WorldWideScience

Sample records for extrinsic axon guidance

  1. Optofluidic control of axonal guidance

    Science.gov (United States)

    Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

    2013-03-01

    Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

  2. Extrinsic and intrinsic regulation of axon regeneration at a crossroads.

    Science.gov (United States)

    Kaplan, Andrew; Ong Tone, Stephan; Fournier, Alyson E

    2015-01-01

    Repair of the injured spinal cord is a major challenge in medicine. The limited intrinsic regenerative response mounted by adult central nervous system (CNS) neurons is further hampered by astrogliosis, myelin debris and scar tissue that characterize the damaged CNS. Improved axon regeneration and recovery can be elicited by targeting extrinsic factors as well as by boosting neuron-intrinsic growth regulators. Our knowledge of the molecular basis of intrinsic and extrinsic regulators of regeneration has expanded rapidly, resulting in promising new targets to promote repair. Intriguingly certain neuron-intrinsic growth regulators are emerging as promising targets to both stimulate growth and relieve extrinsic inhibition of regeneration. This crossroads between the intrinsic and extrinsic aspects of spinal cord injury is a promising target for effective therapies for this unmet need.

  3. Meninges-derived cues control axon guidance.

    Science.gov (United States)

    Suter, Tracey A C S; DeLoughery, Zachary J; Jaworski, Alexander

    2017-10-01

    The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Guidance of retinal axons in mammals.

    Science.gov (United States)

    Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz

    2017-11-26

    In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Cannabinoid receptor CB2 modulates axon guidance

    DEFF Research Database (Denmark)

    Duff, Gabriel; Argaw, Anteneh; Cecyre, Bruno

    2013-01-01

    on axon guidance. These effects are specific to CB2R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced morphological changes observed at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted...... CB2R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R....

  6. Axon guidance molecules in vascular patterning.

    Science.gov (United States)

    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.

  7. Highly effective photonic cue for repulsive axonal guidance.

    Directory of Open Access Journals (Sweden)

    Bryan J Black

    Full Text Available In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods. These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

  8. Chondroitin-4-sulfation negatively regulates axonal guidance and growth

    Science.gov (United States)

    Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

    2008-01-01

    Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

  9. RGM is a repulsive guidance molecule for retinal axons

    DEFF Research Database (Denmark)

    Monnier, Philippe P; Sierra, Ana; Macchi, Paolo

    2002-01-01

    with known guidance cues, and its messenger RNA is distributed in a gradient with increasing concentration from the anterior to posterior pole of the embryonic tectum. Recombinant RGM at low nanomolar concentration induces collapse of temporal but not of nasal growth cones and guides temporal retinal axons...

  10. Wnt5a regulates midbrain dopaminergic axon growth and guidance.

    Directory of Open Access Journals (Sweden)

    Brette D Blakely

    2011-03-01

    Full Text Available During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM the cues that guide dopaminergic (DA axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway. Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.

  11. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    Science.gov (United States)

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

  12. Quantifying mechanical force in axonal growth and guidance

    Directory of Open Access Journals (Sweden)

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  13. The axonal guidance receptor neogenin promotes acute inflammation.

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    Klemens König

    Full Text Available Neuronal guidance proteins (NGP were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/- demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/- to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

  14. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  15. BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori.

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    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

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    Ryuta Koyama

    2018-05-01

    Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

  17. Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling

    DEFF Research Database (Denmark)

    Cheng, Jin; Sahani, Sadhna; Hausrat, Torben Johann

    2016-01-01

    Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both...

  18. Independent signaling by Drosophila insulin receptor for axon guidance and growth

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    Caroline Rita Li

    2014-01-01

    Full Text Available The Drosophila insulin receptor (DInR regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin-receptor-substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock. In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail, important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock-binding sites were in separate portions of the C-tail from the previously identified Chico-binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth, and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all 5 NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. Mutation of these 5 NPXY motifs did not affect photoreceptor axon guidance, showing that different sites within DInR control growth and axon guidance.

  19. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Pocock, Roger David John

    2014-01-01

    , little is known of its importance in the control of axon guidance. In a screen of prolyl 4-hydroxylase (P4H) mutants, we found that genetic removal of a specific P4H subunit, DPY-18, causes dramatic defects in C. elegans neuroanatomy. In dpy-18 mutant animals, the axons of specific ventral nerve cord......Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  20. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, N; Guan, Y J; Chen, X B [Division of Biomedical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Li, M G [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Schreyer, D J, E-mail: niz504@mail.usask.c [Department of Anatomy and Cell Biology, Cameco MS Neuroscience Research Center, University of Saskatchewan, Saskatoon, S7K 0M7 (Canada)

    2010-12-15

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  1. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    International Nuclear Information System (INIS)

    Zhu, N; Guan, Y J; Chen, X B; Li, M G; Schreyer, D J

    2010-01-01

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  2. A developmental timing switch promotes axon outgrowth independent of known guidance receptors.

    Directory of Open Access Journals (Sweden)

    Katherine Olsson-Carter

    2010-08-01

    Full Text Available To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.

  3. Independent signaling by Drosophila insulin receptor for axon guidance and growth.

    Science.gov (United States)

    Li, Caroline R; Guo, Dongyu; Pick, Leslie

    2013-01-01

    The Drosophila insulin receptor (DInR) regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin receptor substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock). In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail), important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock binding sites were in separate portions of the C-tail from the previously identified Chico binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all five NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. These animals resembled chico mutants, supporting the notion that DInR interacts directly with Chico in vivo to control body size. Mutation of these five NPXY motifs did not affect photoreceptor axon guidance, segregating the roles of DInR in the

  4. Axon guidance pathways served as common targets for human speech/language evolution and related disorders.

    Science.gov (United States)

    Lei, Huimeng; Yan, Zhangming; Sun, Xiaohong; Zhang, Yue; Wang, Jianhong; Ma, Caihong; Xu, Qunyuan; Wang, Rui; Jarvis, Erich D; Sun, Zhirong

    2017-11-01

    Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons.

    Science.gov (United States)

    Nitta, Yohei; Yamazaki, Daisuke; Sugie, Atsushi; Hiroi, Makoto; Tabata, Tetsuya

    2017-01-15

    Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

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    Timothy G Lesnick

    2007-06-01

    Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  7. Beyond Parkinson disease: amyotrophic lateral sclerosis and the axon guidance pathway.

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    Timothy G Lesnick

    2008-01-01

    Full Text Available We recently described a genomic pathway approach to study complex diseases. We demonstrated that models constructed using single nucleotide polymorphisms (SNPs within axon guidance pathway genes were highly predictive of Parkinson disease (PD susceptibility, survival free of PD, and age at onset of PD within two independent whole-genome association datasets. We also demonstrated that several axon guidance pathway genes represented by SNPs within our final models were differentially expressed in PD.Here we employed our genomic pathway approach to analyze data from a whole-genome association dataset of amyotrophic lateral sclerosis (ALS; and demonstrated that models constructed using SNPs within axon guidance pathway genes were highly predictive of ALS susceptibility (odds ratio = 1739.73, p = 2.92x10(-60, survival free of ALS (hazards ratio = 149.80, p = 1.25x10(-74, and age at onset of ALS (R(2 = 0.86, p = 5.96x10(-66. We also extended our analyses of a whole-genome association dataset of PD, which shared 320,202 genomic SNPs in common with the whole-genome association dataset of ALS. We compared for ALS and PD the genes represented by SNPs in the final models for susceptibility, survival free of disease, and age at onset of disease and noted that 52.2%, 37.8%, and 34.9% of the genes were shared respectively.Our findings for the axon guidance pathway and ALS have prior biological plausibility, overlap partially with PD, and may provide important insight into the causes of these and related neurodegenerative disorders.

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

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    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.

  9. The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.

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    Arul Vadivel

    Full Text Available Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C, contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.

  10. MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes.

    Science.gov (United States)

    Kos, Aron; Klein-Gunnewiek, Teun; Meinhardt, Julia; Loohuis, Nikkie F M Olde; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard J; Kolk, Sharon M; Aschrafi, Armaz

    2017-07-01

    MicroRNAs (miRs) are small non-coding RNAs that confer robustness to gene networks through post-transcriptional gene regulation. Previously, we identified miR-338 as a modulator of axonal outgrowth in sympathetic neurons. In the current study, we examined the role of miR-338 in the development of cortical neurons and uncovered its downstream mRNA targets. Long-term inhibition of miR-338 during neuronal differentiation resulted in reduced dendritic complexity and altered dendritic spine morphology. Furthermore, monitoring axon outgrowth in cortical cells revealed that miR-338 overexpression decreased, whereas inhibition of miR-338 increased axonal length. To identify gene targets mediating the observed phenotype, we inhibited miR-338 in cortical neurons and performed whole-transcriptome analysis. Pathway analysis revealed that miR-338 modulates a subset of transcripts involved in the axonal guidance machinery by means of direct and indirect gene targeting. Collectively, our results implicate miR-338 as a novel regulator of cortical neuronal maturation by fine-tuning the expression of gene networks governing cortical outgrowth.

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

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    Elisa eTamariz

    2015-05-01

    Full Text Available 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 reestablish 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.

  12. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia.

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    Katariina Hannula-Jouppi

    2005-10-01

    Full Text Available Dyslexia, or specific reading disability, is the most common learning disorder with a complex, partially genetic basis, but its biochemical mechanisms remain poorly understood. A locus on Chromosome 3, DYX5, has been linked to dyslexia in one large family and speech-sound disorder in a subset of small families. We found that the axon guidance receptor gene ROBO1, orthologous to the Drosophila roundabout gene, is disrupted by a chromosome translocation in a dyslexic individual. In a large pedigree with 21 dyslexic individuals genetically linked to a specific haplotype of ROBO1 (not found in any other chromosomes in our samples, the expression of ROBO1 from this haplotype was absent or attenuated in affected individuals. Sequencing of ROBO1 in apes revealed multiple coding differences, and the selection pressure was significantly different between the human, chimpanzee, and gorilla branch as compared to orangutan. We also identified novel exons and splice variants of ROBO1 that may explain the apparent phenotypic differences between human and mouse in heterozygous loss of ROBO1. We conclude that dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans.

  13. The Axon Guidance Receptor Gene ROBO1 Is a Candidate Gene for Developmental Dyslexia.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Dyslexia, or specific reading disability, is the most common learning disorder with a complex, partially genetic basis, but its biochemical mechanisms remain poorly understood. A locus on Chromosome 3, DYX5, has been linked to dyslexia in one large family and speech-sound disorder in a subset of small families. We found that the axon guidance receptor gene ROBO1, orthologous to the Drosophila roundabout gene, is disrupted by a chromosome translocation in a dyslexic individual. In a large pedigree with 21 dyslexic individuals genetically linked to a specific haplotype of ROBO1 (not found in any other chromosomes in our samples, the expression of ROBO1 from this haplotype was absent or attenuated in affected individuals. Sequencing of ROBO1 in apes revealed multiple coding differences, and the selection pressure was significantly different between the human, chimpanzee, and gorilla branch as compared to orangutan. We also identified novel exons and splice variants of ROBO1 that may explain the apparent phenotypic differences between human and mouse in heterozygous loss of ROBO1. We conclude that dyslexia may be caused by partial haplo-insufficiency for ROBO1 in rare families. Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans.

  14. TIPsy tour guides: How microtubule plus-end tracking proteins (+TIPs facilitate axon guidance

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    Elizabeth A Bearce

    2015-06-01

    Full Text Available 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 in growth cone navigation. Here, we focus on the role of singular pioneer microtubules, 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 microtubules, 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.

  15. Caenorhabditis elegans VEM-1, a novel membrane protein, regulates the guidance of ventral nerve cord-associated axons.

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    Runko, Erik; Kaprielian, Zaven

    2004-10-13

    In the developing CNS, pathfinding growth cones use intermediate target- and pioneer axon-associated guidance cues to navigate along stereotypical trajectories. We previously showed that the novel membrane-associated protein Vema is localized to the floor plate and the optic chiasm, intermediate targets located at the ventral midline of the spinal cord and diencephalon in the developing rodent CNS, respectively. Here, we report that the Caenorhabditis elegans ortholog of vema, vem-1, is expressed by the AVG pioneer midline neuron and by several neurons that extend longitudinally projecting axons into the ventral nerve cord (VNC). In vem-1 mutants and vem-1 (RNAi) animals, a subset of posteriorly projecting interneuron axons either fail to extend ventrally to the VNC and, instead, assume aberrant lateral positions or are inappropriately located in the left tract of the VNC. In addition, ventral motor neuron axons exhibit pathfinding errors within the VNC and along the dorsoventral body axis. The conserved UNC-40/DCC and SAX-3-/Robo receptors mediate signaling events that regulate axon guidance in a wide variety of systems. Double-mutant analyses reveal that vem-1 genetically interacts with unc-40 and is likely to function in parallel with sax-3 to regulate the guidance of a subset of VNC-associated interneuron and motor neuron axons. Consistent with these genetic data, we also show that VEM-1 is capable of physically interacting with UNC-40 but not SAX-3.

  16. Piezoelectric ceramic (PZT) modulates axonal guidance growth of rat cortical neurons via RhoA, Rac1, and Cdc42 pathways.

    Science.gov (United States)

    Wen, Jianqiang; Liu, Meili

    2014-03-01

    Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

  17. A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance.

    Science.gov (United States)

    Clemens, J C; Ursuliak, Z; Clemens, K K; Price, J V; Dixon, J E

    1996-07-19

    We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (dock) (Garrity, P. A., Rao, Y., Salecker, I., and Zipursky, S. L.(1996) Cell 85, 639-650). Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain. The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments. A sequence containing five PXXP motifs from the non-catalytic domain of the PTP is sufficient for interaction with Dock. This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co-precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain. These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.

  18. Axon guidance in the developing ocular motor system and Duane retraction syndrome depends on Semaphorin signaling via alpha2-chimaerin

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    Ferrario, Juan E.; Baskaran, Pranetha; Clark, Christopher; Hendry, Aenea; Lerner, Oleg; Hintze, Mark; Allen, James; Chilton, John K.; Guthrie, Sarah

    2012-01-01

    Eye movements depend on correct patterns of connectivity between cranial motor axons and the extraocular muscles. Despite the clinical importance of the ocular motor system, little is known of the molecular mechanisms underlying its development. We have recently shown that mutations in the Chimaerin-1 gene encoding the signaling protein α2-chimaerin (α2-chn) perturb axon guidance in the ocular motor system and lead to the human eye movement disorder, Duane retraction syndrome (DRS). The axon guidance cues that lie upstream of α2-chn are unknown; here we identify candidates to be the Semaphorins (Sema) 3A and 3C, acting via the PlexinA receptors. Sema3A/C are expressed in and around the developing extraocular muscles and cause growth cone collapse of oculomotor neurons in vitro. Furthermore, RNAi knockdown of α2-chn or PlexinAs in oculomotor neurons abrogates Sema3A/C-dependent growth cone collapse. In vivo knockdown of endogenous PlexinAs or α2-chn function results in stereotypical oculomotor axon guidance defects, which are reminiscent of DRS, whereas expression of α2-chn gain-of-function constructs can rescue PlexinA loss of function. These data suggest that α2-chn mediates Sema3–PlexinA repellent signaling. We further show that α2-chn is required for oculomotor neurons to respond to CXCL12 and hepatocyte growth factor (HGF), which are growth promoting and chemoattractant during oculomotor axon guidance. α2-chn is therefore a potential integrator of different types of guidance information to orchestrate ocular motor pathfinding. DRS phenotypes can result from incorrect regulation of this signaling pathway. PMID:22912401

  19. The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb

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    Rajapaksha Tharinda W

    2011-12-01

    Full Text Available Abstract Background The β-secretase, β-site amyloid precursor protein cleaving enzyme 1 (BACE1, is a prime therapeutic target for lowering cerebral β-amyloid (Aβ levels in Alzheimer's disease (AD. Clinical development of BACE1 inhibitors is being intensely pursued. However, little is known about the physiological functions of BACE1, and the possibility exists that BACE1 inhibition may cause mechanism-based side effects. Indeed, BACE1-/- mice exhibit a complex neurological phenotype. Interestingly, BACE1 co-localizes with presynaptic neuronal markers, indicating a role in axons and/or terminals. Moreover, recent studies suggest axon guidance molecules are potential BACE1 substrates. Here, we used a genetic approach to investigate the function of BACE1 in axon guidance of olfactory sensory neurons (OSNs, a well-studied model of axon targeting in vivo. Results We bred BACE1-/- mice with gene-targeted mice in which GFP is expressed from the loci of two odorant-receptors (ORs, MOR23 and M72, and olfactory marker protein (OMP to produce offspring that were heterozygous for MOR23-GFP, M72-GFP, or OMP-GFP and were either BACE1+/+ or BACE1-/-. BACE1-/- mice had olfactory bulbs (OBs that were smaller and weighed less than OBs of BACE1+/+ mice. In wild-type mice, BACE1 was present in OSN axon terminals in OB glomeruli. In whole-mount preparations and tissue sections, many OB glomeruli from OMP-GFP; BACE1-/- mice were malformed compared to wild-type glomeruli. MOR23-GFP; BACE1-/- mice had an irregular MOR23 glomerulus that was innervated by randomly oriented, poorly fasciculated OSN axons compared to BACE1+/+ mice. Most importantly, M72-GFP; BACE1-/- mice exhibited M72 OSN axons that were mis-targeted to ectopic glomeruli, indicating impaired axon guidance in BACE1-/- mice. Conclusions Our results demonstrate that BACE1 is required for the accurate targeting of OSN axons and the proper formation of glomeruli in the OB, suggesting a role for BACE1 in

  20. Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

    OpenAIRE

    Ding, Qiao; Liao, Song-Jie; Yu, Jian

    2014-01-01

    Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light o...

  1. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

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    Jeffery Glen

    2008-05-01

    Full Text Available Abstract Background The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6Sey/Sey and are abnormally small in Pax6Sey/+ mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results Eyes form in PAX77+/+ embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77+/+ retinae produce a normal range of cell types, including retinal ganglion cells (RGCs. At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77+/+ embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6Sey/+, Pax6+/+, PAX77+ and PAX77+/+ showed that (1 the total number of RGC axons projected by the retina and (2 the proportions that are sorted into the ipsilateral and

  2. Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

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    CAVALCANTE LENY A.

    2002-01-01

    Full Text Available Bilaterally symmetric organisms need to exchange information between the left and right sides of their bodies to integrate sensory input and to coordinate motor control. Thus, an important choice point for developing axons is the Central Nervous System (CNS midline. Crossing of this choice point is influenced by highly conserved, soluble or membrane-bound molecules such as the L1 subfamily, laminin, netrins, slits, semaphorins, Eph-receptors and ephrins, etc. Furthermore, there is much circumstantial evidence for a role of proteoglycans (PGs or their glycosaminoglycan (GAG moieties on axonal growth and guidance, most of which was derived from simplified models. A model of intermediate complexity is that of cocultures of young neurons and astroglial carpets (confluent cultures obtained from medial and lateral sectors of the embryonic rodent midbrain soon after formation of its commissures. Neurite production in these cocultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exerted an inhibitory or non-permissive effect on neuritic growth that was correlated to a higher content of both heparan and chondroitin sulfates (HS and CS. Treatment with GAG lyases shows minor effects of CS and discloses a major inhibitory or non-permissive role for HS. The results are discussed in terms of available knowledge on the binding of HSPGs to interative proteins and underscore the importance of understanding glial polysaccharide arrays in addition to its protein complement for a better understanding of neuron-glial interactions.

  3. Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord

    DEFF Research Database (Denmark)

    Lundfald, Line; Restrepo, C. Ernesto; Butt, Simon J B

    2007-01-01

    , we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing...

  4. The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1

    DEFF Research Database (Denmark)

    Mariani, Luca; Lussi, Yvonne C.; Vandamme, Julien

    2016-01-01

    . Here, we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1...

  5. The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

    Science.gov (United States)

    Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

    2015-01-01

    Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

  6. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    OpenAIRE

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expressio...

  7. Post-guidance signaling by extracellular matrix-associated Slit/Slit-N maintains fasciculation and position of axon tracts in the nerve cord.

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    Krishna Moorthi Bhat

    2017-11-01

    Full Text Available Axon-guidance by Slit-Roundabout (Robo signaling at the midline initially guides growth cones to synaptic targets and positions longitudinal axon tracts in discrete bundles on either side of the midline. Following the formation of commissural tracts, Slit is found also in tracts of the commissures and longitudinal connectives, the purpose of which is not clear. The Slit protein is processed into a larger N-terminal peptide and a smaller C-terminal peptide. Here, I show that Slit and Slit-N in tracts interact with Robo to maintain the fasciculation, the inter-tract spacing between tracts and their position relative to the midline. Thus, in the absence of Slit in post-guidance tracts, tracts de-fasciculate, merge with one another and shift their position towards the midline. The Slit protein is proposed to function as a gradient. However, I show that Slit and Slit-N are not freely present in the extracellular milieu but associated with the extracellular matrix (ECM and both interact with Robo1. Slit-C is tightly associated with the ECM requiring collagenase treatment to release it, and it does not interact with Robo1. These results define a role for Slit and Slit-N in tracts for the maintenance and fasciculation of tracts, thus the maintenance of the hardwiring of the CNS.

  8. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

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    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  9. Accelerated axon outgrowth, guidance, and target reinnervation across nerve transection gaps following a brief electrical stimulation paradigm.

    Science.gov (United States)

    Singh, Bhagat; Xu, Qing-Gui; Franz, Colin K; Zhang, Rumi; Dalton, Colin; Gordon, Tessa; Verge, Valerie M K; Midha, Rajiv; Zochodne, Douglas W

    2012-03-01

    Regeneration of peripheral nerves is remarkably restrained across transection injuries, limiting recovery of function. Strategies to reverse this common and unfortunate outcome are limited. Remarkably, however, new evidence suggests that a brief extracellular electrical stimulation (ES), delivered at the time of injury, improves the regrowth of motor and sensory axons. In this work, the authors explored and tested this ES paradigm, which was applied proximal to transected sciatic nerves in mice, and identified several novel and compelling impacts of the approach. Using thy-1 yellow fluorescent protein mice with fluorescent axons that allow serial in vivo tracking of regeneration, the morphological, electrophysiological, and behavioral indices of nerve regrowth were measured. The authors show that ES is associated with a 30%-50% improvement in several indices of regeneration: regrowth of axons and their partnered Schwann cells across transection sites, maturation of regenerated fibers in gaps spanning transection zones, and entry of axons into their muscle and cutaneous target zones. In parallel studies, the authors analyzed adult sensory neurons and their response to extracellular ES while plated on a novel microelectrode array construct designed to deliver the identical ES paradigm used in vivo. The ES accelerated neurite outgrowth, supporting the concept of a neuron-autonomous mechanism of action. Taken together, these results support a robust role for brief ES following peripheral nerve injuries in promoting regeneration. Electrical stimulation has a wider repertoire of impact than previously recognized, and its impact in vitro supports the hypothesis that a neuron-specific reprogrammed injury response is recruited by the ES protocol.

  10. Regulation of EphA4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function

    DEFF Research Database (Denmark)

    Egea, Joaquim; Nissen, Ulla Vig; Dufour, Audrey

    2005-01-01

    Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also...... requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4 EE), whose kinase is constitutively activated in the absence of ephrinB ligands......, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4EE, including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation...

  11. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA’s effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes. PMID:23119107

  12. The protection of acetylcholinesterase inhibitor on β-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells.

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA's effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes.

  13. Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

    Science.gov (United States)

    Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

    2018-01-17

    Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

  14. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  15. Formation of longitudinal axon pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Hutter, Harald

    2017-11-18

    The small number of neurons and the simple architecture of the Caenorhabditis elegans (C. elegans) nervous system enables researchers to study axonal pathfinding at the level of individually identified axons. Axons in C. elegans extend predominantly along one of the two major body axes, the anterior-posterior axis and the dorso-ventral axis. This review will focus on axon navigation along the anterior-posterior axis, leading to the establishment of the longitudinal axon tracts, with a focus on the largest longitudinal axon tract, the ventral nerve cord (VNC). In the VNC, axons grow out in a stereotypic order, with early outgrowing axons (pioneers) playing an important role in guiding later outgrowing (follower) axons. Genetic screens have identified a number of genes specifically affecting the formation of longitudinal axon tracts. These genes include secreted proteins, putative receptors and adhesion molecules, as well as intracellular proteins regulating the cell's response to guidance cues. In contrast to dorso-ventral navigation, no major general guidance cues required for the establishment of longitudinal pathways have been identified so far. The limited penetrance of defects found in many mutants affecting longitudinal navigation suggests that guidance cues act redundantly in this process. The majority of the axon guidance genes identified in C. elegans are evolutionary conserved, i.e. have homologs in other animals, including vertebrates. For a number of these genes, a role in axon guidance has not been described outside C. elegans. Taken together, studies in C. elegans contribute to a fundamental understanding of the molecular basis of axonal navigation that can be extended to other animals, including vertebrates and probably humans as well. Copyright © 2017. Published by Elsevier Ltd.

  16. Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

    Science.gov (United States)

    Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D

    2017-03-20

    Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Development of the intrinsic and extrinsic innervation of the gut.

    Science.gov (United States)

    Uesaka, Toshihiro; Young, Heather M; Pachnis, Vassilis; Enomoto, Hideki

    2016-09-15

    The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Intrinsic and extrinsic mortality reunited

    DEFF Research Database (Denmark)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P

    2015-01-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However......, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well...... as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic...

  19. Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.

    Science.gov (United States)

    Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric

    2015-03-01

    During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

  20. Extrinsic morphology of graphene

    International Nuclear Information System (INIS)

    Li, Teng

    2011-01-01

    Graphene is intrinsically non-flat and corrugates randomly. Since the corrugating physics of atomically thin graphene is strongly tied to its electronics properties, randomly corrugating morphology of graphene poses a significant challenge to its application in nanoelectronic devices for which precise (digital) control is the key. Recent studies revealed that the morphology of substrate-supported graphene is regulated by the graphene–substrate interaction, thus is distinct from the random intrinsic morphology of freestanding graphene. The regulated extrinsic morphology of graphene sheds light on new pathways to fine tune the properties of graphene. To guide further research to explore these fertile opportunities, this paper reviews recent progress on modeling and experimental studies of the extrinsic morphology of graphene under a wide range of external regulation, including two-dimensional and one-dimensional substrate surface features and one-dimensional and zero-dimensional nanoscale scaffolds (e.g. nanowires and nanoparticles)

  1. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  2. Retinoic acid signaling in axonal regeneration

    Directory of Open Access Journals (Sweden)

    Radhika ePuttagunta

    2012-01-01

    Full Text Available Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARß2, to induce axonal regeneration following spinal cord injury (SCI. Recently, it has been shown that in dorsal root ganglia neurons, cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβ agonists, in cerebellar granule neurons and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARß pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.

  3. A growing field: The regulation of axonal regeneration by Wnt signaling.

    Science.gov (United States)

    Garcia, Armando L; Udeh, Adanna; Kalahasty, Karthik; Hackam, Abigail S

    2018-01-01

    The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone

  4. Acute nutritional axonal neuropathy.

    Science.gov (United States)

    Hamel, Johanna; Logigian, Eric L

    2018-01-01

    This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018. © 2017 Wiley Periodicals, Inc.

  5. Axons take a dive

    Science.gov (United States)

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2015-01-01

    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  6. Intrinsic and extrinsic mortality reunited.

    Science.gov (United States)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P; van Bodegom, David; Westendorp, Rudi G J

    2015-07-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering

    Czech Academy of Sciences Publication Activity Database

    Šmít, Daniel; Fouquet, C.; Pincet, F.; Zápotocký, Martin; Trembleau, A.

    2017-01-01

    Roč. 6, Apr 19 (2017), č. článku e19907. ISSN 2050-084X R&D Projects: GA ČR(CZ) GA14-16755S; GA MŠk(CZ) 7AMB12FR002 Institutional support: RVO:67985823 Keywords : biophysics * cell adhesion * coarsening * developmental biology * mathematical model * mechanical tension * axon guidance Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 7.725, year: 2016

  8. Electrophysiology of Axonal Constrictions

    Science.gov (United States)

    Johnson, Christopher; Jung, Peter; Brown, Anthony

    2013-03-01

    Axons of myelinated neurons are constricted at the nodes of Ranvier, where they are directly exposed to the extracellular space and where the vast majority of the ion channels are located. These constrictions are generated by local regulation of the kinetics of neurofilaments the most important cytoskeletal elements of the axon. In this paper we discuss how this shape affects the electrophysiological function of the neuron. Specifically, although the nodes are short (about 1 μm) in comparison to the distance between nodes (hundreds of μm) they have a substantial influence on the conduction velocity of neurons. We show through computational modeling that nodal constrictions (all other features such as numbers of ion channels left constant) reduce the required fiber diameter for a given target conduction velocity by up to 50% in comparison to an unconstricted axon. We further show that the predicted optimal fiber morphologies closely match reported fiber morphologies. Supported by The National Science Foundation (IOS 1146789)

  9. Glia to axon RNA transfer.

    Science.gov (United States)

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A

    2014-03-01

    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased. Copyright © 2013 Wiley Periodicals, Inc.

