resistance. This includes UPEC strains from the recently emerged and globally disseminated sequence type 131 (ST131), which is now the dominant fluoroquinolone-resistant UPEC clone worldwide. Most ST131 strains are motile and produce H4-type flagella. Here, we applied a combination of saturated Tn5 mutagenesis and transposon directed insertion site sequencing (TraDIS) as a high throughput genetic screen and identified 30 genes associated with enhanced motility of the reference ST131 strain EC958. This included 12 genes that repress motility of E. coli K-12, four of which (lrhA, ihfA, ydiV, lrp) were confirmed in EC958. Other genes represented novel factors that impact motility, and we focused our investigation on characterisation of the mprA, hemK and yjeA genes. Mutation of each of these genes in EC958 led to increased transcription of flagellar genes (flhD and fliC), increased expression of the FliC flagellin, enhanced flagella synthesis and a hyper-motile phenotype. Complementation restored all of these properties to wild-type level. We also identified Tn5 insertions in several intergenic regions (IGRs) on the EC958 chromosome that were associated with enhanced motility; this included flhDC and EC958_1546. In both of these cases, the Tn5 insertions were associated with increased transcription of the downstream gene(s), which resulted in enhanced motility. The EC958_1546 gene encodes a phage protein with similarity to esterase/deacetylase enzymes involved in the hydrolysis of sialic acid derivatives found in human mucus. We showed that over-expression of EC958_1546 led to enhanced motility of EC958 as well as the UPEC strains CFT073 and UTI89, demonstrating its activity affects the motility of different UPEC strains. Overall, this study has identified and characterised a number of novel factors associated with enhanced

  2. Replaceable filters and cones for flared-tubing connectors

    NASA Technical Reports Server (NTRS)

    Grant, L. E.; Howland, B. T.

    1970-01-01

    Connector is modified by machining the cone from one end before the fitting is bored to accommodate a metallic-filament type of slip-in filter. Thus, when surface of the cone is damaged, only the cone needs replacement.

  3. Cellular Scale Anisotropic Topography Guides Schwann Cell Motility

    PubMed Central

    Mitchel, Jennifer A.; Hoffman-Kim, Diane

    2011-01-01

    Directed migration of Schwann cells (SC) is critical for development and repair of the peripheral nervous system. Understanding aspects of motility specific to SC, along with SC response to engineered biomaterials, may inform strategies to enhance nerve regeneration. Rat SC were cultured on laminin-coated microgrooved poly(dimethyl siloxane) platforms that were flat or presented repeating cellular scale anisotropic topographical cues, 30 or 60 µm in width, and observed with timelapse microscopy. SC motion was directed parallel to the long axis of the topography on both the groove floor and the plateau, with accompanying differences in velocity and directional persistence in comparison to SC motion on flat substrates. In addition, feature dimension affected SC morphology, alignment, and directional persistence. Plateaus and groove floors presented distinct cues which promoted differential motility and variable interaction with the topographical features. SC on the plateau surfaces tended to have persistent interactions with the edge topography, while SC on the groove floors tended to have infrequent contact with the corners and walls. Our observations suggest the capacity of SC to be guided without continuous contact with a topographical cue. SC exhibited a range of distinct motile morphologies, characterized by their symmetry and number of extensions. Across all conditions, SC with a single extension traveled significantly faster than cells with more or no extensions. We conclude that SC motility is complex, where persistent motion requires cellular asymmetry, and that anisotropic topography with cellular scale features can direct SC motility. PMID:21949703

  4. Electroacupuncture at LI11 promotes jejunal motility via the parasympathetic pathway.

    PubMed

    Hu, Xuanming; Yuan, Mengqian; Yin, Yin; Wang, Yidan; Li, Yuqin; Zhang, Na; Sun, Xueyi; Yu, Zhi; Xu, Bin

    2017-06-21

    Gastrointestinal motility disorder has been demonstrated to be regulated by acupuncture treatment. The mechanisms underlying the effects of acupuncture stimulation of abdominal and lower limb acupoints on gastrointestinal motility have been thoroughly studied; however, the physiology underlying the effects of acupuncture on the forelimbs to mediate gastrointestinal motility requires further exploration. The aim of this study was to determine whether electroacupuncture (EA) at LI11 promotes jejunal motility, whether the parasympathetic pathway participates in this effect, and if so, which somatic afferent nerve fibres are involved. A manometric balloon was used to observe jejunal motility. The effects and mechanisms of EA at LI11 were explored in male Sprague-Dawley rats with or without drug administration (propranolol, clenbuterol, acetylcholine, and atropine) and with or without vagotomy. Three types of male mice (β 1 β 2 receptor-knockout [β 1 β 2 -/- ] mice, M 2 M 3 receptor-knockout [M 2 M 3 -/- ] mice and wild-type [WT] mice) were also studied by using different EA intensities (1, 2, 4, 6, and 8 mA). A total of 72 rats and 56 mice were included in the study. EA at LI11 increased the contractile amplitude of jejunal motility in the majority of both rats and mice. However, EA at LI11 did not enhance jejunal motility in rats administered atropine, rats that underwent vagotomy, and M 2 M 3 -‍‍/- mice (at all intensities). In WT mice, EA at LI11 significantly increased jejunal motility at all intensities except 1 mA, and a plateau was reached at intensities greater than 4 mA. Our results suggest that EA at LI11 promotes jejunal motility primarily by exciting the parasympathetic pathway, and that Aδ-fibres and C-fibres may play important roles in the process.

  5. Thiols of flagellar proteins are essential for progressive motility in human spermatozoa.

    PubMed

    Cabrillana, María Eugenia; Monclus, María de Los Ángeles; Lancellotti, Tania Estefania Sáez; Boarelli, Paola Vanina; Vincenti, Amanda Edith; Fornés, Miguel Matias; Sanabria, Eduardo Alfredo; Fornés, Miguel Walter

    2017-07-01

    Male infertility is a disorder of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. The presence of low-motile or immotile spermatozoa is one of many causes of infertility; however, this observation provides little or no information regarding the pathogenesis of the malfunction. Good sperm motility depends on correct assembly of the sperm tail in the testis and efficient maturation during epididymal transit. Thiols of flagellar proteins, such as outer dense fibre protein 1 (ODF1), are oxidised to form disulfides during epididymal transit and the spermatozoa become motile. This study was designed to determine how oxidative changes in protein thiol status affect progressive motility in human spermatozoa. Monobromobimane (mBBr) was used as a specific thiol marker and disruptor of sperm progressive motility. When mBBr was blocked by dithiothreitol it did not promote motility changes. The analysis of mBBr-treated spermatozoa revealed a reduction of progressive motility and an increased number of spermatozoa with non-progressive motility without affecting ATP production. Laser confocal microscopy and western blot analysis showed that one of the mBBr-positive proteins reacted with an antibody to ODF1. Monobromobimane fluorescence intensity of the sperm tail was lower in normozoospermic than asthenozoospermic men, suggesting that thiol oxidation in spermatozoa of asthenozoospermic men is incomplete. Our findings indicate that mBBr affects the thiol status of ODF1 in human spermatozoa and interferes with progressive motility.

  6. hemingway is required for sperm flagella assembly and ciliary motility in Drosophila.

    PubMed

    Soulavie, Fabien; Piepenbrock, David; Thomas, Joëlle; Vieillard, Jennifer; Duteyrat, Jean-Luc; Cortier, Elisabeth; Laurençon, Anne; Göpfert, Martin C; Durand, Bénédicte

    2014-04-01

    Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left-right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604-amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.

  7. The relationship between gastrointestinal motility and gastric dilatation-volvulus in dogs.

    PubMed

    Gazzola, Krista M; Nelson, Laura L

    2014-09-01

    Gastric dilatation-volvulus (GDV) is a devastating disease that most commonly affects large and giant-breed dogs. Though a number of risk factors have been associated with the development of GDV, the etiology of GDV remains unclear. Abnormal gastric motility patterns and delayed gastric emptying have been previously described in dogs following GDV. Work evaluating the effects of gastropexy procedures and changes to gastric motility after experimental GDV has not found the same changes as those found in dogs with naturally occurring GDV. Although the role of abnormal gastric motility in dogs with GDV will need to be clarified with additional research, such study is likely to be facilitated by improved access to and development of noninvasive measurement techniques for the evaluation of gastric emptying and other motility parameters. In particular, the availability of Food and Drug Administration-approved wireless motility devices for the evaluation of gastrointestinal motility is particularly promising in the study of GDV and other functional gastrointestinal diseases of large and giant-breed dogs. Published by Elsevier Inc.

  8. The effects of longitudinal chromatic aberration and a shift in the peak of the middle-wavelength sensitive cone fundamental on cone contrast

    PubMed Central

    Rucker, F. J.; Osorio, D.

    2009-01-01

    Longitudinal chromatic aberration is a well-known imperfection of visual optics, but the consequences in natural conditions, and for the evolution of receptor spectral sensitivities are less well understood. This paper examines how chromatic aberration affects image quality in the middle-wavelength sensitive (M-) cones, viewing broad-band spectra, over a range of spatial frequencies and focal planes. We also model the effects on M-cone contrast of moving the M-cone fundamental relative to the long- and middle-wavelength (L- and M-cone) fundamentals, while the eye is accommodated at different focal planes or at a focal plane that maximizes luminance contrast. When the focal plane shifts towards longer (650 nm) or shorter wavelengths (420 nm) the effects on M-cone contrast are large: longitudinal chromatic aberration causes total loss of M-cone contrast above 10 to 20 c/d. In comparison, the shift of the M-cone fundamental causes smaller effects on M-cone contrast. At 10 c/d a shift in the peak of the M-cone spectrum from 560 nm to 460 nm decreases M-cone contrast by 30%, while a 10 nm blue-shift causes only a minor loss of contrast. However, a noticeable loss of contrast may be seen if the eye is focused at focal planes other than that which maximizes luminance contrast. The presence of separate long- and middle-wavelength sensitive cones therefore has a small, but not insignificant cost to the retinal image via longitudinal chromatic aberration. This aberration may therefore be a factor limiting evolution of visual pigments and trichromatic color vision. PMID:18639571

  9. Cone rod dystrophies

    PubMed Central

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  10. Aging of human short-wave cone pathways

    PubMed Central

    Shinomori, Keizo; Werner, John S.

    2012-01-01

    The retinal image is sampled concurrently, and largely independently, by three physiologically and anatomically distinct pathways, each with separate ON and OFF subdivisions. The retinal circuitry giving rise to an ON pathway receiving input from the short-wave-sensitive (S) cones is well understood, but the S-cone OFF circuitry is more controversial. Here, we characterize the temporal properties of putative S-cone ON and OFF pathways in younger and older observers by measuring thresholds for stimuli that produce increases or decreases in S-cone stimulation, while the middle- and long-wave-sensitive cones are unmodulated. We characterize the data in terms of an impulse response function, the theoretical response to a flash of infinitely short duration, from which the response to any temporally varying stimulus may be predicted. Results show that the S-cone response to increments is faster than to decrements, but this difference is significantly greater for older individuals. The impulse response function amplitudes for increment and decrement responses are highly correlated across individuals, whereas the timing is not. This strongly suggests that the amplitude is controlled by neural circuitry that is common to S-cone ON and OFF responses (photoreceptors), whereas the timing is controlled by separate postreceptoral pathways. The slower response of the putative OFF pathway is ascribed to different retinal circuitry, possibly attributable to a sign-inverting amacrine cell not present in the ON pathway. It is significant that this pathway is affected selectively in the elderly by becoming slower, whereas the temporal properties of the S-cone ON response are stable across the life span of an individual. PMID:22847416

  11. HTL resummation in the light cone gauge

    NASA Astrophysics Data System (ADS)

    Chen, Qi; Hou, De-fu

    2018-04-01

    The light cone gauge with light cone variables is often used in pQCD calculations in relativistic heavy-ion collision physics. The Hard Thermal Loops (HTL) resummation is an indispensable technique for hot QCD calculation. It was developed in covariant gauges with conventional Minkowski varaiables; we shall extend this method to the light cone gauge. In the real time formalism, using the Mandelstam-Leibbrant prescription of (n·K)‑1, we calculate the transverse and longitudinal components of the gluon HTL self energy, and prove that there are no infrared divergences. With this HTL self energy, we derive the HTL resummed gluon propagator in the light cone gauge. We also calculate the quark HTL self energy and the resummed quark propagator in the light cone gauge and find it is gauge independent. As application examples, we analytically calculate the damping rates of hard quarks and gluons with the HTL resummed gluon propagator in the light cone gauge and showed that they are gauge independent. The final physical results are identical to those computed in covariant gauge, as they should be. Supported by National Natural Science Foundation of China (11375070, 11735007, 11521064)

  12. An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro

    PubMed Central

    Chitsaz, Daryan; Morales, Daniel; Law, Chris; Kania, Artur

    2015-01-01

    During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs) to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as “collapsed” or “extended”. The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in ‘collapsed’ GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay. PMID:26496644

  13. Thermoelastic Damping in Cone Microcantilever Resonator

    NASA Astrophysics Data System (ADS)

    Li, Pu; Zhou, Hongyue

    2017-07-01

    Microbeams with continuous or discontinuous variable cross-section have been applied in Microelectromechanical Systems (MEMS) resonators, such as tapered microbeam, torsion microbeam and stepped microbeam. Thermoelastic damping (TED), which is verified as a fundamental energy lost mechanism for microresonators, is calculated by the Zener’s model and Lifshits and Roukes’s (LR) model in general. However, for non-uniform microbeam resonators, these two classical models are not suitable in some cases. On the basis of Zener’s theory, a TED model for cone microcantilever with rectangular cross-section has been derived in this study. The comparison of results obtained by the present model and Finite Element Method (FEM) model proves that the proposed model is able to predict TED value for cone microcantilever. In addition, TED in cone microcantilever is nearly same as TED in wedge microcantilever. The results show that quality factors (Q-factors) of cone microcantilever and wedge microcantilever are larger than Q-factor of uniform microbeam at low frequencies. The Debye peak value of a uniform microcantilever is equal to 0.5Δ E , while those of cone microcantilever and wedge microcantilever are about 0.438ΔE and 0.428ΔE, respectively.

  14. 3D modelling of the Tejeda Caldera cone-sheet swarm, Gran Canaria, Canary Islands, Spain

    NASA Astrophysics Data System (ADS)

    Samrock, Lisa K.; Jensen, Max J.; Burchardt, Steffi; Troll, Valentin R.; Mattsson, Tobias; Geiger, Harri

    2015-04-01

    . 2011, and references therein), and we discuss the implications of this architecture for the feeding system of the Tejeda volcano and the associated temporal variations of cone-sheet emplacement. References: Burchardt, S., Tanner, D.C., Troll, V.R., Krumbholz, M., Gustafsson, L.E. (2011) Three-dimensional geometry of concentric intrusive sheet swarms in the Geitafell and the Dyrfjöll volcanoes, eastern Iceland. Geochemistry, Geophysics, Geosystems 12(7): Q0AB09. Burchardt, S., Troll, V.R., Mathieu, L., Emeleus, H.C., Donaldson, C.H. (2013) Ardnamruchan 3D cone-sheet architecture explained by a single elongate magma chamber. Scientific Reports 3:2891. Schirnick, C. (1996) Formation of an intracaldera cone sheet dike swarm (Tejeda Caldera, Gran Canaria) (Dissertation). Christian-Albrechts-Universität, Kiel, Germany. Schirnick, C., van den Bogaard, P., Schmincke, H.-U. (1999) Cone-sheet formation and intrusive growth of an oceanic island - The Miocene Tejeda complex on Gran Canaria (Canary Islands). Geology, 27: 207-210.

  15. NHERF Links the N-Cadherin/Catenin Complex to the Platelet-derived Growth Factor Receptor to Modulate the Actin Cytoskeleton and Regulate Cell Motility

    PubMed Central

    Theisen, Christopher S.; Wahl, James K.; Johnson, Keith R.

    2007-01-01

    Using phage display, we identified Na+/H+ exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, β-catenin. We showed that the second of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts with a PDZ-binding motif at the very carboxy terminus of β-catenin. N-cadherin expression has been shown to induce motility in a number of cell types. The first PDZ domain of NHERF is known to bind platelet-derived growth factor-receptor β (PDGF-Rβ), and the interaction of PDGF-Rβ with NHERF leads to enhanced cell spreading and motility. Here we show that β-catenin and N-cadherin are in a complex with NHERF and PDGF-Rβ at membrane ruffles in the highly invasive fibrosarcoma cell line HT1080. Using a stable short hairpin RNA system, we showed that HT1080 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded area in a scratch assay, similar to cells treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is unable to associate with β-catenin had increased stress fibers, reduced lamellipodia, and impaired cell migration. Using HeLa cells, which express little to no PDGF-R, we introduced PDGF-Rβ and showed that it coimmunoprecipitates with N-cadherin and that PDGF-dependent cell migration was reduced in these cells when we knocked-down expression of N-cadherin or NHERF. These studies implicate N-cadherin and β-catenin in cell migration via PDGF-R–mediated signaling through the scaffolding molecule NHERF. PMID:17229887

  16. Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis.

    PubMed

    Tu, Joanna H; Foote, Katharina G; Lujan, Brandon J; Ratnam, Kavitha; Qin, Jia; Gorin, Michael B; Cunningham, Emmett T; Tuten, William S; Duncan, Jacque L; Roorda, Austin

    2017-09-01

    Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. A patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. Despite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely

  17. Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells.

    PubMed

    Ishimoto, Takatsugu; Miyake, Keisuke; Nandi, Tannistha; Yashiro, Masakazu; Onishi, Nobuyuki; Huang, Kie Kyon; Lin, Suling Joyce; Kalpana, Ramnarayanan; Tay, Su Ting; Suzuki, Yuka; Cho, Byoung Chul; Kuroda, Daisuke; Arima, Kota; Izumi, Daisuke; Iwatsuki, Masaaki; Baba, Yoshifumi; Oki, Eiji; Watanabe, Masayuki; Saya, Hideyuki; Hirakawa, Kosei; Baba, Hideo; Tan, Patrick

    2017-07-01

    Fibroblasts that interact with cancer cells are called cancer-associated fibroblasts (CAFs), which promote progression of different tumor types. We investigated the characteristics and functions of CAFs in diffuse-type gastric cancers (DGCs) by analyzing features of their genome and gene expression patterns. We isolated CAFs and adjacent non-cancer fibroblasts (NFs) from 110 gastric cancer (GC) tissues from patients who underwent gastrectomy in Japan from 2008 through 2016. Cells were identified using specific markers of various cell types by immunoblot and flow cytometry. We selected pairs of CAFs and NFs for whole-exome and RNA sequencing analyses, and compared expression of specific genes using quantitative reverse transcription PCR. Protein levels and phosphorylation were compared by immunoblot and immunofluorescence analyses. Rhomboid 5 homolog 2 (RHBDF2) was overexpressed from a transgene in fibroblasts or knocked down using small interfering RNAs. Motility and invasiveness of isolated fibroblasts and GC cell lines (AGS, KATOIII, MKN45, NUGC3, NUGC4, OCUM-2MD3 and OCUM-12 cell lines) were quantified by real-time imaging analyses. We analyzed 7 independent sets of DNA microarray data from patients with GC and associated expression levels of specific genes with patient survival times. Nude mice were given injections of OCUM-2MD3 in the stomach wall; tumors and metastases were collected and analyzed by immunohistochemistry. Many of the genes with increased expression in CAFs compared with NFs were associated with transforming growth factor beta 1 (TGFB1) activity. When CAFs were cultured in extracellular matrix, they became more motile than NFs; DGC cells incubated with CAFs were also more motile and invasive in vitro than DGC cells not incubated with CAFs. When injected into nude mice, CAF-incubated DGC cells invaded a greater number of lymphatic vessels than NF-incubated DGC cells. We identified RHBDF2 as a gene overexpressed in CAFs compared with NFs

  18. The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

    PubMed Central

    Daum, Janine M; Keles, Özkan; Holwerda, Sjoerd JB; Kohler, Hubertus; Rijli, Filippo M

    2017-01-01

    High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility. PMID:29106373

  19. Characterization of Pro-Inflammatory Flagellin Proteins Produced by Lactobacillus ruminis and Related Motile Lactobacilli

    PubMed Central

    Neville, B. Anne; Forde, Brian M.; Claesson, Marcus J.; Darby, Trevor; Coghlan, Avril; Nally, Kenneth; Ross, R. Paul; O’Toole, Paul W.

    2012-01-01

    Lactobacillus ruminis is one of at least twelve motile but poorly characterized species found in the genus Lactobacillus. Of these, only L. ruminis has been isolated from mammals, and this species may be considered as an autochthonous member of the gastrointestinal microbiota of humans, pigs and cows. Nine L. ruminis strains were investigated here to elucidate the biochemistry and genetics of Lactobacillus motility. Six strains isolated from humans were non-motile while three bovine isolates were motile. A complete set of flagellum biogenesis genes was annotated in the sequenced genomes of two strains, ATCC25644 (human isolate) and ATCC27782 (bovine isolate), but only the latter strain produced flagella. Comparison of the L. ruminis and L. mali DSM20444T motility loci showed that their genetic content and gene-order were broadly similar, although the L. mali motility locus was interrupted by an 11.8 Kb region encoding rhamnose utilization genes that is absent from the L. ruminis motility locus. Phylogenetic analysis of 39 motile bacteria indicated that Lactobacillus motility genes were most closely related to those of motile carnobacteria and enterococci. Transcriptome analysis revealed that motility genes were transcribed at a significantly higher level in motile L. ruminis ATCC27782 than in non-motile ATCC25644. Flagellin proteins were isolated from L. ruminis ATCC27782 and from three other Lactobacillus species, while recombinant flagellin of aflagellate L. ruminis ATCC25644 was expressed and purified from E. coli. These native and recombinant Lactobacillus flagellins, and also flagellate L. ruminis cells, triggered interleukin-8 production in cultured human intestinal epithelial cells in a manner suppressed by short interfering RNA directed against Toll-Like Receptor 5. This study provides genetic, transcriptomic, phylogenetic and immunological insights into the trait of flagellum-mediated motility in the lactobacilli. PMID:22808200

  20. Relationship between Porcine Sperm Motility and Sperm Enzymatic Activity using Paper-based Devices

    NASA Astrophysics Data System (ADS)

    Matsuura, Koji; Huang, Han-Wei; Chen, Ming-Cheng; Chen, Yu; Cheng, Chao-Min

    2017-04-01

    Mammalian sperm motility has traditionally been analyzed to determine fertility using computer-assisted semen analysis (CASA) systems. To develop low-cost and robust male fertility diagnostics, we created a paper-based MTT assay and used it to estimate motile sperm concentration. When porcine sperm motility was inhibited using sperm enzyme inhibitors for sperm enzymes related to mitochondrial activity and glycolysis, we simultaneously recorded sperm motility and enzymatic reactivity using a portable motility analysis system (iSperm) and a paper-based MTT assay, respectively. When using our paper-based MTT-assay, we calculated the area mean value signal intensity (AMV) to evaluate enzymatic reactivity. Both sperm motility and AMV decreased following treatment with iodoacetamide (IODO) and 3-bromopyruvic acid (3BP), both of which are inhibitors of glycolytic enzymes including glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found a correlation between recorded motility using iSperm and AMV from our paper-based assay (P < 0.05), suggesting that a sperm-related enzymatic reaction is involved in sperm motility. Under this protocol, MTT reduction was coupled with catalysis of GAPDH and was promoted by electron transfer from NADH. Based on this inhibitor study, sperm motility can be estimated using our paper-based MTT-assay.

  1. Morphological characteristics of motile plants for dynamic motion

    NASA Astrophysics Data System (ADS)

    Song, Kahye; Yeom, Eunseop; Kim, Kiwoong; Lee, Sang Joon

    2014-11-01

    Most plants have been considered as non-motile organisms. However, plants move in response to environmental changes for survival. In addition, some species drive dynamic motions in a short period of time. Mimosa pudica is a plant that rapidly shrinks its body in response to external stimuli. It has specialized organs that are omnidirectionally activated due to morphological features. In addition, scales of pinecone open or close up depending on humidity for efficient seed release. A number of previous studies on the dynamic motion of plants have been investigated in a biochemical point of view. In this study, the morphological characteristics of those motile organs were investigated by using X-ray CT and micro-imaging techniques. The results show that the dynamic motions of motile plants are supported by structural features related with water transport. These studies would provide new insight for better understanding the moving mechanism of motile plant in morphological point of view. This research was financially supported by the Creative Research Initiative of the Ministry of Science, ICT and Future Planning (MSIP) and the National Research Foundation (NRF) of Korea (Grant Number: 2008-0061991).