  10. Regularized strings with extrinsic curvature

    International Nuclear Information System (INIS)

    Ambjoern, J.; Durhuus, B.

    1987-07-01

    We analyze models of discretized string theories, where the path integral over world sheet variables is regularized by summing over triangulated surfaces. The inclusion of curvature in the action is a necessity for the scaling of the string tension. We discuss the physical properties of models with extrinsic curvature terms in the action and show that the string tension vanishes at the critical point where the bare extrinsic curvature coupling tends to infinity. Similar results are derived for models with intrinsic curvature. (orig.)

  11. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  12. Signal propagation along the axon.

    Science.gov (United States)

    Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

    2018-03-08

    Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Imaging with extrinsic Raman labels

    NARCIS (Netherlands)

    Sijtsema, N M; Duindam, J J; Puppels, G J; Otto, C; Greve, J

    1996-01-01

    In two separate examples we demonstrate the use of extrinsic Raman scattering probes for imaging of biological samples. First, the distribution of cholesterol in a rat eye Lens is determined with the use of the Raman scattered light from filipin, a molecule which binds specifically to cholesterol.

  14. Extrinsic CPT Violation in Neutrino Oscillations

    International Nuclear Information System (INIS)

    Ohlsson, Tommy

    2004-01-01

    In this talk, we investigate extrinsic CPT violation in neutrino oscillations in matter with three flavors. Note that extrinsic CPT violation is different from intrinsic CPT violation. Extrinsic CPT violation is one way of quantifying matter effects, whereas intrinsic CPT violation would mean that the CPT invariance theorem is not valid. We present analytical formulas for the extrinsic CPT probability differences and discuss their implications for long-baseline experiments and neutrino factory setups

  15. DISCO interacting protein 2 determines direction of axon projection under the regulation of c-Jun N-terminal kinase in the Drosophila mushroom body

    International Nuclear Information System (INIS)

    Nitta, Yohei; Sugie, Atsushi

    2017-01-01

    Precisely controlled axon guidance for complex neuronal wiring is essential for appropriate neuronal function. c-Jun N-terminal kinase (JNK) was found to play a role in axon guidance recently as well as in cell proliferation, protection and apoptosis. In spite of many genetic and molecular studies on these biological processes regulated by JNK, how JNK regulates axon guidance accurately has not been fully explained thus far. To address this question, we use the Drosophila mushroom body (MB) as a model since the α/β axons project in two distinct directions. Here we show that DISCO interacting protein 2 (DIP2) is required for the accurate direction of axonal guidance. DIP2 expression is under the regulation of Basket (Bsk), the Drosophila homologue of JNK. We additionally found that the Bsk/DIP2 pathway is independent from the AP-1 transcriptional factor complex pathway, which is directly activated by Bsk. In conclusion, our findings revealed DIP2 as a novel effector downstream of Bsk modulating the direction of axon projection. - Highlights: • DIP2 is required for accurate direction of axon guidance in Drosophila mushroom body. • DIP2 is a downstream of JNK in the axon guidance of Drosophila mushroom body neuron. • JNK/DIP2 pathway is independent from JNK/AP-1 transcriptional factor complex pathway.

  16. Intrinsic and extrinsic innervation of the heart in zebrafish (Danio rerio).

    Science.gov (United States)

    Stoyek, Matthew R; Croll, Roger P; Smith, Frank M

    2015-08-01

    In the vertebrate heart the intracardiac nervous system is the final common pathway for autonomic control of cardiac output, but the neuroanatomy of this system is not well understood. In this study we investigated the innervation of the heart in a model vertebrate, the zebrafish. We used antibodies against acetylated tubulin, human neuronal protein C/D, choline acetyltransferase, tyrosine hydroxylase, neuronal nitric oxide synthase, and vasoactive intestinal polypeptide to visualize neural elements and their neurotransmitter content. Most neurons were located at the venous pole in a plexus around the sinoatrial valve; mean total number of cells was 197 ± 23, and 92% were choline acetyltransferase positive, implying a cholinergic role. The plexus contained cholinergic, adrenergic, and nitrergic axons and vasoactive intestinal polypeptide-positive terminals, some innervating somata. Putative pacemaker cells near the plexus showed immunoreactivity for hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and the transcription factor Islet-1 (Isl1). The neurotracer neurobiotin showed that extrinsic axons from the left and right vagosympathetic trunks innervated the sinoatrial plexus proximal to their entry into the heart; some extrinsic axons from each trunk also projected into the medial dorsal plexus region. Extrinsic axons also innervated the atrial and ventricular walls. An extracardiac nerve trunk innervated the bulbus arteriosus and entered the arterial pole of the heart to innervate the proximal ventricle. We have shown that the intracardiac nervous system in the zebrafish is anatomically and neurochemically complex, providing a substrate for autonomic control of cardiac effectors in all chambers. © 2015 Wiley Periodicals, Inc.

  17. The genetics of axonal transport and axonal transport disorders.

    Directory of Open Access Journals (Sweden)

    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  18. Extrinsic incentives and tax compliance

    OpenAIRE

    Sour, Laura; Gutiérrez Andrade, Miguel Ángel

    2011-01-01

    This paper models the impact of extrinsic incentives in a tax compliance model. It also provides experimental evidence that confirms the existence of a positive relationship between rewards and tax compliance. If individuals are audited, rewards for honest taxpayers are effective in increasing the level of tax compliance. These results are particularly relevant in countries where there is little respect for tax law since rewards can contribute to crowding in the intrinsic motivation to comply.

  19. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-07-03

    Semi-insulating Gallium Nitride, 4H and 6H Silicon Carbide are attractive materials for compact, high voltage, extrinsic, photoconductive switches due to their wide bandgap, high dark resistance, high critical electric field strength and high electron saturation velocity. These wide bandgap semiconductors are made semi-insulating by the addition of vanadium (4H and 6HSiC) and iron (2H-GaN) impurities that form deep acceptors. These deep acceptors trap electrons donated from shallow donor impurities. The electrons can be optically excited from these deep acceptor levels into the conduction band to transition the wide bandgap semiconductor materials from a semi-insulating to a conducting state. Extrinsic photoconductive switches with opposing electrodes have been constructed using vanadium compensated 6H-SiC and iron compensated 2H-GaN. These extrinsic photoconductive switches were tested at high voltage and high power to determine if they could be successfully used as the closing switch in compact medical accelerators.

  20. Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons.

    Science.gov (United States)

    McCormick, Aleesha M; Jarmusik, Natalie A; Leipzig, Nic D

    2015-12-01

    Immobilization of axon guidance cues offers a powerful tissue regenerative strategy to control the presentation and spatial location of these biomolecules. We use our previously developed immobilization strategy to specifically tether recombinant biotinylated nerve growth factor (bNGF) and biotinylated semaphorin3A (bSema3A) to chitosan films as an outgrowth and guidance platform. DRG neurite length and number for a range of single cues of immobilized bNGF or bSema3A were examined to determine a concentration response. Next single and dual cues of bNGF and bSema3A were immobilized and DRG guidance was assessed in response to a step concentration change from zero. Overall, immobilized groups caused axon extension, retraction and turning depending on the ratio of bNGF and bSema3A immobilized in the encountered region. This response indicated the exquisite sensitivity of DRG axons to both attractive and repulsive tethered cues. bSema3A concentrations of 0.10 and 0.49 ng/mm(2), when co-immobilized with bNGF (at 0.86 and 0.43 ng/mm(2) respectively), caused axons to turn away from the co-immobilized region. Immunocytochemical analysis showed that at these bSema3A concentrations, axons inside the co-immobilized region display microtubule degradation and breakdown of actin filaments. At the lowest bSema3A concentration (0.01 ng/mm(2)) co-immobilized with a higher bNGF concentration (2.16 ng/mm(2)), neurite lengths are shorter in the immobilized area, but bNGF dominates the guidance mechanism as neurites are directed toward the immobilized region. Future applications can pattern these cues in various geometries and gradients in order to better modulate axon guidance in terms of polarity, extension and branching. Nervous system formation and regeneration requires key molecules for guiding the growth cone and nervous system patterning. In vivo these molecules work in conjunction with one another to modulate axon guidance, and often they are tethered to limit spatial

  1. The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

    Science.gov (United States)

    Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

    2018-06-01

    We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam

    Science.gov (United States)

    Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung

    2012-01-01

    Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636

  3. BmRobo1a and BmRobo1b control axon repulsion in the silkworm Bombyx mori.

    Science.gov (United States)

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    The development of the nervous system is based on the growth and connection of axons, and axon guidance molecules are the dominant regulators during this course. Robo, as the receptor of axon guidance molecule Slit, plays a key role as a conserved repellent cue for axon guidance during the development of the central nervous system. However, the function of Robo in the silkworm Bombyx mori is unknown. In this study, we cloned two novel robo genes in B. mori (Bmrobo1a and Bmrobo1b). BmRobo1a and BmRobo1b lack an Ig and a FNIII domain in the extracellular region and the CC0 and CC2 motifs in the intracellular region. BmRobo1a and BmRobo1b were colocalized with BmSlit in the neuropil. Knock-down of Bmrobo1a and Bmrobo1b by RNA interference (RNAi) resulted in abnormal development of axons. Our results suggest that BmRobo1a and BmRobo1b have repulsive function in axon guidance, even though their structures are different from Robo1 of other species. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Axon density and axon orientation dispersion in children born preterm

    NARCIS (Netherlands)

    Kelly, Claire E.; Thompson, Deanne K.; Chen, Jian; Leemans, Alexander; Adamson, Christopher L.; Inder, Terrie E.; Cheong, Jeanie L Y; Doyle, Lex W.; Anderson, Peter J.

    2016-01-01

    Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density

  5. Selective axonal growth of embryonic hippocampal neurons according to topographic features of various sizes and shapes

    Directory of Open Access Journals (Sweden)

    Christine E Schmidt

    2010-12-01

    Full Text Available David Y Fozdar1*, Jae Y Lee2*, Christine E Schmidt2–6, Shaochen Chen1,3–5,7,1Departments of Mechanical Engineering, 2Chemical Engineering, 3Biomedical Engineering; 4Center for Nano Molecular Science and Technology; 5Texas Materials Institute; 6Institute of Neuroscience; 7Microelectronics Research Center, The University of Texas at Austin, Austin, TX, USA *Contributed equally to this workPurpose: Understanding how surface features influence the establishment and outgrowth of the axon of developing neurons at the single cell level may aid in designing implantable scaffolds for the regeneration of damaged nerves. Past studies have shown that micropatterned ridge-groove structures not only instigate axon polarization, alignment, and extension, but are also preferred over smooth surfaces and even neurotrophic ligands.Methods: Here, we performed axonal-outgrowth competition assays using a proprietary four-quadrant topography grid to determine the capacity of various micropatterned topographies to act as stimuli sequestering axon extension. Each topography in the grid consisted of an array of microscale (approximately 2 µm or submicroscale (approximately 300 nm holes or lines with variable dimensions. Individual rat embryonic hippocampal cells were positioned either between two juxtaposing topographies or at the borders of individual topographies juxtaposing unpatterned smooth surface, cultured for 24 hours, and analyzed with respect to axonal selection using conventional imaging techniques.Results: Topography was found to influence axon formation and extension relative to smooth surface, and the distance of neurons relative to topography was found to impact whether the topography could serve as an effective cue. Neurons were also found to prefer submicroscale over microscale features and holes over lines for a given feature size.Conclusion: The results suggest that implementing physical cues of various shapes and sizes on nerve guidance conduits

  6. Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons

    NARCIS (Netherlands)

    Rochlin, M William; O'Connor, R.; Giger, Roman J; Verhaagen, J; Farbman, A I

    2000-01-01

    Geniculate (gustatory) and trigeminal (somatosensory) afferents take different routes to the tongue during rat embryonic development. To learn more about the mechanisms controlling neurite outgrowth and axon guidance, we are studying the roles of diffusible factors. We previously profiled the in

  7. Vesicular trafficking of semaphorin 3A is activity-dependent and differs between axons and dendrites

    NARCIS (Netherlands)

    de Wit, Joris; Toonen, Ruud F; Verhaagen, J.; Verhage, Matthijs

    Secreted semaphorins act as guidance cues in the developing nervous system and may have additional functions in mature neurons. How semaphorins are transported and secreted by neurons is poorly understood. We find that endogenous semaphorin 3A (Sema3A) displays a punctate distribution in axons and

  8. The axonal cytoskeleton : from organization to function

    NARCIS (Netherlands)

    Kevenaar, Josta T; Hoogenraad, Casper C

    The axon is the single long fiber that extends from the neuron and transmits electrical signals away from the cell body. The neuronal cytoskeleton, composed of microtubules (MTs), actin filaments and neurofilaments, is not only required for axon formation and axonal transport but also provides the

  9. Slowing of axonal regeneration is correlated with increased axonal viscosity during aging

    Directory of Open Access Journals (Sweden)

    Heidemann Steven R

    2010-10-01

    Full Text Available Abstract Background As we age, the speed of axonal regeneration declines. At the biophysical level, why this occurs is not well understood. Results To investigate we first measured the rate of axonal elongation of sensory neurons cultured from neonatal and adult rats. We found that neonatal axons grew 40% faster than adult axons (11.5 µm/hour vs. 8.2 µm/hour. To determine how the mechanical properties of axons change during maturation, we used force calibrated towing needles to measure the viscosity (stiffness and strength of substrate adhesion of neonatal and adult sensory axons. We found no significant difference in the strength of adhesions, but did find that adult axons were 3 times intrinsically stiffer than neonatal axons. Conclusions Taken together, our results suggest decreasing axonal stiffness may be part of an effective strategy to accelerate the regeneration of axons in the adult peripheral nervous system.

  10. Defining intrinsic vs. extrinsic atopic dermatitis.

    Science.gov (United States)

    Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

    2015-06-16

    Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

  11. Conduction of impulses by axons regenerated in a Schwann cell graft in the transected adult rat thoracic spinal cord.

    Science.gov (United States)

    Pinzon, A; Calancie, B; Oudega, M; Noga, B R

    2001-06-01

    Central nervous system axons regenerate into a Schwann cell implant placed in the transected thoracic spinal cord of an adult rat. The present study was designed to test whether these regenerated axons are capable of conducting action potentials. Following the transection and removal of a 4- to 5-mm segment of the thoracic spinal cord (T8-T9), a polymer guidance channel filled with a mixture of adult rat Schwann cells and Matrigel was grafted into a 4- to 5-mm-long gap in the transected thoracic spinal cord. The two cut ends of the spinal cord were eased into the guidance channel openings. Transected control animals received a channel containing Matrigel only. Three months after implantation, electrophysiological studies were performed. Tungsten microelectrodes were used for monopolar stimulation of regenerated axons within the Schwann cell graft. Glass microelectrodes were used to record responses in the spinal cord rostral to the stimulation site. Evoked responses to electrical stimulation of the axon cable were found in two out of nine Schwann cell-grafted animals. These responses had approximate latencies in the range of those of myelinated axons. No responses were seen in any of the Matrigel-grafted animals. Histological analysis revealed that the two cases that showed evoked potentials had the largest number of myelinated axons present in the cable. This study demonstrates that axons regenerating through Schwann cell grafts in the complete transected spinal cord can produce measurable evoked responses following electrical stimulation. Copyright 2001 Wiley-Liss, Inc.

  12. EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice.

    Directory of Open Access Journals (Sweden)

    Yona Goldshmit

    Full Text Available Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries.

  13. Fitness, Extrinsic Complexity and Informing Science

    Directory of Open Access Journals (Sweden)

    Grandon Gill

    2017-03-01

    We raise concerns about society’s continuing investment in academic research that discounts the extrinsic complexity of the domains under study. Future Research We highlight a need for research to operationalize the concepts of fitness and complexity in practice.

  14. Intrinsic and extrinsic motivation for smoking cessation.

    Science.gov (United States)

    Curry, S; Wagner, E H; Grothaus, L C

    1990-06-01

    An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking.

  15. The spinning particle with extrinsic curvature

    International Nuclear Information System (INIS)

    Dhar, A.

    1988-01-01

    We construct and analyse an action for the spinning particle which contains an extrinsic curvature term. A possible generalization of this construction to the case of the spinning string is also discussed. (orig.)

  16. Image Guidance

    Science.gov (United States)

    Guidance that explains the process for getting images approved in One EPA Web microsites and resource directories. includes an appendix that shows examples of what makes some images better than others, how some images convey meaning more than others

  17. SAD kinases sculpt axonal arbors of sensory neurons through long and short-term responses to neurotrophin signals

    Science.gov (United States)

    Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.

    2013-01-01

    SUMMARY Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex, but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short duration signals from extrinsic cues to sculpt axon arbors within the CNS. PMID:23790753

  18. SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals.

    Science.gov (United States)

    Lilley, Brendan N; Pan, Y Albert; Sanes, Joshua R

    2013-07-10

    Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The age factor in axonal repair after spinal cord injury: A focus on neuron-intrinsic mechanisms.

    Science.gov (United States)

    Geoffroy, Cédric G; Meves, Jessica M; Zheng, Binhai

    2017-06-23

    Age is an important consideration for recovery and repair after spinal cord injury. Spinal cord injury is increasingly affecting the middle-aged and aging populations. Despite rapid progress in research to promote axonal regeneration and repair, our understanding of how age can modulate this repair is rather limited. In this review, we discuss the literature supporting the notion of an age-dependent decline in axonal growth after central nervous system (CNS) injury. While both neuron-intrinsic and extrinsic factors are involved in the control of axon growth after injury, here we focus on possible intrinsic mechanisms for this age-dependent decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Early development of the circumferential axonal pathway in mouse and chick spinal cord.

    Science.gov (United States)

    Holley, J A

    1982-03-10

    The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

  1. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.

    Science.gov (United States)

    Lizbinski, Kristyn M; Dacks, Andrew M

    2017-01-01

    Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

  3. Elucidation of axonal transport by radioautography

    International Nuclear Information System (INIS)

    Droz, Bernard.

    1979-01-01

    Radioautography permits to distinguish various pathways within the axons: the axoplasm which includes soluble enzymes and constituents of the cytoskeleton moving with slow axoplasmic flow; the mitochondria which are conveyed as organelles; the smooth endoplasmic reticulum which ensures the fast axonal transport of membrane constituents delivered to axolemma, synaptic vesicles, presynaptic membranes or mitochondria. Furthermore radioautography makes it possible to visualize intercellular exchanges of molecules between axon and glia

  4. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve disorders or injury. Following loss of axonal continuity, the isolated nerve stump distal to the lesion undergoes Wallerian degeneration in several phases. In the initial 'latent' phase......, action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  5. Axonal regeneration in zebrafish spinal cord

    Science.gov (United States)

    Hui, Subhra Prakash

    2018-01-01

    Abstract In the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals. PMID:29721326

  6. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

    Science.gov (United States)

    Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

    2017-01-01

    The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

  7. Constitutively expressed Protocadherin-α regulates the coalescence and elimination of homotypic olfactory axons through its cytoplasmic region

    Directory of Open Access Journals (Sweden)

    Sonoko eHasegawa

    2012-10-01

    Full Text Available Olfactory sensory neuron (OSN axons coalesce into specific glomeruli in the olfactory bulb (OB according to their odorant receptor (OR expression. Several guidance molecules enhance the coalescence of homotypic OSN projections, in an OR-specific- and neural-activity-dependent manner. However, the mechanism by which homotypic OSN axons are organized into glomeruli is unsolved. We previously reported that the clustered protocadherin-α (Pcdh-α family of diverse cadherin-related molecules plays roles in the coalescence and elimination of homotypic OSN axons throughout development. Here we showed that the elimination of small ectopic homotypic glomeruli required the constitutive expression of a Pcdh-α isoform and Pcdh-α’s cytoplasmic region, but not OR specificity or neural activity. These results suggest that Pcdh-α proteins provide a cytoplasmic signal to regulate repulsive activity for homotypic OSN axons independently of OR expression and neural activity. The counterbalancing effect of Pcdh-α proteins for the axonal coalescence mechanisms mediated by other olfactory guidance molecules indicate a possible mechanism for the organization of homotypic OSN axons into glomeruli during development.

  8. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

    Science.gov (United States)

    Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

    2018-03-20

    Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

  9. Differential effects of myostatin deficiency on motor and sensory axons.

    Science.gov (United States)

    Jones, Maria R; Villalón, Eric; Northcutt, Adam J; Calcutt, Nigel A; Garcia, Michael L

    2017-12-01

    Deletion of myostatin in mice (MSTN -/- ) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear whether loss of myostatin affects motor, sensory, or both types of axons. Using the MSTN -/- mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Axon diameter and myelin thickness were increased in motor axons of MSTN -/- mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, whereas internode length is established independently. Muscle Nerve 56: E100-E107, 2017. © 2017 Wiley Periodicals, Inc.

  10. Intrinsic and Extrinsic Motivation among Collegiate Instrumentalists

    Science.gov (United States)

    Diaz, Frank M.

    2010-01-01

    The purpose of this study was to gather and compare information on measures of intrinsic and extrinsic motivation among instrumentalists enrolled in collegiate ensembles. A survey instrument was developed to gather information concerning demographic data and responses to questions on motivational preference. Participants were undergraduate and…

  11. Intrinsic and extrinsic effects on image memorability.

    Science.gov (United States)

    Bylinskii, Zoya; Isola, Phillip; Bainbridge, Constance; Torralba, Antonio; Oliva, Aude

    2015-11-01

    Previous studies have identified that images carry the attribute of memorability, a predictive value of whether a novel image will be later remembered or forgotten. Here we investigate the interplay between intrinsic and extrinsic factors that affect image memorability. First, we find that intrinsic differences in memorability exist at a finer-grained scale than previously documented. Second, we test two extrinsic factors: image context and observer behavior. Building on prior findings that images that are distinct with respect to their context are better remembered, we propose an information-theoretic model of image distinctiveness. Our model can automatically predict how changes in context change the memorability of natural images. In addition to context, we study a second extrinsic factor: where an observer looks while memorizing an image. It turns out that eye movements provide additional information that can predict whether or not an image will be remembered, on a trial-by-trial basis. Together, by considering both intrinsic and extrinsic effects on memorability, we arrive at a more complete and fine-grained model of image memorability than previously available. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The relationship between primary school teachers extrinsic ...

    African Journals Online (AJOL)

    The study investigated the relationship between primary school teacher's extrinsic motivation and pupils' academic performance in Cross river State, Nigeria. Ex Post Facto research design was adopted for the study. The population of the study consisted of 17,221 teachers and 68,201 Primary Six Pupils in the three ...

  13. miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

    Science.gov (United States)

    Mandrekar-Colucci, Shweta; Hall, Jodie C.E.; Sweet, David R.; Schmitt, Philipp J.; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia

    2016-01-01

    Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails

  14. Axon-Axon Interactions Regulate Topographic Optic Tract Sorting via CYFIP2-Dependent WAVE Complex Function.

    Science.gov (United States)

    Cioni, Jean-Michel; Wong, Hovy Ho-Wai; Bressan, Dario; Kodama, Lay; Harris, William A; Holt, Christine E

    2018-03-07

    The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2's function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics, and optic tract sorting. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. VOL 6. NO. 1 2015 EXTRINSIC FACTORS THAT AFFECT ...

    African Journals Online (AJOL)

    Frederick Iraki

    Keywords: Job satisfaction, clergy, extrinsic motivation, extrinsic factors ... woman's work conditions and rewards are inferior to those of a man in comparable positions (a ... that they have embraced the need to professionalize their systems.

  16. Intrinsic and extrinsic factors influencing large African herbivore movements

    NARCIS (Netherlands)

    Venter, J.A.; Prins, H.H.T.; Mashanova, A.; Boer, de W.F.; Slotow, R.

    2015-01-01

    Understanding environmental as well as anthropogenic factors that influence large herbivore ecological patterns and processes should underpin their conservation and management. We assessed the influence of intrinsic, extrinsic environmental and extrinsic anthropogenic factors on movement behaviour

  17. Dynamics of mitochondrial transport in axons

    Directory of Open Access Journals (Sweden)

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  18. Asian International Graduate Students’ Extrinsic Motivation to Pursue Degrees

    OpenAIRE

    Naomi Takashiro

    2017-01-01

    The author examined the types of extrinsic motivation for Asian international graduate students pursuing graduate degrees. The theoretical framework used was extrinsic motivation within Self-Determination Theory. Even though the presence of Asian international graduate students is steadily increasing worldwide, research into their extrinsic motivation is scarce. It is important for educators to explore and understand Asian international graduate students’ extrinsic motivation since such stude...

  19. Dynamics of target recognition by interstitial axon branching along developing cortical axons.

    Science.gov (United States)

    Bastmeyer, M; O'Leary, D D

    1996-02-15

    Corticospinal axons innervate their midbrain, hindbrain, and spinal targets by extending collateral branches interstitially along their length. To establish that the axon shaft rather than the axonal growth cone is responsible for target recognition in this system, and to characterize the dynamics of interstitial branch formation, we have studied this process in an in vivo-like setting using slice cultures from neonatal mice containing the entire pathway of corticospinal axons. Corticospinal axons labeled with the dye 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (or Dil) were imaged using time-lapse video microscopy of their pathway overlying the basilar pons, their major hindbrain target. The axon shaft millimeters behind the growth cone exhibits several dynamic behaviors, including the de novo formation of varicosities and filopodia-like extensions, and a behavior that we term "pulsation," which is characterized by a variable thickening and thining of short segments of the axon. An individual axon can have multiple sites of branching activity, with many of the branches being transient. These dynamic behaviors occur along the portion of the axon shaft overlying the basilar pons, but not just caudal to it. Once the collaterals extend into the pontine neuropil, they branch further in the neuropil, while the parent axon becomes quiescent. Thus, the branching activity is spatially restricted to specific portions of the axon, as well as temporally restricted to a relatively brief time window. These findings provide definitive evidence that collateral branches form de novo along corticospinal axons and establish that the process of target recognition in this system is a property of the axon shaft rather than the leading growth cone.

  20. Cargo distributions differentiate pathological axonal transport impairments.

    Science.gov (United States)

    Mitchell, Cassie S; Lee, Robert H

    2012-05-07

    Axonal transport is an essential process in neurons, analogous to shipping goods, by which energetic and cellular building supplies are carried downstream (anterogradely) and wastes are carried upstream (retrogradely) by molecular motors, which act as cargo porters. Impairments in axonal transport have been linked to devastating and often lethal neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis, Huntington's, and Alzheimer's. Axonal transport impairment types include a decrease in available motors for cargo transport (motor depletion), the presence of defective or non-functional motors (motor dilution), and the presence of increased or larger cargos (protein aggregation). An impediment to potential treatment identification has been the inability to determine what type(s) of axonal transport impairment candidates that could be present in a given disease. In this study, we utilize a computational model and common axonal transport experimental metrics to reveal the axonal transport impairment general characteristics or "signatures" that result from three general defect types of motor depletion, motor dilution, and protein aggregation. Our results not only provide a means to discern these general impairments types, they also reveal key dynamic and emergent features of axonal transport, which potentially underlie multiple impairment types. The identified characteristics, as well as the analytical method, can be used to help elucidate the axonal transport impairments observed in experimental and clinical data. For example, using the model-predicted defect signatures, we identify the defect candidates, which are most likely to be responsible for the axonal transport impairments in the G93A SOD1 mouse model of ALS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis

    DEFF Research Database (Denmark)

    Martel, Britta Cathrina; Litman, Thomas; Hald, Andreas

    2016-01-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared...... with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among...... patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD....

  2. Axonal inclusions in the crab Hemigrapsus nudus.

    Science.gov (United States)

    Smith, R S

    1978-10-01

    Light microscopic examination of living giant axons from the walking legs of Hemigrapsus nudus revealed intra-axonal inclusions which were usually several tens of micrometers long and about 5 micron wide. The inclusions were filled with small light-scattering particles. The inclusions were shown, by thin section electron microscopy, to be composed largely 68% by volume) of mitochondria. Each inclusion was surrounded by membrane bounded spaces which are presumed to represent a part of the smooth endoplasmic reticulum. Similar inclusions were not found in the leg axons of a variety of other decapod crustaceans.

  3. Extrinsic spin Nernst effect from first principles.

    Science.gov (United States)

    Tauber, Katarina; Gradhand, Martin; Fedorov, Dmitry V; Mertig, Ingrid

    2012-07-13

    We present an ab initio description of the thermal transport phenomenon called the spin Nernst effect. It refers to generation of a spin accumulation or a pure spin current transverse to an applied temperature gradient. This is similar to the intensively studied spin Hall effect described by intrinsic and extrinsic mechanisms due to an applied electric field. Analogously, several contributions are present for the spin Nernst effect. Here we investigate the extrinsic skew scattering mechanism which is dominant in the limit of dilute alloys. Our calculations are based on a fully relativistic Korringa-Kohn-Rostoker method and a solution of the linearized Boltzmann equation. As a first application, we consider a Cu host with Au, Ti, and Bi impurities.

  4. Extrinsic and intrinsic curvatures in thermodynamic geometry

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini Mansoori, Seyed Ali, E-mail: shossein@bu.edu [Department of Physics, Boston University, 590 Commonwealth Ave., Boston, MA 02215 (United States); Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mirza, Behrouz, E-mail: b.mirza@cc.iut.ac.ir [Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Sharifian, Elham, E-mail: e.sharifian@ph.iut.ac.ir [Department of Physics, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2016-08-10

    We investigate the intrinsic and extrinsic curvatures of a certain hypersurface in thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner–Nordström-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant Q hypersurface has the same sign as the heat capacity around the phase transition points. The intrinsic curvature of the hypersurface can also be divergent at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN (J-zero hypersurface) and Kerr black holes (Q-zero hypersurface) ones [1]. This approach can easily be generalized to an arbitrary thermodynamic system.

  5. Extrinsic and intrinsic curvatures in thermodynamic geometry

    International Nuclear Information System (INIS)

    Hosseini Mansoori, Seyed Ali; Mirza, Behrouz; Sharifian, Elham

    2016-01-01

    We investigate the intrinsic and extrinsic curvatures of a certain hypersurface in thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner–Nordström-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant Q hypersurface has the same sign as the heat capacity around the phase transition points. The intrinsic curvature of the hypersurface can also be divergent at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN (J-zero hypersurface) and Kerr black holes (Q-zero hypersurface) ones [1]. This approach can easily be generalized to an arbitrary thermodynamic system.

  6. Intrinsic and extrinsic geometry of random surfaces

    International Nuclear Information System (INIS)

    Jonsson, T.

    1992-01-01

    We prove that the extrinsic Hausdorff dimension is always greater than or equal to the intrinsic Hausdorff dimension in models of triangulated random surfaces with action which is quadratic in the separation of vertices. We furthermore derive a few naive scaling relations which relate the intrinsic Hausdorff dimension to other critical exponents. These relations suggest that the intrinsic Hausdorff dimension is infinite if the susceptibility does not diverge at the critical point. (orig.)

  7. Extrinsic Fabry-Perot ultrasonic detector

    Science.gov (United States)

    Kidwell, J. J.; Berthold, John W., III

    1996-10-01

    We characterized the performance of a commercial fiber optic extrinsic Fabry-Perot interferometer for use as an ultrasonic sensor, and compared the performance with a standard lead zirconate titanate (PZT) detector. The interferometer was unstabilized. The results showed that the fiber sensor was about 12 times less sensitive than the PZT detector. Ultrasonic frequency response near 100 kHz was demonstrated. We describe the design of the fiber sensor, the details of the tests performed, and potential applications.

  8. Altered intrinsic and extrinsic connectivity in schizophrenia.

    Science.gov (United States)

    Zhou, Yuan; Zeidman, Peter; Wu, Shihao; Razi, Adeel; Chen, Cheng; Yang, Liuqing; Zou, Jilin; Wang, Gaohua; Wang, Huiling; Friston, Karl J

    2018-01-01

    Schizophrenia is a disorder characterized by functional dysconnectivity among distributed brain regions. However, it is unclear how causal influences among large-scale brain networks are disrupted in schizophrenia. In this study, we used dynamic causal modeling (DCM) to assess the hypothesis that there is aberrant directed (effective) connectivity within and between three key large-scale brain networks (the dorsal attention network, the salience network and the default mode network) in schizophrenia during a working memory task. Functional MRI data during an n-back task from 40 patients with schizophrenia and 62 healthy controls were analyzed. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes, we found that intrinsic (within-region) and extrinsic (between-region) effective connectivity involving prefrontal regions were abnormal in schizophrenia. Specifically, in patients (i) inhibitory self-connections in prefrontal regions of the dorsal attention network were decreased across task conditions; (ii) extrinsic connectivity between regions of the default mode network was increased; specifically, from posterior cingulate cortex to the medial prefrontal cortex; (iii) between-network extrinsic connections involving the prefrontal cortex were altered; (iv) connections within networks and between networks were correlated with the severity of clinical symptoms and impaired cognition beyond working memory. In short, this study revealed the predominance of reduced synaptic efficacy of prefrontal efferents and afferents in the pathophysiology of schizophrenia.

  9. Intrinsic-extrinsic factors in sport motivation.

    Science.gov (United States)

    Pedersen, Darhl M

    2002-10-01

    Participants were 83 students (36 men and 47 women). 10 intrinsic-extrinsic factors involved in sport motivation were obtained. The factors were generated from items obtained from the participants rather than items from the experimenter. This was done to avoid the possible influence of preconceptions on the part of the experimenter regarding what the final dimensions may be. Obtained motivational factors were Social Reinforcement, Fringe Benefits, Fame and Fortune, External Forces, Proving Oneself, Social Benefits, Mental Enrichment, Expression of Self, Sense of Accomplishment, and Self-enhancement. Each factor was referred to an intrinsic-extrinsic dimension to describe its relative position on that dimension. The order of the factors as listed indicates increasing intrinsic motivation. i.e., the first four factors were rated in the extrinsic range, whereas the remaining six were rated to be in the intrinsic range. Next, the participants rated the extent to which each of the various factors was involved in their decision to participate in sport activities. The pattern of use of the motivational factors was the same for both sexes except that men indicated greater use of the Fringe Benefits factor. Overall, the more intrinsic a sport motivation factor was rated, the more likely it was to be rated as a factor in actual sport participation.

  10. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Vrancken, A. F. J. E.; van Schaik, I. N.; Hughes, R. A. C.; Notermans, N. C.

    2004-01-01

    BACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic

  11. Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

    Science.gov (United States)

    Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

    2017-07-25

    Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

  12. Slow Muscle Precursors Lay Down a Collagen XV Matrix Fingerprint to Guide Motor Axon Navigation.

    Science.gov (United States)

    Guillon, Emilie; Bretaud, Sandrine; Ruggiero, Florence

    2016-03-02

    The extracellular matrix (ECM) provides local positional information to guide motoneuron axons toward their muscle target. Collagen XV is a basement membrane component mainly expressed in skeletal muscle. We have identified two zebrafish paralogs of the human COL15A1 gene, col15a1a and col15a1b, which display distinct expression patterns. Here we show that col15a1b is expressed and deposited in the motor path ECM by slow muscle precursors also called adaxial cells. We further demonstrate that collagen XV-B deposition is both temporally and spatially regulated before motor axon extension from the spinal cord in such a way that it remains in this region after the adaxial cells have migrated toward the periphery of the myotome. Loss- and gain-of-function experiments in zebrafish embryos demonstrate that col15a1b expression and subsequent collagen XV-B deposition and organization in the motor path ECM depend on a previously undescribed two-step mechanism involving Hedgehog/Gli and unplugged/MuSK signaling pathways. In silico analysis predicts a putative Gli binding site in the col15a1b proximal promoter. Using col15a1b promoter-reporter constructs, we demonstrate that col15a1b participates in the slow muscle genetic program as a direct target of Hedgehog/Gli signaling. Loss and gain of col15a1b function provoke pathfinding errors in primary and secondary motoneuron axons both at and beyond the choice point where axon pathway selection takes place. These defects result in muscle atrophy and compromised swimming behavior, a phenotype partially rescued by injection of a smyhc1:col15a1b construct. These reveal an unexpected and novel role for collagen XV in motor axon pathfinding and neuromuscular development. In addition to the archetypal axon guidance cues, the extracellular matrix provides local information that guides motor axons from the spinal cord to their muscle targets. Many of the proteins involved are unknown. Using the zebrafish model, we identified an

  13. Con-nectin axons and dendrites.

    Science.gov (United States)

    Beaudoin, Gerard M J

    2006-07-03

    Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

  14. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Directory of Open Access Journals (Sweden)

    Hiroaki Mochizuki

    2011-05-01

    Full Text Available Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of

  15. Utilizing Combined Methodologies to Define the Role of Plasma Membrane Delivery During Axon Branching and Neuronal Morphogenesis.

    Science.gov (United States)

    Winkle, Cortney C; Hanlin, Christopher C; Gupton, Stephanie L

    2016-03-16

    During neural development, growing axons extend to multiple synaptic partners by elaborating axonal branches. Axon branching is promoted by extracellular guidance cues like netrin-1 and results in dramatic increases to the surface area of the axonal plasma membrane. Netrin-1-dependent axon branching likely involves temporal and spatial control of plasma membrane expansion, the components of which are supplied through exocytic vesicle fusion. These fusion events are preceded by formation of SNARE complexes, comprising a v-SNARE, such as VAMP2 (vesicle-associated membrane protein 2), and plasma membrane t-SNAREs, syntaxin-1 and SNAP25 (synaptosomal-associated protein 25). Detailed herein isa multi-pronged approach used to examine the role of SNARE mediated exocytosis in axon branching. The strength of the combined approach is data acquisition at a range of spatial and temporal resolutions, spanning from the dynamics of single vesicle fusion events in individual neurons to SNARE complex formation and axon branching in populations of cultured neurons. This protocol takes advantage of established biochemical approaches to assay levels of endogenous SNARE complexes and Total Internal Reflection Fluorescence (TIRF) microscopy of cortical neurons expressing VAMP2 tagged with a pH-sensitive GFP (VAMP2-pHlourin) to identify netrin-1 dependent changes in exocytic activity in individual neurons. To elucidate the timing of netrin-1-dependent branching, time-lapse differential interference contrast (DIC) microscopy of single neurons over the order of hours is utilized. Fixed cell immunofluorescence paired with botulinum neurotoxins that cleave SNARE machinery and block exocytosis demonstrates that netrin-1 dependent axon branching requires SNARE-mediated exocytic activity.

  16. Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

    Directory of Open Access Journals (Sweden)

    Drescher Uwe

    2010-06-01

    Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

  17. EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

    Czech Academy of Sciences Publication Activity Database

    Eva, R.; Koseki, H.; Kanamarlapudi, V.; Fawcett, James

    2017-01-01

    Roč. 130, č. 21 (2017), s. 3663-3675 ISSN 0021-9533 Institutional support: RVO:68378041 Keywords : axon regeneration * axon transport * neuronal polarisation Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 4.431, year: 2016

  18. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Letzkus, Johannes J.; Stuart, Greg J.

    2007-01-01

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action

  19. Sugar Antennae for Guidance Signals: Syndecans and Glypicans Integrate Directional Cues for Navigating Neurons

    Directory of Open Access Journals (Sweden)

    Christa Rhiner

    2006-01-01

    Full Text Available Attractive and repulsive signals guide migrating nerve cells in all directions when the nervous system starts to form. The neurons extend thin processes, axons, that connect over wide distances with other brain cells to form a complicated neuronal network. One of the most fascinating questions in neuroscience is how the correct wiring of billions of nerve cells in our brain is controlled. Several protein families are known to serve as guidance cues for navigating neurons and axons. Nevertheless, the combinatorial potential of these proteins seems to be insufficient to sculpt the entire neuronal network and the appropriate formation of connections. Recently, heparan sulfate proteoglycans (HSPGs, which are present on the cell surface of neurons and in the extracellular matrix through which neurons and axons migrate, have been found to play a role in regulating cell migration and axon guidance. Intriguingly, the large number of distinct modifications that can be put onto the sugar side chains of these PGs would in principle allow for an enormous diversity of HSPGs, which could help in regulating the vast number of guidance choices taken by individual neurons. In this review, we will focus on the role of the cell surface HSPGs syndecan and glypican and specific HS modifications in promoting neuronal migration, axon guidance, and synapse formation.

  20. Intrinsic and extrinsic neuromodulation of motor circuits.

    Science.gov (United States)

    Katz, P S

    1995-12-01

    Neuromodulation of motor circuits by extrinsic inputs provides enormous flexibility in the production of behavior. Recent work has shown that neurons intrinsic to central pattern-generating circuits can evoke neuromodulatory effects in addition to their neurotransmitting actions. Modulatory neurons often elicit a multitude of different effects attributable to actions at different receptors and/or through the release of co-transmitters. Differences in neuromodulation between species can account for differences in behavior. Modulation of neuromodulation may provide an additional level of flexibility to motor circuits.

  1. Do intrinsic and extrinsic motivation relate differently to employee outcomes?

    OpenAIRE

    Kuvaas, Bard; Buch, Robert; Weibel, Antoinette; Dysvik, Anders; Nerstad, Christina

    2017-01-01

    In most theories that address how individual financial incentives affect work performance, researchers have assumed that two types of motivation—intrinsic and extrinsic—mediate the relationship between incentives and performance. Empirically, however, extrinsic motivation is rarely investigated. To explore the predictive validity of these theories of intrinsic and extrinsic motivation in work settings, we tested how both intrinsic and extrinsic motivation affected supervisor-ra...

  2. Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

    Science.gov (United States)

    Zambonin, Jessica L.; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R.; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M.; Turnbull, Doug M.; Trapp, Bruce D.; Lassmann, Hans; Franklin, Robin J. M.

    2011-01-01

    Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in

  3. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  4. Creatine pretreatment protects cortical axons from energy depletion in vitro

    Science.gov (United States)

    Shen, Hua; Goldberg, Mark P.

    2012-01-01

    Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. In line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. PMID:22521466

  5. Evidence for a role of srGAP3 in the positioning of commissural axons within the ventrolateral funiculus of the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    Claire Bacon

    Full Text Available Slit-Robo signaling guides commissural axons away from the floor-plate of the spinal cord and into the longitudinal axis after crossing the midline. In this study we have evaluated the role of the Slit-Robo GTPase activating protein 3 (srGAP3 in commissural axon guidance using a knockout (KO mouse model. Co-immunoprecipitation experiments confirmed that srGAP3 interacts with the Slit receptors Robo1 and Robo2 and immunohistochemistry studies showed that srGAP3 co-localises with Robo1 in the ventral and lateral funiculus and with Robo2 in the lateral funiculus. Stalling axons have been reported in the floor-plate of Slit and Robo mutant spinal cords but our axon tracing experiments revealed no dorsal commissural axon stalling in the floor plate of the srGAP3 KO mouse. Interestingly we observed a significant thickening of the ventral funiculus and a thinning of the lateral funiculus in the srGAP3 KO spinal cord, which has also recently been reported in the Robo2 KO. However, axons in the enlarged ventral funiculus of the srGAP3 KO are Robo1 positive but do not express Robo2, indicating that the thickening of the ventral funiculus in the srGAP3 KO is not a Robo2 mediated effect. We suggest a role for srGAP3 in the lateral positioning of post crossing axons within the ventrolateral funiculus.

  6. Intrinsic and Extrinsic Motivation for Stereotypic and Repetitive Behavior

    Science.gov (United States)

    Joosten, Annette V.; Bundy, Anita C.; Einfeld, Stewart L.

    2009-01-01

    This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess…

  7. A prototype empirical framework of intrinsic and extrinsic EERQI indicators

    NARCIS (Netherlands)

    Mooij, Ton

    2012-01-01

    The research question is: What do statistical analyses show us about the relationships between intrinsic and extrinsic indicators of quality and what does this mean when constructing a prototype EERQI framework? The pilot study involved the scoring on both intrinsic and extrinsic indica-tors for 177

  8. A reduced covariant string model for the extrinsic string

    International Nuclear Information System (INIS)

    Botelho, L.C.L.

    1989-01-01

    It is studied a reduced covariant string model for the extrinsic string by using Polyakov's path integral formalism. On the basis of this reduced model it is suggested that the extrinsic string has its critical dimension given by 13. Additionally, it is calculated in a simple way Poliakov's renormalization group law for the string rigidity coupling constants. (A.C.A.S.) [pt

  9. Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain.

    Science.gov (United States)

    Zhang, Sanbing; Cui, Huixian; Wang, Lei; Kang, Lin; Huang, Guannan; Du, Juan; Li, Sha; Tanaka, Hideaki; Su, Yuhong

    2016-07-01

    The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. © 2016 The Histochemical Society.

  10. Extrinsic Isoperimetric Analysis on Submanifolds with Curvatures bounded from below

    DEFF Research Database (Denmark)

    Markvorsen, Steen; Palmer, Vicente

    2010-01-01

    and on the radial part of the intrinsic unit normals at the boundaries of the extrinsic spheres, respectively. In the same vein we also establish lower bounds on the mean exit time for Brownian motions in the extrinsic balls, i.e. lower bounds for the time it takes (on average) for Brownian particles to diffuse......We obtain upper bounds for the isoperimetric quotients of extrinsic balls of submanifolds in ambient spaces which have a lower bound on their radial sectional curvatures. The submanifolds are themselves only assumed to have lower bounds on the radial part of the mean curvature vector field...... within the extrinsic ball from a given starting point before they hit the boundary of the extrinsic ball. In those cases, where we may extend our analysis to hold all the way to infinity, we apply a capacity comparison technique to obtain a sufficient condition for the submanifolds to be parabolic, i...

  11. Asian International Graduate Students’ Extrinsic Motivation to Pursue Degrees

    Directory of Open Access Journals (Sweden)

    Naomi Takashiro

    2017-04-01

    Full Text Available The author examined the types of extrinsic motivation for Asian international graduate students pursuing graduate degrees. The theoretical framework used was extrinsic motivation within Self-Determination Theory. Even though the presence of Asian international graduate students is steadily increasing worldwide, research into their extrinsic motivation is scarce. It is important for educators to explore and understand Asian international graduate students’ extrinsic motivation since such students would provide unique, distinctive cultural aspects in the classroom in their host countries. The research design employed was qualitative. Semi-structured interviews were conducted with 10 graduate students from four Asian countries. The identified themes were a faculty influence, b personal recognition, and c utility for careers. Asian international graduate students expressed that their ultimate extrinsic motivation was to get professional jobs in academia. The author discussed the implications of these findings for instructors.

  12. Pαx6 expression in postmitotic neurons mediates the growth of axons in response to SFRP1.

    Directory of Open Access Journals (Sweden)

    Alvaro Sebastián-Serrano

    Full Text Available During development, the mechanisms that specify neuronal subclasses are coupled to those that determine their axonal response to guidance cues. Pax6 is a homedomain transcription factor required for the specification of a variety of neural precursors. After cell cycle exit, Pax6 expression is often shut down in the precursor progeny and most postmitotic neurons no longer express detectable levels of the protein. There are however exceptions and high Pax6 protein levels are found, for example, in postmitotic retinal ganglion cells (RGCs, dopaminergic neurons of the olfactory bulb and the limbic system in the telencephalon. The function of Pax6 in these differentiating neurons remains mostly elusive. Here, we demonstrate that Pax6 mediates the response of growing axons to SFRP1, a secreted molecule expressed in several Pax6-positive forebrain territories. Forced expression of Pax6 in cultured postmitotic cortical neurons, which do not normally express Pax6, was sufficient to increment axonal length. Growth was blocked by the addition of anti-SFRP1 antibodies, whereas exogenously added SFRP1 increased axonal growth of Pax6-transfected neurons but not that of control or untransfected cortical neurons. In the reverse scenario, shRNA-mediated knock-down of Pax6 in mouse retinal explants specifically abolished RGCs axonal growth induced by SFRP1, but had no effect on RGCs differentiation and it did not modify the effect of Shh or Netrin on axon growth. Taken together these results demonstrate that expression of Pax6 is necessary and sufficient to render postmitotic neurons competent to respond to SFRP1. These results reveal a novel and unexpected function of Pax6 in postmitotic neurons and situate Pax6 and SFRP1 as pair regulators of axonal connectivity.

  13. [Severe, subacute axonal polyneuropathy due to hypophosphatemia].

    NARCIS (Netherlands)

    Eijk, J.J.J. van; Abdo, W.F.; Deurwaarder, E. den; Zwarts, M.J.; Warrenburg, B.P.C. van de

    2010-01-01

    A 46-year-old man receiving tube feeding because of anorexia and weight loss developed progressive neurological symptoms initially resembling Guillain-Barre syndrome. Eventually axonal neuropathy due to severe hypophosphatemia was diagnosed. Hypophosphatemia can be caused by the so-called refeeding

  14. Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity

    NARCIS (Netherlands)

    Gensel, J.C.; Nakamura, S.; Guan, Z.; Rooijen, van N.; Ankeny, D.P.; Popovich, P.G.

    2009-01-01

    Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally

  15. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Warendorf, Janna; Vrancken, Alexander F.J.E.; van Schaik, Ivo N.; Hughes, Richard A.C.; Notermans, Nicolette C.

    2017-01-01

    Background: Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for

  16. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Warendorf, Janna; Vrancken, Alexander F. J. E.; van Schaik, Ivo N.; Hughes, Richard A. C.; Notermans, Nicolette C.

    2017-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for evaluation of

  17. Outer Electrospun Polycaprolactone Shell Induces Massive Foreign Body Reaction and Impairs Axonal Regeneration through 3D Multichannel Chitosan Nerve Guides

    OpenAIRE

    Duda, Sven; Dreyer, Lutz; Behrens, Peter; Wienecke, Soenke; Chakradeo, Tanmay; Glasmacher, Birgit; Haastert-Talini, Kirsten

    2014-01-01

    We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerv...

  18. Regeneration-associated macrophages: a novel approach to boost intrinsic regenerative capacity for axon regeneration

    Directory of Open Access Journals (Sweden)

    Min Jung Kwon

    2016-01-01

    Full Text Available Axons in central nervous system (CNS do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord injury. Both intrinsic and extrinsic factors are responsible for the regeneration failure. Although intensive research efforts have been invested on extrinsic regeneration inhibitors, the extent to which glial inhibitors contribute to the regeneration failure in vivo still remains elusive. Recent experimental evidence has rekindled interests in intrinsic factors for the regulation of regeneration capacity in adult mammals. In this review, we propose that activating macrophages with pro-regenerative molecular signatures could be a novel approach for boosting intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model in which regeneration of central branches of dorsal root ganglia sensory neurons is enhanced by a preceding injury to the peripheral branches, we have demonstrated that perineuronal macrophages surrounding dorsal root ganglia neurons are critically involved in the maintenance of enhanced regeneration capacity. Neuron-derived chemokine (C-C motif ligand 2 (CCL2 seems to mediate neuron-macrophage interactions conveying injury signals to perineuronal macrophages taking on a soley pro-regenerative phenotype, which we designate as regeneration-associated macrophages (RAMs. Manipulation of the CCL2 signaling could boost regeneration potential mimicking the conditioning injury, suggesting that the chemokine-mediated RAM activation could be utilized as a regenerative therapeutic strategy for CNS injuries.

  19. Diffusion by extrinsic noise in the kicked Harper map

    International Nuclear Information System (INIS)

    Park, Gunyoung; Chang, C. S.

    2001-01-01

    A significantly improved analytic understanding of the extrinsically driven diffusion process is presented in a nonlinear dynamical system in which the phase space is divided into periodic two-dimensional tiles of regular motion, separated by a connected separatrix network (web) [previously studied by A. J. Lichtenberg and Blake P. Wood, Phys. Rev. Lett. >62, 2213 (1989)]. The system is represented by the usual 'kicked Harper map' with added extrinsic noise terms. Three different diffusion regimes are found depending upon the strength of the extrinsic perturbation l relative to the web and regular motions. When the extrinsic noise is dominant over the intrinsic stochasticity and the regular rotation motions in the tile, diffusion obeys the random phase scaling l 2 . When the extrinsic noise is dominant over the intrinsic stochasticity, but weaker than the regular rotation motion, the diffusion scales as lK 1/2 , where K is the strength of the intrinsic kick. These findings agree well with numerical simulation results. When the extrinsic noise process is weaker than the stochastic web process, we analytically reproduce the well-known numerical result: The web diffusion is reduced by the ratio of phase-space areas of intrinsic to extrinsic stochasticity

  20. Dissecting Repulsive Guidance Molecule/Neogenin function and signaling during neural development

    NARCIS (Netherlands)

    van den Heuvel, D.M.A.

    2013-01-01

    During neural development a series of precisely ordered cellular processes acts to establish a functional brain comprising millions of neurons and many more neuronal connections. Neogenin and its repulsive guidance molecule (RGM) ligands contribute to neuronal network formation by inducing axon

  1. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

    Directory of Open Access Journals (Sweden)

    Ren Song

    2016-02-01

    Full Text Available Infection by alphaherpesviruses, including herpes simplex virus (HSV and pseudorabies virus (PRV, typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS. Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs. The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β or gamma interferon (IFN-γ significantly diminished the number of herpes simplex virus 1 (HSV-1 and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1 only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.

  2. Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans

    Science.gov (United States)

    Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin

    2017-01-01

    Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans. Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. PMID:28283540

  3. Intrinsic and Extrinsic Motivations: Classic Definitions and New Directions.

    Science.gov (United States)

    Ryan; Deci

    2000-01-01

    Intrinsic and extrinsic types of motivation have been widely studied, and the distinction between them has shed important light on both developmental and educational practices. In this review we revisit the classic definitions of intrinsic and extrinsic motivation in light of contemporary research and theory. Intrinsic motivation remains an important construct, reflecting the natural human propensity to learn and assimilate. However, extrinsic motivation is argued to vary considerably in its relative autonomy and thus can either reflect external control or true self-regulation. The relations of both classes of motives to basic human needs for autonomy, competence and relatedness are discussed. Copyright 2000 Academic Press.

  4. Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.

    Science.gov (United States)

    Zhao, Jiagang; Sun, Woong; Cho, Hyo Min; Ouyang, Hong; Li, Wenlin; Lin, Ying; Do, Jiun; Zhang, Liangfang; Ding, Sheng; Liu, Yizhi; Lu, Paul; Zhang, Kang

    2013-01-04

    Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

  5. miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair.

    Science.gov (United States)

    Gaudet, Andrew D; Mandrekar-Colucci, Shweta; Hall, Jodie C E; Sweet, David R; Schmitt, Philipp J; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia; Popovich, Phillip G

    2016-08-10

    Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. Axon regeneration after spinal cord injury (SCI) fails due to neuron

  6. Axon degeneration: make the Schwann cell great again

    Directory of Open Access Journals (Sweden)

    Keit Men Wong

    2017-01-01

    Full Text Available Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration (WD, which occurs after acute axonal injury. In the peripheral nervous system (PNS, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system (CNS, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well-documented that Schwann cells (SCs have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs 'sense' axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro-degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent findings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.

  7. Intrinsic and extrinsic measurement for Brownian motion

    International Nuclear Information System (INIS)

    Castro-Villarreal, Pavel

    2014-01-01

    Based upon the Smoluchowski equation on curved manifolds, three physical observables are considered for Brownian displacement, namely geodesic displacement s, Euclidean displacement δR, and projected displacement δR ⊥ . The Weingarten–Gauss equations are used to calculate the mean-square Euclidean displacements in the short-time regime. Our findings show that from an extrinsic point of view the geometry of the space affects the Brownian motion in such a way that the particle’s diffusion is decelerated, contrasting with the intrinsic point of view where dynamics is controlled by the sign of the Gaussian curvature (Castro-Villarreal, 2010 J. Stat. Mech. P08006). Furthermore, it is possible to give exact formulas for 〈δR〉 and 〈δR 2 〉 on spheres and minimal surfaces, which are valid for all values of time. In the latter case, surprisingly, Brownian motion corresponds to the usual diffusion in flat geometries, albeit minimal surfaces have non-zero Gaussian curvature. Finally, the two-dimensional case is emphasized due to its close relation to surface self-diffusion in fluid membranes. (paper)

  8. Free Radicals and Extrinsic Skin Aging

    Directory of Open Access Journals (Sweden)

    Borut Poljšak

    2012-01-01

    Full Text Available Human skin is constantly directly exposed to the air, solar radiation, environmental pollutants, or other mechanical and chemical insults, which are capable of inducing the generation of free radicals as well as reactive oxygen species (ROS of our own metabolism. Extrinsic skin damage develops due to several factors: ionizing radiation, severe physical and psychological stress, alcohol intake, poor nutrition, overeating, environmental pollution, and exposure to UV radiation (UVR. It is estimated that among all these environmental factors, UVR contributes up to 80%. UV-induced generation of ROS in the skin develops oxidative stress, when their formation exceeds the antioxidant defence ability of the target cell. The primary mechanism by which UVR initiates molecular responses in human skin is via photochemical generation of ROS mainly formation of superoxide anion (O2−•, hydrogen peroxide (H2O2, hydroxyl radical (OH•, and singlet oxygen (1O2. The only protection of our skin is in its endogenous protection (melanin and enzymatic antioxidants and antioxidants we consume from the food (vitamin A, C, E, etc.. The most important strategy to reduce the risk of sun UVR damage is to avoid the sun exposure and the use of sunscreens. The next step is the use of exogenous antioxidants orally or by topical application and interventions in preventing oxidative stress and in enhanced DNA repair.