  2. Short-wavelength cone-opponent retinal ganglion cells in mammals.

    PubMed

    Marshak, David W; Mills, Stephen L

    2014-03-01

    In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

  3. [Motility disorders of the esophagus].

    PubMed

    Bruder, E; Rougemont, A-L; Furlano, R I; Schneider, J F; Mayr, J; Haecker, F-M; Beier, K; Schneider, J; Weber, P; Berberich, T; Cathomas, G; Meier-Ruge, W A

    2013-03-01

    Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

  4. High-Throughput, Motility-Based Sorter for Microswimmers such as C. elegans

    PubMed Central

    Yuan, Jinzhou; Zhou, Jessie; Raizen, David M.; Bau, Haim H.

    2015-01-01

    Animal motility varies with genotype, disease, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method is implemented in a simple microfluidic device capable of sorting thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriches for known C. elegans motility mutants. Furthermore, using this device, we isolate low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates C. elegans sleep. By performing genetic complementation tests, we demonstrate that our motility-based sorting device efficiently isolates mutants for the same gene identified by tedious visual inspection of behavior on an agar surface. Therefore, our motility-based sorter is capable of performing high throughput gene discovery approaches to investigate fundamental biological processes. PMID:26008643

  5. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  6. Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina

    PubMed Central

    Sabesan, Ramkumar; Sincich, Lawrence C.

    2017-01-01

    A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red–green color vision emerges after the first retinal synapse. SIGNIFICANCE STATEMENT We present evidence for spatially antagonistic interactions between individual

  7. Cone photoreceptor definition on adaptive optics retinal imaging

    PubMed Central

    Muthiah, Manickam Nick; Gias, Carlos; Chen, Fred Kuanfu; Zhong, Joe; McClelland, Zoe; Sallo, Ferenc B; Peto, Tunde; Coffey, Peter J; da Cruz, Lyndon

    2014-01-01

    Aims To quantitatively analyse cone photoreceptor matrices on images captured on an adaptive optics (AO) camera and assess their correlation to well-established parameters in the retinal histology literature. Methods High resolution retinal images were acquired from 10 healthy subjects, aged 20–35 years old, using an AO camera (rtx1, Imagine Eyes, France). Left eye images were captured at 5° of retinal eccentricity, temporal to the fovea for consistency. In three subjects, images were also acquired at 0, 2, 3, 5 and 7° retinal eccentricities. Cone photoreceptor density was calculated following manual and automated counting. Inter-photoreceptor distance was also calculated. Voronoi domain and power spectrum analyses were performed for all images. Results At 5° eccentricity, the cone density (cones/mm2 mean±SD) was 15.3±1.4×103 (automated) and 13.9±1.0×103 (manual) and the mean inter-photoreceptor distance was 8.6±0.4 μm. Cone density decreased and inter-photoreceptor distance increased with increasing retinal eccentricity from 2 to 7°. A regular hexagonal cone photoreceptor mosaic pattern was seen at 2, 3 and 5° of retinal eccentricity. Conclusions Imaging data acquired from the AO camera match cone density, intercone distance and show the known features of cone photoreceptor distribution in the pericentral retina as reported by histology, namely, decreasing density values from 2 to 7° of eccentricity and the hexagonal packing arrangement. This confirms that AO flood imaging provides reliable estimates of pericentral cone photoreceptor distribution in normal subjects. PMID:24729030

  8. Sperm motility in fishes. I. Effects of temperature and pH: a review.

    PubMed

    Alavi, Sayyed Mohammad Hadi; Cosson, Jacky

    2005-02-01

    Sperm motility is a key factor in allowing us to determine semen quality and fertilizing capacity. Motility in semen is mainly controlled by K+ in salmonids, and probably also in sturgeons, and by osmotic pressure in other freshwater and seawater fish species, but other factors, such as concentration of surrounding metabolites and ions (Ca2+, Mg2+, etc.), pH and temperature also influence motility characteristics. In the present study, we have mainly reviewed and summarized the effects of temperature and pH on the motility of spermatozoa in three fish species: salmonids, cyprinids and sturgeons. Data in the literature show that motility, fertilizing ability and velocity of spermatozoa, as well as the duration of the motility period, depend on the temperature of the assay medium and also of that of the brood fish holding tank. In contrast, the pH of the swimming medium, and thus the intracellular pH of spermatozoa, has less influence on sperm motility parameters in cyprinids, salmonids and sturgeons.

  9. DOS cones along atomic chains

    NASA Astrophysics Data System (ADS)

    Kwapiński, Tomasz

    2017-03-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin-orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears.

  10. The absolute threshold of cone vision

    PubMed Central

    Koeing, Darran; Hofer, Heidi

    2013-01-01

    We report measurements of the absolute threshold of cone vision, which has been previously underestimated due to sub-optimal conditions or overly strict subjective response criteria. We avoided these limitations by using optimized stimuli and experimental conditions while having subjects respond within a rating scale framework. Small (1′ fwhm), brief (34 msec), monochromatic (550 nm) stimuli were foveally presented at multiple intensities in dark-adapted retina for 5 subjects. For comparison, 4 subjects underwent similar testing with rod-optimized stimuli. Cone absolute threshold, that is, the minimum light energy for which subjects were just able to detect a visual stimulus with any response criterion, was 203 ± 38 photons at the cornea, ∼0.47 log units lower than previously reported. Two-alternative forced-choice measurements in a subset of subjects yielded consistent results. Cone thresholds were less responsive to criterion changes than rod thresholds, suggesting a limit to the stimulus information recoverable from the cone mosaic in addition to the limit imposed by Poisson noise. Results were consistent with expectations for detection in the face of stimulus uncertainty. We discuss implications of these findings for modeling the first stages of human cone vision and interpreting psychophysical data acquired with adaptive optics at the spatial scale of the receptor mosaic. PMID:21270115

  11. Programming Retinal Stem Cells into Cone Photoreceptors

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-14-1-0566 TITLE: Programming Retinal Stem Cells into Cone Photoreceptors PRINCIPAL INVESTIGATOR: Joseph A. Brzezinski IV...SUBTITLE 5a. CONTRACT NUMBER Programming Retinal Stem Cells into Cone Photoreceptors 5b. GRANT NUMBER W81XWH-14-1-0566 5c. PROGRAM ELEMENT NUMBER 6...to program human stem cells directly into cones. Using RNA-seq, we identified several genes that are upregulated in advance of the earliest

  12. Microcomputed tomography and shock microdeformation studies on shatter cones

    NASA Astrophysics Data System (ADS)

    Zaag, Patrice Tristan; Reimold, Wolf Uwe; Hipsley, Christy Anna

    2016-08-01

    One of the aspects of impact cratering that are still not fully understood is the formation of shatter cones and related fracturing phenomena. Yet, shatter cones have been applied as an impact-diagnostic criterion for decades without the role of shock waves and target rock defects in their formation having been elucidated ever. We have tested the application of the nondestructive microcomputed tomography (μCT) method to visualize the interior of shatter cones in order to possibly resolve links between fracture patterns and shatter cone surface features (striations and intervening "valleys"). Shatter-coned samples from different impact sites and in different lithologies were investigated for their μCT suitability, with a shatter cone in sandstone from the Serra da Cangalha impact structure (Brazil) remaining as the most promising candidate because of the fracture resolution achieved. To validate the obtained CT data, the scanned specimen was cut into three orthogonal sets of thin sections. Scans with 13 μm resolution were obtained. μCT scans and microscopic analysis unraveled an orientation of subplanar fractures and related fluid inclusion trails, and planar fracture (PF) orientations in the interior of shatter cones. Planar deformation features (PDF) were observed predominantly near the shatter cone surface. Previously undescribed varieties of feather features (FF), in the form of lamellae emanating from curviplanar and curved fractures, as well as an "arrowhead"-like FF development with microlamellae originating from both sides of a PF, were observed. The timing of shatter cone formation was investigated by establishing temporal relations to the generation of various shock microscopic effects. Shatter cones are, thus, generated post- or syn-formation of PF, FF, subplanar fractures, and PDF. The earliest possible time for shatter cone formation is during the late stage of the compressional phase, that is, shock wave passage, of an impact event.

  13. A Hydraulically Operated Pine Cone Cutter

    Treesearch

    Carl W. Fatzinger; M.T. Proveaux

    1971-01-01

    Mature cones of slash pine (Pinus elliottii Engelm. var. elliottii) and longleaf pine (P. palustris Mill.) can be easily bisected along their longitudinal axes with the hydraulic pine cone cutter described. This cutter eliminates the two major problems of earlier models--undue operator fatigue and the...

  14. The nuclear high excitation outflow cone in NGC 1365

    NASA Astrophysics Data System (ADS)

    Per Lindblad, Olof; Hjelm, Maja; Jörsäter, Steven; Kristen, Helmuth

    The morphology and kinematics of the high excitation outflow cone in the nuclear region of the Seyfert 1.5 galaxy NGC 1365 is investigated. An empirical model based on ground-based [OIII] emission line data consists of a somewhat hollow double cone with its apex at the Seyfert nucleus. The cone axis is well aligned in space with the normal to the symmetry plane of the galaxy and the position angle of its projection on the sky coincides closely with that of a jet-like radio feature. The opening angle of the cone is 100° and the orientation such that the line of sight to the Seyfert 1.5 nucleus falls inside the cone. The outflow velocities within the cone are accelerated and fall off towards the edge.

  15. Evaporation-induced patterns from droplets containing motile and nonmotile bacteria.

    PubMed

    Nellimoottil, Tittu Thomas; Rao, Pinjala Nagaraju; Ghosh, Siddhartha Sankar; Chattopadhyay, Arun

    2007-08-14

    In this letter, we report the observations of specific pattern formation from the evaporation of aqueous droplets containing motile and nonmotile bacteria. We found that when motile bacteria were present the droplet evaporated into disclike patterned deposits of bacteria. However, when the bacteria were made nonmotile by treatment with liquid nitrogen, the droplet evaporated into ringlike deposits. We also observed that bacteria with higher motility produced more uniformly deposited disclike patterns. Furthermore, we propose a model with numerical simulations to explain the mechanism of formation of these patterns. The model is based on the advective fluid flow from the center of the droplet toward the edge due to enhanced evaporation from the edge of the pinned droplet in comparison to that from the free surface. For the case of motile bacteria, we have added another velocity parameter toward the axis of the droplet and directed against the fluid flow in order to account for the disclike pattern formation. The numerical simulations match the experimental observations well. The present work, by qualitative and quantitative understanding of the evaporation of bacteria droplets, demonstrates that the inherent bacterial motility is primarily responsible for the formation of these differential patterns.

  16. Bidirectional motility of the fission yeast kinesin-5, Cut7

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edamatsu, Masaki, E-mail: cedam@mail.ecc.u-tokyo.ac.jp

    Highlights: • Motile properties of Cut7 (fission yeast kinesin-5) were studied for the first time. • Half-length Cut7 moved toward plus-end direction of microtubule. • Full-length Cut7 moved toward minus-end direction of microtubule. • N- and C-terminal microtubule binding sites did not switch the motile direction. - Abstract: Kinesin-5 is a homotetrameric motor with its motor domain at the N-terminus. Kinesin-5 crosslinks microtubules and functions in separating spindle poles during mitosis. In this study, the motile properties of Cut7, fission yeast kinesin-5, were examined for the first time. In in vitro motility assays, full-length Cut7 moved toward minus-end of microtubules,more » but the N-terminal half of Cut7 moved toward the opposite direction. Furthermore, additional truncated constructs lacking the N-terminal or C-terminal regions, but still contained the motor domain, did not switch the motile direction. These indicated that Cut7 was a bidirectional motor, and microtubule binding regions at the N-terminus and C-terminus were not involved in its directionality.« less

  17. Cone photoreceptor definition on adaptive optics retinal imaging.

    PubMed

    Muthiah, Manickam Nick; Gias, Carlos; Chen, Fred Kuanfu; Zhong, Joe; McClelland, Zoe; Sallo, Ferenc B; Peto, Tunde; Coffey, Peter J; da Cruz, Lyndon

    2014-08-01

    To quantitatively analyse cone photoreceptor matrices on images captured on an adaptive optics (AO) camera and assess their correlation to well-established parameters in the retinal histology literature. High resolution retinal images were acquired from 10 healthy subjects, aged 20-35 years old, using an AO camera (rtx1, Imagine Eyes, France). Left eye images were captured at 5° of retinal eccentricity, temporal to the fovea for consistency. In three subjects, images were also acquired at 0, 2, 3, 5 and 7° retinal eccentricities. Cone photoreceptor density was calculated following manual and automated counting. Inter-photoreceptor distance was also calculated. Voronoi domain and power spectrum analyses were performed for all images. At 5° eccentricity, the cone density (cones/mm(2) mean±SD) was 15.3±1.4×10(3) (automated) and 13.9±1.0×10(3) (manual) and the mean inter-photoreceptor distance was 8.6±0.4 μm. Cone density decreased and inter-photoreceptor distance increased with increasing retinal eccentricity from 2 to 7°. A regular hexagonal cone photoreceptor mosaic pattern was seen at 2, 3 and 5° of retinal eccentricity. Imaging data acquired from the AO camera match cone density, intercone distance and show the known features of cone photoreceptor distribution in the pericentral retina as reported by histology, namely, decreasing density values from 2 to 7° of eccentricity and the hexagonal packing arrangement. This confirms that AO flood imaging provides reliable estimates of pericentral cone photoreceptor distribution in normal subjects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Temporal and spatial characteristics of cone degeneration in RCS rats.

    PubMed

    Huang, Yan Ming; Yin, Zheng Qin; Liu, Kang; Huo, Shu Jia

    2011-03-01

    The temporal and spatial characteristics of cone degeneration in the Royal College of Surgeons (RCS) rat were studied to provide information for treatment strategies of retinitis pigmentosa. Nonpigmented dystrophic RCS rats (RCS) and pigmented nondystrophic RCS rats (controls) were used. Cone processes were visualized with peanut agglutinin (PNA). Cone development appears to have been completed by postnatal day 21 (P21) in both the RCS and control rats. Signs of cone degeneration were obvious by P30, with shorter outer segments (OSs) and enlarged inner segments (ISs). At that time, 81.7% of the cones retained stained ISs. The rate of IS density decline was slower in the peripheral, nasal, and superior retina, and only 43.6% of the cones with ISs were present at P45. By P60, PNA-labeled cone ISs were distorted and restricted to the peripheral retina, and by P90, few cone pedicles were detected. Our findings indicate that therapeutic strategies aimed at rescuing cones in the degenerating retina should be applied before P21 and no later than P45 while substantial numbers of cones retain their ISs. Either the middle or peripheral regions of the nasal and superior retina are the best locations for transplantation strategies.

  19. Chemical composition and antimicrobial activity of essential oil from cones of Pinus koraiensis.

    PubMed

    Lee, Jeong-Ho; Yang, Hye-Young; Lee, Hong-Sub; Hong, Soon-Kwang

    2008-03-01

    The essential oil from the cones of Pinus koraiensis was prepared after removing the seeds, and its chemical composition analyzed using gas chromatography-mass spectrometry (GC-MS). Hydrodistillation of the P. koraiensis cones yielded 1.07% (v/w) of essential oil, which was almost three times the amount of essential oil extracted from the needles of the same plant. Moreover, the antimicrobial activities of the oil against the growth of Gram-positive bacteria, Gram-negative bacteria, and fungi were evaluated using the agar disc diffusion method and broth microdilution method. Eighty-seven components, comprising about 96.8% of the total oil, were identified. The most abundant oil components were limonene (27.90%), alpha-pinene (23.89%), beta-pinene (12.02%), 3-carene (4.95%), beta-myrcene (4.53%), isolongifolene (3.35%), (-)-bornyl acetate (2.02%), caryophyllene (1.71%), and camphene (1.54%). The essential oil was confirmed to have significant antimicrobial activities, especially against pathogenic fungal strains such as Candida glabrata YFCC 062 and Cryptococcus neoformans B 42419. Therefore, the present results indicate that the essential oil from the cones of Pinus koraiensis can be used in various ways as a nontoxic and environmentally friendly disinfectant.

  20. Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome

    NASA Astrophysics Data System (ADS)

    Mauriac, Stephanie A.; Hien, Yeri E.; Bird, Jonathan E.; Carvalho, Steve Dos-Santos; Peyroutou, Ronan; Lee, Sze Chim; Moreau, Maite M.; Blanc, Jean-Michel; Geyser, Aysegul; Medina, Chantal; Thoumine, Olivier; Beer-Hammer, Sandra; Friedman, Thomas B.; Rüttiger, Lukas; Forge, Andrew; Nürnberg, Bernd; Sans, Nathalie; Montcouquiol, Mireille

    2017-04-01

    Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ~200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin. Using single-molecule tracking, we report that loss of Gpsm2 leads to decreased outgrowth and a disruption of actin dynamics in neuronal growth cones. Our results elucidate the aetiology of CMCS and highlight a new molecular role for Gpsm2/Gαi3 in the regulation of actin dynamics in epithelial and neuronal tissues.

  1. Divalent Cation Control of Flagellar Motility in African Trypanosomes

    NASA Astrophysics Data System (ADS)

    Westergard, Anna M.; Hutchings, Nathan R.

    2005-03-01

    Changes in calcium concentration have been shown to dynamically affect flagellar motility in several eukaryotic systems. The African trypanosome is a monoflagellated protozoan parasite and the etiological agent of sleeping sickness. Although cell motility has been implicated in disease progression, very little is currently known about biochemical control of the trypanosome flagellum. In this study, we assess the effects of extracellular changes in calcium and nickel concentration on trypanosome flagellar movement. Using a flow through chamber, we determine the relative changes in motility in individual trypanosomes in response to various concentrations of calcium and nickel, respectively. Extracellular concentrations of calcium and nickel (as low as 100 micromolar) significantly inhibit trypanosome cell motility. The effects are reversible, as indicated by the recovery of motion after removal of the calcium or nickel from the chamber. We are currently investigating the specific changes in flagellar oscillation and coordination that result from calcium and nickel, respectively. These results verify the presence of a calcium-responsive signaling mechanism(s) that regulates flagellar beat in trypanosomes.

  2. The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse*

    PubMed Central

    Sullivan, Chelsea S.; Kümper, Maike; Temple, Brenda S.; Maness, Patricia F.

    2016-01-01

    Establishment of a proper balance of excitatory and inhibitory connectivity is achieved during development of cortical networks and adjusted through synaptic plasticity. The neural cell adhesion molecule (NCAM) and the receptor tyrosine kinase EphA3 regulate the perisomatic synapse density of inhibitory GABAergic interneurons in the mouse frontal cortex through ephrin-A5-induced growth cone collapse. In this study, it was demonstrated that binding of NCAM and EphA3 occurred between the NCAM Ig2 domain and EphA3 cysteine-rich domain (CRD). The binding interface was further refined through molecular modeling and mutagenesis and shown to be comprised of complementary charged residues in the NCAM Ig2 domain (Arg-156 and Lys-162) and the EphA3 CRD (Glu-248 and Glu-264). Ephrin-A5 induced co-clustering of surface-bound NCAM and EphA3 in GABAergic cortical interneurons in culture. Receptor clustering was impaired by a charge reversal mutation that disrupted NCAM/EphA3 association, emphasizing the importance of the NCAM/EphA3 binding interface for cluster formation. NCAM enhanced ephrin-A5-induced EphA3 autophosphorylation and activation of RhoA GTPase, indicating a role for NCAM in activating EphA3 signaling through clustering. NCAM-mediated clustering of EphA3 was essential for ephrin-A5-induced growth cone collapse in cortical GABAergic interneurons, and RhoA and a principal effector, Rho-associated protein kinase, mediated the collapse response. This study delineates a mechanism in which NCAM promotes ephrin-A5-dependent clustering of EphA3 through interaction of the NCAM Ig2 domain and the EphA3 CRD, stimulating EphA3 autophosphorylation and RhoA signaling necessary for growth cone repulsion in GABAergic interneurons in vitro, which may extend to remodeling of axonal terminals of interneurons in vivo. PMID:27803162

  3. Transforming growth factor-β1 deteriorates microrheological characteristics and motility of mature dendritic cells in concentration-dependent fashion.

    PubMed

    Zheng, Qinni; Long, Jinhua; Jia, Binbin; Xu, Xiaoli; Zhang, Chunlin; Li, Long; Wen, Zongyao; Jin, Feng; Yao, Weijuan; Zeng, Zhu

    2014-01-01

    Dendritic cells (DCs) are potent and specialized antigen-presenting cells that play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Tumor cells can escape from immune attack by secreting suppressive cytokines which solely or cooperatively impair the immune function and microrheological properties of DCs. However, the underlying mechanisms are not fully defined. Transforming growth factor-β1 (TGF-β1) has been identified as a major cytokine in the tumor microenvironment. To determine the effects of TGF-β1 on mature DCs (mDCs) from microrheological viewpoint, cells were treated with different concentrations of TGF-β1. The results showed that the impaired microrheological parameters, including osmotic fragility, electrophoretic mobility, deformability, membrane fluidity, F-actin organization and so on, as well as motilities of mDCs relied heavily on TGF-β1 concentration. Moreover, these changes were correlated with the expression levels of fascin1, cofilin1, phosphorylated cofilin1 and profilin, this could be one of the crucial aspects of immune escape mechanisms of tumors, hinting that the signal pathway of TGF-β1 should be blocked in appropriate way before performing DCs-based immunotherapy against cancer. It is clinically important to understand the biological behavior of DCs and immune escape mechanism of tumor as well as how to improve efficiency of the anti-tumor therapy based on DCs.

  4. Motility, Force Generation, and Energy Consumption of Unicellular Parasites.

    PubMed

    Hochstetter, Axel; Pfohl, Thomas

    2016-07-01

    Motility is a key factor for pathogenicity of unicellular parasites, enabling them to infiltrate and evade host cells, and perform several of their life-cycle events. State-of-the-art methods of motility analysis rely on a combination of optical tweezers with high-resolution microscopy and microfluidics. With this technology, propulsion forces, energies, and power generation can be determined so as to shed light on the motion mechanisms, chemotactic behavior, and specific survival strategies of unicellular parasites. With these new tools in hand, we can elucidate the mechanisms of motility and force generation of unicellular parasites, and identify ways to manipulate and eventually inhibit them. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. S cones: Evolution, retinal distribution, development, and spectral sensitivity.

    PubMed

    Hunt, David M; Peichl, Leo

    2014-03-01

    S cones expressing the short wavelength-sensitive type 1 (SWS1) class of visual pigment generally form only a minority type of cone photoreceptor within the vertebrate duplex retina. Hence, their primary role is in color vision, not in high acuity vision. In mammals, S cones may be present as a constant fraction of the cones across the retina, may be restricted to certain regions of the retina or may form a gradient across the retina, and in some species, there is coexpression of SWS1 and the long wavelength-sensitive (LWS) class of pigment in many cones. During retinal development, SWS1 opsin expression generally precedes that of LWS opsin, and evidence from genetic studies indicates that the S cone pathway may be the default pathway for cone development. With the notable exception of the cartilaginous fishes, where S cones appear to be absent, they are present in representative species from all other vertebrate classes. S cone loss is not, however, uncommon; they are absent from most aquatic mammals and from some but not all nocturnal terrestrial species. The peak spectral sensitivity of S cones depends on the spectral characteristics of the pigment present. Evidence from the study of agnathans and teleost fishes indicates that the ancestral vertebrate SWS1 pigment was ultraviolet (UV) sensitive with a peak around 360 nm, but this has shifted into the violet region of the spectrum (>380 nm) on many separate occasions during vertebrate evolution. In all cases, the shift was generated by just one or a few replacements in tuning-relevant residues. Only in the avian lineage has tuning moved in the opposite direction, with the reinvention of UV-sensitive pigments.

  6. Advances in Valveless Piezoelectric Pump with Cone-shaped Tubes

    NASA Astrophysics Data System (ADS)

    Zhang, Jian-Hui; Wang, Ying; Huang, Jun

    2017-07-01

    This paper reviews the development of valveless piezoelectric pump with cone-shaped tube chronologically, which have widely potential application in biomedicine and micro-electro-mechanical systems because of its novel principles and deduces the research direction in the future. Firstly, the history of valveless piezoelectric pumps with cone-shaped tubes is reviewed and these pumps are classified into the following types: single pump with solid structure or plane structure, and combined pump with parallel structure or series structure. Furthermore, the function of each type of cone-shaped tubes and pump structures are analyzed, and new directions of potential expansion of valveless piezoelectric pumps with cone-shaped tubes are summarized and deduced. The historical argument, which is provided by the literatures, that for a valveless piezoelectric pump with cone-shaped tubes, cone angle determines the flow resistance and the flow resistance determines the flow direction. The argument is discussed in the reviewed pumps one by one, and proved to be convincing. Finally, it is deduced that bionics is pivotal in the development of valveless piezoelectric pump with cone-shaped tubes from the perspective of evolution of biological structure. This paper summarizes the current valveless piezoelectric pumps with cone-shaped tubes and points out the future development, which may provide guidance for the research of piezoelectric actuators.