  9. Plasma opening switch with extrinsic magnetic field

    CERN Document Server

    Dolgachev, G; Maslennikov, D

    2001-01-01

    Summary form only given, as follows. We have demonstrated in series of experiments that plasma opening switch (POS) switching voltage (UPOS) is defined by energy density (w) deposited in the POS plasma. If we then consider a plasma erosion mainly responsible for the effect of POS switching (the erosion effect could be described by Hall or Child-Langmuir models) the energy density (w) could be measured as a function of a system "macro-parameter" such as the initial charging voltage of the capacity storage system (the Marx pulsed voltage generator) UMarx. The POS voltage in this case could be given by UPOS"aw=aUMarx4/7, where a is a constant. This report demonstrates that for the high-impedance POS which has limited charge density transferred through the POS plasma a"2.5 (MV3/7) with no external magnetic field applied. The use of the extrinsic magnetic field allows to increase a up to 3.6 (MV3/7) and to achieve higher voltages at the opening phase - UPOS=3.6UMarx4/7. To verify this approach set of experimental ...

  10. Radiation effects in IRAS extrinsic infrared detectors

    Science.gov (United States)

    Varnell, L.; Langford, D. E.

    1982-01-01

    During the calibration and testing of the Infrared Astronomy Satellite (IRAS) focal plane, it was observed that the extrinsic photoconductor detectors were affected by gamma radiation at dose levels of the order of one rad. Since the flight environment will subject the focal plane to dose levels of this order from protons in single pass through the South Atlantic Anomaly, an extensive program of radiation tests was carried out to measure the radiation effects and to devise a method to counteract these effects. The effects observed after irradiation are increased responsivity, noise, and rate of spiking of the detectors after gamma-ray doses of less than 0.1 rad. The detectors can be returned almost to pre-irradiation performance by increasing the detector bias to breakdown and allowing a large current to flow for several minutes. No adverse effects on the detectors have been observed from this bias boost, and this technique will be used for IRAS with frequent calibration to ensure the accuracy of observations made with the instrument.

  11. Extrinsic spin Hall effect in graphene

    Science.gov (United States)

    Rappoport, Tatiana

    The intrinsic spin-orbit coupling in graphene is extremely weak, making it a promising spin conductor for spintronic devices. In addition, many applications also require the generation of spin currents in graphene. Theoretical predictions and recent experimental results suggest one can engineer the spin Hall effect in graphene by greatly enhancing the spin-orbit coupling in the vicinity of an impurity. The extrinsic spin Hall effect then results from the spin-dependent skew scattering of electrons by impurities in the presence of spin-orbit interaction. This effect can be used to efficiently convert charge currents into spin-polarized currents. I will discuss recent experimental results on spin Hall effect in graphene decorated with adatoms and metallic cluster and show that a large spin Hall effect can appear due to skew scattering. While this spin-orbit coupling is small if compared with what it is found in metals, the effect is strongly enhanced in the presence of resonant scattering, giving rise to robust spin Hall angles. I will present our single impurity scattering calculations done with exact partial-wave expansions and complement the analysis with numerical results from a novel real-space implementation of the Kubo formalism for tight-binding Hamiltonians. The author acknowledges the Brazilian agencies CNPq, CAPES, FAPERJ and INCT de Nanoestruturas de Carbono for financial support.

  12. Graphic Turbulence Guidance

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Forecast turbulence hazards identified by the Graphical Turbulence Guidance algorithm. The Graphical Turbulence Guidance product depicts mid-level and upper-level...

  13. Graphical Turbulence Guidance - Composite

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Forecast turbulence hazards identified by the Graphical Turbulence Guidance algorithm. The Graphical Turbulence Guidance product depicts mid-level and upper-level...

  14. Career guidance in communities

    DEFF Research Database (Denmark)

    Thomsen, Rie

    for the development of a critically reflexive career guidance practice. The considerations are organised around seven elements. 1. Creating opportunity, structure and access 2. Entering a community and increasing visibility 3. Providing guidance in communities 4. Exploring potentials in guidance situations 5...... in career guidance practices as well as in the lives of the people in the communities. This paper falls into two parts: The first part considers the collective as the starting point for the development of meaningful career guidance activities. Based on previous research on career guidance in communities......The aim of this paper is to inspire practitioners and professionals to leave their offices to bring career guidance into communities that might not identify with career guidance in the first instance. By making the effort to engage with communities, practitioners may bring about a critical change...

  15. Axonal excitability properties in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2006-07-01

    To investigate axolemmal ion channel function in patients diagnosed with sporadic amyotrophic lateral sclerosis (ALS). A recently described threshold tracking protocol was implemented to measure multiple indices of axonal excitability in 26 ALS patients by stimulating the median motor nerve at the wrist. The excitability indices studied included: stimulus-response curve (SR); strength-duration time constant (tauSD); current/threshold relationship; threshold electrotonus to a 100 ms polarizing current; and recovery curves to a supramaximal stimulus. Compound muscle action potential (CMAP) amplitudes were significantly reduced in ALS patients (ALS, 2.84+/-1.17 mV; controls, 8.27+/-1.09 mV, P<0.0005) and the SR curves for both 0.2 and 1 ms pulse widths were shifted in a hyperpolarized direction. Threshold electrotonus revealed a greater threshold change to both depolarizing and hyperpolarizing conditioning stimuli, similar to the 'fanned out' appearance that occurs with membrane hyperpolarization. The tauSD was significantly increased in ALS patients (ALS, 0.50+/-0.03 ms; controls, 0.42+/-0.02 ms, P<0.05). The recovery cycle of excitability following a conditioning supramaximal stimulus revealed increased superexcitability in ALS patients (ALS, 29.63+/-1.25%; controls, 25.11+/-1.01%, P<0.01). Threshold tracking studies revealed changes indicative of widespread dysfunction in axonal ion channel conduction, including increased persistent Na+ channel conduction, and abnormalities of fast paranodal K+ and internodal slow K+ channel function, in ALS patients. An increase in persistent Na+ conductances coupled with reduction in K+ currents would predispose axons of ALS patients to generation of fasciculations and cramps. Axonal excitability studies may provide insight into mechanisms responsible for motor neuron loss in ALS.

  16. Regulation of axonal development by the nuclear protein hindsight (pebbled) in the Drosophila visual system.

    Science.gov (United States)

    Oliva, Carlos; Sierralta, Jimena

    2010-08-15

    The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. Copyright 2010 Elsevier Inc. All rights reserved.

  17. The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding.

    Science.gov (United States)

    Zinovyeva, Anna Y; Graham, Serena M; Cloud, Veronica J; Forrester, Wayne C

    2006-01-01

    Histone proteins play integral roles in chromatin structure and function. Histones are subject to several types of posttranslational modifications, including acetylation, which can produce transcriptional activation. The converse, histone deacetylation, is mediated by histone deacetylases (HDACs) and often is associated with transcriptional silencing. We identified a new mutation, cw2, in the Caenorhabditis elegans hda-1 gene, which encodes a histone deacetylase. Previous studies showed that a mutation in hda-1, e1795, or reduction of hda-1 RNA by RNAi causes defective vulval and gonadal development leading to sterility. The hda-1(cw2) mutation causes defective vulval development and reduced fertility, like hda-1(e1795), albeit with reduced severity. Unlike the previously reported hda-1 mutation, hda-1(cw2) mutants are viable as homozygotes, although many die as embryos or larvae, and are severely uncoordinated. Strikingly, in hda-1(cw2) mutants, axon pathfinding is defective; specific axons often appear to wander randomly or migrate in the wrong direction. In addition, the long range migrations of three neuron types and fasciculation of the ventral nerve cord are defective. Together, our studies define a new role for HDA-1 in nervous system development, and provide the first evidence for HDAC function in regulating neuronal axon guidance.

  18. The influence of electrospun fibre size on Schwann cell behaviour and axonal outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Gnavi, S., E-mail: sara.gnavi@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Fornasari, B.E., E-mail: benedettaelena.fornasari@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Tonda-Turo, C., E-mail: chiara.tondaturo@polito.it [Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Politecnico of Torino, Torino 10100 (Italy); Ciardelli, G., E-mail: gianluca.ciardelli@polito.it [Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Politecnico of Torino, Torino 10100 (Italy); CNR-IPCF UOS, Pisa 56124 (Italy); Zanetti, M., E-mail: marco.zanetti@unito.it [Nanostructured Interfaces and Surfaces, Department of Chemistry, University of Torino, Torino 10100 (Italy); Geuna, S., E-mail: stefano.geuna@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Perroteau, I., E-mail: isabelle.perroteau@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy)

    2015-03-01

    Fibrous substrates functioning as temporary extracellular matrices can be prepared easily by electrospinning, yielding fibrous matrices suitable as internal fillers for nerve guidance channels. In this study, gelatin micro- or nano-fibres were prepared by electrospinning by tuning the gelatin concentration and solution flow rate. The effect of gelatin fibre diameter on cell adhesion and proliferation was tested in vitro using explant cultures of Schwann cells (SC) and dorsal root ganglia (DRG). Cell adhesion was assessed by quantifying the cell spreading area, actin cytoskeleton organization and focal adhesion complex formation. Nano-fibres promoted cell spreading and actin cytoskeleton organization, increasing cellular adhesion and the proliferation rate. However, both migration rate and motility, quantified by transwell and time lapse assays respectively, were greater in cells cultured on micro-fibres. Finally, there was more DRG axon outgrowth on micro-fibres. These data suggest that the topography of electrospun gelatin fibres can be adjusted to modulate SC and axon organization and that both nano- and micro-fibres are promising fillers for the design of devices for peripheral nerve repair. - Highlights: • Electrospinning used to produce gelatin nano- and micro-fibre matrices. • Nano-fibre matrices promote Schwann cell organization and increase proliferation rate. • Micro-fibre matrices promote Schwann cell migration. • Micro-fibre matrices promote axonal outgrowth.

  19. Histological methods for assessing myelin sheaths and axons in human nerve trunks.

    Science.gov (United States)

    Miko, T L; Gschmeissner, S E

    1994-03-01

    Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods.

  20. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C; Lai, Yi Ming

    2011-01-01

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master

  1. The effect of extrinsic motivation on cycle time trial performance

    NARCIS (Netherlands)

    Hulleman, M.; de Koning, J.J.; Hettinga, F.J.; Foster, C.

    2007-01-01

    PURPOSE: Athletes occasionally follow pacing patterns that seem unreasonably aggressive compared with those of prerace performances, potentially because of the motivation provided by competition. This study evaluated the effect of extrinsic motivation on cyclists' time trial performance. METHODS:

  2. On the isoperimetric rigidity of extrinsic minimal balls

    DEFF Research Database (Denmark)

    Markvorsen, Steen; Palmer, V.

    2003-01-01

    We consider an m-dimensional minimal submanifold P and a metric R-sphere in the Euclidean space R-n. If the sphere has its center p on P, then it will cut out a well defined connected component of P which contains this center point. We call this connected component an extrinsic minimal R-ball of P....... The quotient of the volume of the extrinsic ball and the volume of its boundary is not larger than the corresponding quotient obtained in the space form standard situation, where the minimal submanifold is the totally geodesic linear subspace R-m. Here we show that if the minimal submanifold has dimension...... larger than 3, if P is not too curved along the boundary of an extrinsic minimal R-ball, and if the inequality alluded to above is an equality for the extrinsic minimal ball, then the minimal submanifold is totally geodesic....

  3. The detrimental effects of extrinsic reinforcement on "Intrinsic motivation".

    Science.gov (United States)

    Dickinson, A M

    1989-01-01

    Extrinsic consequences have been criticized on the grounds that they decrease intrinsic motivation or internally initiated behavior. Two popular rationales for this criticism, Lepper's overjustification hypothesis (1981) and Deci's motivational theory (Deci & Ryan, 1985), are reviewed and the criticism is then redefined behaviorally. "Intrinsically controlled" behavior is defined as behavior maintained by response-produced reinforcers, and the question concerning extrinsic consequences is thus restated as follows: When behavior is maintained by response-produced stimuli, does extrinsic reinforcement decrease the reinforcing value of those stimuli? The empirical support for this detrimental effect is summarized briefly, and several possible explanations for the phenomenon are offered. Research results that reflect on the effect's generality and social significance are discussed next, with the conclusion that the effect is transient and not likely to occur at all if extrinsic rewards are reinforcing, noncompetitive, based on reasonable performance standards, and delivered repetitively.

  4. CT-semiotics and clinical aspects of extrinsic allergic alveolitis

    International Nuclear Information System (INIS)

    Skrynnikova, I.P.; Momot, N.V.; Vakulenko, I.P.; Tanasichuk-Gazhieva, N.V

    2003-01-01

    Extrinsic allergic alveolitis can be a difficult diagnostic problem. The comparison of the results of CT research with the clinical immunological and morphological data allowed to define the forms and diagnose the characteristic symptoms of the disease

  5. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  6. On intrinsic and extrinsic origin of plasmon peaks

    International Nuclear Information System (INIS)

    Takayama, Shoichi; Kawai, Jun

    2008-01-01

    The origin of the plasmon loss peaks in X-ray photoelectron spectra are discussed based on the (1) intrinsic, (2) extrinsic, (3) quantum interference between (1) and (2), and (4) mixture of (1) and (2). It was believed that the major part of plasmon was due to the extrinsic, the present analysis concludes the major part is intrinsic, depending the excitation energy. This analysis is based on the electron reflection spectra, but valid for X-ray photoelectron spectra. (author)

  7. The effects of extrinsic rewards on children's intrinsic motivation

    OpenAIRE

    大槻, 千秋

    1981-01-01

    An experiment was conducted with preschool children to test whether a person's intrinsic motivation in an activity may be decreased by extrinsic salient rewards in Japan like in America. Children solved some jigsaw puzzles and received assorted candies, then they were observed how long they did other jigsaw puzzles. The results showed that the effects of extrinsic rewards on intrinsic motivation in an activity varied with the subject's social background. In uptown children's intrinsic motivat...

  8. The Effect of Extrinsic Motivational Factors Towards Iba Student Achievement

    OpenAIRE

    Pangemanan, Sifrid S.; Saerang, David Paul Elia; Rondonuwu, Mariska

    2014-01-01

    The reason students can facing the world of competition because they have a motivation. A thing that help students to get their motivation when they are not get a motivation by themself is through extrinsic motivational factors. There are two objectives of this research are to analyze the effect of extrinsic motivational factors towards student achievement and to identify the most influental factors on student achievement. The method is multiple linear regression analysis to examine the effec...

  9. Self-perception of intrinsic and extrinsic motivation.

    Science.gov (United States)

    Calder, B J; Staw, B M

    1975-04-01

    Self-perception theory predicts that intrinsic and extrinsic motivation do not combine additively but rather interact. To test this predicted interaction, intrinsic and extrinsic motivation were both manipulated as independent variables. The results revealed a significant interaction for task satisfaction and a trend for the interaction on a behavioral measure. These results are discussed in terms of a general approach to the self-perception of motivation.

  10. Separating intrinsic from extrinsic fluctuations in dynamic biological systems.

    Science.gov (United States)

    Hilfinger, Andreas; Paulsson, Johan

    2011-07-19

    From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.

  11. Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery.

    Science.gov (United States)

    Hou, Shaoping; Nicholson, LaShae; van Niekerk, Erna; Motsch, Melanie; Blesch, Armin

    2012-09-19

    Previous studies have shown that injured dorsal column sensory axons extend across a spinal cord lesion site if axons are guided by a gradient of neurotrophin-3 (NT-3) rostral to the lesion. Here we examined whether continuous NT-3 delivery is necessary to sustain regenerated axons in the injured spinal cord. Using tetracycline-regulated (tet-off) lentiviral gene delivery, NT-3 expression was tightly controlled by doxycycline administration. To examine axon growth responses to regulated NT-3 expression, adult rats underwent a C3 dorsal funiculus lesion. The lesion site was filled with bone marrow stromal cells, tet-off-NT-3 virus was injected rostral to the lesion site, and the intrinsic growth capacity of sensory neurons was activated by a conditioning lesion. When NT-3 gene expression was turned on, cholera toxin β-subunit-labeled sensory axons regenerated into and beyond the lesion/graft site. Surprisingly, the number of regenerated axons significantly declined when NT-3 expression was turned off, whereas continued NT-3 expression sustained regenerated axons. Quantification of axon numbers beyond the lesion demonstrated a significant decline of axon growth in animals with transient NT-3 expression, only some axons that had regenerated over longer distance were sustained. Regenerated axons were located in white matter and did not form axodendritic synapses but expressed presynaptic markers when closely associated with NG2-labeled cells. A decline in axon density was also observed within cellular grafts after NT-3 expression was turned off possibly via reduction in L1 and laminin expression in Schwann cells. Thus, multiple mechanisms underlie the inability of transient NT-3 expression to fully sustain regenerated sensory axons.

  12. Extrinsic value orientation and affective forecasting: overestimating the rewards, underestimating the costs.

    Science.gov (United States)

    Sheldon, Kennon M; Gunz, Alexander; Nichols, Charles P; Ferguson, Yuna

    2010-02-01

    We examined affective forecasting errors as a possible explanation of the perennial appeal of extrinsic values and goals. Study 1 found that although people relatively higher in extrinsic (money, fame, image) compared to intrinsic (growth, intimacy, community) value orientation (REVO) are less happy, they nevertheless believe that attaining extrinsic goals offers a strong potential route to happiness. Study 2's longitudinal experimental design randomly assigned participants to pursue either 3 extrinsic or 3 intrinsic goals over 4 weeks, and REVO again predicted stronger forecasts regarding extrinsic goals. However, not even extrinsically oriented participants gained well-being benefits from attaining extrinsic goals, whereas all participants tended to gain in happiness from attaining intrinsic goals. Study 3 showed that the effect of REVO on forecasts is mediated by extrinsic individuals' belief that extrinsic goals will satisfy autonomy and competence needs. It appears that some people overestimate the emotional benefits of achieving extrinsic goals, to their potential detriment.

  13. Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

    Science.gov (United States)

    Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

    2015-11-01

    The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Can injured adult CNS axons regenerate by recapitulating development?

    Science.gov (United States)

    Hilton, Brett J; Bradke, Frank

    2017-10-01

    In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

  15. Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

    Science.gov (United States)

    Yao, L; Daly, W; Newland, B; Yao, S; Wang, W; Chen, B K K; Madigan, N; Windebank, A; Pandit, A

    2013-12-01

    Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

  16. INTRINSIC AND EXTRINSIC MOTIVATION - AN INVESTIGATION OF PERFORMANCE CORRELATION

    Directory of Open Access Journals (Sweden)

    Abrudan Maria-Madela

    2011-07-01

    Full Text Available A series of research untaken in the last decade have revealed some interesting aspects regarding the effects of different types of motivation on performance. Among the researchers who have shown interest in this field we can number: Richard Ryan, Edward Deci, Sam Glucksberg, Dan Ariely, Robert Eisenhower, Linda Shanock, analysts from London School of Economics, and others. Their findings suggest that extrinsic incentives may have a negative impact on overall performance, but a general agreement in this respect has not been reached. In this paper we intend to shed some light upon the relationship between intrinsic and extrinsic motivation and performance. Experts define intrinsic motivation as being the execution of a task or activity because of the inherent satisfaction arising from it rather than due to some separate outcome. In contrast with intrinsic motivation, we speak of extrinsic motivation whenever an activity is done in order to attain some separable outcome. With the purpose of contributing to the clarification of the links between concepts, we initiated and conducted an explanatory research. The research is based on the analysis of the relations between the results obtained by third year students and their predominant type of motivation. For this, we formulated and tested four work hypotheses using a combination of quantitative methods (investigation and qualitative methods (focus group. After the validation of the questionnaires, the respondents were divided into four categories: intrinsically motivated, extrinsically motivated, both intrinsically and extrinsically motivated and unmotivated. To analyze the collected data, we made use of Excel and SPSS. Some of the primary conclusions of the research are as follows: as the average increases, the percent of individuals having both extrinsic and intrinsic motivation is decreasing; the highest percentage of unmotivated students is concentrated in the highest average category; Female

  17. Quantifying intrinsic and extrinsic variability in stochastic gene expression models.

    Science.gov (United States)

    Singh, Abhyudai; Soltani, Mohammad

    2013-01-01

    Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters.

  18. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    Science.gov (United States)

    Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

    2012-01-01

    Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

  19. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

    2007-01-01

    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...... at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein...

  20. [EXTRINSIC AND INTRINSIC FACTORS FOR FALLS THAT CAUSED HIP FRACTURE].

    Science.gov (United States)

    Tsur, Atzmon; Shakeer, Nael; Segal, Zvi; Itah, Dorit; Eluz, Dana

    2017-05-01

    Among the reasons described as possibly causing falls in older and elderly people are extrinsic factors such as bumping into objects, slipping on a wet floor, etc., and intrinsic factors - those that occur suddenly without warning. To investigate the connection between the reasons for falls, extrinsic or intrinsic and different medical and nonmedical factors. The survey included 82 people, 53 women and 29 men, who fell and broke their hip, underwent surgery, and were treated at the Rehabilitation Department. Data showed that 39 people fell due to extrinsic factors and 43 due to intrinsic reasons. We examined the correlation with several factors, both medical and non-medical, that may have influenced the scenario of each group. Falls due to extrinsic reasons took place at all hours of the day and night, mainly in people who were alone and who wore shoes or sandals at the time of the fall and who either suffered from slight or no disturbances in attention and concentration. Falls due to intrinsic reasons occurred mainly during rest or sleep hours, in people who walked barefoot or with socks or slippers and who suffered moderate or severe disturbances in attention and concentration. Although the differences in the extrinsic vs. intrinsic reasons for falls that led to broken hips were fairly clear, it would be difficult to recommend new tools for prevention of this phenomenon. Trying to predict an infrequent future event such as a traumatic fall is inherently difficult.

  1. Extrinsic versus intrinsic hand muscle dominance in finger flexion.

    Science.gov (United States)

    Al-Sukaini, A; Singh, H P; Dias, J J

    2016-05-01

    This study aims to identify the patterns of dominance of extrinsic or intrinsic muscles in finger flexion during initiation of finger curl and mid-finger flexion. We recorded 82 hands of healthy individuals (18-74 years) while flexing their fingers and tracked the finger joint angles of the little finger using video motion tracking. A total of 57 hands (69.5%) were classified as extrinsic dominant, where the finger flexion was initiated and maintained at proximal interphalangeal and distal interphalangeal joints. A total of 25 (30.5%) were classified as intrinsic dominant, where the finger flexion was initiated and maintained at the metacarpophalangeal joint. The distribution of age, sex, dominance, handedness and body mass index was similar in the two groups. This knowledge may allow clinicians to develop more efficient rehabilitation regimes, since intrinsic dominant individuals would not initiate extrinsic muscle contraction till later in finger flexion, and might therefore be allowed limited early active motion. For extrinsic dominant individuals, by contrast, initial contraction of extrinsic muscles would place increased stress on the tendon repair site if early motion were permitted. © The Author(s) 2016.

  2. Iron-59 absorption from soy hulls: intrinsic vs extrinsic labeling

    International Nuclear Information System (INIS)

    Lykken, G.I.; Mahalko, J.R.; Nielsen, E.J.; Dintzis, F.R.

    1986-01-01

    As part of an evaluation of the validity of the extrinsic labeling technique for measuring iron absorption, absorption from soy hulls extrinsically labeled ( 59 Fe added to bread dough) was compared with that from soy hulls intrinsically labeled ( 59 Fe incorporated into the soy plant during growth). Century soybeans were grown in a greenhouse. After pods had formed and were filling, each plant was stem injected twice, at 3 day intervals, with 22 μCi 59 Fe as FeCl 2 in 25 μl of 0.5 M HCl solution. After the plants had senesced, the soybeans were harvested, dried, shelled and the hulls removed. Standard meals containing 3.5 mg Fe/meal and up to 0.06 μCi 59 Fe in a soy hull bun were fed on 2 consecutive days to free-living volunteers in a crossover design. Absorption of 59 Fe was greater from intrinsically labeled soy hulls than from extrinsically labeled soy hulls, 20 +/- 20% vs 15 +/- 11% (n=14, p > 0.05 by paired t-test). Apparent absorption ranged from 1.3% to 77% from intrinsically labeled soy hulls and .5% to 29% from extrinsically labeled soy hulls with the highest absorption occurring in persons with low serum ferritin (S.F. < 8 ng/ml). These findings provide additional evidence that the extrinsic labeling method is a valid measure of iron bioavailability to humans

  3. Emotion impairs extrinsic source memory--An ERP study.

    Science.gov (United States)

    Mao, Xinrui; You, Yuqi; Li, Wen; Guo, Chunyan

    2015-09-01

    Substantial advancements in understanding emotional modulation of item memory notwithstanding, controversies remain as to how emotion influences source memory. Using an emotional extrinsic source memory paradigm combined with remember/know judgments and two key event-related potentials (ERPs)-the FN400 (a frontal potential at 300-500 ms related to familiarity) and the LPC (a later parietal potential at 500-700 ms related to recollection), our research investigated the impact of emotion on extrinsic source memory and the underlying processes. We varied a semantic prompt (either "people" or "scene") preceding a study item to manipulate the extrinsic source. Behavioral data indicated a significant effect of emotion on "remember" responses to extrinsic source details, suggesting impaired recollection-based source memory in emotional (both positive and negative) relative to neutral conditions. In parallel, differential FN400 and LPC amplitudes (correctly remembered - incorrectly remembered sources) revealed emotion-related interference, suggesting impaired familiarity and recollection memory of extrinsic sources associated with positive or negative items. These findings thus lend support to the notion of emotion-induced memory trade off: while enhancing memory of central items and intrinsic/integral source details, emotion nevertheless disrupts memory of peripheral contextual details, potentially impairing both familiarity and recollection. Importantly, that positive and negative items result in comparable memory impairment suggests that arousal (vs. affective valence) plays a critical role in modulating dynamic interactions among automatic and elaborate processes involved in memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Intrinsic and extrinsic spin Hall effects of Dirac electrons

    International Nuclear Information System (INIS)

    Fukazawa, Takaaki; Kohno, Hiroshi; Fujimoto, Junji

    2017-01-01

    We investigate the spin Hall effect (SHE) of electrons described by the Dirac equation, which is used as an effective model near the L-points in bismuth. By considering short-range nonmagnetic impurities, we calculate the extrinsic as well as intrinsic contributions on an equal footing. The vertex corrections are taken into account within the ladder type and the so-called skew-scattering type. The intrinsic SHE which we obtain is consistent with that of Fuseya et al. It is found that the extrinsic contribution dominates the intrinsic one when the system is metallic. The extrinsic SHE due to the skew scattering is proportional to Δ/n i u, where 2Δ is the band gap, n i is the impurity concentration, and u is the strength of the impurity potential. (author)

  5. Extrinsic Motivation Index: A New Tool for Managing Labor Productivity

    Directory of Open Access Journals (Sweden)

    Berumen, S.A.

    2016-07-01

    Full Text Available The objective of this paper is to provide a tool of practical significance for HR managers and firm executives. This tool, which is called Extrinsic Motivation Index (EMI, is meant to measure the extrinsic motivation of employees. By measuring employees' extrinsic motivation, managers are able to track job satisfaction and, subsequently, implement measures aiming both to raise job satisfaction and to improve organizational commitment. In order to test the validity of the model, we apply the EMI to Faculty members at Spanish and German universities. We also carry out simulation experiments in order to to address all possible situations an organization most probably will have to deal with. The results point out significant differences in the level of motivation and commitment of Faculty members. Additionally, the analysis shows several ways in which an organization may manage job satisfaction issues according to on its level of resources.

  6. Intrinsic and extrinsic motivation for stereotypic and repetitive behavior.

    Science.gov (United States)

    Joosten, Annette V; Bundy, Anita C; Einfeld, Stewart L

    2009-03-01

    This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess anxiety as an intrinsic motivator. Rasch analysis of data from 279 MASs (74 children) revealed that the items formed two unidimensional scales. Anxiety was a more likely intrinsic motivator than sensory seeking for children with dual diagnoses; the reverse was true for children with intellectual disability only. Escape and gaining a tangible object were the most common extrinsic motivators for those with dual diagnoses and attention and escape for children with intellectual disability.

  7. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.

    Science.gov (United States)

    Martel, Britta C; Litman, Thomas; Hald, Andreas; Norsgaard, Hanne; Lovato, Paola; Dyring-Andersen, Beatrice; Skov, Lone; Thestrup-Pedersen, Kristian; Skov, Søren; Skak, Kresten; Poulsen, Lars K

    2016-06-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation-associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Parallel simulation of axon growth in the nervous system

    NARCIS (Netherlands)

    J. Wensch; B.P. Sommeijer (Ben)

    2002-01-01

    textabstractIn this paper we discuss a model from neurobiology, which describes theoutgrowth of axons from neurons in the nervous system. The model combines ordinary differential equations, defining the movement of the axons, with parabolic partial differential equations. The parabolic equations

  9. A dam for retrograde axonal degeneration in multiple sclerosis?

    NARCIS (Netherlands)

    Balk, L.J.; Twisk, J.W.R.; Steenwijk, M.D.; Daams, M.; Tewarie, P.; Killestein, J.; Uitdehaag, B.M.J.; Polman, C.H.; Petzold, A.F.S.

    2014-01-01

    Objective: Trans-synaptic axonal degeneration is a mechanism by which neurodegeneration can spread from a sick to a healthy neuron in the central nervous system. This study investigated to what extent trans-synaptic axonal degeneration takes place within the visual pathway in multiple sclerosis

  10. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Stuart, Greg J.

    2008-01-01

    Action potential threshold is thought to be lowest in the axon, but when measured using conventional techniques, we found that action potential voltage threshold of rat cortical pyramidal neurons was higher in the axon than at other neuronal locations. In contrast, both current threshold and voltage

  11. Intrinsic and extrinsic motivation and intention to breast-feed.

    Science.gov (United States)

    Wells, Kristen J; Thompson, Nancy J; Kloeblen-Tarver, Amy S

    2002-01-01

    To examine the feasibility of using the cognitive evaluation theory to examine pregnant women's intention to breast-feed. A questionnaire designed to measure intrinsic and extrinsic motivation was administered to 228 pregnant women. Results provide evidence for reliability and validity of the revised instrument in this population. A factor analysis suggests the instrument measures 2 types of intrinsic motivation, one type of extrinsic motivation, and motivation related to the baby. The instrument distinguished differences in motivation between women who intend to breast-feed and those who intend to formula feed. This study helps elucidate motivational factors involved in infant-feeding decisions.

  12. Extrinsic passivation of silicon surfaces for solar cells

    OpenAIRE

    Bonilla, R.S.; Reichel, C.; Hermle, M.; Martins, G.; Wilshaw, P.R.

    2015-01-01

    In the present work we study the extent to which extrinsic chemical and field effect passivation can improve the overall electrical passivation quality of silicon dioxide on silicon. Here we demonstrate that, when optimally applied, extrinsic passivation can produce surface recombination velocities below 1.2 cm/s in planar 1 Omega cm n-type Si. This is largely due to the additional field effect passivation component which reduces the recombination velocity below 2.13 cm/s. On textured surface...

  13. CONSUMER EVALUATIONS OF BEAUTIFICATION PRODUCTS: EFFECTS OF EXTRINSIC CUES

    Directory of Open Access Journals (Sweden)

    Md. Humayun Kabir Chowdhury

    2006-01-01

    Full Text Available This study investigates the influence of extrinsic cues, i.e. brand image, perceived price, perceived quality, and perceived country of origin on consumers' evaluative judgments for beautification products. Multi-item measures were used for data collection. Resultsrevealed that three extrinsic cues: brand image, perceived quality, and perceived country of origin have positive and significant influence on consumers' brand evaluation of beautification brands. Only perceived price has shown no such influence on consumers' brand evaluation. Finally, unanswered questions and future researchdirections are presented.

  14. SnoN facilitates axonal regeneration after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  15. Internodal function in normal and regenerated mammalian axons

    DEFF Research Database (Denmark)

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found...... that regenerated internodes remain persistently short though this abnormality did not seem to influence recovery in conduction. It remains unclear to which extent abnormalities in axonal function itself may contribute to the poor outcome of nerve regeneration. METHODS: We review experimental evidence indicating...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  16. Motor Axonal Regeneration After Partial and Complete Spinal Cord Transection

    Science.gov (United States)

    Lu, Paul; Blesch, Armin; Graham, Lori; Wang, Yaozhi; Samara, Ramsey; Banos, Karla; Haringer, Verena; Havton, Leif; Weishaupt, Nina; Bennett, David; Fouad, Karim; Tuszynski, Mark H.

    2012-01-01

    We subjected rats to either partial mid-cervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared to several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair, and the need for additional control and shaping of axonal regeneration. PMID:22699902

  17. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    This paper proposes a technique for a previously unaddressed problem, namely, mapping axon diameter in crossing fiber regions, using diffusion MRI. Direct measurement of tissue microstructure of this kind using diffusion MRI offers a new class of biomarkers that give more specific information about...... tissue than measures derived from diffusion tensor imaging. Most existing techniques for axon diameter mapping assume a single axon orientation in the tissue model, which limits their application to only the most coherently oriented brain white matter, such as the corpus callosum, where the single...... model to enable axon diameter mapping in voxels with crossing fibers. We show in simulation that the technique can provide robust axon diameter estimates in a two-fiber crossing with the crossing angle as small as 45 degrees. Using ex vivo imaging data, we further demonstrate the feasibility...

  18. Axonal loss in the multiple sclerosis spinal cord revisited.

    Science.gov (United States)

    Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

    2018-05-01

    Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

  19. Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.

    Science.gov (United States)

    Fan, Xueping; Labrador, Juan Pablo; Hing, Huey; Bashaw, Greg J

    2003-09-25

    Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Here we present evidence that the SH3-SH2 adaptor protein Dreadlocks (Dock), the p21-activated serine-threonine kinase (Pak), and the Rac1/Rac2/Mtl small GTPases can function during Robo repulsion. Loss-of-function and genetic interaction experiments suggest that limiting the function of Dock, Pak, or Rac partially disrupts Robo repulsion. In addition, Dock can directly bind to Robo's cytoplasmic domain, and the association of Dock and Robo is enhanced by stimulation with Slit. Furthermore, Slit stimulation can recruit a complex of Dock and Pak to the Robo receptor and trigger an increase in Rac1 activity. These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance.

  20. 4S RNA is transported axonally in normal and regenerating axons of the sciatic nerves of rats

    Energy Technology Data Exchange (ETDEWEB)

    Lindquist, T D; Ingoglia, N A; Gould, R M [Departments of Physiology and Neuroscience, New Jersey Medical School, Newark, NJ, USA

    1982-12-28

    Experiments were designed to determine if following injection of (/sup 3/H)uridine into the lumbar spinal cord of the rat, (/sup 3/H)RNA could be demonstrated within axons of the sciatic nerve, and if 4S RNA is the predominant predominant RNA species present in these axons.

  1. Extracellular sugar modifications provide instructive and cell-specific information for axon-guidance choices.

    NARCIS (Netherlands)

    Bulow, H.E.; Tjoe, N.; Townley, R.A.; Didiano, D.; Kuppevelt, A.H.M.S.M. van; Hobert, O.

    2008-01-01

    Heparan sulfates (HSs) are extraordinarily complex extracellular sugar molecules that are critical components of multiple signaling systems controlling neuronal development. The molecular complexity of HSs arises through a series of specific modifications, including sulfations of sugar residues and

  2. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  3. Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance

    NARCIS (Netherlands)

    V.C. Seitan (Vlad); P.A. Banks (Peter); S. Laval (Steve); N.A. Majid (Nazia); D. Dorsett (Dale); A. Rana (Amer); J. Smith (Jeremy); A. Bateman (Alex); S. Krpic (Sanja); A. Hostert (Arnd); S.M. Rollins; H. Erdjument-Bromage (Hediye); P. Tempst (Paul); C.Y. Benard (Claire); S. Hekimi (Siegfried); S.F. Newbury (Sarah); T. Strachan (Tom)

    2006-01-01

    textabstractSaccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside

  4. CT Accuracy of Extrinsic Tongue Muscle Invasion in Oral Cavity Cancer.

    Science.gov (United States)

    Junn, J C; Baugnon, K L; Lacayo, E A; Hudgins, P A; Patel, M R; Magliocca, K R; Corey, A S; El-Deiry, M; Wadsworth, J T; Beitler, J J; Saba, N F; Liu, Y; Aiken, A H

    2017-02-01

    Extrinsic tongue muscle invasion in oral cavity cancer upstages the primary tumor to a T4a. Despite this American Joint Committee on Cancer staging criterion, no studies have investigated the accuracy or prognostic importance of radiologic extrinsic tongue muscle invasion, the feasibility of standardizing extrinsic tongue muscle invasion reporting, or the degree of agreement across different disciplines: radiology, surgery, and pathology. The purpose of this study was to assess the agreement among radiology, surgery, and pathology for extrinsic tongue muscle invasion and to determine the imaging features most predictive of extrinsic tongue muscle invasion with surgical/pathologic confirmation. Thirty-three patients with untreated primary oral cavity cancer were included. Two head and neck radiologists, 3 otolaryngologists, and 1 pathologist prospectively evaluated extrinsic tongue muscle invasion. Fourteen of 33 patients had radiologic extrinsic tongue muscle invasion; however, only 8 extrinsic tongue muscle invasions were confirmed intraoperatively. Pathologists were unable to determine extrinsic tongue muscle invasion in post-formalin-fixed samples. Radiologic extrinsic tongue muscle invasion had 100% sensitivity, 76% specificity, 57% positive predictive value, and 100% negative predictive value with concurrent surgical-pathologic evaluation of extrinsic tongue muscle invasion as the criterion standard. On further evaluation, the imaging characteristic most consistent with surgical-pathologic evaluation positive for extrinsic tongue muscle invasion was masslike enhancement. Evaluation of extrinsic tongue muscle invasion is a subjective finding for all 3 disciplines. For radiology, masslike enhancement of extrinsic tongue muscle invasion most consistently corresponded to concurrent surgery/pathology evaluation positive for extrinsic tongue muscle invasion. Intraoperative surgical and pathologic evaluation should be encouraged to verify radiologic extrinsic tongue

  5. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  6. Generalized isoperimetric inequalities for extrinsic balls in minimal submanifolds

    DEFF Research Database (Denmark)

    Markvorsen, Steen; Palmer, Vicente

    2002-01-01

    The volume of an extrinsic ball in a minimal submanifold has a well defined lower bound when the ambient manifold has an upper bound on its sectional curvatures, see e.g. [2] and [10]. When this upper bound is non-positive, the second named author has shown an isoperimetric inequality for such do...

  7. Binding of intrinsic and extrinsic features in working memory.

    Science.gov (United States)

    Ecker, Ullrich K H; Maybery, Murray; Zimmer, Hubert D

    2013-02-01

    There is ongoing debate concerning the mechanisms of feature binding in working memory. In particular, there is controversy regarding the extent to which these binding processes are automatic. The present article demonstrates that binding mechanisms differ depending on whether the to-be-integrated features are perceived as forming a coherent object. We presented a series of experiments that investigated the binding of color and shape, whereby color was either an intrinsic feature of the shape or an extrinsic feature of the shape's background. Results show that intrinsic color affected shape recognition, even when it was incidentally studied and irrelevant for the recognition task. In contrast, extrinsic color did not affect shape recognition, even when the association of color and shape was encoded and retrievable on demand. This strongly suggests that binding of intrinsic intra-item information but not extrinsic contextual information is obligatory in visual working memory. We highlight links to perception as well as implicit and explicit long-term memory, which suggest that the intrinsic-extrinsic dimension is a principle relevant to multiple domains of human cognition. 2013 APA, all rights reserved

  8. Dominance dynamics of competition between intrinsic and extrinsic grouping cues.

    Science.gov (United States)

    Luna, Dolores; Villalba-García, Cristina; Montoro, Pedro R; Hinojosa, José A

    2016-10-01

    In the present study we examined the dominance dynamics of perceptual grouping cues. We used a paradigm in which participants selectively attended to perceptual groups based on several grouping cues in different blocks of trials. In each block, single and competing grouping cues were presented under different exposure durations (50, 150 or 350ms). Using this procedure, intrinsic vs. intrinsic cues (i.e. proximity and shape similarity) were compared in Experiment 1; extrinsic vs. extrinsic cues (i.e. common region and connectedness) in Experiment 2; and intrinsic vs. extrinsic cues (i.e. common region and shape similarity) in Experiment 3. The results showed that in Experiment 1, no dominance of any grouping cue was found: shape similarity and proximity grouping cues showed similar reaction times (RTs) and interference effects. In contrast, in Experiments 2 and 3, common region dominated processing: (i) RTs to common region were shorter than those to connectedness (Exp. 2) or shape similarity (Exp. 3); and (ii) when the grouping cues competed, common region interfered with connectedness (Exp. 2) and shape similarity (Exp. 3) more than vice versa. The results showed that the exposure duration of stimuli only affected the connectedness grouping cue. An important result of our experiments indicates that when two grouping cues compete, both the non-attended intrinsic cue in Experiment 1, and the non-dominant extrinsic cue in Experiments 2 and 3, are still perceived and they are not completely lost. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Alberta Consumers' Valuation of Extrinsic and Intrinsic Red Meat Attributes

    DEFF Research Database (Denmark)

    Steiner, Bodo; Gao, Fei; Unterschultz, Jim

    2010-01-01

    This paper analyzes Alberta consumers’ perceptions toward extrinsic and intrinsic attributes of bison and beef steaks. In contrast to published Canadian consumer studies on bison meat that were undertaken prior to May 2003, before the first BSE case of Canadian origin was identified in beef cattle...

  10. Extrinsic photoresponse enhancement under additional intrinsic photoexcitation in organic semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Kounavis, P., E-mail: pkounavis@upatras.gr [Department of Electrical and Computer Engineering, School of Engineering, University of Patras, 26504 Patras (Greece)

    2016-06-28

    Dual light beam photoresponse experiments are employed to explore the photoresponse under simultaneous extrinsic and intrinsic photoexcitation of organic semiconductors. The photoresponse of a red modulated light extrinsic photoexcitation is found that can be significantly enhanced under an additional blue bias-light intrinsic photoexcitation in two terminal pentacene films on glass substrates. From the frequency resolved photoresponse, it is deduced that the phenomenon of photoresponse enhancement can be attributed to an increase in the extrinsic photogeneration rate of the red modulated light and/or an improvement of the drift velocity of carriers under an additional blue light intrinsic photoexcitation. The possible predominant extrinsic photogeneration mechanism, which can be compatible with the observed dependence of the photoresponse enhancement on the frequency and on the light intensities of the red and blue light excitation, is the singlet exciton dissociation through electron transfer to acceptor-like traps. Moreover, an improvement in the drift velocity of carriers traversing grain boundaries with potential energy barriers, which may be reduced by trapping of minority carriers created from the intrinsic photoexcitation, may partly contribute to the photoresponse enhancement.

  11. Magnetic order in graphite: Experimental evidence, intrinsic and extrinsic difficulties

    International Nuclear Information System (INIS)

    Esquinazi, P.; Barzola-Quiquia, J.; Spemann, D.; Rothermel, M.; Ohldag, H.; Garcia, N.; Setzer, A.; Butz, T.

    2010-01-01

    We discuss recently obtained data using different experimental methods including magnetoresistance measurements that indicate the existence of metal-free high-temperature magnetic order in graphite. Intrinsic as well as extrinsic difficulties to trigger magnetic order by irradiation of graphite are discussed in view of recently published theoretical work.

  12. Extrinsic photoresponse enhancement under additional intrinsic photoexcitation in organic semiconductors

    International Nuclear Information System (INIS)

    Kounavis, P.

    2016-01-01

    Dual light beam photoresponse experiments are employed to explore the photoresponse under simultaneous extrinsic and intrinsic photoexcitation of organic semiconductors. The photoresponse of a red modulated light extrinsic photoexcitation is found that can be significantly enhanced under an additional blue bias-light intrinsic photoexcitation in two terminal pentacene films on glass substrates. From the frequency resolved photoresponse, it is deduced that the phenomenon of photoresponse enhancement can be attributed to an increase in the extrinsic photogeneration rate of the red modulated light and/or an improvement of the drift velocity of carriers under an additional blue light intrinsic photoexcitation. The possible predominant extrinsic photogeneration mechanism, which can be compatible with the observed dependence of the photoresponse enhancement on the frequency and on the light intensities of the red and blue light excitation, is the singlet exciton dissociation through electron transfer to acceptor-like traps. Moreover, an improvement in the drift velocity of carriers traversing grain boundaries with potential energy barriers, which may be reduced by trapping of minority carriers created from the intrinsic photoexcitation, may partly contribute to the photoresponse enhancement.

  13. Extrinsic Rewards and Intrinsic Motivation in Education: Reconsidered Once Again.

    Science.gov (United States)

    Deci, Edward L.; Koestner, Richard; Ryan, Richard M.

    2001-01-01

    Reviews the results of a meta analysis (E. Deci, R. Koestner, and R. Ryan, 1999) that shows that tangible extrinsic rewards do have a substantial undermining effect on intrinsic motivation. Discusses results, which support cognitive evaluation theory, in terms of their relevance for educational practice. (SLD)

  14. College Student Intrinsic and/or Extrinsic Motivation and Learning.

    Science.gov (United States)

    Lin, Yi-Guang; McKeachie, Wilbert J.

    This paper investigates the joint effects of intrinsic and extrinsic goals on college students' learning in an introductory psychology course, a biology course, and several social science courses. The study questioned whether higher levels of motivation lead to better student performance. College students were surveyed using the Intrinsic Goal…

  15. Critical dimension of strings with an extrinsic curvature

    International Nuclear Information System (INIS)

    Matsuki, T.; Viswanathan, K.S.

    1988-01-01

    The conformal anomaly is calculated by using the path-integral method to determine the critical dimension for a string theory with an extrinsic curvature by appropriately defining the first-order form of this Lagrangian. The critical dimension, defined by the vanishing of the Liouville kinetic term, is found to be D = 26, the same as for the ordinary bosonic string theory

  16. Impact of Mentoring on Perceived Adequacy of Extrinsic ...

    African Journals Online (AJOL)

    This study examined the impact of informal mentoring on perceived adequacy of extrinsic organizational rewards such as pay, promotion and fringe benefit. Data were obtained from 161 employees through a survey of a public health organisation in south-western Nigeria. Hierarchical regression analysis revealed that ...

  17. Extrinsic motivation and job satisfaction of teachers' in public post ...

    African Journals Online (AJOL)

    This study was aimed at evaluating the relationship between extrinsic motivation and the job satisfaction of teachers' in public post primary schools in Cross River State, Nigeria. A sample of 125 teachers' was randomly drawn for the study. A four point likert-type questionnaire was used to gather data which was analyzed ...

  18. The Effects of Extrinsic Rewards on Admissions Counselors' Performance

    Science.gov (United States)

    Gardner-Engel, Miriam

    2010-01-01

    This study examines the best ways to motivate college admissions counselors. A review of literature revealed multiple perspectives on intrinsic and extrinsic as well as tangible and intangible rewards. Primary research was designed to examine the impact of tangible rewards and verbal reinforcements with a convenience sample of nine college…

  19. The extrinsic influence of carbon fibre reinforced plastic laminates to ...

    Indian Academy of Sciences (India)

    The extrinsic influence of carbon fibre reinforced plastic laminates to strengthen steel structures ... The intrinsic advantages of strengthening the steel-based structures by the use of fibre reinforced plastic (FRP) material have ... Sadhana | News.

  20. Extrinsic Reinforcement in the Classroom: Bribery or Best Practice

    Science.gov (United States)

    Akin-Little, K. Angeleque; Eckert, Tanya L.; Lovett, Benjamin J.; Little, Steven G.

    2004-01-01

    The debate over the effects of the use of extrinsic reinforcement in classrooms, businesses, and societal settings has been occurring for over 30 years. Some theorists have cautioned against the use of reward, whereas others have found little, if any, detrimental effect. This article examines the debate with an emphasis on data-based findings. The…

  1. Modelling of Extrinsic Fiber Optic Sagnac Ultrasound Interferometer ...

    African Journals Online (AJOL)

    Ultrasonic waves are used extensively in nondestructive testing both for characterization of material properties, in this paper, we describe a fiber optic sensor suitable for detection of ultrasonic waves. This sensor is based on an extrinsic fiber optic sagnac interferometer. The proposed sensor model can act as a conventional ...

  2. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    NARCIS (Netherlands)

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    Background According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and

  3. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    NARCIS (Netherlands)

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background: According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and

  4. Optimal Aerocapture Guidance

    Data.gov (United States)

    National Aeronautics and Space Administration — The main goal of my research is to develop, implement, verify, and validate an optimal numerical predictor-corrector aerocapture guidance algorithm that is...

  5. Coral Reef Guidance

    Science.gov (United States)

    Guidance prepared by EPA and Army Corps of Engineers concerning coral reef protection under the Clean Water Act, Marine Protection, Research, and Sanctuaries Act, Rivers and Harbors Act, and Federal Project Authorities.

  6. Laser Guidance Analysis Facility

    Data.gov (United States)

    Federal Laboratory Consortium — This facility, which provides for real time, closed loop evaluation of semi-active laser guidance hardware, has and continues to be instrumental in the development...

  7. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    OpenAIRE

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background: According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic ...

  8. Engagement in Classroom Learning: Creating Temporal Participation Incentives for Extrinsically Motivated Students through Bonus Credits

    Science.gov (United States)

    Rassuli, Ali

    2012-01-01

    Extrinsic inducements to adjust students' learning motivations have evolved within 2 opposing paradigms. Cognitive evaluation theories claim that controlling factors embedded in extrinsic rewards dissipate intrinsic aspirations. Behavioral theorists contend that if engagement is voluntary, extrinsic reinforcements enhance learning without ill…

  9. Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-actin in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas R Cheever

    2011-03-01

    Full Text Available The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA, suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

  10. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    Directory of Open Access Journals (Sweden)

    Andrew D. Nelson

    2017-05-01

    Full Text Available Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of

  11. Does extrinsic goal framing enhance extrinsic goal-oriented individuals' learning and performance? An experimental test of the match perspective versus self-determination theory

    OpenAIRE

    Vansteenkiste, Maarten; Timmermans, Tinneke; Lens, Willy; Soenens, Bart; Van den Broeck, Anja

    2008-01-01

    Previous work within self-determination theory has shown that experimentally framing a learning activity in terms of extrinsic rather than intrinsic goals results in poorer conceptual learning and performance, presumably because extrinsic goal framing detracts attention from the learning activity and is less directly satisfying of basic psychological needs. According to the match perspective, experimental extrinsic, compared to intrinsic, goal framing should enhance learning and performance f...

  12. Neurotrophin Signaling via Long-Distance Axonal Transport

    Science.gov (United States)

    Chowdary, Praveen D.; Che, Dung L.; Cui, Bianxiao

    2012-05-01

    Neurotrophins are a family of target-derived growth factors that support survival, development, and maintenance of innervating neurons. Owing to the unique architecture of neurons, neurotrophins that act locally on the axonal terminals must convey their signals across the entire axon for subsequent regulation of gene transcription in the cell nucleus. This long-distance retrograde signaling, a motor-driven process that can take hours or days, has been a subject of intense interest. In the last decade, live-cell imaging with high sensitivity has significantly increased our capability to track the transport of neurotrophins, their receptors, and subsequent signals in real time. This review summarizes recent research progress in understanding neurotrophin-receptor interactions at the axonal terminal and their transport dynamics along the axon. We emphasize high-resolution studies at the single-molecule level and also discuss recent technical advances in the field.

  13. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard

    2002-01-01

    cells, while other fibers were unmyelinated. Immunohistochemistry demonstrated that some of the regenerated fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a central origin. These findings suggest that there is a considerable amount of spontaneous regeneration after spinal cord......Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total...... length of all NF-immunolabeled axons within the lesion cavities was increased 6- to 10-fold at 5, 10, and 15 wk post-lesion compared with 1 wk post-surgery. In ultrastructural studies we found the putatively regenerating axons within the lesion to be associated either with oligodendrocytes or Schwann...

  14. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

    In prior exploratory research, we had designed a fiber optic sensor utilizing a long period Bragg grating for the purpose of detecting action potentials in axons optically, through a change in index...

  15. Functional characterization and axonal transport of quantum dot labeled BDNF

    OpenAIRE

    Xie, Wenjun; Zhang, Kai; Cui, Bianxiao

    2012-01-01

    Brain derived neurotrophic factor (BDNF) plays a key role in the growth, development and maintenance of the central and peripheral nervous systems. Exogenous BDNF activates its membrane receptors at the axon terminal, and subsequently sends regulation signals to the cell body. To understand how BDNF signal propagates in neurons, it is important to follow the trafficking of BDNF after it is internalized at the axon terminal. Here we labeled BDNF with bright, photostable quantum dot (QD-BDNF) a...

  16. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Directory of Open Access Journals (Sweden)

    Parisa eLotfi

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D Y-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a Y-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  17. Self-amplifying autocrine actions of BDNF in axon development

    OpenAIRE

    Cheng, Pei-Lin; Song, Ai-Hong; Wong, Yu-Hui; Wang, Sheng; Zhang, Xiang; Poo, Mu-Ming

    2011-01-01

    A critical step in neuronal development is the formation of axon/dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine f...

  18. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  19. Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

    Science.gov (United States)

    Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

    2015-01-01

    The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

  20. Kinematics of turnaround and retrograde axonal transport

    International Nuclear Information System (INIS)

    Snyder, R.E.

    1986-01-01

    Rapid axonal transport of a pulse of 35 S-methionine-labelled material was studied in vitro in the sensory neurons of amphibian sciatic nerve using a position-sensitive detector. For 10 nerves studied at 23.0 +/- 0.2 degrees C it was found that a pulse moved in the anterograde direction characterized by front edge, peak, and trailing edge transport rates of (mm/d) 180.8 +/- 2.2 (+/- SEM), 176.6 +/- 2.3, and 153.7 +/- 3.0, respectively. Following its arrival at a distal ligature, a smaller pulse was observed to move in the retrograde direction characterized by front edge and peak transport rates of 158.0 +/- 7.3 and 110.3 +/- 3.5, respectively, indicating that retrograde transport proceeds at a rate of 0.88 +/- 0.04 that of anterograde. The retrograde pulse was observed to disperse at a rate greater than the anterograde. Reversal of radiolabel at the distal ligature began 1.49 +/- 0.15 h following arrival of the first radiolabel. Considerable variation was seen between preparations in the way radiolabel accumulated in the end (ligature) regions of the nerve. Although a retrograde pulse was seen in all preparations, in 7 of 10 preparations there was no evidence of this pulse accumulating within less than 2-3 mm of a proximal ligature; however, accumulation was observed within less than 5 mm in all preparations

  1. Extrinsic CPT violation in neutrino oscillations in matter

    International Nuclear Information System (INIS)

    Jacobson, Magnus; Ohlsson, Tommy

    2004-01-01

    We investigate matter-induced (or extrinsic) CPT violation effects in neutrino oscillations in matter. Especially, we present approximate analytical formulas for the CPT-violating probability differences for three flavor neutrino oscillations in matter with an arbitrary matter density profile. Note that we assume that the CPT invariance theorem holds, which means that the CPT violation effects arise entirely because of the presence of matter. As special cases of matter density profiles, we consider constant and step-function matter density profiles, which are relevant for neutrino oscillation physics in accelerator and reactor long baseline experiments as well as neutrino factories. Finally, the implications of extrinsic CPT violation on neutrino oscillations in matter for several past, present, and future long baseline experiments are estimated

  2. Developmental time windows for axon growth influence neuronal network topology.

    Science.gov (United States)

    Lim, Sol; Kaiser, Marcus

    2015-04-01

    Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation during early development, either starting at the same time for all neurons (parallel, i.e., maximally overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e., no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: Neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening up the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.

  3. Parametric Probability Distribution Functions for Axon Diameters of Corpus Callosum

    Directory of Open Access Journals (Sweden)

    Farshid eSepehrband

    2016-05-01

    Full Text Available Axon diameter is an important neuroanatomical characteristic of the nervous system that alters in the course of neurological disorders such as multiple sclerosis. Axon diameters vary, even within a fiber bundle, and are not normally distributed. An accurate distribution function is therefore beneficial, either to describe axon diameters that are obtained from a direct measurement technique (e.g., microscopy, or to infer them indirectly (e.g., using diffusion-weighted MRI. The gamma distribution is a common choice for this purpose (particularly for the inferential approach because it resembles the distribution profile of measured axon diameters which has been consistently shown to be non-negative and right-skewed. In this study we compared a wide range of parametric probability distribution functions against empirical data obtained from electron microscopy images. We observed that the gamma distribution fails to accurately describe the main characteristics of the axon diameter distribution, such as location and scale of the mode and the profile of distribution tails. We also found that the generalized extreme value distribution consistently fitted the measured distribution better than other distribution functions. This suggests that there may be distinct subpopulations of axons in the corpus callosum, each with their own distribution profiles. In addition, we observed that several other distributions outperformed the gamma distribution, yet had the same number of unknown parameters; these were the inverse Gaussian, log normal, log logistic and Birnbaum-Saunders distributions.

  4. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  5. Comparison of exit time moment spectra for extrinsic metric balls

    DEFF Research Database (Denmark)

    Hurtado, Ana; Markvorsen, Steen; Palmer, Vicente

    2012-01-01

    We prove explicit upper and lower bounds for the $L^1$-moment spectra for the Brownian motion exit time from extrinsic metric balls of submanifolds $P^m$ in ambient Riemannian spaces $N^n$. We assume that $P$ and $N$ both have controlled radial curvatures (mean curvature and sectional curvature...... obtain new intrinsic comparison results for the exit time spectra for metric balls in the ambient manifolds $N^n$ themselves....