  7. Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts

    PubMed Central

    Lowery, Jason; Jain, Nikhil; Kuczmarski, Edward R.; Mahammad, Saleemulla; Goldman, Anne; Gelfand, Vladimir I.; Opal, Puneet; Goldman, Robert D.

    2016-01-01

    Giant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large aggregates and bundles of IFs. In this study, we show that both the distribution and motility of mitochondria are altered in GAN fibroblasts and this is attributable to their association with vimentin IF aggregates and bundles. Transient expression of wild-type gigaxonin in GAN fibroblasts reduces the number of IF aggregates and bundles, restoring mitochondrial motility. Conversely, silencing the expression of gigaxonin in control fibroblasts leads to changes in IF organization similar to that of GAN patient fibroblasts and a coincident loss of mitochondrial motility. The inhibition of mitochondrial motility in GAN fibroblasts is not due to a global inhibition of organelle translocation, as lysosome motility is normal. Our findings demonstrate that it is the pathological changes in IF organization that cause the loss of mitochondrial motility. PMID:26700320

  8. Peroxisomes, lipid droplets, and endoplasmic reticulum “hitchhike” on motile early endosomes

    PubMed Central

    Guimaraes, Sofia C.; Schuster, Martin; Bielska, Ewa; Dagdas, Gulay; Kilaru, Sreedhar; Meadows, Ben R.A.; Schrader, Michael

    2015-01-01

    Intracellular transport is mediated by molecular motors that bind cargo to be transported along the cytoskeleton. Here, we report, for the first time, that peroxisomes (POs), lipid droplets (LDs), and the endoplasmic reticulum (ER) rely on early endosomes (EEs) for intracellular movement in a fungal model system. We show that POs undergo kinesin-3– and dynein-dependent transport along microtubules. Surprisingly, kinesin-3 does not colocalize with POs. Instead, the motor moves EEs that drag the POs through the cell. PO motility is abolished when EE motility is blocked in various mutants. Most LD and ER motility also depends on EE motility, whereas mitochondria move independently of EEs. Covisualization studies show that EE-mediated ER motility is not required for PO or LD movement, suggesting that the organelles interact with EEs independently. In the absence of EE motility, POs and LDs cluster at the growing tip, whereas ER is partially retracted to subapical regions. Collectively, our results show that moving EEs interact transiently with other organelles, thereby mediating their directed transport and distribution in the cell. PMID:26620910

  9. Topology-optimized dual-polarization Dirac cones

    NASA Astrophysics Data System (ADS)

    Lin, Zin; Christakis, Lysander; Li, Yang; Mazur, Eric; Rodriguez, Alejandro W.; Lončar, Marko

    2018-02-01

    We apply a large-scale computational technique, known as topology optimization, to the inverse design of photonic Dirac cones. In particular, we report on a variety of photonic crystal geometries, realizable in simple isotropic dielectric materials, which exhibit dual-polarization Dirac cones. We present photonic crystals of different symmetry types, such as fourfold and sixfold rotational symmetries, with Dirac cones at different points within the Brillouin zone. The demonstrated and related optimization techniques open avenues to band-structure engineering and manipulating the propagation of light in periodic media, with possible applications to exotic optical phenomena such as effective zero-index media and topological photonics.

  10. Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters

    PubMed Central

    Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong

    2016-01-01

    ABSTRACT The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. IMPORTANCE Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. PMID:27068592

  11. Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters.

    PubMed

    Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong; Alexandre, Gladys

    2016-06-15

    The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Gliding Motility of Babesia bovis Merozoites Visualized by Time-Lapse Video Microscopy

    PubMed Central

    Asada, Masahito; Goto, Yasuyuki; Yahata, Kazuhide; Yokoyama, Naoaki; Kawai, Satoru; Inoue, Noboru; Kaneko, Osamu; Kawazu, Shin-ichiro

    2012-01-01

    Background Babesia bovis is an apicomplexan intraerythrocytic protozoan parasite that induces babesiosis in cattle after transmission by ticks. During specific stages of the apicomplexan parasite lifecycle, such as the sporozoites of Plasmodium falciparum and tachyzoites of Toxoplasma gondii, host cells are targeted for invasion using a unique, active process termed “gliding motility”. However, it is not thoroughly understood how the merozoites of B. bovis target and invade host red blood cells (RBCs), and gliding motility has so far not been observed in the parasite. Methodology/Principal Findings Gliding motility of B. bovis merozoites was revealed by time-lapse video microscopy. The recorded images revealed that the process included egress of the merozoites from the infected RBC, gliding motility, and subsequent invasion into new RBCs. The gliding motility of B. bovis merozoites was similar to the helical gliding of Toxoplasma tachyzoites. The trails left by the merozoites were detected by indirect immunofluorescence assay using antiserum against B. bovis merozoite surface antigen 1. Inhibition of gliding motility by actin filament polymerization or depolymerization indicated that the gliding motility was driven by actomyosin dependent process. In addition, we revealed the timing of breakdown of the parasitophorous vacuole. Time-lapse image analysis of membrane-stained bovine RBCs showed formation and breakdown of the parasitophorous vacuole within ten minutes of invasion. Conclusions/Significance This is the first report of the gliding motility of B. bovis. Since merozoites of Plasmodium parasites do not glide on a substrate, the gliding motility of B. bovis merozoites is a notable finding. PMID:22506073

  13. Linear diffusion model dating of cinder cones in Central Anatolia, Turkey

    NASA Astrophysics Data System (ADS)

    O'Sadnick, L. G.; Reid, M. R.; Cline, M. L.; Cosca, M. A.; Kuscu, G.

    2013-12-01

    The progressive decrease in slope angle, cone height and cone height/width ratio over time provides the basis for geomorphic dating of cinder cones using linear diffusion models. Previous research using diffusion models to date cinder cones has focused on the cone height/width ratio as the basis for dating cones of unknown age [1,2]. Here we apply linear diffusion models to dating cinder cones. A suite of 16 cinder cones from the Hasandağ volcano area of the Neogene-Quaternary Central Anatolian Volcanic Zone, for which samples are available, were selected for morphologic dating analysis. New 40Ar/39Ar dates for five of these cones range from 62 × 4 to 517 × 9 ka. Linear diffusion models were used to model the erosional degradation of each cone. Diffusion coefficients (κ) for the 5 cinder cones with known ages were constrained by comparing various modeled slope profiles to the current slope profile. The resulting κ is 7.5×0.5 m2kyr-1. Using this κ value, eruption ages were modeled for the remaining 11 cinder cones and range from 53×3 to 455×30 ka. These ages are within the range of ages previously reported for cinder cones in the Hasandağ region. The linear diffusion model-derived ages are being compared to additional new 40Ar/39Ar dates in order to further assess the applicability of morphological dating to constrain the ages of cinder cones. The relatively well-constrained κ value we obtained by applying the linear diffusion model to cinder cones that range in age by nearly 500 ka suggests that this model can be used to date cinder cones. This κ value is higher than the well-established value of κ =3.9 for a cinder cone in a similar climate [3]. Therefore our work confirms the importance of determining appropriate κ values from nearby cones with known ages. References 1. C.A. Wood, J. Volcanol. Geotherm. Res. 8, 137 (1980) 2. D.M. Wood, M.F. Sheridan, J. Volcanol. Geotherm. Res. 83, 241 (1998) 3. J.D. Pelletier, M.L. Cline, Geology 35, 1067 (2007)

  14. Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe.

    PubMed

    Carlson, Dustin A; Kahrilas, Peter J; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A; Wong, Ian; Pandolfino, John E

    2016-12-01

    Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was <2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.

  15. Accuracy and Landmark Error Calculation Using Cone-Beam Computed Tomography–Generated Cephalograms

    PubMed Central

    Grauer, Dan; Cevidanes, Lucia S. H.; Styner, Martin A.; Heulfe, Inam; Harmon, Eric T.; Zhu, Hongtu; Proffit, William R.

    2010-01-01

    Objective To evaluate systematic differences in landmark position between cone-beam computed tomography (CBCT)–generated cephalograms and conventional digital cephalograms and to estimate how much variability should be taken into account when both modalities are used within the same longitudinal study. Materials and Methods Landmarks on homologous cone-beam computed tomographic–generated cephalograms and conventional digital cephalograms of 46 patients were digitized, registered, and compared via the Hotelling T2 test. Results There were no systematic differences between modalities in the position of most landmarks. Three landmarks showed statistically significant differences but did not reach clinical significance. A method for error calculation while combining both modalities in the same individual is presented. Conclusion In a longitudinal follow-up for assessment of treatment outcomes and growth of one individual, the error due to the combination of the two modalities might be larger than previously estimated. PMID:19905853

  16. Ocean acidification reduces sperm flagellar motility in broadcast spawning reef invertebrates.

    PubMed

    Morita, Masaya; Suwa, Ryota; Iguchi, Akira; Nakamura, Masako; Shimada, Kazuaki; Sakai, Kazuhiko; Suzuki, Atsushi

    2010-05-01

    Ocean acidification is now recognized as a threat to marine ecosystems; however, the effect of ocean acidification on fertilization in marine organisms is still largely unknown. In this study, we focused on sperm flagellar motility in broadcast spawning reef invertebrates (a coral and a sea cucumber). Below pH 7.7, the pH predicted to occur within the next 100 years, sperm flagellar motility was seriously impaired in these organisms. Considering that sperm flagellar motility is indispensable for transporting the paternal haploid genome for fertilization, fertilization taking place in seawater may decline in the not too distant future. Urgent surveys are necessary for a better understanding of the physiological consequences of ocean acidification on sperm flagellar motility in a wide range of marine invertebrates.

  17. Effect of Cobalt on Sperm Motility in an Endangered Trout Species, Salmo coruhensis.

    PubMed

    Kocabaş, Mehmet; Kutluyer, Filiz

    2017-12-01

    Experiments were designed to examine the in vitro effect of cobalt on sperm motility of the endangered trout species (Salmo coruhensis). Sperm samples were diluted in an immobilizing solution, and activated in a motility-activation solution that was supplemented with cobalt at concentrations of 1, 10, 100 and 1000 mg/L. The percentage of motile sperm and duration of motility were determined. Cobalt concentrations of 1-100 mg/L had a positive effect on the percentage of motile sperm and duration of motility compared to the control group, while a concentration of 1000 mg/L resulted in decreases in these parameters (p < 0.05). The percentages of motile sperm at cobalt concentrations of 0, 1, 10, 100 and 1000 mg/L were 83.33% ± 0.25%, 88.33% ± 0.34%, 89.00% ± 0.57%, 90.00% ± 0.87% and 42.50% ± 0.45%, respectively; and the time durations over which the sperm remained motile were 72.00 ± 0.63, 74.83 ± 0.28, 77.40 ± 0.47, 81.14 ± 0.78, and 50.25 ± 0.67 s, respectively. This study has shown that sperm motility and duration were significantly enhanced (p < 0.05) at cobalt concentrations of 1, 10 and 100 mg/L, relative to controls, and significantly decreased at 1000 mg/L.

  18. Esophageal motility abnormalities in gastroesophageal reflux disease

    PubMed Central

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-01-01

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. PMID:24868489

  19. Esophageal motility abnormalities in gastroesophageal reflux disease.

    PubMed

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-05-06

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

  20. Guidance of Axons by Local Coupling of Retrograde Flow to Point Contact Adhesions.

    PubMed

    Nichol, Robert H; Hagen, Kate M; Lumbard, Derek C; Dent, Erik W; Gómez, Timothy M

    2016-02-17

    Growth cones interact with the extracellular matrix (ECM) through integrin receptors at adhesion sites termed point contacts. Point contact adhesions link ECM proteins to the actin cytoskeleton through numerous adaptor and signaling proteins. One presumed function of growth cone point contacts is to restrain or "clutch" myosin-II-based filamentous actin (F-actin) retrograde flow (RF) to promote leading edge membrane protrusion. In motile non-neuronal cells, myosin-II binds and exerts force upon actin filaments at the leading edge, where clutching forces occur. However, in growth cones, it is unclear whether similar F-actin-clutching forces affect axon outgrowth and guidance. Here, we show in Xenopus spinal neurons that RF is reduced in rapidly migrating growth cones on laminin (LN) compared with non-integrin-binding poly-d-lysine (PDL). Moreover, acute stimulation with LN accelerates axon outgrowth over a time course that correlates with point contact formation and reduced RF. These results suggest that RF is restricted by the assembly of point contacts, which we show occurs locally by two-channel imaging of RF and paxillin. Further, using micropatterns of PDL and LN, we demonstrate that individual growth cones have differential RF rates while interacting with two distinct substrata. Opposing effects on RF rates were also observed in growth cones treated with chemoattractive and chemorepulsive axon guidance cues that influence point contact adhesions. Finally, we show that RF is significantly attenuated in vivo, suggesting that it is restrained by molecular clutching forces within the spinal cord. Together, our results suggest that local clutching of RF can control axon guidance on ECM proteins downstream of axon guidance cues. Here, we correlate point contact adhesions directly with clutching of filamentous actin retrograde flow (RF), which our findings strongly suggest guides developing axons. Acute assembly of new point contact adhesions is temporally and

  1. Computation of supersonic laminar viscous flow past a pointed cone at angle of attack in spinning and coning motion

    NASA Technical Reports Server (NTRS)

    Agarwal, R.; Rakich, J. V.

    1978-01-01

    Computational results obtained with a parabolic Navier-Stokes marching code are presented for supersonic viscous flow past a pointed cone at angle of attack undergoing a combined spinning and coning motion. The code takes into account the asymmetries in the flow field resulting from the motion and computes the asymmetric shock shape, crossflow and streamwise shear, heat transfer, crossflow separation and vortex structure. The side force and moment are also computed. Reasonably good agreement is obtained with the side force measurements of Schiff and Tobak. Comparison is also made with the only available numerical inviscid analysis. It is found that the asymmetric pressure loads due to coning motion are much larger than all other viscous forces due to spin and coning, making viscous forces negligible in the combined motion.

  2. Automated identification of cone photoreceptors in adaptive optics retinal images.

    PubMed

    Li, Kaccie Y; Roorda, Austin

    2007-05-01

    In making noninvasive measurements of the human cone mosaic, the task of labeling each individual cone is unavoidable. Manual labeling is a time-consuming process, setting the motivation for the development of an automated method. An automated algorithm for labeling cones in adaptive optics (AO) retinal images is implemented and tested on real data. The optical fiber properties of cones aided the design of the algorithm. Out of 2153 manually labeled cones from six different images, the automated method correctly identified 94.1% of them. The agreement between the automated and the manual labeling methods varied from 92.7% to 96.2% across the six images. Results between the two methods disagreed for 1.2% to 9.1% of the cones. Voronoi analysis of large montages of AO retinal images confirmed the general hexagonal-packing structure of retinal cones as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the reliability and practicality of having an automated solution to this problem.

  3. Gastrointestinal motility in relation to spontaneous meal occurrence in domestic fowls.

    PubMed

    Savory, C J

    1987-10-01

    The relationship between gastrointestinal (GI) motility and spontaneous feeding activity was investigated in five immature domestic hens, by recording simultaneously their feeding and contraction of the gizzard and duodenum. Different parameters of GI motility were interrelated, and gizzard contraction frequency (GCF) was used as an overall index of motility. Significant (P less than 0.05) changes in GCF relative to mealtimes varied between individual birds and between different meal length classes. The most consistent change was a rapid increase in GCF at the start of meals, followed by a decline which usually commenced before the end of long meals, but after the end of shorter ones. The increase in GCF commenced before the start of meals in one bird which had longer inter-meal intervals than the rest. There were no consistent changes in GCF at the ends of intervals or meals that might suggest a causal association between motility and hunger and satiety. It is suggested that the observed variation in GI motility may be accounted for mainly by variation in extrinsic stimulation from the vagus nerve.

  4. Multiscale Characterization of Bacterial Swarming Illuminates Principles Governing Directed Surface Motility

    NASA Astrophysics Data System (ADS)

    Strickland, Ben; Hoeger, Kentaro; Ursell, Tristan

    In many systems, individual characteristics interact, leading to the spontaneous emergence of order and complexity. In biological settings like microbes, such collective behaviors can imbue a variety of benefits to constituent individuals, including increased spatial range, improved access to nutrients, and enhanced resistance to antibiotic threats. To untangle the biophysical underpinnings of collective motility, we use passive tracers and a curated genetic library of Bacillus subtilis, including motile, non-motile, biofilm-deficient, and non-chemotactic mutants. We characterize and connect individual behavior on the microscopic scale to macroscopic colony morphology and motility of dendritic swarming. We analyze the persistence and dynamics of coordinated movement on length scales up to 4 orders of magnitude larger than that of individual cells, revealing rapid and directed responses of microbial groups to external stimuli, such as avoidance dynamics across chemical gradients. Our observations uncover the biophysical interplay between individual motility, surface wetness, phenotypic diversity, and external physical forces that robustly precipitate coordinated group behavior in microbes, and suggest general principles that govern the transition from individual to group behavior.

  5. Bacterial motility complexes require the actin-like protein, MreB and the Ras homologue, MglA.

    PubMed

    Mauriello, Emilia M F; Mouhamar, Fabrice; Nan, Beiyan; Ducret, Adrien; Dai, David; Zusman, David R; Mignot, Tâm

    2010-01-20

    Gliding motility in the bacterium Myxococcus xanthus uses two motility engines: S-motility powered by type-IV pili and A-motility powered by uncharacterized motor proteins and focal adhesion complexes. In this paper, we identified MreB, an actin-like protein, and MglA, a small GTPase of the Ras superfamily, as essential for both motility systems. A22, an inhibitor of MreB cytoskeleton assembly, reversibly inhibited S- and A-motility, causing rapid dispersal of S- and A-motility protein clusters, FrzS and AglZ. This suggests that the MreB cytoskeleton is involved in directing the positioning of these proteins. We also found that a DeltamglA motility mutant showed defective localization of AglZ and FrzS clusters. Interestingly, MglA-YFP localization mimicked both FrzS and AglZ patterns and was perturbed by A22 treatment, consistent with results indicating that both MglA and MreB bind to motility complexes. We propose that MglA and the MreB cytoskeleton act together in a pathway to localize motility proteins such as AglZ and FrzS to assemble the A-motility machineries. Interestingly, M. xanthus motility systems, like eukaryotic systems, use an actin-like protein and a small GTPase spatial regulator.

  6. Bacterial motility complexes require the actin-like protein, MreB and the Ras homologue, MglA

    PubMed Central

    Mauriello, Emilia M F; Mouhamar, Fabrice; Nan, Beiyan; Ducret, Adrien; Dai, David; Zusman, David R; Mignot, Tâm

    2010-01-01

    Gliding motility in the bacterium Myxococcus xanthus uses two motility engines: S-motility powered by type-IV pili and A-motility powered by uncharacterized motor proteins and focal adhesion complexes. In this paper, we identified MreB, an actin-like protein, and MglA, a small GTPase of the Ras superfamily, as essential for both motility systems. A22, an inhibitor of MreB cytoskeleton assembly, reversibly inhibited S- and A-motility, causing rapid dispersal of S- and A-motility protein clusters, FrzS and AglZ. This suggests that the MreB cytoskeleton is involved in directing the positioning of these proteins. We also found that a ΔmglA motility mutant showed defective localization of AglZ and FrzS clusters. Interestingly, MglA–YFP localization mimicked both FrzS and AglZ patterns and was perturbed by A22 treatment, consistent with results indicating that both MglA and MreB bind to motility complexes. We propose that MglA and the MreB cytoskeleton act together in a pathway to localize motility proteins such as AglZ and FrzS to assemble the A-motility machineries. Interestingly, M. xanthus motility systems, like eukaryotic systems, use an actin-like protein and a small GTPase spatial regulator. PMID:19959988

  7. The role of adhesins in bacteria motility modification

    NASA Astrophysics Data System (ADS)

    Conrad, Jacinta; Gibiansky, Maxsim; Jin, Fan; Gordon, Vernita; Motto, Dominick; Shrout, Joshua; Parsek, Matthew; Wong, Gerard

    2010-03-01

    Bacterial biofilms are multicellular communities responsible for a broad range of infections. To investigate the early-stage formation of biofilms, we have developed high-throughput techniques to quantify the motility of surface-associated bacteria. We translate microscopy movies of bacteria into a searchable database of trajectories using tracking algorithms adapted from colloidal physics. By analyzing the motion of both wild-type (WT) and isogenic knockout mutants, we have previously characterized fundamental motility mechanisms in P. aeruginosa. Here, we develop biometric routines to recognize signatures of adhesion and trapping. We find that newly attached bacteria move faster than previously adherent bacteria, and are more likely to be oriented out-of-plane. Motility appendages influence the bacterium's ability to become trapped: WT bacteria exhibit two types of trapped trajectories, whereas flagella-deficient bacteria rarely become trapped. These results suggest that flagella play a key role in adhesion.

  8. Isolation of Salmonella mutants resistant to the inhibitory effect of Salicylidene acylhydrazides on flagella-mediated motility.

    PubMed

    Martinez-Argudo, Isabel; Veenendaal, Andreas K J; Liu, Xia; Roehrich, A Dorothea; Ronessen, Maria C; Franzoni, Giulia; van Rietschoten, Katerine N; Morimoto, Yusuke V; Saijo-Hamano, Yumiko; Avison, Matthew B; Studholme, David J; Namba, Keiichi; Minamino, Tohru; Blocker, Ariel J

    2013-01-01

    Salicylidene acylhydrazides identified as inhibitors of virulence-mediating type III secretion systems (T3SSs) potentially target their inner membrane export apparatus. They also lead to inhibition of flagellar T3SS-mediated swimming motility in Salmonella enterica serovar. Typhimurium. We show that INP0404 and INP0405 act by reducing the number of flagella/cell. These molecules still inhibit motility of a Salmonella ΔfliH-fliI-fliJ/flhB((P28T)) strain, which lacks three soluble components of the flagellar T3S apparatus, suggesting that they are not the target of this drug family. We implemented a genetic screen to search for the inhibitors' molecular target(s) using motility assays in the ΔfliH-fliI/flhB((P28T)) background. Both mutants identified were more motile than the background strain in the absence of the drugs, although HM18 was considerably more so. HM18 was more motile than its parent strain in the presence of both drugs while DI15 was only insensitive to INP0405. HM18 was hypermotile due to hyperflagellation, whereas DI15 was not hyperflagellated. HM18 was also resistant to a growth defect induced by high concentrations of the drugs. Whole-genome resequencing of HM18 indicated two alterations within protein coding regions, including one within atpB, which encodes the inner membrane a-subunit of the F(O)F(1)-ATP synthase. Reverse genetics indicated that the alteration in atpB was responsible for all of HM18's phenotypes. Genome sequencing of DI15 uncovered a single A562P mutation within a gene encoding the flagellar inner membrane protein FlhA, the direct role of which in mediating drug insensitivity could not be confirmed. We discuss the implications of these findings in terms of T3SS export apparatus function and drug target identification.