  6. Are competition and extrinsic motivation reliable predictors of academic cheating?

    OpenAIRE

    Gábor eOrosz; Gábor eOrosz; Gábor eOrosz; Dávid eFarkas; Dávid eFarkas; Dávid eFarkas; Christine eRoland-Levy

    2013-01-01

    Previous studies suggest that extrinsic motivation and competition are reliable predictors of academic cheating. The aim of the present questionnaire study was to separate the effects of motivation- and competition-related variables on academic cheating by Hungarian high school students (N = 620, M = 264, F = 356). Structural equation modeling showed that intrinsic motivation has a negative effect, and amotivation has a positive indirect effect on self-reported academic cheating. In contrast,...

  7. Are Competition and Extrinsic Motivation Reliable Predictors of Academic Cheating?

    OpenAIRE

    Orosz, G?bor; Farkas, D?vid; Roland-L?vy, Christine

    2013-01-01

    Previous studies suggest that extrinsic motivation and competition are reliable predictors of academic cheating. The aim of the present questionnaire study was to separate the effects of motivation- and competition-related variables on academic cheating by Hungarian high school students (N = 620, M = 264, F = 356). Structural equation modeling showed that intrinsic motivation has a negative effect, and amotivation has a positive indirect effect on self-reported academic cheating. In contrast,...

  8. Near-UV laser treatment of extrinsic dental enamel stains.

    Science.gov (United States)

    Schoenly, J E; Seka, W; Featherstone, J D B; Rechmann, P

    2012-04-01

    The selective ablation of extrinsic dental enamel stains using a 400-nm laser is evaluated at several fluences for completely removing stains with minimal damage to the underlying enamel. A frequency-doubled Ti:sapphire laser (400-nm wavelength, 60-nanosecond pulse duration, 10-Hz repetition rate) was used to treat 10 extracted human teeth with extrinsic enamel staining. Each tooth was irradiated perpendicular to the surface in a back-and-forth motion over a 1-mm length using an ∼300-µm-diam 10th-order super-Gaussian beam with fluences ranging from 0.8 to 6.4 J/cm(2) . Laser triangulation determined stain depth and volume removed by measuring 3D surface images before and after irradiation. Scanning electron microscopy evaluated the surface roughness of enamel following stain removal. Fluorescence spectroscopy measured spectra of unbleached and photobleached stains in the spectral range of 600-800 nm. Extrinsic enamel stains are removed with laser fluences between 0.8 and 6.4 J/cm(2) . Stains removed on sound enamel leave behind a smooth enamel surface. Stain removal in areas with signs of earlier cariogenic acid attacks resulted in isolated and randomly located laser-induced, 50-µm-diam enamel pits. These pits contain 0.5-µm diam, smooth craters indicative of heat transfer from the stain to the enamel and subsequent melting and water droplet ejection. Ablation stalling of enamel stains is typically observed at low fluences (Laser ablation of extrinsic enamel stains at 400 nm is observed to be most efficient above 3 J/cm(2) with minimal damage to the underlying enamel. Unsound underlying enamel is also observed to be selectively removed after irradiation. Copyright © 2012 Wiley Periodicals, Inc.

  9. Recovery of colonic transit following extrinsic nerve damage in rats.

    Science.gov (United States)

    Ridolfi, Timothy J; Tong, Wei Dong; Kosinski, Lauren; Takahashi, Toku; Ludwig, Kirk A

    2011-06-01

    Injury to pelvic sympathetic and parasympathetic nerves from surgical and obstetrical trauma has long been cited as a cause for abnormal colorectal motility in humans. Using a rat model, acute transaction of these extrinsic nerves has been shown to effect colorectal motility. The aim of this study is to determine in a rat model how transection of these extrinsic nerves affects colonic transit over time. Eighty-two Sprague-Dawley rats underwent placement of a tunneled catheter into the proximal colon. Bilateral hypogastric, pelvic nerves (HGN and PN) or both were transected in 66 rats. The remaining 16 rats received a sham operation. Colonic transit was evaluated at postoperative days (PODs) 1, 3, and 7 by injecting and calculating the geometric center (GC) of the distribution of (51)Cr after 3 h of propagation. At POD 1, transection of PNs significantly delayed colonic transit (GC = 4.9, p < 0.05), while transection of HGNs (GC = 8.5, p < 0.05) or transection of both nerves (GC = 7.8, p < 0.05) significantly accelerated colonic transit, when compared with sham operation (GC = 6.0). A significant trend toward recovery was noted in both the HGN and PN transection groups at POD 7. Damage to the extrinsic sympathetic and/or parasympathetic PNs affects colonic transit acutely. These changes in large bowel motor function normalize over time implicating a compensatory mechanism within the bowel itself.

  10. Intrinsic and extrinsic geometries of a tidally deformed black hole

    International Nuclear Information System (INIS)

    Vega, Ian; Poisson, Eric; Massey, Ryan

    2011-01-01

    A description of the event horizon of a perturbed Schwarzschild black hole is provided in terms of the intrinsic and extrinsic geometries of the null hypersurface. This description relies on a Gauss-Codazzi theory of null hypersurfaces embedded in spacetime, which extends the standard theory of spacelike and timelike hypersurfaces involving the first and second fundamental forms. We show that the intrinsic geometry of the event horizon is invariant under a reparameterization of the null generators, and that the extrinsic geometry depends on the parameterization. Stated differently, we show that while the extrinsic geometry depends on the choice of gauge, the intrinsic geometry is gauge invariant. We apply the formalism to solutions to the vacuum field equations that describe a tidally deformed black hole. In a first instance, we consider a slowly varying, quadrupolar tidal field imposed on the black hole, and in a second instance, we examine the tide raised during a close parabolic encounter between the black hole and a small orbiting body.

  11. Aging in the Male Face: Intrinsic and Extrinsic Factors.

    Science.gov (United States)

    Keaney, Terrence C

    2016-07-01

    Gender is one of the most significant factors that influence facial anatomy and behavior, both key factors in the aging process. To review male facial anatomy, physiology, and behavior and how it contributes to sexual dimorphism in facial aging. A MEDLINE search was performed for publications on gender differences in facial anatomy, aging, cutaneous physiology, and behavior. There are differences in both intrinsic and extrinsic aging factors in men. Men have a thicker epidermis and dermis with more active cutaneous appendages including hair growth. Male skin has a reduced antioxidant capacity and increased ultraviolet-induced immunosuppression. The male face is larger and has a unique square shape with less subcutaneous soft tissue, especially at the medial cheek. Men are also more prone to smoking and exhibiting poor sun-protective behavior. The differences in intrinsic and extrinsic aging factors contribute to poor facial aging in men. Men develop more severe rhytides in a unique pattern, show increased periocular aging changes, and are more prone to hair loss. This review provides insight into the factors contributing to accelerated male facial aging. Understanding gender differences in aging will help physicians tailor cosmetic treatments for men and minimize extrinsic aging factors.

  12. Are competition and extrinsic motivation reliable predictors of academic cheating?

    Directory of Open Access Journals (Sweden)

    Gábor eOrosz

    2013-02-01

    Full Text Available Previous studies suggest that extrinsic motivation and competition are reliable predictors of academic cheating. The aim of the present questionnaire study was to separate the effects of motivation- and competition-related variables on academic cheating by Hungarian high school students (N = 620, M = 264, F = 356. Structural equation modeling showed that intrinsic motivation has a negative effect, and amotivation has a positive indirect effect on self-reported academic cheating. In contrast, extrinsic motivation had no significant effect. Indirect positive influence on cheating, based on some characteristics of hypercompetition, was also found, whereas attitudes towards self-developmental competition had a mediated negative influence. Neither constructive nor destructive competitive classroom climate had a significant impact on academic dishonesty. Acceptance of cheating and guilt has significant and direct effect on self-reported cheating. In comparison with them, the effects of motivational and competition-related variables are relatively small, even negligible. These results suggest that extrinsic motivation and competition are not amongst the most reliable predictors of academic cheating behavior.

  13. Are competition and extrinsic motivation reliable predictors of academic cheating?

    Science.gov (United States)

    Orosz, Gábor; Farkas, Dávid; Roland-Lévy, Christine

    2013-01-01

    Previous studies suggest that extrinsic motivation and competition are reliable predictors of academic cheating. The aim of the present questionnaire study was to separate the effects of motivation- and competition-related variables on academic cheating by Hungarian high school students (N = 620, M = 264, F = 356). Structural equation modeling showed that intrinsic motivation has a negative effect, and amotivation has a positive indirect effect on self-reported academic cheating. In contrast, extrinsic motivation had no significant effect. Indirect positive influence on cheating, based on some characteristics of hypercompetition, was also found, whereas attitudes toward self-developmental competition had a mediated negative influence. Neither constructive nor destructive competitive classroom climate had a significant impact on academic dishonesty. Acceptance of cheating and guilt has significant and direct effect on self-reported cheating. In comparison with them, the effects of motivational and competition-related variables are relatively small, even negligible. These results suggest that extrinsic motivation and competition are not amongst the most reliable predictors of academic cheating behavior.

  14. Effects of empathic paraphrasing - Extrinsic emotion regulation in social conflict

    Directory of Open Access Journals (Sweden)

    Maria eSeehausen

    2012-11-01

    Full Text Available In the present study, we investigated the effects of empathic paraphrasing as an extrinsic emotion regulation technique in social conflict. We hypothesized that negative emotions elicited by social conflict can be regulated extrinsically in a conversation by a listener following the narrator’s perspective and verbally expressing cognitive empathy.20 participants were interviewed on an ongoing or recently self-experienced social conflict. The interviewer utilized ten standardized open questions inviting participants to describe their perception of the conflict. After each of the ten descriptions, the interviewer responded by either paraphrasing or taking notes (control condition. Valence ratings pertaining to the current emotional state were assessed during the interview along with psychophysiological and voice recordings.Participants reported feeling less negative after hearing the interviewer paraphrase what they had said. In addition, we found a lower sound intensity of participants' voices when answering to questions following a paraphrase. At the physiological level, skin conductance response, as well as heart rate, was higher during paraphrasing than during taking notes, while blood volume pulse amplitude was lower during paraphrasing, indicating higher autonomic arousal.The results show that demonstrating cognitive empathy through paraphrasing can extrinsically regulate negative emotion on a short-term basis. Paraphrasing led to enhanced autonomic activation in recipients, while at the same time influencing emotional valence in the direction of feeling better. A possible explanation for these results is that being treated in an empathic manner may stimulate a more intense emotion processing helping to transform and resolve the conflict.

  15. Stochastic synchronization of neuronal populations with intrinsic and extrinsic noise.

    KAUST Repository

    Bressloff, Paul C

    2011-05-03

    We extend the theory of noise-induced phase synchronization to the case of a neural master equation describing the stochastic dynamics of an ensemble of uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The master equation formulation of stochastic neurodynamics represents the state of each population by the number of currently active neurons, and the state transitions are chosen so that deterministic Wilson-Cowan rate equations are recovered in the mean-field limit. We apply phase reduction and averaging methods to a corresponding Langevin approximation of the master equation in order to determine how intrinsic noise disrupts synchronization of the population oscillators driven by a common extrinsic noise source. We illustrate our analysis by considering one of the simplest networks known to generate limit cycle oscillations at the population level, namely, a pair of mutually coupled excitatory (E) and inhibitory (I) subpopulations. We show how the combination of intrinsic independent noise and extrinsic common noise can lead to clustering of the population oscillators due to the multiplicative nature of both noise sources under the Langevin approximation. Finally, we show how a similar analysis can be carried out for another simple population model that exhibits limit cycle oscillations in the deterministic limit, namely, a recurrent excitatory network with synaptic depression; inclusion of synaptic depression into the neural master equation now generates a stochastic hybrid system.

  16. The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans.

    Science.gov (United States)

    Florica, Roxana Oriana; Hipolito, Victoria; Bautista, Stephen; Anvari, Homa; Rapp, Chloe; El-Rass, Suzan; Asgharian, Alimohammad; Antonescu, Costin N; Killeen, Marie T

    2017-10-01

    The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5. A mutation in the gene for the MIG-14/Wntless protein also enhances defects in a strain lacking either UNC-5 or UNC-6, suggesting that the ENU-3 and Wnt pathways function parallel to the Netrin pathway in directing motor neuron axon outgrowth. Our evidence suggests that the ENU-3 proteins are novel members of the Wnt pathway in nematodes. Five of the six members of the ENU-3 family are predicted to be single-pass trans-membrane proteins. The expression pattern of ENU-3.1 was consistent with plasma membrane localization. One family member, ENU-3.6, lacks the predicted signal peptide and the membrane-spanning domain. In HeLa cells ENU-3.6 had a cytoplasmic localization and caused actin dependent processes to appear. We conclude that the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Axonal Conduction Delays, Brain State, and Corticogeniculate Communication.

    Science.gov (United States)

    Stoelzel, Carl R; Bereshpolova, Yulia; Alonso, Jose-Manuel; Swadlow, Harvey A

    2017-06-28

    Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40-50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40-50 ms. Here, in the corticogeniculate

  18. In vivo testing of a 3D bifurcating microchannel scaffold inducing separation of regenerating axon bundles in peripheral nerves

    Science.gov (United States)

    Stoyanova, Irina I.; van Wezel, Richard J. A.; Rutten, Wim L. C.

    2013-12-01

    Artificial nerve guidance channels enhance the regenerative effectiveness in an injured peripheral nerve but the existing design so far has been limited to basic straight tubes simply guiding the growth to bridge the gap. Hence, one of the goals in development of more effective neuroprostheses is to create bidirectional highly selective neuro-electronic interface between a prosthetic device and the severed nerve. A step towards improving selectivity for both recording and stimulation have been made with some recent in vitro studies which showed that three-dimensional (3D) bifurcating microchannels can separate neurites growing on a planar surface and bring them into contact with individual electrodes. Since the growing axons in vivo have the innate tendency to group in bundles surrounded by connective tissue, one of the big challenges in neuro-prosthetic interface design is how to overcome it. Therefore, we performed experiments with 3D bifurcating guidance scaffolds implanted in the sciatic nerve of rats to test if this new channel architecture could trigger separation pattern of ingrowth also in vivo. Our results showed that this new method enabled the re-growth of neurites into channels with gradually diminished width (80, 40 and 20 µm) and facilitated the separation of the axonal bundles with 91% success. It seems that the 3D bifurcating scaffold might contribute towards conveying detailed neural control and sensory feedback to users of prosthetic devices, and thus could improve the quality of their daily life.

  19. Does Extrinsic Goal Framing Enhance Extrinsic Goal-Oriented Individuals' Learning and Performance? An Experimental Test of the Match Perspective versus Self-Determination Theory

    Science.gov (United States)

    Vansteenkiste, Maarten; Timmermans, Tinneke; Lens, Willy; Soenens, Bart; Van den Broeck, Anja

    2008-01-01

    Previous work within self-determination theory has shown that experimentally framing a learning activity in terms of extrinsic rather than intrinsic goals results in poorer conceptual learning and performance, presumably because extrinsic goal framing detracts attention from the learning activity and is less directly satisfying of basic…

  20. Modelling in vivo action potential propagation along a giant axon.

    Science.gov (United States)

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  1. Threshold guidance update

    International Nuclear Information System (INIS)

    Wickham, L.E.

    1986-01-01

    The Department of Energy (DOE) is developing the concept of threshold quantities for use in determining which waste materials must be handled as radioactive waste and which may be disposed of as nonradioactive waste at its sites. Waste above this concentration level would be managed as radioactive or mixed waste (if hazardous chemicals are present); waste below this level would be handled as sanitary waste. Last years' activities (1984) included the development of a threshold guidance dose, the development of threshold concentrations corresponding to the guidance dose, the development of supporting documentation, review by a technical peer review committee, and review by the DOE community. As a result of the comments, areas have been identified for more extensive analysis, including an alternative basis for selection of the guidance dose and the development of quality assurance guidelines. Development of quality assurance guidelines will provide a reasonable basis for determining that a given waste stream qualifies as a threshold waste stream and can then be the basis for a more extensive cost-benefit analysis. The threshold guidance and supporting documentation will be revised, based on the comments received. The revised documents will be provided to DOE by early November. DOE-HQ has indicated that the revised documents will be available for review by DOE field offices and their contractors

  2. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

  3. PIV Logon Configuration Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Glen Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-03-04

    This document details the configurations and enhancements implemented to support the usage of federal Personal Identity Verification (PIV) Card for logon on unclassified networks. The guidance is a reference implementation of the configurations and enhancements deployed at the Los Alamos National Laboratory (LANL) by Network and Infrastructure Engineering – Core Services (NIE-CS).

  4. Electrically conductive biodegradable polymer composite for nerve regeneration: electricity-stimulated neurite outgrowth and axon regeneration.

    Science.gov (United States)

    Zhang, Ze; Rouabhia, Mahmoud; Wang, Zhaoxu; Roberge, Christophe; Shi, Guixin; Roche, Phillippe; Li, Jiangming; Dao, Lê H

    2007-01-01

    Normal and electrically stimulated PC12 cell cultures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane sulfonic acid showed a significantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy-coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7-8.4 microA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myelinated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats.

  5. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  6. Mechanistic logic underlying the axonal transport of cytosolic proteins

    Science.gov (United States)

    Scott, David A.; Das, Utpal; Tang, Yong; Roy, Subhojit

    2011-01-01

    Proteins vital to presynaptic function are synthesized in the neuronal perikarya and delivered into synapses via two modes of axonal transport. While membrane-anchoring proteins are conveyed in fast axonal transport via motor-driven vesicles, cytosolic proteins travel in slow axonal transport; via mechanisms that are poorly understood. We found that in cultured axons, populations of cytosolic proteins tagged to photoactivable-GFP (PA-GFP) move with a slow motor-dependent anterograde bias; distinct from vesicular-trafficking or diffusion of untagged PA-GFP. The overall bias is likely generated by an intricate particle-kinetics involving transient assembly and short-range vectorial spurts. In-vivo biochemical studies reveal that cytosolic proteins are organized into higher-order structures within axon-enriched fractions that are largely segregated from vesicles. Data-driven biophysical modeling best predicts a scenario where soluble molecules dynamically assemble into mobile supra-molecular structures. We propose a model where cytosolic proteins are transported by dynamically assembling into multi-protein complexes that are directly/indirectly conveyed by motors. PMID:21555071

  7. Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth

    Directory of Open Access Journals (Sweden)

    Hai Li

    2016-07-01

    Full Text Available Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT and geranylgeranyl transferase I (PGGT-1. Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS. Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans.

  8. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    Science.gov (United States)

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  9. Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury

    Directory of Open Access Journals (Sweden)

    János Sándor

    2009-12-01

    Full Text Available Calcium-induced, calpain-mediated proteolysis (CMSP has recently been implicated to the pathogenesis of diffuse (traumatic axonal injury (TAI. Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

  10. Subtypes of GABAergic neurons project axons in the neocortex

    Directory of Open Access Journals (Sweden)

    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  11. Characterization of patients with head trauma and traumatic axonal injury

    International Nuclear Information System (INIS)

    Mosquera Betancourt, Dra.C. Gretel; Van Duc, Dr. Hanh; Casares Delgado, Dr. Jorge Alejandro; Hernández González, Dr. Erick Héctor

    2016-01-01

    Background: traumatic axonal injury is characterized by multifocal lesions, consequences of primary, secondary and tertiary damage which is able to cause varying degrees of disability. Objective: to characterize patients with traumatic axonal injury. Methods: a cross-sectional analytical study was conducted from January 2014 to December 2015. The target population was composed of 35 patients over age 18 whose diagnosis was traumatic axonal injury type I and IV of the Marshall computed tomographic (CT) classification. With the data collected from medical records revisions and direct observation, a database was created in SPSS for its processing through univariate and multivariate techniques. Results: male patients between 18 and 30 years old without bad habits prevailed. Most of the patients survived and death was associated with the presence of severe traumatic axonal injury, Marshall computed tomographic (CT) classification degree III, complications and presence of trauma in thorax, abdomen and cervical spine. Conclusions: diagnosis of traumatic axonal injury is based on the clinical radiological correlation based on images from tomography and it is confirmed by Magnetic resonance imaging (MRI). Histological study shows injuries that are not demonstrated in the most advanced radiological studies. Its prevention is the most fundamental base in medical assistance, followed by neurocritical attention oriented by neuromonitoring. (author)

  12. Functional complexity of the axonal growth cone: a proteomic analysis.

    Directory of Open Access Journals (Sweden)

    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  13. Navigating neurites utilize cellular topography of Schwann cell somas and processes for optimal guidance

    Science.gov (United States)

    Lopez-Fagundo, Cristina; Mitchel, Jennifer A.; Ramchal, Talisha D.; Dingle, Yu-Ting L.; Hoffman-Kim, Diane

    2013-01-01

    The path created by aligned Schwann cells (SCs) after nerve injury underlies peripheral nerve regeneration. We developed geometric bioinspired substrates to extract key information needed for axon guidance by deconstructing the topographical cues presented by SCs. We have previously reported materials that directly replicate SC topography with micro- and nanoscale resolution, but a detailed explanation of the means of directed axon extension on SC topography has not yet been described. Here, using neurite tracing and time-lapse microscopy, we analyzed the SC features that influence axon guidance. Novel poly(dimethylsiloxane) materials, fabricated via photolithography, incorporated bioinspired topographical components with the shapes and sizes of aligned SCs, namely somas and processes, where the length of the processes were varied but the soma geometry and dimensions were kept constant. Rat dorsal root ganglia neurites aligned to all materials presenting bioinspired topography after a 5 days in culture and to bioinspired materials presenting soma and process features after only 17 hours in culture. Key findings of this study were: Neurite response to underlying bioinspired topographical features was time dependent, where at 5 days, neurites aligned most strongly to materials presenting combinations of soma and process features, with higher than average density of either process or soma features; but at 17 hours they aligned more strongly to materials presenting average densities of soma and process features and to materials presenting process features only. These studies elucidate the influence of SC topography on axon guidance in a time-dependent setting and have implications for the optimization of nerve regeneration strategies. PMID:23557939

  14. Axonal transport and axon sprouting in the adult rat dentate gyrus: an autoradiographic study

    International Nuclear Information System (INIS)

    Goldowitz, D.; Cotman, C.W.

    1980-01-01

    In response to an entorhinal lesion, the commissural and associational afferents to the dentate gyrus have been shown to expand beyond their normal terminal zone into the area denervated by the entorhinal lesion. The present study has investigated the axonal transport of [ 3 H]-labeled proteins in the commissural and associational projections following an entorhinal lesion. Injections of [ 3 H]proline, [ 3 H]leucine or [ 3 H)fucose were given in the vicinity of the commissural and associational cells of origin before, immediately subsequent to, or at 5 to 15 days after the entorhinal lesion. The disposition of previously- or newly-synthesized proteins was examined in the commissural and associational terminal field at different times after an entorhinal lesion by light-microscopic autoradiography. (author)

  15. Axonal transport and axon sprouting in the adult rat dentate gyrus: an autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Goldowitz, D; Cotman, C W [California Univ., Irvine (USA)

    1980-12-01

    In response to an entorhinal lesion, the commissural and associational afferents to the dentate gyrus have been shown to expand beyond their normal terminal zone into the area denervated by the entorhinal lesion. The present study has investigated the axonal transport of (/sup 3/H)-labeled proteins in the commissural and associational projections following an entorhinal lesion. Injections of (/sup 3/H)proline, (/sup 3/H)leucine or (/sup 3/H)fucose were given in the vicinity of the commissural and associational cells of origin before, immediately subsequent to, or at 5 to 15 days after the entorhinal lesion. The disposition of previously- or newly-synthesized proteins was examined in the commissural and associational terminal field at different times after an entorhinal lesion by light-microscopic autoradiography.

  16. Localization of mRNA in vertebrate axonal compartments by in situ hybridization.

    Science.gov (United States)

    Sotelo-Silveira, José Roberto; Calliari, Aldo; Kun, Alejandra; Elizondo, Victoria; Canclini, Lucía; Sotelo, José Roberto

    2011-01-01

    The conclusive demonstration of RNA in vertebrate axons by in situ hybridization (ISH) has been elusive. We review the most important reasons for difficulties, including low concentration of axonal RNAs, localization in specific cortical domains, and the need to isolate axons. We demonstrate the importance of axon micro-dissection to obtain a whole mount perspective of mRNA distribution in the axonal territory. We describe a protocol to perform fluorescent ISH in isolated axons and guidelines for the preservation of structural and molecular integrity of cortical RNA-containing domains (e.g., Periaxoplasmic Ribosomal Plaques, or PARPs) in isolated axoplasm.

  17. The influence of extrinsic motivation on competition-based selection.

    Science.gov (United States)

    Sänger, Jessica; Wascher, Edmund

    2011-10-10

    The biased competition approach to visuo-spatial attention proposes that the selection of competing information is effected by the saliency of the stimulus as well as by an intention-based bias of attention towards behavioural goals. Wascher and Beste (2010) [32] showed that the detection of relevant information depends on its relative saliency compared to irrelevant conflicting stimuli. Furthermore the N1pc, N2pc and N2 of the EEG varied with the strength of the conflict. However, this system could also be modulated by rather global mechanisms like attentional effort. The present study investigates such modulations by testing the influence of extrinsic motivation on the selection of competing stimuli. Participants had to detect a luminance change in various conditions among others against an irrelevant orientation change. Half of the participants were motivated to maximize their performance by the announcement of a monetary reward for correct responses. Participants who were motivated had lower error rates than participants who were not motivated. The event-related lateralizations of the EEG showed no motivation-related effect on the N1pc, which reflects the initial saliency driven orientation of attention towards the more salient stimulus. The subsequent N2pc was enhanced in the motivation condition. Extrinsic motivation was also accompanied by enhanced fronto-central negativities. Thus, the data provide evidence that the improvement of selection performance when participants were extrinsically motivated by announcing a reward was not due to changes in the initial saliency based processing of information but was foremost mediated by improved higher-level mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Theory of extrinsic and intrinsic heterojunctions in thermal equilibrium

    Science.gov (United States)

    Von Ross, O.

    1980-01-01

    A careful analysis of an abrupt heterojunction consisting of two distinct semiconductors either intrinsic or extrinsic is presented. The calculations apply to a one-dimensional, nondegenerate structure. Taking into account all appropriate boundary conditions, it is shown that the intrinsic Fermi level shows a discontinuity at the interface between the two materials which leads to a discontinuity of the valence band edge equal to the difference in the band gap energies of the two materials. The conduction band edge stays continuous however. This result is independent of possible charged interface states and in sharp contrast to the Anderson model. The reasons for this discrepancy are discussed.

  19. Rigid particle revisited: Extrinsic curvature yields the Dirac equation

    Energy Technology Data Exchange (ETDEWEB)

    Deriglazov, Alexei, E-mail: alexei.deriglazov@ufjf.edu.br [Depto. de Matemática, ICE, Universidade Federal de Juiz de Fora, MG (Brazil); Laboratory of Mathematical Physics, Tomsk Polytechnic University, 634050 Tomsk, Lenin Ave. 30 (Russian Federation); Nersessian, Armen, E-mail: arnerses@ysu.am [Yerevan State University, 1 Alex Manoogian St., Yerevan 0025 (Armenia); Laboratory of Mathematical Physics, Tomsk Polytechnic University, 634050 Tomsk, Lenin Ave. 30 (Russian Federation)

    2014-03-01

    We reexamine the model of relativistic particle with higher-derivative linear term on the first extrinsic curvature (rigidity). The passage from classical to quantum theory requires a number of rather unexpected steps which we report here. We found that, contrary to common opinion, quantization of the model in terms of so(3.2)-algebra yields massive Dirac equation. -- Highlights: •New way of canonical quantization of relativistic rigid particle is proposed. •Quantization made in terms of so(3.2) angular momentum algebra. •Quantization yields massive Dirac equation.

  20. The effect of extrinsic motivation on cycle time trial performance.

    Science.gov (United States)

    Hulleman, Michiel; De Koning, Jos J; Hettinga, Florentina J; Foster, Carl

    2007-04-01

    Athletes occasionally follow pacing patterns that seem unreasonably aggressive compared with those of prerace performances, potentially because of the motivation provided by competition. This study evaluated the effect of extrinsic motivation on cyclists' time trial performance. Well-trained recreational cyclists (N=7) completed four 1500-m laboratory time trials including a practice trial, two self-paced trials, and a trial where a monetary reward was offered. Time, total power output, power output attributable to aerobic and anaerobic metabolic sources, VO2, and HR were measured. The time required for the second, third, and last (extrinsically motivated) time trials was 133.1 +/- 2.1, 134.1 +/- 3.4, and 133.6 +/- 3.0 s, respectively, and was not different (P>0.05). There were no differences for total (396 +/- 19, 397 +/- 23, and 401 +/- 17 W), aerobic (253 +/- 12, 254 +/- 10, and 246 +/- 13 W), and anaerobic (143 +/- 14, 143 +/- 21, and 155 +/- 11 W) power output. The highest VO2 was not different over consecutive time trials (3.76 +/- 0.19, 3.73 +/- 0.16, and 3.71 +/- 0.22 L x min(-1)). When ranked by performance, without reference to the extrinsic motivation (131.9 +/- 2.4, 133.4 +/- 2.4, and 135.4 +/- 2.5 s), there was a significant difference for the first 100 m and from 100 to 300 m in power output, with a larger total power (560 +/- 102, 491 +/- 82, and 493 +/- 93; and 571 +/- 94, 513 +/- 41, and 484 +/- 88 W) and power attributable to anaerobic sources (446 +/- 100, 384 +/- 80, and 324 +/- 43; and 381 +/- 87, 383 +/- 90, and 289 +/- 91 W) for the fastest trial. Extrinsic motivation did not change the time trial performance, suggesting that 1500-m performance is extremely stable and not readily changeable with simple external motivation. The results suggest that spontaneous improvement in performance for time trials of this duration is attributable to greater early power output, which is primarily attributable to anaerobic metabolic sources.