  9. Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

    PubMed

    Lunding, J A; Nordström, L M; Haukelid, A-O; Gilja, O H; Berstad, A; Hausken, T

    2008-06-01

    Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

  10. VEGF-A/VEGFR-2 signaling plays an important role for the motility of pancreas cancer cells.

    PubMed

    Doi, Yosuke; Yashiro, Masakazu; Yamada, Nobuya; Amano, Ryosuke; Noda, Satoru; Hirakawa, Kosei

    2012-08-01

    Pancreatic cancer is one of the most lethal solid tumors. Vascular endothelial growth factor receptors (VEGFRs) are expressed not only by endothelial cells but also by pancreatic cancer cells. VEGFRs might play an important role for the development of pancreatic cancer cells. The purpose of this study was to evaluate the efficacy of VEGF/VEGFR-2-targeted therapy in pancreatic carcinoma. Five pancreatic carcinoma cell lines were used. The expression level of VEGFR-2 of cancer cells was examined by RT-PCR and Western blot. The effects of VEGFs, bevacizumab as an anti-VEGF antibody, sunitinib as a tyrosine kinase inhibitor against VEGFRs, and VEGF-R2 siRNA on the motility activity of pancreatic cancer cells were examined by invasion assay and wound healing assay. The effect of VEGF, bevacizumab, and sunitinib on the phosphorylation of VEGFR-2 and downstream effecter molecules, MAPK and PI3K, was examined by western blot. Pancreatic cancer cell lines expressed VEGFR-2. VEGF-A significantly increased the motility of pancreas cancer cells, which was inhibited by VEGFR-2 siRNA. Conditioned medium from pancreas cancer cells significantly stimulated the motility of pancreas cancer cells. VEGF/VEGFR inhibitors, bevacizumab and sunitinib, significantly decreased the motility of pancreas cancer cells. VEGFR-2 phosphorylation level of pancreas cancer cells was increased by VEGF-A. Bevacizumab and sunitinib decreased the level of VEGFR-2 phosphorylation, p-ERK, and p-Akt expression. VEGF-A decreased zonula occludens (ZO-1) or ZO-2 expression in pancreas cancer cells. VEGF-A/VEGFR-2 signaling plays an important role in inducing invasion and migration of pancreatic cancer cells.

  11. Motility analysis of bacteria-based microrobot (bacteriobot) using chemical gradient microchamber.

    PubMed

    Park, Daechul; Park, Sung Jun; Cho, Sunghoon; Lee, Yeonkyung; Lee, Yu Kyung; Min, Jung-Joon; Park, Bang Ju; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2014-01-01

    A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber. © 2013 Wiley Periodicals, Inc.

  12. Ostrich specific semen diluent and sperm motility characteristics during in vitro storage.

    PubMed

    Smith, A M J; Bonato, M; Dzama, K; Malecki, I A; Cloete, S W P

    2018-06-01

    The dilution of semen is a very important initial process for semen processing and evaluation, storage and preservation in vitro and efficient artificial insemination. The aim of the study was to evaluate the effect of two synthetic diluents (OS1 and OS2) on ostrich sperm motility parameters during in vitro storage. Formulation of OS1 was based on macro minerals (Na, K, P, Ca, Mg) and OS2 on the further addition of micro minerals (Se and Zn), based on mineral concentration determined in the ostrich seminal plasma (SP). Sperm motility was evaluated at different processing stages (neat, after dilution, during storage and after storage) by measuring several sperm motility variables using the Sperm Class Analyzer® (SCA). Processing (dilution, cooling and storage) of semen for in vitro storage purposes decreased the values for all sperm motility variables measured. The percentage motile (MOT) and progressive motile (PMOT) sperm decreased 20% to 30% during 24 h of storage, independent of diluent type. Quality of sperm swim (LIN, STR and WOB), however, was sustained during the longer storage periods (48 h) with the OS2 diluent modified with Se and Zn additions. Quality of sperm swim with use of OS1 was 6% to 8% less for the LIN, STR, and WOB variables. Male fitted as a fixed effect accounted for >60% of the variation for certain sperm motility variables (PMOT, MOT, VCL, VSL, VAP and ALH) evaluated at different processing stages. Semen from specific males had sustained sperm motility characteristics to a greater extent than that of other males during the 24-h storage period. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Hydrodynamic Contributions to Amoeboid Cell Motility

    NASA Astrophysics Data System (ADS)

    Lewis, Owen; Guy, Robert

    2011-11-01

    Understanding the methods by which cells move is a fundamental problem in modern biology. Recent evidence has shown that the fluid dynamics of cytoplasm can play a vital role in cellular motility. The slime mold Physarum polycephalum provides an excellent model organism for the study of amoeboid motion. In this research, we use both analytic and computational models to investigate intracellular fluid flow in a simple model of Physarum. In both models, of we are specifically interested in stresses generated by cytoplasmic flow which act in the direction of cellular motility. In our numerical model, the Immersed Boundary Method is used to account for such stresses. We investigate the relationship between contraction waves, low waves and locomotive forces, and attempt characterize conditions necessary to generate directed motion.

  14. Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

    PubMed Central

    Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

    2014-01-01

    Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions. PMID:24550448

  15. Autocrine regulation of human sperm motility by tachykinins.

    PubMed

    Pinto, Francisco M; Ravina, Cristina G; Subiran, Nerea; Cejudo-Román, Antonio; Fernández-Sánchez, Manuel; Irazusta, Jon; Garrido, Nicolas; Candenas, Luz

    2010-08-26

    We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

  16. Techniques for optimizing nanotips derived from frozen taylor cones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirsch, Gregory

    Optimization techniques are disclosed for producing sharp and stable tips/nanotips relying on liquid Taylor cones created from electrically conductive materials with high melting points. A wire substrate of such a material with a preform end in the shape of a regular or concave cone, is first melted with a focused laser beam. Under the influence of a high positive potential, a Taylor cone in a liquid/molten state is formed at that end. The cone is then quenched upon cessation of the laser power, thus freezing the Taylor cone. The tip of the frozen Taylor cone is reheated by the lasermore » to allow its precise localized melting and shaping. Tips thus obtained yield desirable end-forms suitable as electron field emission sources for a variety of applications. In-situ regeneration of the tip is readily accomplished. These tips can also be employed as regenerable bright ion sources using field ionization/desorption of introduced chemical species.« less

  17. An Analysis Model for Water Cone Subsidence in Bottom Water Drive Reservoirs

    NASA Astrophysics Data System (ADS)

    Wang, Jianjun; Xu, Hui; Wu, Shucheng; Yang, Chao; Kong, lingxiao; Zeng, Baoquan; Xu, Haixia; Qu, Tailai

    2017-12-01

    Water coning in bottom water drive reservoirs, which will result in earlier water breakthrough, rapid increase in water cut and low recovery level, has drawn tremendous attention in petroleum engineering field. As one simple and effective method to inhibit bottom water coning, shut-in coning control is usually preferred in oilfield to control the water cone and furthermore to enhance economic performance. However, most of the water coning researchers just have been done on investigation of the coning behavior as it grows up, the reported studies for water cone subsidence are very scarce. The goal of this work is to present an analytical model for water cone subsidence to analyze the subsidence of water cone when the well shut in. Based on Dupuit critical oil production rate formula, an analytical model is developed to estimate the initial water cone shape at the point of critical drawdown. Then, with the initial water cone shape equation, we propose an analysis model for water cone subsidence in bottom water reservoir reservoirs. Model analysis and several sensitivity studies are conducted. This work presents accurate and fast analytical model to perform the water cone subsidence in bottom water drive reservoirs. To consider the recent interests in development of bottom drive reservoirs, our approach provides a promising technique for better understanding the subsidence of water cone.

  18. Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022).

    PubMed

    González Barrios, Andrés F; Zuo, Rongjun; Hashimoto, Yoshifumi; Yang, Li; Bentley, William E; Wood, Thomas K

    2006-01-01

    The cross-species bacterial communication signal autoinducer 2 (AI-2), produced by the purified enzymes Pfs (nucleosidase) and LuxS (terminal synthase) from S-adenosylhomocysteine, directly increased Escherichia coli biofilm mass 30-fold. Continuous-flow cells coupled with confocal microscopy corroborated these results by showing the addition of AI-2 significantly increased both biofilm mass and thickness and reduced the interstitial space between microcolonies. As expected, the addition of AI-2 to cells which lack the ability to transport AI-2 (lsr null mutant) failed to stimulate biofilm formation. Since the addition of AI-2 increased cell motility through enhanced transcription of five motility genes, we propose that AI-2 stimulates biofilm formation and alters its architecture by stimulating flagellar motion and motility. It was also found that the uncharacterized protein B3022 regulates this AI-2-mediated motility and biofilm phenotype through the two-component motility regulatory system QseBC. Deletion of b3022 abolished motility, which was restored by expressing b3022 in trans. Deletion of b3022 also decreased biofilm formation significantly, relative to the wild-type strain in three media (46 to 74%) in 96-well plates, as well as decreased biomass (8-fold) and substratum coverage (19-fold) in continuous-flow cells with minimal medium (growth rate not altered and biofilm restored by expressing b3022 in trans). Deleting b3022 changed the wild-type biofilm architecture from a thick (54-mum) complex structure to one that contained only a few microcolonies. B3022 positively regulates expression of qseBC, flhD, fliA, and motA, since deleting b3022 decreased their transcription by 61-, 25-, 2.4-, and 18-fold, respectively. Transcriptome analysis also revealed that B3022 induces crl (26-fold) and flhCD (8- to 27-fold). Adding AI-2 (6.4 muM) increased biofilm formation of wild-type K-12 MG1655 but not that of the isogenic b3022, qseBC, fliA, and motA mutants. Adding

  19. An evolutionary link between capsular biogenesis and surface motility in bacteria.

    PubMed

    Agrebi, Rym; Wartel, Morgane; Brochier-Armanet, Céline; Mignot, Tâm

    2015-05-01

    Studying the evolution of macromolecular assemblies is important to improve our understanding of how complex cellular structures evolved, and to identify the functional building blocks that are involved. Recent studies suggest that the macromolecular complexes that are involved in two distinct processes in Myxococcus xanthus - surface motility and sporulation - are derived from an ancestral polysaccharide capsule assembly system. In this Opinion article, we argue that the available data suggest that the motility machinery evolved from this capsule assembly system following a gene duplication event, a change in carbohydrate polymer specificity and the acquisition of additional proteins by the motility complex, all of which are key features that distinguish the motility and sporulation systems. Furthermore, the presence of intermediates of these systems in bacterial genomes suggests a testable evolutionary model for their emergence and spread.

  20. Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function.

    PubMed

    Swegen, Aleona; Lambourne, Sarah Renay; Aitken, R John; Gibb, Zamira

    2016-11-01

    Media used for equine sperm storage often contain relatively high concentrations of glucose, even though stallion spermatozoa preferentially utilize oxidative phosphorylation (OXPHOS) over glycolysis to generate ATP and support motility. Rosiglitazone is an antidiabetic compound that enhances metabolic flexibility and glucose utilization in various cell types, but its effects on sperm metabolism are unknown. This study investigated the effects of rosiglitazone on stallion sperm function in vitro, along with the possible role of AMP-activated protein kinase (AMPK) in mediating these effects. Spermatozoa were incubated with or without rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (CC; an AMPK inhibitor). Sperm motility, viability, reactive oxygen species production, mitochondrial membrane potential (mMP), ATP content, and glucose uptake capacity were measured. Samples incubated with rosiglitazone displayed significantly higher motility, percentage of cells with normal mMP, ATP content, and glucose uptake capacity, while sperm viability was unaffected. The percentage of spermatozoa positive for mitochondrial ROS was also significantly lower in rosiglitazone-treated samples. AMPK localized to the sperm midpiece, and its phosphorylation, was increased in rosiglitazone-treated spermatozoa. CC decreased sperm AMPK phosphorylation and reduced sperm motility, and successfully inhibited the effects of rosiglitazone. Inclusion of rosiglitazone in a room temperature sperm storage medium maintained sperm motility above 60% for 6 days, attaining significantly higher motility than sperm stored in control media. The ability of rosiglitazone to substantially alleviate the time-dependent deterioration of stallion spermatozoa by diverting metabolism away from OXPHOS and toward glycolysis has novel implications for the long-term, functional preservation of these cells. © 2016 by the Society for the Study of Reproduction

  1. Directionality of Individual Cone Photoreceptors in the Parafoveal Region

    PubMed Central

    Morris, Hugh J.; Blanco, Leonardo; Codona, Johanan L.; Li, Simone; Choi, Stacey S.; Doble, Nathan

    2015-01-01

    The pointing direction of cone photoreceptors can be inferred from the Stiles-Crawford Effect of the First Kind (SCE-I) measurement. Healthy retinas have tightly packed cones with a SCE-I function peak either centered in the pupil or with a slight nasal bias. Various retinal pathologies can change the profile of the SCE-I function implying that the arrangement or the light capturing properties of the cone photoreceptors are affected. Measuring the SCE-I may reveal early signs of photoreceptor change before actual cell apoptosis occurs. In vivo retinal imaging with adaptive optics (AO) was used to measure the pointing direction of individual cones at eight retinal locations in four control human subjects. Retinal images were acquired by translating an aperture in the light delivery arm through 19 different locations across a subject’s entrance pupil. Angular tuning properties of individual cones were calculated by fitting a Gaussian to the reflected intensity profile of each cone projected onto the pupil. Results were compared to those from an accepted psychophysical SCE-I measurement technique. The maximal difference in cone directionality of an ensemble of cones, ρ̄, between the major and minor axes of the Gaussian fit was 0.05 versus 0.29 mm−2 in one subject. All four subjects were found to have a mean nasal bias of 0.81 mm with a standard deviation of ±0.30 mm in the peak position at all retinal locations with mean ρ̄ value decreasing by 23% with increasing retinal eccentricity. Results show that cones in the parafoveal region converge towards the center of the pupillary aperture, confirming the anterior pointing alignment hypothesis. PMID:26494187

  2. Calcium/calmodulin and cAMP/protein kinase-A pathways regulate sperm motility in the stallion.

    PubMed

    Lasko, Jodi; Schlingmann, Karen; Klocke, Ann; Mengel, Grace Ann; Turner, Regina

    2012-06-01

    In spite of the importance of sperm motility to fertility in the stallion, little is known about the signaling pathways that regulate motility in this species. In other mammals, calcium/calmodulin signaling and the cyclic AMP/protein kinase-A pathway are involved in sperm motility regulation. We hypothesized that these pathways also were involved in the regulation of sperm motility in the stallion. Using immunoblotting, calmodulin and the calmodulin-dependent protein kinase II β were shown to be present in stallion sperm and with indirect immunofluorescence calmodulin was localized to the acrosome and flagellar principal piece. Additionally, inhibition of either calmodulin or protein kinase-A significantly reduced sperm motility without affecting viability. Following inhibition of calmodulin, motility was not restored with agonists of the cyclic AMP/protein kinase-A pathway. These data suggest that calcium/calmodulin and cyclic AMP/protein kinase-A pathways are involved in the regulation of stallion sperm motility. The failure of cyclic AMP/protein kinase-A agonists to restore motility of calmodulin inhibited sperm suggests that both pathways may be required to support normal motility. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Roles of ion transport in control of cell motility.

    PubMed

    Stock, Christian; Ludwig, Florian T; Hanley, Peter J; Schwab, Albrecht

    2013-01-01

    Cell motility is an essential feature of life. It is essential for reproduction, propagation, embryonic development, and healing processes such as wound closure and a successful immune defense. If out of control, cell motility can become life-threatening as, for example, in metastasis or autoimmune diseases. Regardless of whether ciliary/flagellar or amoeboid movement, controlled motility always requires a concerted action of ion channels and transporters, cytoskeletal elements, and signaling cascades. Ion transport across the plasma membrane contributes to cell motility by affecting the membrane potential and voltage-sensitive ion channels, by inducing local volume changes with the help of aquaporins and by modulating cytosolic Ca(2+) and H(+) concentrations. Voltage-sensitive ion channels serve as voltage detectors in electric fields thus enabling galvanotaxis; local swelling facilitates the outgrowth of protrusions at the leading edge while local shrinkage accompanies the retraction of the cell rear; the cytosolic Ca(2+) concentration exerts its main effect on cytoskeletal dynamics via motor proteins such as myosin or dynein; and both, the intracellular and the extracellular H(+) concentration modulate cell migration and adhesion by tuning the activity of enzymes and signaling molecules in the cytosol as well as the activation state of adhesion molecules at the cell surface. In addition to the actual process of ion transport, both, channels and transporters contribute to cell migration by being part of focal adhesion complexes and/or physically interacting with components of the cytoskeleton. The present article provides an overview of how the numerous ion-transport mechanisms contribute to the various modes of cell motility.

  4. Esophageal motility in children with suspected gastroesophageal reflux disease.

    PubMed

    Hoffman, Ilse; De Greef, Toon; Haesendonck, Nancy; Tack, Jan

    2010-06-01

    Motility abnormalities in adults with gastroesophageal reflux disease (GERD) include nontransmitted contractions, reduced distal esophageal contraction amplitude, and simultaneous contractions. Information on esophageal body motility in children with GERD is scarce. Our aim was to study esophageal motility patterns in children with GERD, taking into account the presence of anatomical abnormalities and neurological impairment, the effect of age on esophageal motility in GERD, and the relation between esophageal manometry and GERD severity parameters (acid exposure and presence of esophagitis). Consecutive children referred for severe GER(D) symptoms underwent a barium swallow, upper endoscopy, pH monitoring, and stationary water-perfused esophageal manometry. Mean lower esophageal sphincter (LES) pressure and velocity of propagation in the proximal and distal esophagus decreased with age in this group of children with GERD (all P < 0.01). Severely disturbed esophageal motility was found in children with previous esophageal atresia. Patients with psychomotor retardation had significantly lower occurrence of peristaltic waves (94% +/- 21% vs 79% +/- 38%; P = 0.001), distal propagation velocity (0.8 +/- 0.4 vs 0.6 +/- 0.5 cm/s; P = 0.05), and distal contraction duration (3.1 +/- 0.8 vs 3.4 +/- 1 seconds; P = 0.05). None of the manometric characteristics differed between patients with normal or abnormal esophageal pH monitoring or with or without erosive esophagitis. LES pressure and esophageal velocity decreased with increasing age. Esophageal manometry is severely impaired in children with esophageal atresia and psychomotor retardation. No specific esophageal motor abnormalities related to the presence of endoscopic esophagitis or abnormal pH monitoring were found.

  5. Loss and gain of cone types in vertebrate ciliary photoreceptor evolution.

    PubMed

    Musser, Jacob M; Arendt, Detlev

    2017-11-01

    Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Effect of 655 nm laser different powers on dog sperm motility parameters

    NASA Astrophysics Data System (ADS)

    Corral-Baqués, M. I.; Rigau, T.; Rivera, M. M.; Rodríguez-Gil, J. E.; Rigau, J.

    2006-04-01

    Introduction: One of the most appreciated features of the sperm is its motility, which depends on a big energy consumption despite differences among species. Laser acts direct or indirectly on mitochondria increasing ATP production. Material and method: By means of a Computer Aided Sperm Analysis (CASA) we have studied the effects of a 655 nm continuous wave diode laser irradiation at different power outputs with a dose of 3.3418 J on sperm motility. After an eosine-nigrosine stain to establish its quality, the second fraction of fresh beagle dog sperm was divided into 5 groups, 1 control and four to be irradiated respectively with an average output power of 6.84 mW, 15.43 mW, 33.05 mW and 49.66 mW. At times 0 and 45 minutes from irradiation pictures were taken and analysed with the Sperm class Analyzer SCA2002 programme. The motility parameters of 4987 spermatozoa studied were: curvilinear velocity (VCL), progressive velocity (VSL), straightness (STR), wobble (WOB), average path velocity (VAP), linearity (LIN), mean amplitude of lateral head displacement (ALHmed), beat cross frequency (BCF) and the total motility (MT). At time 15 minutes after irradiation a hypoosmotic swelling test (HOST) was done. Results: Several motility parameters that affect the overall motile sperm subpopulation structure have been changed by different output powers of a 655 nm diode laser irradiation, and prevents the decrease of the sperm motility properties along time.

  7. Nano-cone resistive memory for ultralow power operation.

    PubMed

    Kim, Sungjun; Jung, Sunghun; Kim, Min-Hwi; Kim, Tae-Hyeon; Bang, Suhyun; Cho, Seongjae; Park, Byung-Gook

    2017-03-24

    SiN x -based nano-structure resistive memory is fabricated by fully silicon CMOS compatible process integration including particularly designed anisotropic etching for the construction of a nano-cone silicon bottom electrode (BE). Bipolar resistive switching characteristics have significantly reduced switching current and voltage and are demonstrated in a nano-cone BE structure, as compared with those in a flat BE one. We have verified by systematic device simulations that the main cause of reduction in the performance parameters is the high electric field being more effectively concentrated at the tip of the cone-shaped BE. The greatly improved nonlinearity of the nano-cone resistive memory cell will be beneficial in the ultra-high-density crossbar array.

  8. High-resolution impedance manometry parameters enhance the esophageal motility evaluation in non-obstructive dysphagia patients without a major Chicago Classification motility disorder.

    PubMed

    Carlson, D A; Omari, T; Lin, Z; Rommel, N; Starkey, K; Kahrilas, P J; Tack, J; Pandolfino, J E

    2017-03-01

    High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We aimed to perform a collaborative analysis of HRIM metrics to evaluate patients with non-obstructive dysphagia. Fourteen asymptomatic controls (58% female; ages 20-50) and 41 patients (63% female; ages 24-82), 18 evaluated for dysphagia and 23 for reflux (non-dysphagia patients), with esophageal motility diagnoses of normal motility or ineffective esophageal motility, were evaluated with HRIM and a global dysphagia symptom score (Brief Esophageal Dysphagia Questionnaire). HRIM was analyzed to assess Chicago Classification metrics, automated pressure-flow metrics, the esophageal impedance integral (EII) ratio, and the bolus flow time (BFT). Significant symptom-metric correlations were detected only with basal EGJ pressure, EII ratio, and BFT. The EII ratio, BFT, and impedance ratio differed between controls and dysphagia patients, while the EII ratio in the upright position was the only measure that differentiated dysphagia from non-dysphagia patients. The EII ratio and BFT appear to offer an improved diagnostic evaluation in patients with non-obstructive dysphagia without a major esophageal motility disorder. Bolus retention as measured with the EII ratio appears to carry the strongest association with dysphagia, and thus may aid in the characterization of symptomatic patients with otherwise normal manometry. © 2016 John Wiley & Sons Ltd.

  9. Norepinephrine and dopamine increase motility, biofilm formation, and virulence of Vibrio harveyi

    PubMed Central

    Yang, Qian; Anh, Nguyen D. Q.; Bossier, Peter; Defoirdt, Tom

    2014-01-01

    Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine (NE) and dopamine (Dopa) increased growth in serum-supplemented medium, siderophore production, swimming motility, and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, NE-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopa-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesize that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host. PMID:25414697

  10. Growth-mediated autochemotactic pattern formation in self-propelling bacteria

    NASA Astrophysics Data System (ADS)

    Mukherjee, Mrinmoy; Ghosh, Pushpita

    2018-01-01

    Bacteria, while developing a multicellular colony or biofilm, can undergo pattern formation by diverse intricate mechanisms. One such route is directional movement or chemotaxis toward or away from self-secreted or externally employed chemicals. In some bacteria, the self-produced signaling chemicals or autoinducers themselves act as chemoattractants or chemorepellents and thereby regulate the directional movements of the cells in the colony. In addition, bacteria follow a certain growth kinetics which is integrated in the process of colony development. Here, we study the interplay of bacterial growth dynamics, cell motility, and autochemotactic motion with respect to the self-secreted diffusive signaling chemicals in spatial pattern formation. Using a continuum model of motile bacteria, we show growth can act as a crucial tuning parameter in determining the spatiotemporal dynamics of a colony. In action of growth dynamics, while chemoattraction toward autoinducers creates arrested phase separation, pattern transitions and suppression can occur for a fixed chemorepulsive strength.

  11. The toxic effect of opioid analgesics on human sperm motility in vitro.

    PubMed

    Xu, Bo; Wang, Zhi-Ping; Wang, Yan-Juan; Lu, Pei-Hua; Wang, Li-Jun; Wang, Xiao-Hai

    2013-04-01

    Opioid analgesics are the most common therapeutic analgesic for acute pain. In this study, the toxicological and pharmacological features of a group of opioid analgesics were characterized by the motility of human sperm. Aliquots of sperm were incubated with various concentrations of opioid analgesics in vitro. Computer-assisted sperm analysis was used to assess sperm motility at 15 minutes, 2 hours, and 4 hours after drug addition to the medium. Butorphanol and dezocine showed marked reduction of motility after incubation with sperm for 15 minutes. Butorphanol was more effective than dezocine in immobilizing sperm. Other opioids studied, such as fentanyl, alfentanil, and sufentanil, showed only partial inhibitory activity. Based on the data reported herein, we have found that butorphanol and dezocine exert a sperm-immobilizing effect. However, fentanyl, alfentanil, and sufentanil exhibit only partial inhibition of sperm motility. Given the increasing use of opioids and their potential effect on sperm motility, these findings are greatly relevant to male reproductive health.

  12. Cone calorimeter tests of wood composites

    Treesearch

    Robert H. White; Kuma Sumathipala

    2013-01-01

    The cone calorimeter is widely used for the determination of the heat release rate (HRR) of building products and other materials. As part of an effort to increase the availability of cone calorimeter data on wood products, the U.S. Forest Products Laboratory and the American Wood Council conducted this study on composite wood products in cooperation with the Composite...

  13. Transposon Insertions of magellan-4 That Impair Social Gliding Motility in Myxococcus xanthus

    PubMed Central

    Youderian, Philip; Hartzell, Patricia L.

    2006-01-01

    Myxococcus xanthus has two different mechanisms of motility, adventurous (A) motility, which permits individual cells to glide over solid surfaces, and social (S) motility, which permits groups of cells to glide. To identify the genes involved in S-gliding motility, we mutagenized a ΔaglU (A−) strain with the defective transposon, magellan-4, and screened for S− mutants that form nonmotile colonies. Sequence analysis of the sites of the magellan-4 insertions in these mutants and the alignment of these sites with the M. xanthus genome sequence show that two-thirds of these insertions lie within 27 of the 37 nonessential genes known to be required for social motility, including those necessary for the biogenesis of type IV pili, exopolysaccharide, and lipopolysaccharide. The remaining insertions also identify 31 new, nonessential genes predicted to encode both structural and regulatory determinants of S motility. These include three tetratricopeptide repeat proteins, several regulators of transcription that may control the expression of genes involved in pilus extension and retraction, and additional enzymes involved in polysaccharide metabolism. Three insertions that abolish S motility lie within genes predicted to encode glycolytic enzymes, suggesting that the signal for pilus retraction may be a simple product of exopolysaccharide catabolism. PMID:16299386

  14. PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

    PubMed

    Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

    2016-04-07

    Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

  15. Hurricane track forecast cones from fluctuations

    PubMed Central

    Meuel, T.; Prado, G.; Seychelles, F.; Bessafi, M.; Kellay, H.

    2012-01-01

    Trajectories of tropical cyclones may show large deviations from predicted tracks leading to uncertainty as to their landfall location for example. Prediction schemes usually render this uncertainty by showing track forecast cones representing the most probable region for the location of a cyclone during a period of time. By using the statistical properties of these deviations, we propose a simple method to predict possible corridors for the future trajectory of a cyclone. Examples of this scheme are implemented for hurricane Ike and hurricane Jimena. The corridors include the future trajectory up to at least 50 h before landfall. The cones proposed here shed new light on known track forecast cones as they link them directly to the statistics of these deviations. PMID:22701776

  16. Variability in human cone topography assessed by adaptive optics scanning laser ophthalmoscopy

    PubMed Central

    Zhang, Tianjiao; Godara, Pooja; Blanco, Ernesto R.; Griffin, Russell L; Wang, Xiaolin; Curcio, Christine A.; Zhang, Yuhua

    2015-01-01

    Purpose To assess between- and within-individual variability of macular cone topography in the eyes of young adults. Design Observational case series. Methods Cone photoreceptors in 40 eyes of 20 subjects aged 19–29 years with normal maculae were imaged using a research adaptive optics scanning laser ophthalmoscope. Refractive errors ranged from −3.0 D to 0.63 D and differed by <0.50 D in fellow eyes. Cone density was assessed on a two-dimensional sampling grid over the central 2.4 mm × 2.4 mm. Between-individual variability was evaluated by coefficient of variation (CV). Within-individual variability was quantified by maximum difference and root-mean-square (RMS). Cones were cumulated over increasing eccentricity. Results Peak densities of foveal cones are 168,162 ± 23,529 cones/mm2 (mean ± SD) (CV = 0.14). The number of cones within the cone-dominated foveola (0.8–0.9 mm diameter) is 38,311 ± 2,319 (CV = 0.06). The RMS cone density difference between fellow eyes is 6.78%, and the maximum difference is 23.6%. Mixed model statistical analysis found no difference in the association between eccentricity and cone density in the superior/nasal (p=0.8503), superior/temporal (p=0.1551), inferior/nasal (p=0.8609), and inferior/temporal (p=0.6662) quadrants of fellow eyes. Conclusions New instrumentation imaged the smallest foveal cones, thus allowing accurate assignment of foveal centers and assessment of variability in macular cone density in a large sample of eyes. Though cone densities vary significantly in the fovea, the total number of foveolar cones are very similar both between- and within-subjects. Thus, the total number of foveolar cones may be an important measure of cone degeneration and loss. PMID:25935100

  17. Analysis of electrical noise in turtle cones

    PubMed Central

    Lamb, T. D.; Simon, E. J.

    1977-01-01

    1. Properties of the light-sensitive voltage noise in cones in the retina of the turtle, Pseudemys scripta elegans, have been studied by intracellular recording. 2. Suppression of the noise by light was a function of the hyperpolarizing response of a cone but not of the size or pattern of illumination. 3. Power density spectra of the noise were fitted in many cones by the product of two Lorentzians with characteristic time constants τ1 and τ2 averaging 40 and 7 msec respectively. The spectra of some cells were peaked and could be fitted by a resonance curve. 4. Spectra in dim light exhibited decreased low frequency power. They could often be fitted by a product of two Lorentzians using the same value of τ2 as used in darkness but decreasing τ1 and the zero frequency asymptote. An e-fold reduction in τ1 occurred with lights which hyperpolarized by 4-7 mV. 5. Injection of hyperpolarizing currents of about 0·1-0·2 nA into weakly coupled cones reduced the noise, and also reduced the sensitivity to dim flashes. 6. The variance-voltage relation during steady illumination of different intensities differed from cone to cone. Dim lights increased the noise in some cells and decreased it in others, but moderately bright lights which gave steady responses of more than about one third maximal reduced the noise in all cells. 7. When the cell was transiently depolarized during the differentiated component following steady illumination, the noise was less than it was after prolonged darkness. 8. In the after-effect of bright light, the time course of recovery of noise was the same as that of flash sensitivity and voltage. The noise was reduced e-fold for hyperpolarizations averaging 3 mV while for sensitivity this reduction occurred for 1·3 mV. For a given hyperpolarization the noise was lower during the after-effect than during steady dim illumination. 9. When a series of dim flashes was delivered to a cone, no significant increase in variance over the dark noise was

  18. Mouse cones require an arrestin for normal inactivation of phototransduction.

    PubMed

    Nikonov, Sergei S; Brown, Bruce M; Davis, Jason A; Zuniga, Freddi I; Bragin, Alvina; Pugh, Edward N; Craft, Cheryl M

    2008-08-14

    Arrestins are proteins that arrest the activity of G protein-coupled receptors (GPCRs). While it is well established that normal inactivation of photoexcited rhodopsin, the GPCR of rod phototransduction, requires arrestin (Arr1), it has been controversial whether the same requirement holds for cone opsin inactivation. Mouse cone photoreceptors express two distinct visual arrestins: Arr1 and Arr4. By means of recordings from cones of mice with one or both arrestins knocked out, this investigation establishes that a visual arrestin is required for normal cone inactivation. Arrestin-independent inactivation is 70-fold more rapid in cones than in rods, however. Dual arrestin expression in cones could be a holdover from ancient genome duplication events that led to multiple isoforms of arrestin, allowing evolutionary specialization of one form while the other maintains the basic function.

  19. Genetic Analysis of Collective Motility of Paenibacillus sp. NAIST15-1

    PubMed Central

    Kobayashi, Kazuo; Kanesaki, Yu

    2016-01-01

    Bacteria have developed various motility mechanisms to adapt to a variety of solid surfaces. A rhizosphere isolate, Paenibacillus sp. NAIST15-1, exhibited unusual motility behavior. When spotted onto 1.5% agar media, Paenibacillus sp. formed many colonies, each of which moved around actively at a speed of 3.6 μm/sec. As their density increased, each moving colony began to spiral, finally forming a static round colony. Despite its unusual motility behavior, draft genome sequencing revealed that both the composition and organization of flagellar genes in Paenibacillus sp. were very similar to those in Bacillus subtilis. Disruption of flagellar genes and flagellar stator operons resulted in loss of motility. Paenibacillus sp. showed increased transcription of flagellar genes and hyperflagellation on hard agar media. Thus, increased flagella and their rotation drive Paenibacillus sp. motility. We also identified a large extracellular protein, CmoA, which is conserved only in several Paenibacillus and related species. A cmoA mutant could neither form moving colonies nor move on hard agar media; however, motility was restored by exogenous CmoA. CmoA was located around cells and enveloped cell clusters. Comparison of cellular behavior between the wild type and cmoA mutant indicated that extracellular CmoA is involved in drawing water out of agar media and/or smoothing the cell surface interface. This function of CmoA probably enables Paenibacillus sp. to move on hard agar media. PMID:27764113

  20. Image reconstruction from cone-beam projections with attenuation correction

    NASA Astrophysics Data System (ADS)

    Weng, Yi

    1997-07-01

    In single photon emission computered tomography (SPECT) imaging, photon attenuation within the body is a major factor contributing to the quantitative inaccuracy in measuring the distribution of radioactivity. Cone-beam SPECT provides improved sensitivity for imaging small organs. This thesis extends the results for 2D parallel- beam and fan-beam geometry to 3D parallel-beam and cone- beam geometries in order to derive filtered backprojection reconstruction algorithms for the 3D exponential parallel-beam transform and for the exponential cone-beam transform with sampling on a sphere. An exact inversion formula for the 3D exponential parallel-beam transform is obtained and is extended to the 3D exponential cone-beam transform. Sampling on a sphere is not useful clinically and current cone-beam tomography, with the focal point traversing a planar orbit, does not acquire sufficient data to give an accurate reconstruction. Thus a data acquisition method that obtains complete data for cone-beam SPECT by simultaneously rotating the gamma camera and translating the patient bed, so that cone-beam projections can be obtained with the focal point traversing a helix that surrounds the patient was developed. First, an implementation of Grangeat's algorithm for helical cone- beam projections was developed without attenuation correction. A fast new rebinning scheme was developed that uses all of the detected data to reconstruct the image and properly normalizes any multiply scanned data. In the case of attenuation no theorem analogous to Tuy's has been proven. We hypothesized that an artifact-free reconstruction could be obtained even if the cone-beam data are attenuated, provided the imaging orbit satisfies Tuy's condition and the exact attenuation map is known. Cone-beam emission data were acquired by using a circle- and-line and a helix orbit on a clinical SPECT system. An iterative conjugate gradient reconstruction algorithm was used to reconstruct projection data with a

  1. Bursting the Taylor cone bubble

    NASA Astrophysics Data System (ADS)

    Pan, Zhao; Truscott, Tadd

    2014-11-01

    A soap bubble fixed on a surface and placed in an electric field will take on the shape of a cone rather than constant curvature (dome) when the electrical field is not present. The phenomenon was introduced by J. Zeleny (1917) and studied extensively by C.T. Wilson & G.I. Taylor (1925). We revisit the Taylor cone problem by studying the deformation and bursting of soap bubbles in a point charge electric field. A single bubble takes on the shape of a cone in the electric field and a high-speed camera equipped with a micro-lens is used to observe the unsteady dynamics at the tip. Rupture occurs as a very small piece of the tip is torn away from the bubble toward the point charge. Based on experiments, a theoretical model is developed that predicts when rupture should occur. This study may help in the design of foam-removal techniques in engineering and provide a better understanding of an electrified air-liquid interface.

  2. Converging Resonance Cones in the LAPTAG plasma

    NASA Astrophysics Data System (ADS)

    Katz, Cami; Ha, Chris; Gekelman, Walter; Pribyl, Patrick; Agmon, Nathan; Wise, Joe; Baker, Bob

    2013-10-01

    The LAPTAG laboratory is a high school outreach effort that has a 1.5m long 50 cm diameter magnetized plasma device. The plasma is produced by an ICP source (1X109 < n < 5X1011 cm-3) and has computer controlled data acquisition. Ring antennas are used to produce converging resonance cones. The experiment was performed in the quiescent plasma afterglow. The electrostatic cones were produced by rf applied to the rings (80 < f < 120 MHz), where fRF < fcones were clearly measured as well as reflections from the density gradient at the plasma edge. The cone angle compares well to the theoretical value. The two focal points, far removed from the antenna are ideal locations for generating hotspots and density perturbations when the rf power is high. Graphics and movies showing the cone generation at different frequencies will be shown. Work performed at the Basic Plasma Science Facility supported by DOE and NSF.

  3. Identification of phosphoproteins coupled to initiation of motility in live epididymal mouse sperm

    NASA Technical Reports Server (NTRS)

    Tash, J. S.; Bracho, G. E.

    1998-01-01

    A method for collecting live immotile cauda epididymal mouse sperm that initiate motility by dilution into an activation buffer is described. Sperm in collection buffer showed low percent motility (MOT) and population progression (PRG) that increased 10-fold and 9-fold, respectively, during the first 2 min after dilution into activation buffer. Western phosphoserine (pS), phosphothreonine (pT), and phosphotyrosine (pY) analysis revealed a 120 kDa protein that markedly increased in pT content during initiation of motility and may be related to FP130, the motility-coupled axonemal protein of sea urchin sperm. A prominent 82 kDa protein that was pS and pT-phosphorylated in immotile and motile sperm is likely the fibrous sheath component AKAP82 that is phosphorylated during spermatogenesis. Analysis of live human sperm also identified a prominent 120 kDa pT protein. Thus it appears that phosphorylation of FP130 and related 120 kDa proteins in mouse, and perhaps human sperm, represent common targets during motility initiation in sperm. Copyright 1998 Academic Press.

  4. EFFECT OF CRYOPRESERVATION AND THEOPHYLLINE ON MOTILITY CHARACTERISTICS OF LAKE STURGEON (ACIPENSER FULVESCENS) SPERMATOZOA

    EPA Science Inventory

    Computer-assisted motility analysis (CASA) was used to evaluate the effect of cryopreservation and theophylline treatment on sperm motility of lake sturgeon (Acipenser fulvescens).Motility was recorded at 0 and 5 min postactivation.The effect of cryopreservation on sperm acrosin-...

  5. Hydrodynamic Contributions to Amoeboid Cell Motility

    NASA Astrophysics Data System (ADS)

    Lewis, Owen; Guy, Robert

    2012-11-01

    Understanding the methods by which cells move is a fundamental problem in modern biology. Recent evidence has shown that the fluid dynamics of cytoplasm can play a vital role in cellular motility. The slime mold Physarum polycephalum provides an excellent model organism for the study of amoeboid motion. In this research, we use a simply analytic model in conjuction with computational experiments to investigate intracellular fluid flow in a simple model of Physarum. Of particlar interest are stresses generated by cytoplasmic flow which may be used to aid in cellular motility. In our numerical model, the Immersed Boundary Method is used to account for such stresses. We investigate the relationship between contraction waves, flow waves, adhesion, and locomotive forces in an attempt to characterize conditions necessary to generate directed motion.

  6. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins

    NASA Astrophysics Data System (ADS)

    Loisel, Thomas P.; Boujemaa, Rajaa; Pantaloni, Dominique; Carlier, Marie-France

    1999-10-01

    Actin polymerization is essential for cell locomotion and is thought to generate the force responsible for cellular protrusions. The Arp2/3 complex is required to stimulate actin assembly at the leading edge in response to signalling. The bacteria Listeria and Shigella bypass the signalling pathway and harness the Arp2/3 complex to induce actin assembly and to propel themselves in living cells. However, the Arp2/3 complex alone is insufficient to promote movement. Here we have used pure components of the actin cytoskeleton to reconstitute sustained movement in Listeria and Shigella in vitro. Actin-based propulsion is driven by the free energy released by ATP hydrolysis linked to actin polymerization, and does not require myosin. In addition to actin and activated Arp2/3 complex, actin depolymerizing factor (ADF, or cofilin) and capping protein are also required for motility as they maintain a high steady-state level of G-actin, which controls the rate of unidirectional growth of actin filaments at the surface of the bacterium. The movement is more effective when profilin, α-actinin and VASP (for Listeria) are also included. These results have implications for our understanding of the mechanism of actin-based motility in cells.

  7. Mouse Cone Photoreceptors Co-express Two Functional Visual Arrestins

    PubMed Central

    Nikonov, Sergei S.; Brown, Bruce M.; Davis, Jason A.; Zuniga, Freddi I.; Bragin, Alvina; Pugh, Edward N.; Craft, Cheryl M.

    2008-01-01

    Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. Mouse cone photoreceptors express two visual arrestins, Arr1 and Arr4 (Carr). We quantified their expression levels and subcellular distributions in mouse cones: total Arr1 was estimated to be in an ~ 6:1 ratio to cone opsin, about 50-fold higher than Arr4. Recordings from single cones of Arr1−/− and Arr4−/− mice establish that both proteins are competent to arrest the activity of photoactivated S- and M- cone opsins. Recordings from Arr1−/− , Arr4−/− double-knockout mice establish a requirement for at least one of the two visual arrestins for normal cone opsin inactivation at all flash intensities. These recordings also reveal low activity photoproducts of S- and M-opsins that are absent when Grk1 and an arrestin are co-expressed, but which decay 70-fold more rapidly than the comparable photoproducts of rhodopsin in rods. PMID:18701071

  8. Dynamic Recrystallization Kinetics of 690 Alloy During Hot Compression of Double-Cone Samples

    NASA Astrophysics Data System (ADS)

    Wang, Jue; Zhai, Shun-Chao

    2017-03-01

    Hot compression tests of double-cone samples were conducted for 690 alloy to study the kinetic behavior of the complete dynamic recrystallization (DRX) process under low deformation temperatures from 960 to 1080 °C. The microstructure of 82 points in the vertical section of every deformed sample was quantitatively analyzed to determine the DRX fraction. Corresponding strain of these points was calculated by finite element simulations. Kinetic curves of the specimens with different preheating temperatures were then constructed. The features of various boundaries with different misorientation angles were investigated by electron backscatter diffraction technology and transmission electron microscope. The results showed that the strain is continuously and symmetrically distributed along the centerline of the vertical section. Large strain of 1.84 was obtained when the compression amount is 12 mm for double-cone samples. All the fitted kinetic curves display an "S" type, which possess a low growth rate of DRX at the beginning and the end of compression. The critical strain of recrystallization decreases with the increase in preheating temperature, while the completion strain remains around 1.5 for all the samples. The initial and maximum growth rates of DRX fraction have the opposite trend with the change in temperature, which is considered to be attributed to the behaviors of different misorientation boundaries.

  9. Effects of environment factors on initiation of sperm motility in sea cucumber Apostichopus japonicus (Selenka)

    NASA Astrophysics Data System (ADS)

    Yu, Li; Shao, Mingyu; Bao, Zhenmin; Hu, Jingjie; Zhang, Zhifeng

    2011-06-01

    Sperm of sea cucumber Apostichopus japonicus (Selenka) were quiescent in electrolyte NaCl solution and artificial seawater (ASW) and nonelectrolyte glucose and mannitol solutions when the osmolality was less than 200 mOsm kg-1. The sperm started to be motile as a result of increased osmolality, indicating an osmolality-dependent initiation of sperm motility in sea cucumber. After a brief incubation in hypotonic NaCl and glucose solutions with osmolalities of 200 and 400 mOsm kg-1, sperm lost partial motile ability. Sperm became immobilized when pH was 6.0 in NaCl, glucose and mannitol solutions, suggesting that an H+ release is involved in sperm activation. The decreased pH had no effect on the percentage of motile sperm in ASW, whereas it delayed the time period to reach the maximum motility (motilitymax). Extracellular Ca2+ in electrolyte solutions was not essential for motility stimulation but shortened the time of reaching motilitymax. When Ca2+ was mixed in nonelectrolyte solutions the sperm motility was completely suppressed. The K+ channel blocker, quinine, suppressed the sperm motility in electrolyte solution, showing a possible involvement of K+ transport in the process. High K+ concentration did not affect the sperm motility in NaCl solution, but decreased it in ASW and almost entirely suppressed it in nonelectrolyte solutions. The different effects of pH and K+ in ASW and NaCl solution indicate that external ions may also regulate sperm motility.

  10. Earthquake-like dynamics in Myxococcus xanthus social motility

    PubMed Central

    Gibiansky, Maxsim L.; Hu, Wei; Dahmen, Karin A.; Shi, Wenyuan; Wong, Gerard C. L.

    2013-01-01

    Myxococcus xanthus is a bacterium capable of complex social organization. Its characteristic social (“S”)-motility mechanism is mediated by type IV pili (TFP), linear actuator appendages that propel the bacterium along a surface. TFP are known to bind to secreted exopolysaccharides (EPS), but it is unclear how M. xanthus manages to use the TFP-EPS technology common to many bacteria to achieve its unique coordinated multicellular movements. We examine M. xanthus S-motility, using high-resolution particle-tracking algorithms, and observe aperiodic stick–slip movements. We show that they are not due to chemotaxis, but are instead consistent with a constant TFP-generated force interacting with EPS, which functions both as a glue and as a lubricant. These movements are quantitatively homologous to the dynamics of earthquakes and other crackling noise systems. These systems exhibit critical behavior, which is characterized by a statistical hierarchy of discrete “avalanche” motions described by a power law distribution. The measured critical exponents from M. xanthus are consistent with mean field theoretical models and with other crackling noise systems, and the measured Lyapunov exponent suggests the existence of highly branched EPS. Such molecular architectures, which are common for efficient lubricants but rare in bacterial EPS, may be necessary for S-motility: We show that the TFP of leading “locomotive” cells initiate the collective motion of follower cells, indicating that lubricating EPS may alleviate the force generation requirements on the lead cell and thus make S-motility possible. PMID:23341622

  11. Autocrine regulation of human sperm motility by tachykinins

    PubMed Central

    2010-01-01

    Background We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Methods Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). Results The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). Conclusion These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins. PMID:20796280

  12. Correlation between extraocular muscle size and motility restriction in thyroid eye disease.

    PubMed

    Dagi, Lora R; Zoumalan, Christopher I; Konrad, Hindola; Trokel, Stephen L; Kazim, Michael

    2011-01-01

    Evaluate the relationship between extraocular muscle (EOM) size, measured by computed tomography, and ocular motility in thyroid eye disease (TED). This case series is based on a retrospective review of the records of 54 patients (108 orbits) with TED. Main outcome measures included EOM size and degree of motility restriction. The average diameter of each rectus muscle was compared with published norms. Four subpopulations based on Age (< 40 or ≥ 40 years) and State of thyroid eye disease (active or stable) were studied. Versions were measured by the corneal light reflex method. The trend of muscle diameter versus motility restriction was evaluated. The average EOM diameter was greater than the norm in the study cohort and 4 subpopulations. The average diameter was largest in the Older and Active TED subpopulations. The inferior rectus and medial rectus were most frequently restricted in the study cohort and 4 subpopulations. The medial rectus had the strongest trend between increasing diameter and motility restriction, followed by the inferior rectus and the superior muscle group (comprised of the superior rectus and levator palpebrae superioris). However, there was a general lack of strong correlation between the diameter of the rectus muscles and their respective motility, especially in the Younger subpopulation. EOM diameters are larger and have more restricted motility in the Older and Active TED subpopulations. Contrary to prior publications, the correlation between EOM diameters and motility was weak, especially in the Younger subpopulation. These findings suggest that the pathophysiology of EOM enlargement is different based upon the age of the patient and the activity of the orbitopathy.

  13. Ring resonator optical modes in InGaN/GaN structures grown on micro-cone-patterned sapphire substrates

    NASA Astrophysics Data System (ADS)

    Kazanov, D. R.; Pozina, G.; Jmerik, V. N.; Shubina, T. V.

    2018-03-01

    Molecular beam epitaxy (MBE) of III-nitride compounds on specially prepared cone-shaped patterned substrates is being actively developed nowadays, especially for nanophotonic applications. This type of substrates enables the successful growth of hexagonal nanorods (NRs). The insertion of an active quantum-sized region of InGaN inside a GaN NR allows us to enhance the rate of optical transitions by coupling them with resonant optical modes in the NR. However, we have observed the enhancement of emission not only from the NR but also around the circumference region of the cone-shaped base. We have studied this specific feature and demonstrated its impact on the output signal.

  14. Some inversion formulas for the cone transform

    NASA Astrophysics Data System (ADS)

    Terzioglu, Fatma

    2015-11-01

    Several novel imaging applications have lead recently to a variety of Radon type transforms, where integration is made over a family of conical surfaces. We call them cone transforms (in 2D they are also called V-line or broken ray transforms). Most prominently, they are present in the so called Compton camera imaging that arises in medical diagnostics, astronomy, and lately in homeland security applications. Several specific incarnations of the cone transform have been considered separately. In this paper, we address the most general (and overdetermined) cone transform, obtain integral relations between cone and Radon transforms in {{{R}}}n, and a variety of inversion formulas. In many applications (e.g., in homeland security), the signal to noise ratio is very low. So, if overdetermined data is collected (as in the case of Compton imaging), attempts to reduce the dimensionality might lead to essential elimination of the signal. Thus, our main concentration is on obtaining formulas involving overdetermined data.