  1. Older adults' intrinsic and extrinsic motivation toward physical activity.

    Science.gov (United States)

    Dacey, Marie; Baltzell, Amy; Zaichkowsky, Len

    2008-01-01

    To examine how motives discriminate 3 physical activity levels of inactive, active, and sustained maintainers. Six hundred forty-five adults (M age = 63.8) completed stage-of-change and Exercise Motivations Inventory (EMI-2) scales. Exploratory factor analysis established psychometric properties of the EMI-2 suitable for older adults. Six factors emerged in the EMI-2: health and fitness, social/emotional benefits, weight management, stress management, enjoyment, and appearance. Enjoyment contributed most to differentiating activity levels. Moderators of age and gender were delineated. Intrinsic motivation and self-determined extrinsic motivation distinguish older adults' activity levels.

  2. Intrinsic and extrinsic magnetic properties of the naturally layered manganites

    International Nuclear Information System (INIS)

    Berger, A.; Mitchell, J. F.; Miller, D. J.; Jiang, J. S.; Bader, S. D.

    1999-01-01

    Structural and magnetic properties of the two-layered Ruddlesden-Popper phase SrO(La 1-x Sr x MnO 3 ) 2 with x = 0.3--0.5 are highlighted. Intrinsic properties of these naturally layered manganites include a colossal magnetoresistance, a composition-dependent magnetic anisotropy, and almost no remanence. Above the Curie temperature there is a non-vanishing extrinsic magnetization attributed to intergrowths (stacking faults in the layered structure). These lattice imperfections consist of additional or missing manganite layers, as observed in transmission electron microscopy. Their role in influencing the properties of the host material is highlighted

  3. Extrinsic rewards undermine altruistic tendencies in 20-month-olds.

    Science.gov (United States)

    Warneken, Felix; Tomasello, Michael

    2008-11-01

    The current study investigated the influence of rewards on very young children's helping behavior. After 20-month-old infants received a material reward during a treatment phase, they subsequently were less likely to engage in further helping during a test phase as compared with infants who had previously received social praise or no reward at all. This so-called overjustification effect suggests that even the earliest helping behaviors of young children are intrinsically motivated and that socialization practices involving extrinsic rewards can undermine this tendency.

  4. Restorative Management of Intrinsic and Extrinsic Dental Erosion.

    Science.gov (United States)

    Al-Salehi, Samira Kathryn

    2014-12-01

    The restorative management of tooth surface loss is highlighted through the presentation of two advanced cases of dental erosion. On presentation, the causes of the dental erosion in both patients had been previously diagnosed and stopped. The first patient was a 67 year old with intrinsic erosion and an element of attrition where a multidisciplinary approach was used. The other, a 17 year old patient with extrinsic erosion managed via adhesive restorations. Adhesive techniques are a relatively simple, effective and conservative method for the treatment of dental erosion. The two treatment modalities (conventional versus contemporary) are compared and discussed.

  5. Extrinsic wrist ligaments: prevalence of injury by magnetic resonance imaging and association with intrinsic ligament tears.

    Science.gov (United States)

    Taneja, Atul K; Bredella, Miriam A; Chang, Connie Y; Joseph Simeone, F; Kattapuram, Susan V; Torriani, Martin

    2013-01-01

    The objective of this study was to determine the prevalence of extrinsic wrist ligament injury by magnetic resonance imaging and its association with intrinsic ligament tears. We reviewed conventional magnetic resonance images performed over a 5-year period from adult patients in the setting of wrist trauma. Two musculoskeletal radiologists examined the integrity of wrist ligaments and presence of bone abnormalities. In a cohort of 75 subjects, extrinsic ligament injury was present in 75%, with radiolunotriquetral being most frequently affected (45%). Intrinsic ligament injury was present in 60%. Almost half of subjects had combined intrinsic and extrinsic ligament injury. Bone abnormalities were seen in 69%. The rate of extrinsic injury was higher in subjects with bone injury (P = 0.008). There is high prevalence of extrinsic ligament injury in the setting of wrist trauma, especially in the presence of bone abnormalities, with combined injury of intrinsic and extrinsic ligaments in about half of cases.

  6. Perilesional edema in radiation necrosis reflects axonal degeneration

    International Nuclear Information System (INIS)

    Perez-Torres, Carlos J; Yuan, Liya; Schmidt, Robert E; Rich, Keith M; Ackerman, Joseph JH; Garbow, Joel R

    2015-01-01

    Recently, we characterized a Gamma Knife® radiation necrosis mouse model with various magnetic resonance imaging (MRI) protocols to identify biomarkers useful in differentiation from tumors. Though the irradiation was focal to one hemisphere, a contralateral injury was observed that appeared to be localized in the white matter only. Interestingly, this injury was identifiable in T2-weighted images, apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) maps, but not on post-contrast T1-weighted images. This observation of edema independent of vascular changes is akin to the perilesional edema seen in clinical radiation necrosis. The pathology underlying the observed white-matter MRI changes was explored by performing immunohistochemistry for healthy axons and myelin. The presence of both healthy axons and myelin was reduced in the contralateral white-matter lesion. Based on our immunohistochemical findings, the contralateral white-matter injury is most likely due to axonal degeneration

  7. The nano-architecture of the axonal cytoskeleton.

    Science.gov (United States)

    Leterrier, Christophe; Dubey, Pankaj; Roy, Subhojit

    2017-12-01

    The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton.

  8. Growing axons analysis by using Granulometric Size Distribution

    International Nuclear Information System (INIS)

    Gonzalez, Mariela A; Ballarin, Virginia L; Rapacioli, Melina; CelIn, A R; Sanchez, V; Flores, V

    2011-01-01

    Neurite growth (neuritogenesis) in vitro is a common methodology in the field of developmental neurobiology. Morphological analyses of growing neurites are usually difficult because their thinness and low contrast usually prevent to observe clearly their shape, number, length and spatial orientation. This paper presents the use of the granulometric size distribution in order to automatically obtain information about the shape, size and spatial orientation of growing axons in tissue cultures. The results here presented show that the granulometric size distribution results in a very useful morphological tool since it allows the automatic detection of growing axons and the precise characterization of a relevant parameter indicative of the axonal growth spatial orientation such as the quantification of the angle of deviation of the growing direction. The developed algorithms automatically quantify this orientation by facilitating the analysis of these images, which is important given the large number of images that need to be processed for this type of study.

  9. The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

    Science.gov (United States)

    Godzik, Katharina; Coleman, Michael P

    2015-04-01

    The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

  10. Environmental guidance regulatory bulletin

    International Nuclear Information System (INIS)

    1997-01-01

    This document describes the background on expanding public participation in the Resource Conservation and Recovery Act and DOE's response. The bulletin also describes the changes made by the final rule to existing regulations, guidance provided by EPA in the preamble and in the revised RCRA Public Participation Manual, the relationship between public participation and environmental justice, and DOE's recent public participation and environmental justice initiatives

  11. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Jia-Ying Sung

    Full Text Available This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr. Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05, shortened strength-duration time constant (P<0.01, increased superexcitability (P<0.01, decreased subexcitability (P<0.05, decreased accommodation to depolarizing current (P<0.01, and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8 and G2+3 (TNSr 9-24 groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01 in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  12. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

    Directory of Open Access Journals (Sweden)

    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  13. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    International Nuclear Information System (INIS)

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-01-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  14. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  15. Text Summarization Evaluation: Correlating Human Performance on an Extrinsic Task with Automatic Intrinsic Metrics

    National Research Council Canada - National Science Library

    President, Stacy F; Dorr, Bonnie J

    2006-01-01

    This research describes two types of summarization evaluation methods, intrinsic and extrinsic, and concentrates on determining the level of correlation between automatic intrinsic methods and human...

  16. Examining extrinsic factors that influence product acceptance: a review.

    Science.gov (United States)

    Li, X E; Jervis, S M; Drake, M A

    2015-05-01

    Drivers of liking (DOL) studies are useful for product development to formulate acceptable products; however, DOL alone are insufficient for understanding why a product is purchased and repurchased, which is ultimately the indication of a successful product. Ultimately sensory attributes drive product success (that is, repeat and continued purchase). However, ignoring the importance of extrinsic factors may neglect the vital product attributes responsible for the initial purchase, which may in turn, affect repeat purchase. The perception of sensory attributes assessed by DOL is mitigated by external perceptions of quality. If the sensory attributes do not deliver based upon the quality cues, the product will not be acceptable. Four key extrinsic factors that affect DOL are the perceived satiety, brand and labeling, price, and the emotional impact to decision making. In order to more thoroughly understand what the DOL for a product is, these 4 product cues should be considered in conjunction with sensory attribute perception to gain a holistic understanding of product acceptance. © 2015 Institute of Food Technologists®

  17. Intrinsic and Extrinsic Science: A Dialectic of Scientific Fame.

    Science.gov (United States)

    Feist, Gregory J

    2016-11-01

    In this article, I argue that scientific fame and impact exists on a continuum from the mundane to the transformative/revolutionary. Ideally, one achieves fame and impact in science by synthesizing two extreme career prototypes: intrinsic and extrinsic research. The former is guided by interest, curiosity, passion, gut, and intuition for important untapped topics. The latter is guided by money, grants, and/or what is being published in top-tier journals. Assessment of fame and impact in science ultimately rests on productivity (publication) and some variation of its impact (citations). In addition to those traditional measures of impact, there are some relatively new metrics (e.g., the h index and altmetrics). If psychology is to achieve consensual cumulative progress and better rates of replication, I propose that upcoming psychologists would do well to understand that success is not equal to fame and that individual career success is not necessarily the same as disciplinary success. Finally, if one is to have a successful and perhaps even famous career in psychological science, a good strategy would be to synthesize intrinsic and extrinsic motives for one's research. © The Author(s) 2016.

  18. The effect of extrinsic attributes on liking of cottage cheese.

    Science.gov (United States)

    Hubbard, E M; Jervis, S M; Drake, M A

    2016-01-01

    Preference mapping studies with cottage cheese have demonstrated that cottage cheese liking is influenced by flavor, texture, curd size, and dressing content. However, extrinsic factors such as package, label claims, and brand name may also influence liking and have not been studied. The objective of this study was to evaluate the role of package attributes and brand on the liking of cottage cheese. A conjoint survey with Kano analysis (n=460) was conducted to explore the effect of extrinsic attributes (brand, label claim, milkfat content, and price) on liking. Following the survey, 150 consumers evaluated intrinsic attributes of 7 cottage cheeses with and without brand information in a 2-d crossover design. Results were evaluated by 2-way ANOVA and multivariate analyses. Milkfat content and price had the highest influence on liking by conjoint analysis. Cottage cheese with 2% milkfat and a low price was preferred. Specific label claims such as "excellent source of calcium (>10%)" were more attractive to consumers than "low sodium" or "extra creamy." Branding influenced overall liking and purchase intent for cottage cheeses to differing degrees. For national brands, acceptance scores were enhanced in the presence of the brand. An all-natural claim was more appealing than organic by conjoint analysis and this result was also confirmed with consumer acceptance testing. Findings from this study can help manufacturers, as well as food marketers, better target their products and brands with attributes that drive consumer choice. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Extrinsic labelling of zinc and calcium in bread

    International Nuclear Information System (INIS)

    Fredlund, Kerstin; Rossander-Hulthen, Lena; Isaksson, Mats; Almgren, Annette; Sandberg, A.-S.

    2002-01-01

    This study investigated the effect of different means of extrinsic administration of 65 Zn and 47 Ca in white wheat flour bread on the measured absorption. Eight healthy subjects were served 80 g of labelled bread as a standardized breakfast after an overnight fast on three occasions. Extrinsic labelling of the meals with 65 Zn and 47 Ca was done in three ways: (a) by adding the isotopes to the bread 16 h before it was served, (b) by adding the isotopes shortly before serving or (c) by adding the isotopes to the water used in dough making. Zinc and calcium chloride corresponding to 3.2 mg (49 μmol) zinc and 275 mg (6.9 mmol) calcium in one portion were added to the dough. Whole-body retention was measured by whole-body counting. The fractional absorption of zinc was (a) 0.243±0.122, (b) 0.217±0.101 and (c) 0.178±0.063 (mean±SD), and the fractional absorption of calcium (expressed as calcium retention on day 7) was (a) 0.351±0.108, (b) 0.357±0.131 and (c) 0.334±0.117 (mean±SD). No significant difference (p>0.05) was seen between the different ways for either zinc nor calcium

  20. Intrinsic and extrinsic influences on children's acceptance of new foods.

    Science.gov (United States)

    Blissett, Jackie; Fogel, Anna

    2013-09-10

    The foods that tend to be rejected by children include those which may have greatest importance for later health. This paper reviews some of the intrinsic and extrinsic influences on preschool children's eating behavior, with particular reference to their acceptance of new foods into their diet. Factors conceptualized as intrinsic to the child in this review include sensory processing, taste perception, neophobia, and temperament. The important extrinsic determinants of children's food acceptance which are reviewed include parental and peer modeling, the family food environment, infant feeding practices including breastfeeding and age at weaning, concurrent feeding practices including restriction, pressure to eat, prompting and reward, and the taste & energy content of foods. Children's willingness to accept new foods is influenced by a wide range of factors that likely have individual and also interactive effects on children's willingness to taste, and then continue to eat, new foods. The literature lacks longitudinal and experimental studies, which will be particularly important in determining interventions most likely to be effective in facilitating children's acceptance of healthy foods. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Extrinsic stretching narrowing and anterior indentation of the rectosigmoid junction

    International Nuclear Information System (INIS)

    Schulman, A.; Fataar, S.

    1979-01-01

    Thirty-five cases of extrinsic narrowing or anterior indentation of the rectosigmoid junction (RSJ) have been studied. The RSJ lies directly behind the pouch of Douglas which is a favoured site for peritoneal metastasis, abscess and endometriosis. Any space-occupying lesion of sufficient size at this site will indent the anterior aspects of the RSJ. Causes include distension or tumour of the ileum or sigmoid colon, gross ascites (when the patient is erect), and tumours below the pelvic peritonium, such as gynaecological neoplasm and internal iliac artery aneurysm. When a desmoplastic metastasis in the pouch of Douglas infiltrates the outer layers of the RSJ, the fibrosis produces an eccentric shortening on its anterior aspect, which in turn causes a pleating of the mucosa with the folds radiating towards the shortened area. This is also seen with primary pelvic carcinomas directly adherent to the rectum, endometriosis with repeated bleeding and increasing eccentric, submucosal fibrosis, and chronic abscess in the pouch of Douglas. Not all extrinsic narrowing of the RSJ are pathological. One case of anterior indentation followed operation for rectal prolapse. Ten additional cases showed narrowing due to a technical artefact air-distended colon rising into the upper abdomen to cause stretching at the RSJ. As with ascites, this narrowing due to 'high-rise sigmoid' disappeared when the patients became recumbent and the colonic air redistributed. (author)

  2. Prevalence and Extrinsic Risk Factors for Dental Erosion in Adolescents.

    Science.gov (United States)

    Mafla, Ana C; Cerón-Bastidas, Ximena A; Munoz-Ceballos, Maria E; Vallejo-Bravo, Diana C; Fajardo-Santacruz, Maria C

    This manuscript examined the prevalence and extrinsic risk factors for dental erosion (DE) in early and middle adolescents in Pasto, Colombia. Dental erosion was evaluated in a random sample of 384 individuals aged 10-15 years attending three primary and high schools in this cross-sectional study. Clinical dental assessment for DE was done using O'Sullivan index. Data on general sociodemographic variables and extrinsic risks factors were obtained. Descriptive and univariate binary logistic regression analyses were performed. Dental erosion was observed in 57.3% of individuals. The univariate binary logistic regression analysis showed that frequency of drinking natural fruit juices (OR 2.670, 95% CI 1.346 - 5.295, P=0.004) and their pH (OR 2.303, 95% CI 1.292 - 4.107, P=0.004) were more associated with the odd of DE in early adolescence. However, a high SES (OR 10.360, 95% CI 3.700 - 29.010, P<0.001) and frequency of snacks with artificial lemon taste (OR 3.659, 95% CI 1.506 - 8.891, P=0.003) were highly associated with the risk of DE in middle adolescence. The results suggest that DE is a prevalent condition in adolescents living in a city in southern Colombia. The transition from early to middle adolescence implies new bio-psychosocial changes, which increase the risk for DE.

  3. Trends in the design of nerve guidance channels in peripheral nerve tissue engineering.

    Science.gov (United States)

    Chiono, Valeria; Tonda-Turo, Chiara

    2015-08-01

    The current trend of peripheral nerve tissue engineering is the design of advanced nerve guidance channels (NGCs) acting as physical guidance for regeneration of nerves across lesions. NGCs should present multifunctional properties aiming to direct the sprouting of axons from the proximal nerve end, to concentrate growth factors secreted by the injured nerve ends, and to reduce the ingrowth of scar tissue into the injury site. A critical aspect in the design of NGCs is conferring them the ability to provide topographic, chemotactic and haptotactic cues that lead to functional nerve regeneration thus increasing the axon growth rate and avoiding or minimizing end-organ (e.g. muscle) atrophy. The present work reviews the recent state of the art in NGCs engineering and defines the external guide and internal fillers structural and compositional requirements that should be satisfied to improve nerve regeneration, especially in the case of large gaps (>2 cm). Techniques for NGCs fabrication were described highlighting the innovative approaches direct to enhance the regeneration of axon stumps compared to current clinical treatments. Furthermore, the possibility to apply stem cells as internal cues to the NGCs was discussed focusing on scaffold properties necessary to ensure cell survival. Finally, the optimized features for NGCs design were summarized showing as multifunctional cues are needed to produce NGCs having improved results in clinics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Studies of axon-glial cell interactions and periaxonal K+ homeostasis--II. The effect of axonal stimulation, cholinergic agents and transport inhibitors on the resistance in series with the axon membrane.

    Science.gov (United States)

    Hassan, S; Lieberman, E M

    1988-06-01

    The small electrical resistance in series with the axon membrane is generally modeled as the intercellular pathway for current flow through the periaxonal glial (Schwann cell) sheath. The series resistance of the medial giant axon of the crayfish, Procambarus clarkii, was found to vary with conditions known to affect the electrical properties of the periaxonal glia. Series resistance was estimated from computer analysed voltage waveforms generated by axial wire-constant current and space clamp techniques. The average series resistance for all axons was 6.2 +/- 0.5 omega cm2 (n = 128). Values ranged between 1 and 30 omega cm2. The series resistance of axons with low resting membrane resistance (less than 1500 omega cm2) increased an average of 30% when stimulated for 45 s to 7 min (50 Hz) whereas the series resistance of high membrane resistance (greater than 1500 omega cm2) axons decreased an average of 10%. Carbachol (10(-7) M) caused the series resistance of low membrane resistance axons to decrease during stimulation but had no effect on high membrane resistance axons. d-Tubocurare (10(-8) M) caused the series resistance of high membrane resistance axons to increase during stimulation but had no effect on low membrane resistance axons. Bumetanide, a Na-K-Cl cotransport inhibitor and low [K+]o, prevented the stimulation-induced increase in series resistance of low membrane resistance axons but had no effect on the high membrane resistance axons. The results suggest that the series resistance of axons varies in response to the activity of the glial K+ uptake mechanisms stimulated by the appearance of K+ in the periaxonal space during action potential generation.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Guidance of vascular development: lessons from the nervous system.

    Science.gov (United States)

    Larrivée, Bruno; Freitas, Catarina; Suchting, Steven; Brunet, Isabelle; Eichmann, Anne

    2009-02-27

    The vascular system of vertebrates consists of an organized, branched network of arteries, veins, and capillaries that penetrates all the tissues of the body. One of the most striking features of the vascular system is that its branching pattern is highly stereotyped, with major and secondary branches forming at specific sites and developing highly conserved organ-specific vascular patterns. The factors controlling vascular patterning are not yet completely understood. Recent studies have highlighted the anatomic and structural similarities between blood vessels and nerves. The 2 networks are often aligned, with nerve fibers and blood vessels following parallel routes. Furthermore, both systems require precise control over their guidance and growth. Several molecules with attractive and repulsive properties have been found to modulate the proper guidance of both nerves and blood vessels. These include the Semaphorins, the Slits, and the Netrins and their receptors. In this review, we describe the molecular mechanisms by which blood vessels and axons achieve proper path finding and the molecular cues that are involved in their guidance.

  6. PSD Increment Consumption Guidance

    Science.gov (United States)

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  7. Investigation on the mechanism of peripheral axonal injury in glaucoma

    Directory of Open Access Journals (Sweden)

    Jun- Hong Zhao

    2013-05-01

    Full Text Available AIM: To compare the angles of longitudinal section of sclera around optic nerve heads and the never fiber layer changes in healthy adults and patients with glaucoma, and to investigate the mechanism of peripheral retinal axonal injury, with the combined knowledge of biomechanics. METHODS: The optical nerves and their peripheral tissue specimen in the 12 eyes from health adult donators and 12 eyes from glaucoma patient donators were dyed by Glees' method to compare the angles of longitudinal section of sclera around optic nerve heads(through optic nerve center, and to observe the anatomical features of the peripheral retinal axons. RESULTS: The mean angle of longitudinal section of sclera around optic nerve in healthy adults was 73.3°, while that in patients with absolute glaucoma was 75.6°. The difference showed no significance(t=1.44, P>0.05. There was a sharp bend in the course of peripheral optical fiber in healthy adults. However, the optic nerve fiber disappeared completely in patients with glaucoma end stage. CONCLUSION: The angle between the medial edge and leading edge of sclera(around optic nerve headsis an acute angle. The optical fiber in glaucoma end stage disappeared completely. The phenomenon may be related to high intraocular pressure, the sclera shape, the shear modulus of sclera and axons, and “axonal bending-injury” mechanism.

  8. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  9. Multiple sclerosis and anterograde axonal degeneration study by magnetic resonance

    International Nuclear Information System (INIS)

    Martinez Pardo, P.; Capdevila Cirera, A.; Sanz Marin, P.M.; Gili Planas, J.

    1993-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system that affects specifically the myelin. Its diagnosis by imaging techniques is, since the development of magnetic resonance (MR), relatively simple, and its occasional association with anterograde axonal degeneration (WD) has been reported. In both disorders, there is a lengthening of the T1 and T2 relaxation times. In the present report, 76 patients with MS with less than 4 plaques in the typical periventricular position were studied retrospectively, resulting in a rate of association with anterograde axonal degeneration of 8%. We consider that in spite of their same behavior in MR,MS and WD, with moreover represent completely different pathologies, are perfectly differential by MR. The S-E images with longer repetition and echo times in the axial and coronal planes have proved to be those most sensitive for this differentiation. Given that MS is specific pathology of then myelin, the axonal damages in delayed until several plaques adjacent to an axon affect it. We consider that this, added to the restriction of our study group (less than 4 plaques), is the cause of the pow percentage of the MS-WD association in our study. (Author)

  10. Chronic severe axonal polyneuropathy associated with hyperthyroidism and multivitamin deficiency.

    Science.gov (United States)

    Sugie, Kazuma; Umehara, Fujio; Kataoka, Hiroshi; Kumazawa, Aya; Ueno, Satoshi

    2012-01-01

    Hyperthyroidism is often associated with various neuromuscular disorders, most commonly proximal myopathy. Peripheral nerve involvement in hyperthyroidism is very uncommon and has rarely been reported. We describe a 29-year-old woman with untreated hyperthyroidism who presented with chronic severe axonal sensory-motor polyneuropathy. Peripheral nerve involvement developed together with other symptoms of hyperthyroidism 2 years before presentation. She also had anorexia nervosa for the past 6 months, resulting in multivitamin deficiency. Electrophysiological and pathological findings as well as clinical manifestations confirmed the diagnosis of severe axonal polyneuropathy. Anorexia nervosa has been considered a manifestation of untreated hyperthyroidism. We considered hyperthyroidism to be an important causal factor in the polyneuropathy in our patient, although peripheral nerve involvement in hyperthyroidism is rare. To our knowledge, this is the first documented case of chronic severe axonal polyneuropathy ascribed to both hyperthyroidism and multivitamin deficiency. Our findings strongly suggest that not only multivitamin deficiency, but also hyperthyroidism can cause axonal polyneuropathy, thus expanding the clinical spectrum of hyperthyroidism.

  11. Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

    Science.gov (United States)

    Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

    2018-05-02

    Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

  12. Botulinum toxin's axonal transport from periphery to the spinal cord.

    Science.gov (United States)

    Matak, Ivica; Riederer, Peter; Lacković, Zdravko

    2012-07-01

    Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve. We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons. These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Computed tomography in diagnosis of diffuse axonal injury

    International Nuclear Information System (INIS)

    Iwadate, Yasuo; Ono, Juniti; Okimura, Yoshitaka; Suda, Sumio; Isobe, Katsumi; Yamaura, Akira.

    1990-01-01

    Diffuse axonal injury (DAI) has been described in instances of prolonged traumatic coma on the basis of the neuropathological findings, but the same findings are also found in patients with cerebral concussion. Experimental studies confirm that the quality of survivors following trauma is directly proportional to the amount of primarily injured-axon. When the injured axon lies in a widespread area of the brain, outcome for the patient is always poor. In a series of 260 severely head-injured patients, based on their poor outcome, 69 (27%) were diagnosed as DAI. Because of their relatively good outcome, eighty-two patients (32%) were classified into non-DAI group. The predominant CT finding of DAI patients was intraparenchymal deep-seated hemorrhagic lesion. This was observed in 28 patients (41%). Normal CT was also observed in 11 patients (16%). On the other hand, 8 of the non-DAI group (10%) manifested deep-seated lesions. Diffuse cerebral swelling (DCS) appeared in both groups in the same incidence. Subarachnoid hematoma in the perimesencephalic cistern (SAH (PMC)) and intraventricular hematoma (IVH) were observed in 64% of the DAI group, and in 23% of the non-DAI group. The available evidence indicates that various types of hematoma seen in the deep-seated structures of the brain do not have an absolute diagnostic value, but the frequency of hematoma is thought to increase in proportion to the amount of injured-axon. (author)

  14. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Visser, N.A.

    2016-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP

  15. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Directory of Open Access Journals (Sweden)

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  16. Creating Rich Portraits: A Mixed-Methods Approach to Understanding Profiles of Intrinsic and Extrinsic Motivations

    Science.gov (United States)

    Corpus, Jennifer Henderlong; Wormington, Stephanie V.; Haimovitz, Kyla

    2016-01-01

    A person-centered, mixed-methods approach (self-report surveys, semistructured interviews, school records) was used to characterize and evaluate profiles of intrinsic and extrinsic motivations among 243 third- through eighth-grade students. Cluster analysis suggested four distinct profiles: high quantity (high intrinsic, high extrinsic), primarily…

  17. Intrinsic and Extrinsic Origins of the Polar Kerr Effect in a Chiral p-WAVE Superconductor

    Science.gov (United States)

    Goryo, Jun

    Recently, the measurement of the polar Kerr effect (PKE) in the quasi two-dimensional superconductor Sr2RuO4, which is motivated to observe the chirality of px + ipy-wave pairing, has been reported. We clarify that the PKE has intrinsic and extrinsic (disorder-induced) origins. The extrinsic contribution would be dominant in the PKE experiment.

  18. Do people differentiate between intrinsic and extrinsic goals for physical activity?

    Science.gov (United States)

    McLachlan, Sarah; Hagger, Martin S

    2011-04-01

    The distinction between intrinsic and extrinsic goals, and between goal pursuit for intrinsically and extrinsically motivated reasons, is a central premise of self-determination theory. Proponents of the theory have proposed that the pursuit of intrinsic goals and intrinsically motivated goal striving each predict adaptive psychological and behavioral outcomes relative to the pursuit of extrinsic goals and extrinsically motivated goal striving. Despite evidence to support these predictions, research has not explored whether individuals naturally differentiate between intrinsic and extrinsic goals. Two studies tested whether people make this differentiation when recalling goals for leisure-time physical activity. Using memory-recall methods, participants in Study 1 were asked to freely generate physical activity goals. A subsample (N = 43) was asked to code their freely generated goals as intrinsic or extrinsic. In Study 2, participants were asked to recall intrinsic and extrinsic goals after making a decision regarding their future physical activity. Results of these studies revealed that individuals' goal generation and recall exhibited significant clustering by goal type. Participants encountered some difficulties when explicitly coding goals. Findings support self-determination theory and indicate that individuals discriminate between intrinsic and extrinsic goals.