  15. Strain-Mediated Modification of Phagraphene Dirac Cones

    DOE PAGES

    Lopez-Bezanilla, Alejandro

    2016-07-07

    We present a first-principles study on the electronic and dynamical properties of phagraphene [Nano Lett., 2015, 15 (9), pp 6182]. This carbon allotrope exhibits a square unit cell, Dirac cones, and robustness against uniaxial deformation. By analyzing the contribution of each carbon atom orbital in the formation of the electronic states, we conclude that only the pz orbitals of eight out of the twenty atoms in the square unit cell are responsible of the formation of the nano-structure Dirac cones. Spatial symmetry breaking of the underlying honeycomb-like network upon shear stress application leads to a band gap opening. The analysismore » of the phonon spectra demonstrates that the dynamical stability of phagraphene is guaranteed for small distortion angles. Phagraphene is identified here as the first all-C graphitic monolayer with Dirac cones modifiable by a small and realistic physical deformation. The analysis and conclusions of this study can be applied to other monolayered materials exhibiting Dirac cones in square lattices.« less

  16. Noise masking of S-cone increments and decrements.

    PubMed

    Wang, Quanhong; Richters, David P; Eskew, Rhea T

    2014-11-12

    S-cone increment and decrement detection thresholds were measured in the presence of bipolar, dynamic noise masks. Noise chromaticities were the L-, M-, and S-cone directions, as well as L-M, L+M, and achromatic (L+M+S) directions. Noise contrast power was varied to measure threshold Energy versus Noise (EvN) functions. S+ and S- thresholds were similarly, and weakly, raised by achromatic noise. However, S+ thresholds were much more elevated by S, L+M, L-M, L- and M-cone noises than were S- thresholds, even though the noises consisted of two symmetric chromatic polarities of equal contrast power. A linear cone combination model accounts for the overall pattern of masking of a single test polarity well. L and M cones have opposite signs in their effects upon raising S+ and S- thresholds. The results strongly indicate that the psychophysical mechanisms responsible for S+ and S- detection, presumably based on S-ON and S-OFF pathways, are distinct, unipolar mechanisms, and that they have different spatiotemporal sampling characteristics, or contrast gains, or both. © 2014 ARVO.

  17. Variability in bleach kinetics and amount of photopigment between individual foveal cones.

    PubMed

    Bedggood, Phillip; Metha, Andrew

    2012-06-20

    To study the bleaching dynamics of individual foveal cone photoreceptors using an adaptive optics ophthalmoscope. After dark adaptation, cones were progressively bleached and imaged by a series of flashes of 545-nm to 570-nm light at 12 Hz. Intensity measurements were made within the foveal avascular zone (FAZ) to avoid confounding signals from the inner retinal blood supply. Over 1300 cones in this region were identified and tracked through the imaging sequences. A single subject was used who demonstrated the necessary steady fixation, wide FAZ, and resolvability of cones close to the foveal center. The mean intensity of all cones was well-described by first-order kinetics. Individual cones showed marked differences from the mean, both in rate of bleach and amount of photopigment; there was an inverse correlation between these two parameters. A subset of the cones showed large oscillations in intensity consistent with interference from light scattered within the cone outer segment. These cones also bleached more quickly, implying that rapid bleaching induces greater amounts of scatter. Neighboring cones in the fovea display high variability in their optical properties.

  18. Volcanic cones in Hydraotes chaos : implications for the chaotic terrains formation

    NASA Astrophysics Data System (ADS)

    Meresse, S.; Costard, F.; Mangold, N.; Masson, P.; Neukum, G.

    2006-12-01

    Numerous geologic scenarios have been proposed for the chaotic terrains formation. They include (1) sub-ice volcanism and other magma-ice interactions and (2) catastrophic release of groundwater from confined aquifers. The lack of volcanic morphology in the chaos was an handicap for the hypothesis of magma-ice interactions but the HRSC (High Resolution Stereo Camera) images have recently revealed possible volcanic cones inside the Hydraotes chaos. About thirty cones lie on the lowest parts of the chaos at elevation between -4300 and -5100 meters. They have basal diameters of 500-1900 m and heights exceeding 100 m. They are observed on young surface: the south smooth floor and inside the narrow valleys separating the mesas. The cones are relatively fresh. Similar morphologies of small cone-shaped structures have been previously identified in the northern lowlands of Mars (Chryse, Acidalia, Amazonis, Isidis and Elysuim Planitia) but their origin remains uncertain. A number of volcanic or cold climate landforms were proposed as potential terrestrial analogues : Icelandic pseudocraters (or rootless cones), cinder cones, tuff cones, pingos and spatter cones. The morphologic measurements made on the Hydraotes cones argue rather for a volcanic origin in comparison with terrestrial analogues. These first volcanic cones observed in Hydraotes chaos suggest that volcanic or subvolcanic activity might have played an important part in the chaotic terrains formation and outflow channels genesis.

  19. Conical Refraction: new observations and a dual cone model.

    PubMed

    Sokolovskii, G S; Carnegie, D J; Kalkandjiev, T K; Rafailov, E U

    2013-05-06

    We propose a paraxial dual-cone model of conical refraction involving the interference of two cones of light behind the exit face of the crystal. The supporting experiment is based on beam selecting elements breaking down the conically refracted beam into two separate hollow cones which are symmetrical with one another. The shape of these cones of light is a product of a 'competition' between the divergence caused by the conical refraction and the convergence due to the focusing by the lens. The developed mathematical description of the conical refraction demonstrates an excellent agreement with experiment.

  20. HES6 enhances the motility of alveolar rhabdomyosarcoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wickramasinghe, Caroline M; MRC Laboratory of Molecular Biology, Addenbrooke's Hospital Cambridge, CB2 0QH; Domaschenz, Renae

    Absract: HES6, a member of the hairy-enhancer-of-split family of transcription factors, plays multiple roles in myogenesis. It is a direct target of the myogenic transcription factor MyoD and has been shown to regulate the formation of the myotome in development, myoblast cell cycle exit and the organization of the actin cytoskeleton during terminal differentiation. Here we investigate the expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which expresses myogenic genes but fails to differentiate into muscle. We show that HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas expressing PAX/FOXO1 fusion genes (ARMSp). Knockdownmore » of HES6 mRNA in the ARMSp cell line RH30 reduces proliferation and cell motility. This phenotype is rescued by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore, expression microarray analysis indicates that the HES6 knockdown is associated with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN overexpression rescues the motility defect resulting from HES6 knockdown. These findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both proliferation and cell motility.« less

  1. Beneficial effects of relaxin on motility characteristics of stored boar spermatozoa

    USDA-ARS?s Scientific Manuscript database

    Background: Relaxin is detected in seminal plasma of many species and its association with sperm motility may be beneficial in some aspects of assisted reproduction. Here, we immunolocalized relaxin receptors and investigated the effects of exogenous relaxin on motility characteristics, viability, a...

  2. Shatter cones formed in large-scale experimental explosion craters

    NASA Technical Reports Server (NTRS)

    Roddy, D. J.; Davis, L. K.

    1977-01-01

    In 1968, a series of 0.5-ton and 100-ton TNT explosion experiments were conducted in granitic rock near Cedar City, Utah, as part of a basic research program on cratering and shock wave propagation. Of special interest was the formation of an important type of shock metamorphic feature, shatter cones. A description is presented of the first reported occurrence of shatter cones in high explosion trials. A background to shatter cone studies is presented and attention is given to the test program, geology and physical properties of the test medium, the observed cratering, and the formational pressures for shatter cones. The high explosion trials conducted demonstrate beyond any doubt, that shatter cones can be formed by shock wave processes during cratering and that average formational pressures in these crystalline rocks are in the 20-60 kb range.

  3. Bacteria rolling: motilities of rosette colonies in Caulobacter crescentus

    NASA Astrophysics Data System (ADS)

    Zeng, Yu; Liu, Bin

    2016-11-01

    The aquatic bacterium Caulobacter crescentus has two life cycle stages with distinct motilities: freely swimming swarmer cells and immotile stalked cells. Here, we show a new type of movement performed by freely suspended rosettes, spontaneous aggregates of stalked cells aligned radially relative to each other. Reproductive rosette members generate predivisional daughter cells with flagella, inducing rotations of the rosette as a whole. Such rotations exhibit dynamic angular velocities and lead to intermittent linear movements along liquid-solid interfaces, resembling rolling movements. We reconstructed the translational and rotational dynamics of the rosette movements from high-speed filming and long-term tracking. A mechanical model was developed to explain the hydrodynamic mechanism underlying such motilities. Our study illustrated a nontrivial mechanism for clustered bacteria to achieve motilities and sheds light on the adaptive significance of the collective behaviors of microorganisms in complex fluid environments.

  4. Activation of Drosophila hemocyte motility by the ecdysone hormone

    PubMed Central

    Sampson, Christopher J.; Amin, Unum; Couso, Juan-Pablo

    2013-01-01

    Summary Drosophila hemocytes compose the cellular arm of the fly's innate immune system. Plasmatocytes, putative homologues to mammalian macrophages, represent ∼95% of the migratory hemocyte population in circulation and are responsible for the phagocytosis of bacteria and apoptotic tissues that arise during metamorphosis. It is not known as to how hemocytes become activated from a sessile state in response to such infectious and developmental cues, although the hormone ecdysone has been suggested as the signal that shifts hemocyte behaviour from quiescent to migratory at metamorphosis. Here, we corroborate this hypothesis by showing the activation of hemocyte motility by ecdysone. We induce motile behaviour in larval hemocytes by culturing them with 20-hydroxyecdysone ex vivo. Moreover, we also determine that motile cell behaviour requires the ecdysone receptor complex and leads to asymmetrical redistribution of both actin and tubulin cytoskeleton. PMID:24285708

  5. Feed-back modulation of cone synapses by L-horizontal cells of turtle retina.

    PubMed

    Gerschenfeld, H M; Piccolino, M; Neyton, J

    1980-12-01

    Light stimulation of the periphery of the receptive field of turtle cones can evoke both transient and sustained increases of the cone Ca2+ conductance, which may become regenerative. Such increase in the cone Ca2+ conductance evoked by peripheral illumination results from the activation of a polysynaptic pathway involving a feed-back connexion from the L-horizontal cells (L-HC) to the cones. Thus the hyperpolarization of a L-HC by inward current injection can evoke a Ca2+ conductance increase in neighbouring cones. The cone Ca2+ channels thus activated are likely located at its synaptic endings and probably intervene in the cone transmitter release. Therefore the feed-back connexion between L-HC and cones by modifying the Ca2+ conductance of cones could actually modulate the transmitter release from cone synapses. Such feed-back modulation of cone synapses plays a role in the organization of the colour-coded responses of the chromaticity type-horizontal cells and probably of other second order neurones, post-synaptic to the cones. The mechanisms operating the feed-back connexion from L-HC to cones are discussed.

  6. Full utilization of semi-Dirac cones in photonics

    NASA Astrophysics Data System (ADS)

    Yasa, Utku G.; Turduev, Mirbek; Giden, Ibrahim H.; Kurt, Hamza

    2018-05-01

    In this study, realization and applications of anisotropic zero-refractive-index materials are proposed by exposing the unit cells of photonic crystals that exhibit Dirac-like cone dispersion to rotational symmetry reduction. Accidental degeneracy of two Bloch modes in the Brillouin zone center of two-dimensional C2-symmetric photonic crystals gives rise to the semi-Dirac cone dispersion. The proposed C2-symmetric photonic crystals behave as epsilon-and-mu-near-zero materials (ɛeff≈ 0 , μeff≈ 0 ) along one propagation direction, but behave as epsilon-near-zero material (ɛeff≈ 0 , μeff≠ 0 ) for the perpendicular direction at semi-Dirac frequency. By extracting the effective medium parameters of the proposed C4- and C2-symmetric periodic media that exhibit Dirac-like and semi-Dirac cone dispersions, intrinsic differences between isotropic and anisotropic materials are investigated. Furthermore, advantages of utilizing semi-Dirac cone materials instead of Dirac-like cone materials in photonic applications are demonstrated in both frequency and time domains. By using anisotropic transmission behavior of the semi-Dirac materials, photonic application concepts such as beam deflectors, beam splitters, and light focusing are proposed. Furthermore, to the best of our knowledge, semi-Dirac cone dispersion is also experimentally demonstrated for the first time by including negative, zero, and positive refraction states of the given material.

  7. Variation of cone photoreceptor packing density with retinal eccentricity and age.

    PubMed

    Song, Hongxin; Chui, Toco Yuen Ping; Zhong, Zhangyi; Elsner, Ann E; Burns, Stephen A

    2011-09-01

    To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages. High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22-35 years) and 10 older subjects (age range, 50-65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity. As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6-12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average. Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions.

  8. High-resolution impedance manometry parameters enhance the esophageal motility evaluation in non-obstructive dysphagia patients without a major Chicago Classification motility disorder

    PubMed Central

    Carlson, DA; Omari, T; Lin, Z; Rommel, N; Starkey, K; Kahrilas, PJ; Tack, J; Pandolfino, JE

    2016-01-01

    Background High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We aimed to perform a collaborative analysis of HRIM metrics to evaluate patients with non-obstructive dysphagia. Methods 14 asymptomatic controls (58% female; ages 20 – 50) and 41 patients (63% female; ages 24 – 82), 18 evaluated for dysphagia, 23 for reflux (‘non-dysphagia patients’), with esophageal motility diagnoses of normal motility or ineffective esophageal motility were evaluated with HRIM and a global dysphagia symptom score (Brief Esophageal Dysphagia Questionnaire). HRIM were analyzed to assess Chicago Classification metrics, automated pressure-flow metrics, the esophageal impedance integral (EII) ratio, and the bolus flow time (BFT). Key Results Significant symptom-metric correlations were detected only with basal EGJ pressure, EII ratio, and BFT. The EII ratio, BFT, and impedance ratio differed between controls and dysphagia patients, while the EII ratio in the upright position was the only measure that differentiated dysphagia from non-dysphagia patients. Conclusions & Inferences The EII ratio and BFT appear to offer an improved diagnostic evaluation in patients with non-obstructive dysphagia without a major esophageal motility disorder. Bolus retention as measured with the EII ratio appears to carry the strongest association with dysphagia, and thus may aid in the characterization of symptomatic patients with otherwise normal manometry. PMID:27647522

  9. JWFront: Wavefronts and Light Cones for Kerr Spacetimes

    NASA Astrophysics Data System (ADS)

    Frutos Alfaro, Francisco; Grave, Frank; Müller, Thomas; Adis, Daria

    2015-04-01

    JWFront visualizes wavefronts and light cones in general relativity. The interactive front-end allows users to enter the initial position values and choose the values for mass and angular momentum per unit mass. The wavefront animations are available in 2D and 3D; the light cones are visualized using the coordinate systems (t, x, y) or (t, z, x). JWFront can be easily modified to simulate wavefronts and light cones for other spacetime by providing the Christoffel symbols in the program.

  10. Tracking blue cone signals in the primate brain.

    PubMed

    Jayakumar, Jaikishan; Dreher, Bogdan; Vidyasagar, Trichur R

    2013-05-01

    In this paper, we review the path taken by signals originating from the short wavelength sensitive cones (S-cones) in Old World and New World primates. Two types of retinal ganglion cells (RGCs) carrying S-cone signals (blue-On and blue-Off cells) project to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. In all primates, these S-cone signals are relayed through the 'dust-like' (konis in classical Greek) dLGN cells. In New World primates such as common marmoset, these very small cells are known to form distinct and spatially extensive, koniocellular layers. Although in Old World primates, such as macaques, koniocellular layers tend to be very thin, the adjacent parvocellular layers contain distinct koniocellular extensions. It appears that all S-cone signals are relayed through such konio cells, whether they are in the main koniocellular layers or in their colonies within the parvocellular layers of the dLGN. In the primary visual cortex, these signals begin to merge with the signals carried by the other two principal parallel channels, namely the magnocellular and parvocellular channels. This article will also review the possible routes taken by the S-cone signals to reach one of the topographically organised extrastriate visual cortical areas, the middle temporal area (area MT). This area is the major conduit for signals reaching the parietal cortex. Alternative visual inputs to area MT not relayed via the primary visual cortex area (V1) may provide the neurological basis for the phenomenon of 'blindsight' observed in human and non-human primates, who have partial or complete damage to the primary visual cortex. Short wavelength sensitive cone (S-cone) signals to area MT may also play a role in directing visual attention with possible implications for understanding the pathology in dyslexia and some of its treatment options. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

  11. Multiple exposure photographic (MEP) technique: an objective assessment of sperm motility in infertility management.

    PubMed

    Adetoro, O O

    1988-06-01

    Multiple exposure photography (MEP), an objective technique, was used in determining the percentage of motile sperms in the semen samples from 41 males being investigated for infertility. This technique was compared with the conventional subjective ordinary microscopy method of spermatozoal motility assessment. A satisfactory correlation was observed in percentage sperm motility assessment using the two methods but the MEP estimation was more consistent and reliable. The value of this technique of sperm motility study in the developing world is discussed.

  12. Identification of RhoGAP22 as an Akt-Dependent Regulator of Cell Motility in Response to Insulin▿‡

    PubMed Central

    Rowland, Alexander F.; Larance, Mark; Hughes, William E.; James, David E.

    2011-01-01

    Insulin exerts many of its metabolic actions via the canonical phosphatidylinositide 3 kinase (PI3K)/Akt pathway, leading to phosphorylation and 14-3-3 binding of key metabolic targets. We previously identified a GTPase-activating protein (GAP) for Rac1 called RhoGAP22 as an insulin-responsive 14-3-3 binding protein. Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this effect was PI3K dependent. We identified two insulin-responsive 14-3-3 binding sites (pSer16 and pSer395) within RhoGAP22, and mutagenesis studies revealed a complex interplay between the phosphorylation at these two sites. Mutating Ser16 to alanine blocked 14-3-3 binding to RhoGAP22 in vivo, and phosphorylation at Ser16 was mediated by the kinase Akt. Overexpression of a mutant RhoGAP22 that was unable to bind 14-3-3 reduced cell motility in NIH-3T3 fibroblasts, and this effect was dependent on a functional GAP domain. Mutation of the catalytic arginine of the GAP domain of RhoGAP22 potentiated growth factor-stimulated Rac1 GTP loading. We propose that insulin and possibly growth factors such as platelet-derived growth factor may play a novel role in regulating cell migration and motility via the Akt-dependent phosphorylation of RhoGAP22, leading to modulation of Rac1 activity. PMID:21969604

  13. PIKfyve mediates the motility of late endosomes and lysosomes in neuronal dendrites.

    PubMed

    Tsuruta, Fuminori; Dolmetsch, Ricardo E

    2015-09-25

    The endosome/lysosome system in the nervous system is critically important for a variety of neuronal functions such as neurite outgrowth, retrograde transport, and synaptic plasticity. In neurons, the endosome/lysosome system is crucial for the activity-dependent internalization of membrane proteins and contributes to the regulation of lipid level on the plasma membrane. Although homeostasis of membrane dynamics plays important roles in the properties of central nervous systems, it has not been elucidated how endosome/lysosome system is regulated. Here, we report that phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) mediates the motility of late endosomes and lysosomes in neuronal dendrites. Endosomes and lysosomes are highly motile in resting neurons, however knockdown of PIKfyve led to a significant reduction in late endosomes and lysosomes motility. We also found that vesicle acidification is crucial for their motility and PIKfyve is associated with this process indirectly. These data suggest that PIKfyve mediates vesicle motility through the regulation of vesicle integrity in neurons. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Diagnosis of Normal and Abnormal Color Vision with Cone-Specific VEPs.

    PubMed

    Rabin, Jeff C; Kryder, Andrew C; Lam, Dan

    2016-05-01

    Normal color vision depends on normal long wavelength (L), middle wavelength (M), and short wavelength sensitive (S) cones. Hereditary "red-green" color vision deficiency (CVD) is due to a shift in peak sensitivity or lack of L or M cones. Hereditary S cone CVD is rare but can be acquired as an early sign of disease. Current tests detect CVD but few diagnose type or severity, critical for linking performance to real-world demands. The anomaloscope and newer subjective tests quantify CVD but are not applicable to infants or cognitively impaired patients. Our purpose was to develop an objective test of CVD with sensitivity and specificity comparable to current tests. A calibrated visual-evoked potential (VEP) display and Food and Drug Administration-approved system was used to record L, M, and S cone-specific pattern-onset VEPs from 18 color vision normals (CVNs) and 13 hereditary CVDs. VEP amplitudes and latencies were compared between groups to establish VEP sensitivity and specificity. Cone VEPs show 100% sensitivity for diagnosis of CVD and 94% specificity for confirming CVN. L cone (protan) CVDs showed a significant increase in L cone latency (53.1 msec, P < 0.003) and decreased amplitude (10.8 uV, P < 0.0000005) but normal M and S cone VEPs ( P > 0.31). M cone (deutan) CVDs showed a significant increase in M cone latency (31.0 msec, P < 0.000004) and decreased amplitude (8.4 uV, P < 0.006) but normal L and S cone VEPs ( P > 0.29). Cone-specific VEPs offer a rapid, objective test to diagnose hereditary CVD and show potential for detecting acquired CVD in various diseases. This paper describes the efficacy of cone-specific color VEPs for quantification of normal and abnormal color vision. The rapid, objective nature of this approach makes it suitable for detecting color sensitivity loss in infants and the cognitively impaired.

  15. Comparison of Cone Model Parameters for Halo Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Na, Hyeonock; Moon, Y.-J.; Jang, Soojeong; Lee, Kyoung-Sun; Kim, Hae-Yeon

    2013-11-01

    Halo coronal mass ejections (HCMEs) are a major cause of geomagnetic storms, hence their three-dimensional structures are important for space weather. We compare three cone models: an elliptical-cone model, an ice-cream-cone model, and an asymmetric-cone model. These models allow us to determine three-dimensional parameters of HCMEs such as radial speed, angular width, and the angle [ γ] between sky plane and cone axis. We compare these parameters obtained from three models using 62 HCMEs observed by SOHO/LASCO from 2001 to 2002. Then we obtain the root-mean-square (RMS) error between the highest measured projection speeds and their calculated projection speeds from the cone models. As a result, we find that the radial speeds obtained from the models are well correlated with one another ( R > 0.8). The correlation coefficients between angular widths range from 0.1 to 0.48 and those between γ-values range from -0.08 to 0.47, which is much smaller than expected. The reason may be the different assumptions and methods. The RMS errors between the highest measured projection speeds and the highest estimated projection speeds of the elliptical-cone model, the ice-cream-cone model, and the asymmetric-cone model are 376 km s-1, 169 km s-1, and 152 km s-1. We obtain the correlation coefficients between the location from the models and the flare location ( R > 0.45). Finally, we discuss strengths and weaknesses of these models in terms of space-weather application.

  16. Comparison of the WSA-ENLIL model with three CME cone types

    NASA Astrophysics Data System (ADS)

    Jang, Soojeong; Moon, Y.; Na, H.

    2013-07-01

    We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the prediction of geomagnetic storms.Abstract (2,250 Maximum Characters): We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the

  17. Isolation, characterization, and complementation of a motility mutant of Spiroplasma citri.

    PubMed Central

    Jacob, C; Nouzières, F; Duret, S; Bové, J M; Renaudin, J

    1997-01-01

    The helical mollicute Spiroplasma citri, when growing on low-agar medium, forms fuzzy colonies with occasional surrounding satellite colonies due to the ability of the spiroplasmal cells to move through the agar matrix. In liquid medium, these helical organisms flex, twist, and rotate rapidly. By using Tn4001 insertion mutagenesis, a motility mutant was isolated on the basis of its nondiffuse, sharp-edged colonies. Dark-field microscopy observations revealed that the organism flexed at a low frequency and had lost the ability to rotate about the helix axis. In this mutant, the transposon was shown to be inserted into an open reading frame encoding a putative polypeptide of 409 amino acids for which no significant homology with known proteins was found. The corresponding gene, named scm1, was recovered from the wild-type strain and introduced into the motility mutant by using the S. citri oriC plasmid pBOT1 as the vector. The appearance of fuzzy colonies and the observation that spiroplasma cells displayed rotatory and flexional movements showed the motile phenotype to be restored in the spiroplasmal transformants. The functional complementation of the motility mutant proves the scm1 gene product to be involved in the motility mechanism of S. citri. PMID:9244268

  18. Cell motility in cancer invasion and metastasis: insights from simple model organisms.

    PubMed

    Stuelten, Christina H; Parent, Carole A; Montell, Denise J

    2018-05-01

    Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening. We highlight insights derived from each of these organisms, including the detailed signalling network that governs chemotaxis towards chemokines; a novel mechanism of basement membrane invasion; the positive role of E-cadherin in collective direction-sensing; the identification and optimization of kinase inhibitors for metastatic thyroid cancer on the basis of work in flies; and the value of zebrafish for live imaging, especially of vascular remodelling and interactions between tumour cells and host tissues. While the motility of tumour cells and certain host cells promotes metastatic spread, the motility of tumour-reactive T cells likely increases their antitumour effects. Therefore, it is important to elucidate the mechanisms underlying all types of cell motility, with the ultimate goal of identifying combination therapies that will increase the motility of beneficial cells and block the spread of harmful cells.

  19. Vesicle Pool Size at the Salamander Cone Ribbon Synapse

    PubMed Central

    Bartoletti, Theodore M.; Babai, Norbert

    2010-01-01

    Cone light responses are transmitted to postsynaptic neurons by changes in the rate of synaptic vesicle release. Vesicle pool size at the cone synapse constrains the amount of release and can thus shape contrast detection. We measured the number of vesicles in the rapidly releasable and reserve pools at cone ribbon synapses by performing simultaneous whole cell recording from cones and horizontal or off bipolar cells in the salamander retinal slice preparation. We found that properties of spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs) are representative of mEPSCs evoked by depolarizing presynaptic stimulation. Strong, brief depolarization of the cone stimulated release of the entire rapidly releasable pool (RRP) of vesicles. Comparing charge transfer of the EPSC with mEPSC charge transfer, we determined that the fast component of the EPSC reflects release of ∼40 vesicles. Comparing EPSCs with simultaneous presynaptic capacitance measurements, we found that horizontal cell EPSCs constitute 14% of the total number of vesicles released from a cone terminal. Using a fluorescent ribeye-binding peptide, we counted ∼13 ribbons per cone. Together, these results suggest each cone contacts a single horizontal cell at ∼2 ribbons. The size of discrete components in the EPSC amplitude histogram also suggested ∼2 ribbon contacts per cell pair. We therefore conclude there are ∼20 vesicles per ribbon in the RRP, similar to the number of vesicles contacting the plasma membrane at the ribbon base. EPSCs evoked by lengthy depolarization suggest a reserve pool of ∼90 vesicles per ribbon, similar to the number of additional docking sites further up the ribbon. PMID:19923246

  20. Association of seminal plasma motility inhibitors/semenogelins with sperm in asthenozoospermia-infertile men.

    PubMed

    Terai, K; Yoshida, K; Yoshiike, M; Fujime, M; Iwamoto, T

    2010-01-01

    Seminal plasma motility inhibitors (SPMIs) are proteinase-resistant fragments of semenogelin I and II (Sgs), which are the major proteins of semen coagulum. SPMIs inhibit the motility of spermatozoa, and Sgs are thought to be natural regulators of human sperm function. The mechanism underlying sperm motility regulation and its association with defective motility in infertile men remain unclear. The purpose of this study was to investigate the association between SPMIs and spermatozoa in infertile men with asthenozoospermia. Fifty-four semen samples from 37 asthenozoospermic patients and 17 samples from 9 normal healthy subjects were analyzed. Spermatozoa, washed by Percoll density gradients, were immunostained with anti-SPMI antibody and subjected to flow cytometric analysis. The proportion of spermatozoa labeled with the antibody and the average intensity of fluorescence labeling per spermatozoa were analyzed in relation to the parameters used for semen analysis. A significant negative correlation was found between sperm motility and the proportion (R = -0.68) and intensity (R = -0.38) of labeling. These results suggest that SPMIs remain on the sperm surface after liquefaction. This might account for some disorders of sperm motility observed in infertile men with asthenozoospermia. Copyright © 2010 S. Karger AG, Basel.

  1. Numerical Modeling of Shatter Cones Development in Impact Craters

    NASA Technical Reports Server (NTRS)

    Baratoux, D.; Melosh, H. J.

    2003-01-01

    Shatter cones are the characteristic forms of rock fractures in impact structures. They have been used for decades as unequivocal fingerprints of meteoritic impacts on Earth. The abundant data about shapes, apical angles, sizes and distributions of shatter cones for many terrestrial impact structures should provide insights for the determination of impact conditions and characteristics of shock waves produced by high-velocity projectiles in geologic media. However, previously proposed models for the formation of shatter cones do not agree with observations. For example, the widely accepted Johnson-Talbot mechanism requires that the longitudinal stress drops to zero between the arrival of the elastic precursor and the main plastic wave. Unfortunately, observations do not support such a drop. A model has been also proposed to explain the striated features on the surface of shatter cones but can not invoked for their conical shape. The mechanism by which shatter cones form thus remains enigmatic to date. In this paper we present a new model for the formation of shatter cones. Our model has been tested by means of numerical simulations using the hydrocodes SALE 2D enhanced with the Grady-Kipp-Melosh fragmentation model.

  2. History of imaging in orthodontics from Broadbent to cone-beam computed tomography.

    PubMed

    Hans, Mark G; Palomo, J Martin; Valiathan, Manish

    2015-12-01

    The history of imaging and orthodontics is a story of technology informing biology. Advances in imaging changed our thinking as our understanding of craniofacial growth and the impact of orthodontic treatment deepened. This article traces the history of imaging in orthodontics from the invention of the cephalometer by B. Holly Broadbent in 1930 to the introduction of low-cost, low-radiation-dose cone-beam computed tomography imaging in 2015. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  3. Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity

    PubMed Central

    Gray, Alana L.; Coleman, David T.; Shi, Runhua; Cardelli, James A.

    2016-01-01

    Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. PMID:27127175

  4. Variation of Cone Photoreceptor Packing Density with Retinal Eccentricity and Age

    PubMed Central

    Song, Hongxin; Chui, Toco Yuen Ping; Zhong, Zhangyi; Elsner, Ann E.

    2011-01-01

    Purpose. To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages. Methods. High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22–35 years) and 10 older subjects (age range, 50–65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity. Results. As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6–12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average. Conclusions. Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions. PMID:21724911

  5. Modification of Salmonella Typhimurium Motility by the Probiotic Yeast Strain Saccharomyces boulardii

    PubMed Central

    Pontier-Bres, Rodolphe; Prodon, François; Munro, Patrick; Rampal, Patrick; Lemichez, Emmanuel; Peyron, Jean François; Czerucka, Dorota

    2012-01-01

    Background Motility is an important component of Salmonella enterica serovar Typhimurium (ST) pathogenesis allowing the bacteria to move into appropriate niches, across the mucus layer and invade the intestinal epithelium. In vitro, flagellum-associated motility is closely related to the invasive properties of ST. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is widely prescribed for the prophylaxis and treatment of diarrheal diseases caused by bacteria or antibiotics. In case of Salmonella infection, S.b-B has been shown to decrease ST invasion of T84 colon cell line. The present study was designed to investigate the impact of S.b-B on ST motility. Methodology/Principal Findings Experiments were performed on human colonic T84 cells infected by the Salmonella strain 1344 alone or in the presence of S.b-B. The motility of Salmonella was recorded by time-lapse video microscopy. Next, a manual tracking was performed to analyze bacteria dynamics (MTrackJ plugin, NIH image J software). This revealed that the speed of bacterial movement was modified in the presence of S.b-B. The median curvilinear velocity (CLV) of Salmonella incubated alone with T84 decreased from 43.3 µm/sec to 31.2 µm/sec in the presence of S.b-B. Measurement of track linearity (TL) showed similar trends: S.b-B decreased by 15% the number of bacteria with linear tract (LT) and increased by 22% the number of bacteria with rotator tract (RT). Correlation between ST motility and invasion was further established by studying a non-motile flagella-deficient ST strain. Indeed this strain that moved with a CLV of 0.5 µm/sec, presented a majority of RT and a significant decrease in invasion properties. Importantly, we show that S.b-B modified the motility of the pathogenic strain SL1344 and significantly decreased invasion of T84 cells by this strain. Conclusions This study reveals that S.b-B modifies Salmonella's motility and trajectory which may account for the modification of Salmonella

  6. Spontaneous mutations in the flhD operon generate motility heterogeneity in Escherichia coli biofilm.

    PubMed

    Horne, Shelley M; Sayler, Joseph; Scarberry, Nicholas; Schroeder, Meredith; Lynnes, Ty; Prüß, Birgit M

    2016-11-08

    Heterogeneity and niche adaptation in bacterial biofilm involve changes to the genetic makeup of the bacteria and gene expression control. We hypothesized that i) spontaneous mutations in the flhD operon can either increase or decrease motility and that ii) the resulting motility heterogeneity in the biofilm might lead to a long-term increase in biofilm biomass. We allowed the highly motile E. coli K-12 strain MC1000 to form seven- and fourteen-day old biofilm, from which we recovered reduced motility isolates at a substantially greater frequency (5.4 %) than from a similar experiment with planktonic bacteria (0.1 %). Biofilms formed exclusively by MC1000 degraded after 2 weeks. In contrast, biofilms initiated with a 1:1 ratio of MC1000 and its isogenic flhD::kn mutant remained intact at 4 weeks and the two strains remained in equilibrium for at least two weeks. These data imply that an 'optimal' biofilm may contain a mixture of motile and non-motile bacteria. Twenty-eight of the non-motile MC1000 isolates contained an IS1 element in proximity to the translational start of FlhD or within the open reading frames for FlhD or FlhC. Two isolates had an IS2 and one isolate had an IS5 in the open reading frame for FlhD. An additional three isolates contained deletions that included the RNA polymerase binding site, five isolates contained point mutations and small deletions in the open reading frame for FlhC. The locations of all these mutations are consistent with the lack of motility and further downstream within the flhD operon than previously published IS elements that increased motility. We believe that the location of the mutation within the flhD operon determines whether the effect on motility is positive or negative. To test the second part of our hypothesis where motility heterogeneity in a biofilm may lead to a long-term increase in biofilm biomass, we quantified biofilm biomass by MC1000, MC1000 flhD::kn, and mixtures of the two strains at ratios of 1:1, 10

  7. Rab11a differentially modulates epidermal growth factor-induced proliferation and motility in immortal breast cells.

    PubMed

    Palmieri, Diane; Bouadis, Amina; Ronchetti, Ruban; Merino, Maria J; Steeg, Patricia S

    2006-11-01

    The development of cancer prevention strategies depends on the elucidation of molecular pathways underlying oncogenesis. In a previous proteomic study of matched normal breast ducts and Ductal Carcinoma in Situ (DCIS), we identified overexpression of Rab11a in DCIS. Rab11a is not well studied in cancer, but is known to regulate the recycling of internalized cell surface proteins and receptors from the early endosome through the trans-Golgi network. Using immunohistochemistry, we confirmed our observation, noting increased Rab11a expression in 19 of 22 (86%) DCIS cases compared to matched normal breast epithelium. To study the function of Rab11a, immortal, nontumorigenic MCF10A breast cells were stimulated with ligands to the EGF receptor (EGFR) after transfection with empty vector (control), Rab11a, or a S25N dominant-negative (DN) Rab11a. Using an iodinated ligand:receptor recycling assay, transfection of Rab11a accelerated, while DN-Rab11a postponed EGFR recycling in vitro. The signaling and in vitro phenotypic consequences of Rab11a expression and function were studied. Transfection of DN-Rab11a increased Erk1/2 activation downstream of EGF, but exerted no effect on the Akt pathway. Expression of DN-Rab11a inhibited MCF10A proliferation by 50-60%, and also inhibited anchorage-dependent colonization. Notably, DN-Rab11a transfection increased motility toward EGFR ligands. The data provide a first demonstration that Rab11a modulates EGFR recycling, and promotes the proliferation but inhibits the motility of an immortal breast line, consistent with the DCIS phenotype.

  8. Potting Media Affect Growth and Disease Development of Container-Grown Southern Pines

    Treesearch

    William H. Pawuk

    1981-01-01

    Longleaf pine (Pinus palustris Mill.) and shortleaf pine (P. echinata Mill.) seedlings grew best in equal parts of peat and vermiculite with a low pH. Seedlings grew better in shredded pine cone media than pine bark media. Growth increased when soil or vermiculite was added to cone or bark chips. Commercial bark-vermiculite...

  9. Three-dimensional cone-beam computed tomography analysis of enlargement of the pharyngeal airway by the Herbst appliance.

    PubMed

    Iwasaki, Tomonori; Takemoto, Yoshihiko; Inada, Emi; Sato, Hideo; Saitoh, Issei; Kakuno, Eriko; Kanomi, Ryuzo; Yamasaki, Youichi

    2014-12-01

    Pharyngeal airway size is increasingly recognized as an important factor in obstructive sleep apnea. However, few studies have examined the changes of pharyngeal airway form after dental procedures for treating obstructive sleep apnea during growth. The purpose of this study was to evaluate the effect of the Herbst appliance on the 3-dimensional form of the pharyngeal airway using cone-beam computed tomography. Twenty-four Class II subjects (ANB, ≥5°; 11 boys; mean age, 11.6 years) who required Herbst therapy with edgewise treatment had cone-beam computed tomography images taken before and after Herbst treatment. Twenty Class I control subjects (9 boys; mean age, 11.5 years) received edgewise treatment only. The volume, depth, and width of the pharyngeal airway were compared between the groups using measurements from 3-dimensional cone-beam computed tomography images of the entire pharyngeal airway. The increase of the oropharyngeal airway volume in the Herbst group (5000.2 mm(3)) was significantly greater than that of the control group (2451.6 mm(3)). Similarly, the increase of the laryngopharyngeal airway volume in the Herbst group (1941.8 mm(3)) was significantly greater than that of the control group (1060.1 mm(3)). The Herbst appliance enlarges the oropharyngeal and laryngopharyngeal airways. These results may provide a useful assessment of obstructive sleep apnea treatment during growth. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  10. A 40-foot static cone penetrometer

    USGS Publications Warehouse

    Beard, R.M.; Lee, H.J.

    1982-01-01

    The Navy needs a lightweight device for testing seafloor soils to sub bottom depths of 12 meters in water depths to 60 meters. To meet this need a quasistatic cone penetration device that uses water jetting to reduce friction on the cone rod has been developed. This device is called the XSP-40. The 5-ton XSP-40 stands 15 meters tall and pushes a standard 5-ton cone into the seafloor. It is remotely controlled with an electronic unit on the deck of the support vessel. All cone outputs are recorded directly as a function of penetration depth with a strip chart recorder. A full suite of gauges is provided. on the electronic unit for monitoring the XSP-40's performance during a test .. About 40 penetration tests have been performed with very good success. The XSP-40 was field tested in Norton Sound, off the west coast of Alaska. The general objective, in addition to evaluation of the device, was to gather geotechnical information on sediments that may be involved in processes potentially hazardous to offshore development. Four example penetration records are presented from gas charged sediment zones and areas near the Yukon River delta. In general it was determined that soil classification from cone data agreed well with classifications from core samples. Relative densities of the silt-sand to sandy-silt soils were usually very high. The significance of these results are discussed with respect to storm wave, liquefaction. It is concluded that the XSP-40 is a durable and reliable piece of equipment capable of achieving penetration beyond that possible when not using the water jet system.

  11. Effects of scoria-cone eruptions upon nearby human communities

    USGS Publications Warehouse

    Ort, M.H.; Elson, M.D.; Anderson, K.C.; Duffield, W.A.; Hooten, J.A.; Champion, D.E.; Waring, G.

    2008-01-01

    Scoria-cone eruptions are typically low in volume and explosivity compared with eruptions from stratovolcanoes, but they can affect local populations profoundly. Scoria-cone eruption effects vary dramatically due to eruption style, tephra blanket extent, climate, types of land use, the culture and complexity of the affected group, and resulting governmental action. A comparison of a historic eruption (Pari??cutin, Me??xico) with prehistoric eruptions (herein we primarily focus on Sunset Crater in northern Arizona, USA) elucidates the controls on and effects of these variables. Long-term effects of lava flows extend little beyond the flow edges. These flows, however, can be used for defensive purposes, providing refuges from invasion for those who know them well. In arid lands, tephra blankets serve as mulches, decreasing runoff and evaporation, increasing infiltration, and regulating soil temperature. Management and retention of these scoria mulches, which can open new areas for agriculture, become a priority for farming communities. In humid areas, though, the tephra blanket may impede plant growth and increase erosion. Cultural responses to eruptions vary, from cultural collapse, through fragmentation of society, dramatic changes, and development of new technologies, to little apparent change. Eruptions may also be viewed as retribution for poor behavior, and attempts are made to mollify angry gods. ?? 2008 Geological Society of America.

  12. High-Throughput, Motility-Based Sorter for Microswimmers and Gene Discovery Platform

    NASA Astrophysics Data System (ADS)

    Yuan, Jinzhou; Raizen, David; Bau, Haim

    2015-11-01

    Animal motility varies with genotype, disease progression, aging, and environmental conditions. In many studies, it is desirable to carry out high throughput motility-based sorting to isolate rare animals for, among other things, forward genetic screens to identify genetic pathways that regulate phenotypes of interest. Many commonly used screening processes are labor-intensive, lack sensitivity, and require extensive investigator training. Here, we describe a sensitive, high throughput, automated, motility-based method for sorting nematodes. Our method was implemented in a simple microfluidic device capable of sorting many thousands of animals per hour per module, and is amenable to parallelism. The device successfully enriched for known C. elegans motility mutants. Furthermore, using this device, we isolated low-abundance mutants capable of suppressing the somnogenic effects of the flp-13 gene, which regulates sleep-like quiescence in C. elegans. Subsequent genomic sequencing led to the identification of a flp-13-suppressor gene. This research was supported, in part, by NIH NIA Grant 5R03AG042690-02.

  13. Effect of Dai-kenchu-to on gastrointestinal motility and gastric emptying.

    PubMed

    Kawasaki, Naruo; Nakada, Koji; Suzuki, Yutaka; Furukawa, Yoshiyuki; Hanyu, Nobuyoshi; Kashiwagi, Hideyuki

    2009-06-01

    The gastrointestinal symptoms accompanying dysfunction of the remnant stomach were seen after pylorus-preserving operation. Against such complications, Dai-kenchu-to (DKT) is used, but scientific evidences for efficacy are poor. The effect of DKT on gastrointestinal motility and gastric emptying after pylorus-preserving operation was investigated. Using beagle dogs, the experimental models mimicking the state after pylorus-preserving pancreaticoduodenectomy were prepared. We sutured strain gauge transducers to the stomach, duodenum and jejunum and inserted indwelling tubes into the stomach. About 4 weeks after operation, DKT 0.1g/kg was administered during the fasting or fed state. At the same time, the gastric emptying was evaluated by the acetoaminophene method. In the fasting state, administration of DKT enhanced the gastrointestinal motility and accelerated gastric emptying. In the postprandial state, no apparent effect on motility was seen. DKT enhances the gastrointestinal motility after pylorus-preserving pancreaticoduodenectomy in the fasting state. The effect of DKT may not be related to the continuity of the intramural nerve.

  14. Bacterial spread from cell to cell: beyond actin-based motility.

    PubMed

    Kuehl, Carole J; Dragoi, Ana-Maria; Talman, Arthur; Agaisse, Hervé

    2015-09-01

    Several intracellular pathogens display the ability to propagate within host tissues by displaying actin-based motility in the cytosol of infected cells. As motile bacteria reach cell-cell contacts they form plasma membrane protrusions that project into adjacent cells and resolve into vacuoles from which the pathogen escapes, thereby achieving spread from cell to cell. Seminal studies have defined the bacterial and cellular factors that support actin-based motility. By contrast, the mechanisms supporting the formation of protrusions and their resolution into vacuoles have remained elusive. Here, we review recent advances in the field showing that Listeria monocytogenes and Shigella flexneri have evolved pathogen-specific mechanisms of bacterial spread from cell to cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Apparatus and process for an off-surface cone penetrometer sensor

    DOEpatents

    Smail, Timothy R.; French, Phillip J.; Huffman, Russell K.

    2003-04-29

    A cone penetrometer is provided having a pivoting arm which deploys a variable distance from the surface of the cone penetrometer. Sensors placed on the end of the deployable arm provide for data collection outside a compression zone created by the insertion of the cone penetrometer.

  16. Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone Dystrophy Associated with L/M Opsin Interchange Mutations

    PubMed Central

    Greenwald, Scott H.; Kuchenbecker, James A.; Rowlan, Jessica S.; Neitz, Jay; Neitz, Maureen

    2017-01-01

    Purpose Human long (L) and middle (M) wavelength cone opsin genes are highly variable due to intermixing. Two L/M cone opsin interchange mutants, designated LIAVA and LVAVA, are associated with clinical diagnoses, including red-green color vision deficiency, blue cone monochromacy, cone degeneration, myopia, and Bornholm Eye Disease. Because the protein and splicing codes are carried by the same nucleotides, intermixing L and M genes can cause disease by affecting protein structure and splicing. Methods Genetically engineered mice were created to allow investigation of the consequences of altered protein structure alone, and the effects on cone morphology were examined using immunohistochemistry. In humans and mice, cone function was evaluated using the electroretinogram (ERG) under L/M- or short (S) wavelength cone isolating conditions. Effects of LIAVA and LVAVA genes on splicing were evaluated using a minigene assay. Results ERGs and histology in mice revealed protein toxicity for the LVAVA but not for the LIAVA opsin. Minigene assays showed that the dominant messenger RNA (mRNA) was aberrantly spliced for both variants; however, the LVAVA gene produced a small but significant amount of full-length mRNA and LVAVA subjects had correspondingly reduced ERG amplitudes. In contrast, the LIAVA subject had no L/M cone ERG. Conclusions Dramatic differences in phenotype can result from seemingly minor differences in genotype through divergent effects on the dual amino acid and splicing codes. Translational Relevance The mechanism by which individual mutations contribute to clinical phenotypes provides valuable information for diagnosis and prognosis of vision disorders associated with L/M interchange mutations, and it informs strategies for developing therapies. PMID:28516000

  17. Gastrointestinal Motility Variation and Implications for Plasma Level Variation: Oral Drug Products.

    PubMed

    Talattof, Arjang; Price, Judy C; Amidon, Gordon L

    2016-02-01

    The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complexity and inhomogeneity of the gastrointestinal environment. In particular, dosing unpredictably relative to motility phase means the gastrointestinal environment is a random variable within a defined range. Here, we present a mass balance analysis that captures this variation and highlights the effects of gastrointestinal motility, exploring what impacts it ultimately has on plasma levels and the relationship to bioequivalence for high solubility products with both high and low permeability (BCS I and III). Motility-dependent compartmental absorption and transit (MDCAT) mechanistic analysis is developed to describe the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled.

  18. Twelve inequivalent Dirac cones in two-dimensional ZrB2

    NASA Astrophysics Data System (ADS)

    Lopez-Bezanilla, Alejandro

    2018-01-01

    Theoretical evidence of the existence of 12 inequivalent Dirac cones at the vicinity of the Fermi energy in monolayered ZrB2 is presented. Two-dimensional ZrB2 is a mechanically stable d - and p -orbital compound exhibiting a unique electronic structure with two Dirac cones out of high-symmetry points in the irreducible Brillouin zone with a small electron-pocket compensation. First-principles calculations demonstrate that while one of the cones is insensitive to lattice expansion, the second cone vanishes for small perturbation of the vertical Zr position. Internal symmetry breaking with external physical stimuli, along with the relativistic effect of spin-orbit coupling, is able to remove selectively the Dirac cones. A rational explanation in terms of d - and p -orbital mixing is provided to elucidate the origin of the infrequent Dirac cones in a flat structure. The versatility of transition-metal d orbitals combined with the honeycomb lattice provided by the B atoms yields particular features in a two-dimensional material.

  19. Long-term changes in flowering and cone production by longleaf pine

    Treesearch

    William D. Boyer

    1998-01-01

    Abstract.Cone production by longleaf pine has been followed for up to 30 years in regeneration areas at five to nine coastal plain sites from North Carolina to Louisiana. A rapid increase in the size and frequency of cone crops has occured since 1986 following 20 years of relative stability. Cone production for the last 10 years averaged 36 cones per...

  20. Development of a full ice-cream cone model for halo CME structures

    NASA Astrophysics Data System (ADS)

    Na, Hyeonock; Moon, Yong-Jae

    2015-04-01

    The determination of three dimensional parameters (e.g., radial speed, angular width, source location) of Coronal Mass Ejections (CMEs) is very important for space weather forecast. To estimate these parameters, several cone models based on a flat cone or a shallow ice-cream cone with spherical front have been suggested. In this study, we investigate which cone model is proper for halo CME morphology using 33 CMEs which are identified as halo CMEs by one spacecraft (SOHO or STEREO-A or B) and as limb CMEs by the other ones. From geometrical parameters of these CMEs such as their front curvature, we find that near full ice-cream cone CMEs (28 events) are dominant over shallow ice-cream cone CMEs (5 events). So we develop a new full ice-cream cone model by assuming that a full ice-cream cone consists of many flat cones with different heights and angular widths. This model is carried out by the following steps: (1) construct a cone for given height and angular width, (2) project the cone onto the sky plane, (3) select points comprising the outer boundary, (4) minimize the difference between the estimated projection points with the observed ones. We apply this model to several halo CMEs and compare the results with those from other methods such as a Graduated Cylindrical Shell model and a geometrical triangulation method.

  1. Esophageal motility after peroral endoscopic myotomy for achalasia.

    PubMed

    Hu, Yue; Li, Meng; Lu, Bin; Meng, Lina; Fan, Yihong; Bao, Haibiao

    2016-05-01

    Peroral endoscopic myotomy (POEM) has been introduced as a novel endoscopic treatment for achalasia. The aim of this work is to assess the changes in esophageal motility caused by POEM in patients with achalasia. Forty-one patients with achalasia underwent POEM from September 2012 to November 2014. Esophageal motility of all patients was evaluated preoperatively and 1 month after POEM utilizing high-resolution manometry, which was performed with ten water swallows, ten steamed bread swallows, and multiple rapid swallows (MRS). In single swallows, including liquid swallows and bread swallows, all the parameters of lower esophagus sphincter resting pressure (LESP), 4-s integrated relaxation pressure (4sIRP), and intra-bolus pressure (IBP) were decreased between pre- and post-POEM patients (all p < 0.05). Postoperatively, the trend of distal contractile integral (DCI) and distal esophageal peristaltic amplitude declined in subtype II and subtype III (subtype II: p < 0.05; subtype III: p > 0.05), but increased in subtype I (subtype I: p > 0.05). In liquid swallows, the Eckardt score of subtype II patients decreased with DCI, and distal esophageal peristaltic amplitude after POEM was significantly lower compared with those showing increased values of those two parameters (p < 0.05). In MRS, the rate of LES relaxation increased from 66.67 to 95.24%, but without normal response in all achalasia patients. POEM reduces LES pressure in achalasia, and partly restores esophageal motility. POEM displayed varying effect on esophageal motility in patients with different patterns of swallowing. In addition, the changes in parameters associated with esophageal peristalsis correlated with decreases in Eckardt score.

  2. Estimate of oxygen consumption and intracellular zinc concentration of human spermatozoa in relation to motility.

    PubMed

    Henkel, Ralf R; Defosse, Kerstin; Koyro, Hans-Wilhelm; Weissmann, Norbert; Schill, Wolf-Bernhard

    2003-03-01

    To investigate the human sperm oxygen/energy consumption and zinc content in relation to motility. In washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility. The oxygen consumption averaged 0.24 micromol/10(6) sperm x 24h, 0.28 micromol/10(6) live sperm x 24h and 0.85 micromol/10(6) live motile sperm x 24h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/10(6) motile spermatozoa x 24h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/10(6) spermatozoa x 24h. The correlation of the oxygen/energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, respectively). However, when correlating sperm energy consumption with the zinc content, a significant positive relation (r=0.323; P=0.01) was observed. Poorly motile sperm are actually wasting the available energy. Moreover, our data clearly support the "Geometric Clutch Model" of the axoneme function and demonstrate the importance of the outer dense fibers for the generation of sperm motility, especially progressive motility.

  3. Effects of viscosity on sperm motility studied with optical tweezers

    NASA Astrophysics Data System (ADS)

    Hyun, Nicholas; Chandsawangbhuwana, Charlie; Zhu, Qingyuan; Shi, Linda Z.; Yang-Wong, Collin; Berns, Michael W.

    2012-02-01

    The purpose of this study is to analyze human sperm motility and energetics in media with different viscosities. Multiple experiments were performed to collect motility parameters using customized computer tracking software that measures the curvilinear velocity (VCL) and the minimum laser power (Pesc) necessary to hold an individual sperm in an optical trap. The Pesc was measured by using a 1064 nm Nd:YVO4 continuous wave laser that optically traps motile sperm at a power of 450 mW in the focused trap spot. The VCL was measured frame by frame before trapping. In order to study sperm energetics under different viscous conditions sperm were labeled with the fluorescent dye DiOC6(3) to measure membrane potentials of mitochondria in the sperm midpiece. Fluorescence intensity was measured before and during trapping. The results demonstrate a decrease in VCL but an increase in Pesc with increasing viscosity. Fluorescent intensity is the same regardless of the viscosity level indicating no change in sperm energetics. The results suggest that, under the conditions tested, viscosity physically affects the mechanical properties of sperm motility rather than the chemical pathways associated with energetics.

  4. Microfluidic separation of motile sperm with millilitre-scale sample capacity

    NASA Astrophysics Data System (ADS)

    Nosrati, Reza; Vollmer, Marion; Eamer, Lise; Zeidan, Krista; San Gabriel, Maria C.; Zini, Armand; Sinton, David

    2012-11-01

    Isolating motile from non-motile spermatozoa has been a challenge since the establishment of in vitro fertilization. Microfluidic approaches have been employed for this purpose, but current devices are limited by low sample volume. Here, we present a high-throughput microfluidic device that separates spermatozoa from one millilitre of raw semen sample based on the hydrodynamic characteristics of swimming sperm in a confined geometry. The device consists of two layers: an outer injection ring on top aligned with a network of radial microchannels at the bottom guiding motile sperm into an inner collection chamber. This approach (1) maximizes exposure of the sperm to the fluid channels, (2) maximizes surface area density (3) prevents fluid flow bias, and (4) employs a non-Newtonian viscoelastic medium consistent with the in vivo environment. Tests with human and bull spermatozoa indicate an increase in motile sperm concentration from 62.2% in raw semen to 99.2% in separated sample combined with a higher incidence of normal morphology. DNA integrity testing is currently underway. In conclusion, we present an effective one-step procedure to perform semen purification and separation on a millilitre-scale with clinically relevant numbers.

  5. Group X secreted phospholipase A₂ specifically decreases sperm motility in mice.

    PubMed

    Escoffier, Jessica; Pierre, Virginie J; Jemel, Ikram; Munch, Léa; Boudhraa, Zied; Ray, Pierre F; De Waard, Michel; Lambeau, Gérard; Arnoult, Christophe

    2011-10-01

    Different mammalian secreted phospholipases A(2) (sPLA(2) s) are expressed in male reproductive organs and/or in sperm cells but their cellular functions are still not fully characterized. Because several reports indicate a link between cellular lipids and sperm motility, we have investigated the effect of mouse group IIA, IID, IIE, V, and X sPLA(2) s on sperm motility. Among these enzymes, only mouse group X sPLA(2) (mGX sPLA(2) ) acts as a potent inhibitor of sperm motility that decreases track speed (VCL) and lateral displacement of the head (ALH) of both noncapacitated and capacitated sperm. The inhibitory effect of mGX sPLA(2) is dependent on its enzymatic activity because (i) both the proenzyme form of mGX sPLA(2) (pro-mGX) and the H48Q mutant of mGX sPLA(2) have very weak enzymatic activity and are unable to modulate sperm motility and (ii) LY329722, a specific inhibitor of sPLA(2) s, blocks the inhibitory effect of mGX sPLA(2) . Moreover, mGX sPLA(2) exerts a gradual potency on sperm subpopulations with different velocities, an effect which may be linked to the heterogeneity of lipid composition in these sperm subpopulations. Finally, we found that endogenous mGX sPLA(2) released during spontaneous acrosome reaction modulates sperm motility of capacitated sperm. Together, our results suggest a new role of sPLA(2) in sperm physiology where the sPLA2 selects a sperm subpopulation for fertilization based on its effect on sperm motility. Copyright © 2010 Wiley-Liss, Inc.

  6. Effects of hydrogen sulphide on motility patterns in the rat colon

    PubMed Central

    Gil, V; Parsons, SP; Gallego, D; Huizinga, JD; Jimenez, M

    2013-01-01

    Background and Purpose Hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule with putative functions in gastrointestinal motility regulation. Characterization of H2S effects on colonic motility is crucial to establish its potential use as therapeutic agent in the treatment of colonic disorders. Experimental Approach H2S effects on colonic motility were characterized using video recordings and construction of spatio-temporal maps. Microelectrode and muscle bath studies were performed to investigate the mechanisms underlying H2S effects. NaHS was used as the source of H2S. Key Results Rhythmic propulsive motor complexes (RPMCs) and ripples were observed in colonic spatio-temporal maps. Serosal addition of NaHS concentration-dependently inhibited RPMCs. In contrast, NaHS increased amplitude of the ripples without changing their frequency. Therefore, ripples became the predominant motor pattern. Neuronal blockade with lidocaine inhibited RPMCs, which were restored after administration of carbachol. Subsequent addition of NaHS inhibited RPMCs. Luminal addition of NaHS did not modify motility patterns. NaHS inhibited cholinergic excitatory junction potentials, carbachol-induced contractions and hyperpolarized smooth muscle cells, but did not modify slow wave activity. Conclusions and Implications H2S modulated colonic motility inhibiting propulsive contractile activity and enhancing the amplitude of ripples, promoting mixing. Muscle hyperpolarization and inhibition of neurally mediated cholinergic responses contributed to the inhibitory effect on propulsive activity. H2S effects were not related to changes in the frequency of slow wave activity originating in the network of interstitial cells of Cajal located near the submuscular plexus. Luminal H2S did not modify colonic motility probably because of epithelial detoxification. PMID:23297830

  7. Evaluation of esophageal motility utilizing the functional lumen imaging probe (FLIP)

    PubMed Central

    Carlson, Dustin A.; Kahrilas, Peter J.; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A.; Wong, Ian; Pandolfino, John E.

    2016-01-01

    Background Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. Methods 145 patients (ages 18 – 85, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered ‘abnormal’. FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered ‘abnormal’ if EGJ-DI was < 2.8 mm2/mmHg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. Results HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was ‘normal’ in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. Conclusions FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia. PMID:27725650

  8. Curvilinear pigmentary lesions in a rod-cone dystrophy.

    PubMed

    Tamaki, Y; Sawa, M; Yannuzzi, L A

    2005-01-01

    To report a peculiar curvilinear pigmentary lesion in the peripheral fundus in a rod-cone dystrophy. Observational case report. Fundus examination of a 57-year-old woman who was known to have a generalized rod-cone dystrophy since she was 8 years old. The peripheral fundus examination revealed a curvilinear lesion which resembles a well-known finding associated with a presumed ocular histoplasmosis syndrome or multifocal choroiditis. The differential diagnosis of a peculiar curvilinear pigmentary lesion in the peripheral fundus may be expanded to include a generalized rod-cone dystrophy.

  9. Oscillatory flow in a cone-and-plate bioreactor.

    PubMed

    Chung, C A; Tzou, M R; Ho, R W

    2005-08-01

    Motivated by biometric applications, we analyze oscillatory flow in a cone-and-plate geometry. The cone is rotated in a simple harmonic way on a stationary plate. Based on assuming that the angle between the cone and plate is small, we describe the flow analytically by a perturbation method in terms of two small parameters, the Womersley number and the Reynolds number, which account for the influences of the local acceleration and centripetal force, respectively. Working equations for the shear stresses induced both by laminar primary and secondary flows on the plate surface are presented.

  10. Differential encoding of spatial information among retinal on cone bipolar cells

    PubMed Central

    Purgert, Robert J.

    2015-01-01

    The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina. PMID:26203104

  11. Pac-man motility of kinetochores unleashed by laser microsurgery

    PubMed Central

    LaFountain, James R.; Cohan, Christopher S.; Oldenbourg, Rudolf

    2012-01-01

    We report on experiments directly in living cells that reveal the regulation of kinetochore function by tension. X and Y sex chromosomes in crane fly (Nephrotoma suturalis) spermatocytes exhibit an atypical segregation mechanism in which each univalent maintains K-fibers to both poles. During anaphase, each maintains a leading fiber (which shortens) to one pole and a trailing fiber (which elongates) to the other. We used this intriguing behavior to study the motile states that X-Y kinetochores are able to support during anaphase. We used a laser microbeam to either sever a univalent along the plane of sister chromatid cohesion or knock out one of a univalent's two kinetochores to release one or both from the resistive influence of its sister's K-fiber. Released kinetochores with attached chromosome arms moved poleward at rates at least two times faster than normal. Furthermore, fluorescent speckle microscopy revealed that detached kinetochores converted their functional state from reverse pac-man to pac-man motility as a consequence of their release from mechanical tension. We conclude that kinetochores can exhibit pac-man motility, even though their normal behavior is dominated by traction fiber mechanics. Unleashing of kinetochore motility through loss of resistive force is further evidence for the emerging model that kinetochores are subject to tension-sensitive regulation. PMID:22740625

  12. Aldehyde Dehydrogenase Plays a Pivotal Role in the Maintenance of Stallion Sperm Motility.

    PubMed

    Gibb, Zamira; Lambourne, Sarah R; Curry, Benjamin J; Hall, Sally E; Aitken, Robert J

    2016-06-01

    Although stallion spermatozoa produce significant quantities of reactive oxygen species, a lag between 4-hydroxynonenal (4HNE) adduction and the loss of motility in stallion spermatozoa suggests the presence of a robust aldehyde detoxification mechanism. Because there is a paucity of studies characterizing the role of aldehyde dehydrogenase (ALDH) in sperm functionality, the aim of this study was to ascertain the relationship between 4HNE production and motility and ALDH expression by stallion spermatozoa. PCR analysis revealed the presence of the ALDH1A3, ALDH1B1, and ALDH2 isoforms in these cells. Strong correlations (P < 0.001) were found between ALDH expression and various motility parameters of stallion spermatozoa including the percentage of progressive (r = 0.79) and rapidly motile (r = 0.79) spermatozoa, whereas repeated measurements over 24 h revealed highly significant correlations among progressive motility loss, 4HNE accumulation, and ALDH expression (P ≤ 0.001). ALDH inhibition resulted in a spontaneous increase in 4HNE levels in viable cells (21.1 ± 5.8% vs. 42.6 ± 5.2%; P ≤ 0.05) and a corresponding decrease in total motility (41.7 ± 6.2% vs. 6.4 ± 2.6%; P ≤ 0.001) and progressive motility (17.0 ± 4.1% vs. 0.7 ± 0.4%; P ≤ 0.001) of stallion spermatozoa over 24 h. Similarly, inhibition of ALDH in 4HNE-challenged spermatozoa significantly reduced total motility over 4 h (35.4 ± 9.7% vs. 15.3 ± 5.1%, respectively; P ≤ 0.05). This study contributes valuable information about the role of the ALDH enzymes in the maintenance of stallion sperm functionality, with potential diagnostic and in vitro applications for assisted reproductive technologies. © 2016 by the Society for the Study of Reproduction, Inc.

  13. Integrity of the Cone Photoreceptor Mosaic in Oligocone Trichromacy

    PubMed Central

    Rha, Jungtae; Dees, Elise W.; Baraas, Rigmor C.; Wagner-Schuman, Melissa L.; Mollon, John D.; Dubis, Adam M.; Andersen, Mette K. G.; Rosenberg, Thomas; Larsen, Michael; Moore, Anthony T.

    2011-01-01

    Purpose. Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT. Methods. Retinal images were obtained from two brothers (13 and 15 years) and two unrelated subjects, one male (47 years) and one female (24 years). High-resolution images of the cone mosaic were obtained using high-speed adaptive optics (AO) fundus cameras. Visible structures were analyzed for density using custom software. Additional retinal images were obtained using spectral domain optical coherence tomography (SD-OCT), and the four layers of the photoreceptor-retinal pigment epithelium complex (ELM, IS/OS, RPE1, RPE2) were evaluated. Cone photoreceptor length and the thickness of intraretinal layers were measured and compared to previously published normative data. Results. The adult male subject had infantile onset nystagmus while the three other patients did not. In the adult male patient, a normal appearing cone mosaic was observed. However, the three other subjects had a sparse mosaic of cones remaining at the fovea, with no structure visible outside the central fovea. On SD-OCT, the adult male subject had a very shallow foveal pit, with all major retinal layers being visible, and both inner segment (IS) and outer segment (OS) length were within normal limits. In the other three patients, while all four layers were visible in the central fovea and IS length was within normal limits, the OS length was significantly decreased. Peripherally the IS/OS layer decreased in intensity, and the RPE1 layer was no longer discernable, in keeping with the lack of cone

  14. Kinetics of Exocytosis Is Faster in Cones Than in Rods

    PubMed Central

    Rabl, Katalin; Cadetti, Lucia; Thoreson, Wallace B.

    2006-01-01

    Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures of release revealed two kinetic components to the increase in exocytosis as a function of the duration of a step depolarization. In addition to slow sustained components in both cell types, the initial fast component of exocytosis had a time constant of <5 ms in cones, >10-fold faster than that of rods. Rod/cone differences in the kinetics of release were substantiated by a linear correlation between depolarization-evoked capacitance increases and EPSC charge transfer. Experiments on isolated rods indicate that the slower kinetics of exocytosis from rods was not a result of rod–rod coupling. The initial rapid release of vesicles from cones can shape the postsynaptic response and may contribute to the faster responses of cone-driven cells observed at light offset. PMID:15872111

  15. Ptosis, extraocular motility disorder, and myopia as features of pompe disease.

    PubMed

    Slingerland, Niki W R; Polling, Jan Roelof; van Gelder, Catharina M; van der Ploeg, Ans T; Bleyen, Isabel

    2011-03-01

    The assets of this report are a thorough description of new clinical findings, namely the combination of ptosis, extraocular motility disorder and myopia, in consequence of prolonged survival in classic infantile-onset Pompe disease through enzyme therapy. Single case description. This manuscript describes a combination of ptosis, extraocular motility disorder and myopia in a 4.5-year-old patient with classic infantile-onset Pompe disease, who survived through enzyme therapy. This patient was treated with a bilateral frontalis suspension (modified Crawford technique) using prolene 3-0 sutures. The combination of ptosis, extraocular motility disorder and myopia, is a new clinical finding in children with classic infantile-onset Pompe disease.

  16. Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

    PubMed Central

    Hagerman, Gordon F.; Noel, Nicole C. L.; Cao, Sylvia Y.; DuVal, Michèle G.; Oel, A. Phillip; Allison, W. Ted

    2016-01-01

    Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration. PMID:27893779

  17. Calcium-Enhanced Twitching Motility in Xylella fastidiosa Is Linked to a Single PilY1 Homolog

    PubMed Central

    Cruz, Luisa F.; Parker, Jennifer K.; Cobine, Paul A.

    2014-01-01

    The plant-pathogenic bacterium Xylella fastidiosa is restricted to the xylem vessel environment, where mineral nutrients are transported through the plant host; therefore, changes in the concentrations of these elements likely impact the growth and virulence of this bacterium. Twitching motility, dependent on type IV pili (TFP), is required for movement against the transpiration stream that results in basipetal colonization. We previously demonstrated that calcium (Ca) increases the motility of X. fastidiosa, although the mechanism was unknown. PilY1 is a TFP structural protein recently shown to bind Ca and to regulate twitching and adhesion in bacterial pathogens of humans. Sequence analysis identified three pilY1 homologs in X. fastidiosa (PD0023, PD0502, and PD1611), one of which (PD1611) contains a Ca-binding motif. Separate deletions of PD0023 and PD1611 resulted in mutants that still showed twitching motility and were not impaired in attachment or biofilm formation. However, the response of increased twitching at higher Ca concentrations was lost in the pilY1-1611 mutant. Ca does not modulate the expression of any of the X. fastidiosa PilY1 homologs, although it increases the expression of the retraction ATPase pilT during active movement. The evidence presented here suggests functional differences between the PilY1 homologs, which may provide X. fastidiosa with an adaptive advantage in environments with high Ca concentrations, such as xylem sap. PMID:25217013

  18. Calcium-Enhanced Twitching Motility in Xylella fastidiosa Is Linked to a Single PilY1 Homolog.

    PubMed

    Cruz, Luisa F; Parker, Jennifer K; Cobine, Paul A; De La Fuente, Leonardo

    2014-12-01

    The plant-pathogenic bacterium Xylella fastidiosa is restricted to the xylem vessel environment, where mineral nutrients are transported through the plant host; therefore, changes in the concentrations of these elements likely impact the growth and virulence of this bacterium. Twitching motility, dependent on type IV pili (TFP), is required for movement against the transpiration stream that results in basipetal colonization. We previously demonstrated that calcium (Ca) increases the motility of X. fastidiosa, although the mechanism was unknown. PilY1 is a TFP structural protein recently shown to bind Ca and to regulate twitching and adhesion in bacterial pathogens of humans. Sequence analysis identified three pilY1 homologs in X. fastidiosa (PD0023, PD0502, and PD1611), one of which (PD1611) contains a Ca-binding motif. Separate deletions of PD0023 and PD1611 resulted in mutants that still showed twitching motility and were not impaired in attachment or biofilm formation. However, the response of increased twitching at higher Ca concentrations was lost in the pilY1-1611 mutant. Ca does not modulate the expression of any of the X. fastidiosa PilY1 homologs, although it increases the expression of the retraction ATPase pilT during active movement. The evidence presented here suggests functional differences between the PilY1 homologs, which may provide X. fastidiosa with an adaptive advantage in environments with high Ca concentrations, such as xylem sap. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  19. A quantitative evaluation of cell migration by the phagokinetic track motility assay.

    PubMed

    Nogalski, Maciej T; Chan, Gary C T; Stevenson, Emily V; Collins-McMillen, Donna K; Yurochko, Andrew D

    2012-12-04

    Cellular motility is an important biological process for both unicellular and multicellular organisms. It is essential for movement of unicellular organisms towards a source of nutrients or away from unsuitable conditions, as well as in multicellular organisms for tissue development, immune surveillance and wound healing, just to mention a few roles(1,2,3). Deregulation of this process can lead to serious neurological, cardiovascular and immunological diseases, as well as exacerbated tumor formation and spread(4,5). Molecularly, actin polymerization and receptor recycling have been shown to play important roles in creating cellular extensions (lamellipodia), that drive the forward movement of the cell(6,7,8). However, many biological questions about cell migration remain unanswered. The central role for cellular motility in human health and disease underlines the importance of understanding the specific mechanisms involved in this process and makes accurate methods for evaluating cell motility particularly important. Microscopes are usually used to visualize the movement of cells. However, cells move rather slowly, making the quantitative measurement of cell migration a resource-consuming process requiring expensive cameras and software to create quantitative time-lapsed movies of motile cells. Therefore, the ability to perform a quantitative measurement of cell migration that is cost-effective, non-laborious, and that utilizes common laboratory equipment is a great need for many researchers. The phagokinetic track motility assay utilizes the ability of a moving cell to clear gold particles from its path to create a measurable track on a colloidal gold-coated glass coverslip(9,10). With the use of freely available software, multiple tracks can be evaluated for each treatment to accomplish statistical requirements. The assay can be utilized to assess motility of many cell types, such as cancer cells(11,12), fibroblasts(9), neutrophils(13), skeletal muscle cells(14

  20. Antimicrobial resistance prevalence of Aeromonas hydrophila isolates from motile Aeromonas septicemia disease

    NASA Astrophysics Data System (ADS)

    Kusdarwati, R.; Rozi; Dinda, N. D.; Nurjanah, I.

    2018-04-01

    Fish suffer, from bacteria, fungi, virus and parasites or by physical ailments. Gurami (Osphronemus gouramy), nila (Oreochromis niloticus), carp (Cyprinus carpio), catfish (Clarias sp.) were the most reported infections caused by Aeromonas are bacterial hemorrhagic septicemia or Motile Aeromonas Septicemia (MAS). Antibiotics are drugs of natural or synthetic origin that have the capacity to kill or to inhibit the growth of micro-organisms included MAS. However, the use of antibiotics in the long term can cause negative impacts, among others, feared the occurrence of bacterial resistance in certain antibiotics. The results showed five of isolates were sensitive to antibiotics of chloramphenicol, gentamycin, oxytetracycline, cefradoxil and nalidixic acid but resistant to vancomycin colistin sulphate, rifampisin, cephalosporin and novobiocin.