  19. Motor memory is encoded as a gain-field combination of intrinsic and extrinsic action representations.

    Science.gov (United States)

    Brayanov, Jordan B; Press, Daniel Z; Smith, Maurice A

    2012-10-24

    Actions can be planned in either an intrinsic (body-based) reference frame or an extrinsic (world-based) frame, and understanding how the internal representations associated with these frames contribute to the learning of motor actions is a key issue in motor control. We studied the internal representation of this learning in human subjects by analyzing generalization patterns across an array of different movement directions and workspaces after training a visuomotor rotation in a single movement direction in one workspace. This provided a dense sampling of the generalization function across intrinsic and extrinsic reference frames, which allowed us to dissociate intrinsic and extrinsic representations and determine the manner in which they contributed to the motor memory for a trained action. A first experiment showed that the generalization pattern reflected a memory that was intermediate between intrinsic and extrinsic representations. A second experiment showed that this intermediate representation could not arise from separate intrinsic and extrinsic learning. Instead, we find that the representation of learning is based on a gain-field combination of local representations in intrinsic and extrinsic coordinates. This gain-field representation generalizes between actions by effectively computing similarity based on the (Mahalanobis) distance across intrinsic and extrinsic coordinates and is in line with neural recordings showing mixed intrinsic-extrinsic representations in motor and parietal cortices.

  20. The Attitudes of Israeli Arab and Jewish High School Students towards Extrinsic and Intrinsic Values

    Science.gov (United States)

    Gross, Zehavit

    2013-01-01

    The aim of this research was to investigate the attitudes of Israeli Arab (n = 259) and Jewish (n = 259) high school students toward extrinsic and intrinsic values. A questionnaire, which consisted of eight value scales in two groups--extrinsic and intrinsic values--was administered. Participants were asked to state whether they agreed or…

  1. Intrinsic and Extrinsic Interlay Factors in Saudi Graduate Students' Perception of Performance and Success

    Science.gov (United States)

    Maguire, Richard K.; Corbin, Thomas Philip, Jr.

    2015-01-01

    The natural symbiotic relationship between intrinsic and extrinsic factors and how they contribute to student success is undeniable. A plethora of work including self-determination, attribution, and social cognitive theories speak about academic achievement by students having a reciprocity relationship between the extrinsic factors that underline…

  2. Intrinsic and Extrinsic Motivational Factors Related to Educators' Pursuit of Doctoral Degrees

    Science.gov (United States)

    George-Reid, Kimberly A.

    2016-01-01

    The purpose of this study was to identify intrinsic and extrinsic motivational factors for professional doctoral degree attainment among educators. The researcher examined the following intrinsic motivating factors: personal attainment, skill and ability enhancement, and goals. The researcher also included the following extrinsic factors:…

  3. Separation of extrinsic and intrinsic plasmon excitations in Ge KLL Auger spectra

    International Nuclear Information System (INIS)

    Berenyi, Z.; Aszalos-Kiss, B.; Csik, A.; Toth, J.; Koever, L.; Varga, D.

    2002-01-01

    The nature of the Ge satellite structure and the contributions from extrinsic and intrinsic processes were investigated using the ESA-31 electron spectrometer. These measurements are providing the first high energy resolution Ge KLL data. The intensity ratio of the plasmon peaks induced by intrinsic and extrinsic excitation processes is found. (R.P.)

  4. Intrinsic and Extrinsic Motivational Orientations in the Classroom: Age Differences and Academic Correlates

    Science.gov (United States)

    Lepper, Mark R.; Corpus, Jennifer Henderlong; Iyengar, Sheena S.

    2005-01-01

    Age differences in intrinsic and extrinsic motivation and the relationships of each to academic outcomes were examined in an ethnically diverse sample of 797 3rd-grade through 8th-grade children. Using independent measures, the authors found intrinsic and extrinsic motivation to be only moderately correlated, suggesting that they may be largely…

  5. Intrinsic and Extrinsic School Motivation as a Function of Age: The Mediating Role of Autonomy Support

    Science.gov (United States)

    Gillet, Nicolas; Vallerand, Robert J.; Lafreniere, Marc-Andre K.

    2012-01-01

    The main purpose of the present research was to investigate school intrinsic and extrinsic motivation, and amotivation as a function of age in a sample of 1,600 elementary and high school students aged 9-17 years. First, results revealed a systematic decrease in intrinsic motivation and self-determined extrinsic motivation from age 9 to 12 years,…

  6. Extrinsic Motivators Affecting Fourth-Grade Students' Interest and Enrollment in an Instrumental Music Program

    Science.gov (United States)

    Vasil, Martina

    2013-01-01

    The purpose of this study was to investigate fourth-grade students' extrinsic motivators for joining and continuing in a school instrumental music program. Three research questions were investigated: (a) What extrinsic motivators have influenced fourth-grade students' initial interest and continuing participation in an instrumental music program?…

  7. Efficacy test of a toothpaste in reducing extrinsic dental stain

    Science.gov (United States)

    Agustanti, A.; Ramadhani, S. A.; Adiatman, M.; Rahardjo, A.; Callea, M.; Yavuz, I.; Maharani, D. A.

    2017-08-01

    This clinical trial compared the external dental stain reduction achieved by tested toothpaste versus placebo in adult patients. In this double-blind, parallel, randomised clinical trial, 45 female volunteers with a mean age of 20 years old were included. All study subjects front teeth were topically applicated with Silver Diamine Fluoride (SDF) to create external dental stains. Subjects were randomized into test (n=22) and control (n=23) groups. Toothpastes were used for two days to analyse the effects of removing external stains on the labial surfaces of all anterior teeth. VITA Easyshade Advance 4.0 was used to measure dental extrinsic stains changes. The analysis showed statistically significant efficacy of the tested toothpaste in reducing external dental stain caused by SDF, comparing to the placebo toothpaste, after one and two days of usage. The tested toothpaste was effective in reducing dental stain.

  8. MATERIAL ELEMENT MODEL FOR EXTRINSIC SEMICONDUCTORS WITH DEFECTS OF DISLOCATION

    Directory of Open Access Journals (Sweden)

    Maria Paola Mazzeo

    2011-07-01

    Full Text Available In a previous paper we outlined a geometric model for the thermodynamic description of extrinsic semiconductors with defects of dislocation.Applying a geometrization technique, within the rationalextended irreversible thermodynamics with internal variables, the dynamical system for simple material elements of these media, the expressions of the entropy function and the entropy 1-form were obtained. In this contribution we deepen the study of this geometric model. We give a detailed description of the defective media under consideration and of the dislocation core tensor, we introduce the transformation induced by the process and, applying the closure conditions for the entropy 1-form, we derive the necessary conditions for the existence of the entropy function. These and other results are new in the paper.The derivation of the relevant entropy 1-form is the starting point to introduce an extended thermodynamical phase space.

  9. Measurement of spin pumping voltage separated from extrinsic microwave effects

    International Nuclear Information System (INIS)

    Iguchi, Ryo; Saitoh, Eiji

    2017-01-01

    Conversions between spin and charge currents are core technologies in recent spintronics. In this article, we provide methods for estimating inverse spin Hall effects (ISHEs) induced by using microwave-driven spin pumping (SP) as a spin-current generator. ISHE and SP induce an electromotive force at the ferromagnetic or spin-wave resonance, which offers a valuable electric method of studying spin physics in materials. At the resonance, a microwave for exciting the magnetization dynamics induces an additional electromotive force via rf-current rectification and thermoelectric effects. We discuss methods of separating the signals generated from such extrinsic microwave effects by controlling sample structures and configurations. These methods are helpful in performing accurate measurements on ISHE induced by SP, enabling quantitative studies on the conversion between spin and charge currents on various kinds of materials. (author)

  10. Scanning gate microscopy on graphene: charge inhomogeneity and extrinsic doping

    International Nuclear Information System (INIS)

    Jalilian, Romaneh; Tian Jifa; Chen, Yong P; Jauregui, Luis A; Lopez, Gabriel; Roecker, Caleb; Jovanovic, Igor; Yazdanpanah, Mehdi M; Cohn, Robert W

    2011-01-01

    We have performed scanning gate microscopy (SGM) on graphene field effect transistors (GFET) using a biased metallic nanowire coated with a dielectric layer as a contact mode tip and local top gate. Electrical transport through graphene at various back gate voltages is monitored as a function of tip voltage and tip position. Near the Dirac point, the response of graphene resistance to the tip voltage shows significant variation with tip position, and SGM imaging displays mesoscopic domains of electron-doped and hole-doped regions. Our measurements reveal substantial spatial fluctuation in the carrier density in graphene due to extrinsic local doping from sources such as metal contacts, graphene edges, structural defects and resist residues. Our scanning gate measurements also demonstrate graphene's excellent capability to sense the local electric field and charges.

  11. Extrinsic and intrinsic motivation at 30: Unresolved scientific issues.

    Science.gov (United States)

    Reiss, Steven

    2005-01-01

    The undermining effect of extrinsic reward on intrinsic motivation remains unproven. The key unresolved issues are construct invalidity (all four definitions are unproved and two are illogical); measurement unreliability (the free-choice measure requires unreliable, subjective judgments to infer intrinsic motivation); inadequate experimental controls (negative affect and novelty, not cognitive evaluation, may explain "undermining" effects); and biased metareviews (studies with possible floor effects excluded, but those with possible ceiling effects included). Perhaps the greatest error with the undermining theory, however, is that it does not adequately recognize the multifaceted nature of intrinsic motivation (Reiss, 2004a). Advice to limit the use of applied behavior analysis based on "hidden" undermining effects is ideologically inspired and is unsupported by credible scientific evidence.

  12. The string model with the extrinsic curvature term

    International Nuclear Information System (INIS)

    Itoi, C.; Kubota, Hiroshi

    1988-01-01

    The string model with the extrinsic curvature is studied which is a gauge invariant field theory with higher order derivatives. We present an equivalent action without any higher order derivatives which keeps the gauge invariance. We point out the difficulty caused by the second class constraints in Dirac's canonical method. Following a new method for dynamical systems with second class constraints, we construct a equivalent model which has no second class constraints but has a new gauge invariance. This gauge invariance guarantees the equivalence between the original model and new one. We show that the model can be quantized in this formalism. In a simple model, we show the nilpotence of the BRST charge under certain conditions, and discuss the unitarity of the theory. (author)

  13. Auditory word recognition: extrinsic and intrinsic effects of word frequency.

    Science.gov (United States)

    Connine, C M; Titone, D; Wang, J

    1993-01-01

    Two experiments investigated the influence of word frequency in a phoneme identification task. Speech voicing continua were constructed so that one endpoint was a high-frequency word and the other endpoint was a low-frequency word (e.g., best-pest). Experiment 1 demonstrated that ambiguous tokens were labeled such that a high-frequency word was formed (intrinsic frequency effect). Experiment 2 manipulated the frequency composition of the list (extrinsic frequency effect). A high-frequency list bias produced an exaggerated influence of frequency; a low-frequency list bias showed a reverse frequency effect. Reaction time effects were discussed in terms of activation and postaccess decision models of frequency coding. The results support a late use of frequency in auditory word recognition.

  14. Extrinsic factors affecting accuracy of ultrasonic flowmeters for LMFBRs

    International Nuclear Information System (INIS)

    Managan, W.W.

    1976-08-01

    Assuming that ultrasonic flowmeters of suitable intrinsic accuracy are feasible, this report explores factors extrinsic to the flowmeter which affect the accuracy such as asymmetric flow profile, regions of high turbulence and thermal stratification. By integrating isovelocity flow profile maps, the predicted performance of various flowmeter configurations may be compared to experimental data. For the two pipe arrangements analyzed, the single diametral path flowmeter results were within 5 percent of true flow rate. Theoretical correction factors could reduce the error for the straight pipe but increased the error for asymmetrical flow. On the same pipe arrangements a four path ultrasonic flowmeter spaced for Gaussian integration gave less than 1 percent error. For more general conclusions a range of flow profiles produced by typical LMFBR piping arrangements must be analyzed

  15. Oligodendrocyte Development in the Absence of Their Target Axons In Vivo.

    Directory of Open Access Journals (Sweden)

    Rafael Almeida

    Full Text Available Oligodendrocytes form myelin around axons of the central nervous system, enabling saltatory conduction. Recent work has established that axons can regulate certain aspects of oligodendrocyte development and myelination, yet remarkably oligodendrocytes in culture retain the ability to differentiate in the absence of axons and elaborate myelin sheaths around synthetic axon-like substrates. It remains unclear the extent to which the life-course of oligodendrocytes requires the presence of, or signals derived from axons in vivo. In particular, it is unclear whether the specific axons fated for myelination regulate the oligodendrocyte population in a living organism, and if so, which precise steps of oligodendrocyte-cell lineage progression are regulated by target axons. Here, we use live-imaging of zebrafish larvae carrying transgenic reporters that label oligodendrocyte-lineage cells to investigate which aspects of oligodendrocyte development, from specification to differentiation, are affected when we manipulate the target axonal environment. To drastically reduce the number of axons targeted for myelination, we use a previously identified kinesin-binding protein (kbp mutant, in which the first myelinated axons in the spinal cord, reticulospinal axons, do not fully grow in length, creating a region in the posterior spinal cord where most initial targets for myelination are absent. We find that a 73% reduction of reticulospinal axon surface in the posterior spinal cord of kbp mutants results in a 27% reduction in the number of oligodendrocytes. By time-lapse analysis of transgenic OPC reporters, we find that the reduction in oligodendrocyte number is explained by a reduction in OPC proliferation and survival. Interestingly, OPC specification and migration are unaltered in the near absence of normal axonal targets. Finally, we find that timely differentiation of OPCs into oligodendrocytes does not depend at all on the presence of target axons

  16. Time course of ongoing activity during neuritis and following axonal transport disruption.

    Science.gov (United States)

    Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

    2018-05-01

    Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

  17. Extrinsic and intrinsic blood supply to the optic chiasm.

    Science.gov (United States)

    Salaud, Céline; Ploteau, Stéphane; Blery, Pauline; Pilet, Paul; Armstrong, Olivier; Hamel, Antoine

    2018-04-01

    Although there have been many studies of the arterial cerebral blood supply, only seven have described the optic chiasm (OC) blood supply and their results are contradictory. The aim of this study was to analyze the extrinsic and intrinsic OC blood supply on cadaveric specimens using dissections and microcomputer tomography (Micro-CT). Thirteen human specimens were dissected and the internal or common carotid arteries were injected with red latex, China Ink with gelatin or barium sulfate. Three Micro-CTs were obtained to reveal the intrinsic blood supply to the OC. The superior hypophyseal arteries (SupHypA) (13/13) and posterior communicating artery (PCoA) (12/13) supplied the pial network on the inferior side of the OC. The first segment of the anterior cerebral artery (ACA) (10/10), SupHypA (7/10), the anterior communicating artery (ACoA) (9/10), and PComA (1/10) supplied the pial network of its superior side. The intrinsic OC blood supply was divided into three networks (two lateral and one central). Capillaries entering the OC originated principally from the inferior pial network. The lateral network capillaries had the same orientation as the visual lateral pathways, but the central network was not correlated with the nasal fibers crossing into the OC. There was no anastomosis in the pial or intrinsic networks. Only SupHypA, PCoA, ACoA, and ACA were involved in the OC blood supply. Because there was no extrinsic or intrinsic anastomosis, all arteries should be preserved. Tumor compression of the inferior intrinsic arterial network could contribute to visual defects. Clin. Anat. 31:432-440, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Proprioceptive bimanual test in intrinsic and extrinsic coordinates.

    Science.gov (United States)

    Iandolo, Riccardo; Squeri, Valentina; De Santis, Dalia; Giannoni, Psiche; Morasso, Pietro; Casadio, Maura

    2015-01-01

    Is there any difference between matching the position of the hands by asking the subjects to move them to the same spatial location or to mirror-symmetric locations with respect to the body midline? If the motion of the hands were planned in the extrinsic space, the mirror-symmetric task would imply an additional challenge, because we would need to flip the coordinates of the target on the other side of the workspace. Conversely, if the planning were done in intrinsic coordinates, in order to move both hands to the same spot in the workspace, we should compute different joint angles for each arm. Even if both representations were available to the subjects, the two tasks might lead to different results, providing some cue on the organization of the "body schema". In order to answer such questions, the middle fingertip of the non-dominant hand of a population of healthy subjects was passively moved by a manipulandum to 20 different target locations. Subjects matched these positions with the middle fingertip of their dominant hand. For most subjects, the matching accuracy was higher in the extrinsic modality both in terms of systematic error and variability, even for the target locations in which the configuration of the arms was the same for both modalities. This suggests that the matching performance of the subjects could be determined not only by proprioceptive information but also by the cognitive representation of the task: expressing the goal as reaching for the physical location of the hand in space is apparently more effective than requiring to match the proprioceptive representation of joint angles.

  19. Development of raphe serotonin neurons from specification to guidance.

    Science.gov (United States)

    Kiyasova, Vera; Gaspar, Patricia

    2011-11-01

    The main features of the development of the serotonin (5-HT) raphe neurons have been known for many years but more recent molecular studies, using mouse genetics, have since unveiled several intriguing aspects of the specification of the raphe serotonergic system. These studies indicated that, although all 5-HT neurons in the raphe follow the same general program for their specification, there are also clear regional differences in the way that these neurons are specified and are guided towards different brain targets. Here we overview recent progress made in the understanding of the developmental programming of serotonergic neurons in the mouse raphe, emphasizing data showing how heterogeneous subsets of 5-HT neurons may be generated. Serotonergic progenitors are produced in the brainstem in different rhombomeres under the influence of a set of secreted factors, sonic hedgehog and fibroblast growth factors, which determine their position in the neural tube. Two main transcriptional gene networks are involved in the specification of 5-HT identity, with Lmx1b and Pet1 transcription factors as main players. A differential requirement for Pet1 was, however, revealed, which underlies an anatomical and functional diversity. Transcriptional programs controlling 5-HT identity could also impact axon guidance mechanisms directing 5-HT neurons to their targets. Although no direct links have yet been established, a large set of molecular determinants have already been shown to be involved in the growth, axon guidance and targeting of 5-HT raphe neurons, particularly within the forebrain. Alterations in the molecular mechanisms involved in 5-HT development are likely to have significant roles in mood disease predisposition. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Perceived extrinsic mortality risk and reported effort in looking after health: testing a behavioral ecological prediction.

    Science.gov (United States)

    Pepper, Gillian V; Nettle, Daniel

    2014-09-01

    Socioeconomic gradients in health behavior are pervasive and well documented. Yet, there is little consensus on their causes. Behavioral ecological theory predicts that, if people of lower socioeconomic position (SEP) perceive greater personal extrinsic mortality risk than those of higher SEP, they should disinvest in their future health. We surveyed North American adults for reported effort in looking after health, perceived extrinsic and intrinsic mortality risks, and measures of SEP. We examined the relationships between these variables and found that lower subjective SEP predicted lower reported health effort. Lower subjective SEP was also associated with higher perceived extrinsic mortality risk, which in turn predicted lower reported health effort. The effect of subjective SEP on reported health effort was completely mediated by perceived extrinsic mortality risk. Our findings indicate that perceived extrinsic mortality risk may be a key factor underlying SEP gradients in motivation to invest in future health.

  1. Non-cable vehicle guidance

    Energy Technology Data Exchange (ETDEWEB)

    Daugela, G.C.; Willott, A.M.; Chopiuk, R.G.; Thornton, S.E.

    1988-06-01

    The purpose is to determine the most promising driverless mine vehicle guidance systems that are not dependent on buried cables, and to plan their development. The project is presented in two phases: a preliminary study and literature review to determine whether suitable technologies exist to justify further work; and an in-depth assessment and selection of technologies for vehicle guidance. A large number of guidance elements are involved in a completely automated vehicle. The technologies that hold the best potential for development of guidance systems for mine vehicles are ultrasonics, radar, lasers, dead reckoning, and guidance algorithms. The best approach to adaptation of these technologies is on a step by step basis. Guidance modules that are complete in themselves and are designed to be integrated with other modules can provide short term benefits. Two modules are selected for development: the dragline operations monitor and automated machine control for optimized mining (AMCOM). 99 refs., 20 figs., 40 tabs.

  2. Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord.

    Science.gov (United States)

    Blacklaws, Jake; Deska-Gauthier, Dylan; Jones, Christopher T; Petracca, Yanina L; Liu, Mingwei; Zhang, Han; Fawcett, James P; Glover, Joel C; Lanuza, Guillermo M; Zhang, Ying

    2015-09-01

    V3 spinal interneurons (INs) are a group of excitatory INs that play a crucial role in producing balanced and stable gaits in vertebrate animals. In the developing mouse spinal cord, V3 INs arise from the most ventral progenitor domain and form anatomically distinctive subpopulations in adult spinal cords. They are marked by the expression of transcription factor Sim1 postmitotically, but the function of Sim1 in V3 development remains unknown. Here, we used Sim1(Cre) ;tdTomato mice to trace the fate of V3 INs in a Sim1 mutant versus control genetic background during development. In Sim1 mutants, V3 INs are produced normally and maintain a similar position and organization as in wild types before E12.5. Further temporal analysis revealed that the V3 INs in the mutants failed to migrate properly to form V3 subgroups along the dorsoventral axis of the spinal cord. At birth, in the Sim1 mutant the number of V3 INs in the ventral subgroup was normal, but they were significantly reduced in the dorsal subgroup with a concomitant increase in the intermediate subgroup. Retrograde labeling at lumbar level revealed that loss of Sim1 led to a reduction in extension of contralateral axon projections both at E14.5 and P0 without affecting ipsilateral axon projections. These results demonstrate that Sim1 is essential for proper migration and the guidance of commissural axons of the spinal V3 INs. © 2015 Wiley Periodicals, Inc.

  3. An αII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration.

    Science.gov (United States)

    Huang, Claire Yu-Mei; Zhang, Chuansheng; Zollinger, Daniel R; Leterrier, Christophe; Rasband, Matthew N

    2017-11-22

    Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αII spectrin-deficient mice of both sexes and found that, in myelinated axons, αII spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αII spectrin disrupts this organization. Avil-cre;Sptan1 f/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K + channels. We show that the density of nodal βIV spectrin is constant among axons, but the density of nodal αII spectrin increases with axon diameter. Remarkably, Avil-cre;Sptan1 f/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αII spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αII spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier. SIGNIFICANCE STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mechanical forces to which they are exposed (e.g., compression, torsion, and stretch). However, until now, no vertebrate animal model has tested the requirement of the spectrin cytoskeleton in

  4. Outer Electrospun Polycaprolactone Shell Induces Massive Foreign Body Reaction and Impairs Axonal Regeneration through 3D Multichannel Chitosan Nerve Guides

    Directory of Open Access Journals (Sweden)

    Sven Duda

    2014-01-01

    Full Text Available We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT. The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts.

  5. Outer electrospun polycaprolactone shell induces massive foreign body reaction and impairs axonal regeneration through 3D multichannel chitosan nerve guides.

    Science.gov (United States)

    Duda, Sven; Dreyer, Lutz; Behrens, Peter; Wienecke, Soenke; Chakradeo, Tanmay; Glasmacher, Birgit; Haastert-Talini, Kirsten

    2014-01-01

    We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts.

  6. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

    Science.gov (United States)

    Yang, Long; Bashaw, Greg J

    2006-11-22

    Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

  7. Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Wendy A. Morley

    2018-03-01

    Full Text Available Brain injury occurs in two phases: the initial injury itself and a secondary cascade of precise immune-based neurochemical events. The secondary phase is typically functional in nature and characterized by delayed axonal injury with more axonal disconnections occurring than in the initial phase. Axonal injury occurs across the spectrum of disease severity, with subconcussive injury, especially when repetitive, now considered capable of producing significant neurological damage consistent with axonal injury seen in clinically evident concussion, despite no observable symptoms. This review is the first to introduce the concept of environmental subconcussive injury (ESCI and sets out how secondary brain damage from ESCI once past the juncture of microglial activation appears to follow the same neuron-damaging pathway as secondary brain damage from conventional brain injury. The immune response associated with ESCI is strikingly similar to that mounted after conventional concussion. Specifically, microglial activation is followed closely by glutamate and calcium flux, excitotoxicity, reactive oxygen species and reactive nitrogen species (RNS generation, lipid peroxidation, and mitochondrial dysfunction and energy crisis. ESCI damage also occurs in two phases, with the primary damage coming from microbiome injury (due to microbiome-altering events and secondary damage (axonal injury from progressive secondary neurochemical events. The concept of ESCI and the underlying mechanisms have profound implications for the understanding of chronic traumatic encephalopathy (CTE etiology because it has previously been suggested that repetitive axonal injury may be the primary CTE pathogenesis in susceptible individuals and it is best correlated with lifetime brain trauma load. Taken together, it appears that susceptibility to brain injury and downstream neurodegenerative diseases, such as CTE, can be conceptualized as a continuum of brain resilience. At one end

  8. Large-scale Topographical Screen for Investigation of Physical Neural-Guidance Cues

    Science.gov (United States)

    Li, Wei; Tang, Qing Yuan; Jadhav, Amol D.; Narang, Ankit; Qian, Wei Xian; Shi, Peng; Pang, Stella W.

    2015-03-01

    A combinatorial approach was used to present primary neurons with a large library of topographical features in the form of micropatterned substrate for high-throughput screening of physical neural-guidance cues that can effectively promote different aspects of neuronal development, including axon and dendritic outgrowth. Notably, the neuronal-guidance capability of specific features was automatically identified using a customized image processing software, thus significantly increasing the screening throughput with minimal subjective bias. Our results indicate that the anisotropic topographies promote axonal and in some cases dendritic extension relative to the isotropic topographies, while dendritic branching showed preference to plain substrates over the microscale features. The results from this work can be readily applied towards engineering novel biomaterials with precise surface topography that can serve as guidance conduits for neuro-regenerative applications. This novel topographical screening strategy combined with the automated processing capability can also be used for high-throughput screening of chemical or genetic regulatory factors in primary neurons.

  9. Use of self-complementary adeno-associated virus serotype 2 as a tracer for labeling axons: implications for axon regeneration.

    Directory of Open Access Journals (Sweden)

    Yingpeng Liu

    Full Text Available Various types of tracers are available for use in axon regeneration, but they require an extra operational tracer injection, time-consuming immunohistochemical analysis and cause non-specific labeling. Considerable efforts over the past years have explored other methodologies, especially the use of viral vectors, to investigate axon regeneration after injury. Recent studies have demonstrated that self-complementary Adeno-Associated Virus (scAAV induced a high transduction efficiency and faster expression of transgenes. Here, we describe for the first time the use of scAAV2-GFP to label long-projection axons in the corticospinal tract (CST, rubrospinal tract (RST and the central axons of dorsal root ganglion (DRG in the normal and lesioned animal models. We found that scAAV2-GFP could efficiently transduce neurons in the sensorimotor cortex, red nucleus and DRG. Strong GFP expression could be transported anterogradely along the axon to label the numerous axon fibers from CST, RST and central axons of DRG separately. Comparison of the scAAV2 vector with single-stranded (ss AAV2 vector in co-labeled sections showed that the scAAV2 vector induced a faster and stronger transgene expression than the ssAAV2 vector in DRG neurons and their axons. In both spinal cord lesion and dorsal root crush injury models, scAAV-GFP could efficiently label the lesioned and regenerated axons around the lesion cavity and the dorsal root entry zone (DREZ respectively. Further, scAAV2-GFP vector could be combined with traditional tracer to specifically label sensory and motor axons after spinal cord lesion. Thus, we show that using scAAV2-GFP as a tracer is a more effective and efficient way to study axon regeneration following injury.

  10. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  11. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability.

    Science.gov (United States)

    Frielink, N; Schuengel, C; Embregts, P

    2017-07-01

    According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. () proposed a dichotomy of broad subtypes of extrinsic motivation for people with intellectual disability (ID) due to their cognitive limitations. The current study challenges this proposal by testing whether the four subtypes of extrinsic motivation can be differentiated among people with ID as well. The subtypes of extrinsic motivation were measured using two adapted versions of the Self-Regulation Questionnaire, one regarding exercise and one regarding support. In total, 186 adults with mild to borderline ID participated in the study. Results supported the distinction between the four subtypes of extrinsic motivation regarding both exercise and support. In addition, the correlation coefficients supported a quasi-simplex pattern of correlations among the subtypes, indicating that adjacent subtypes were more closely related than non-adjacent subtypes. Moreover, the study showed sufficient Cronbach's alphas and test-retest reliabilities for early stage research. Overall, the results of the current study provide initial evidence for the universality of the four subtypes of extrinsic motivation across populations with and without ID. © 2017 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.

  12. Intrinsic and extrinsic motivation among adolescent ten-pin bowlers in kuala lumpur, malaysia.

    Science.gov (United States)

    Teo, Eng-Wah; Khoo, Selina; Wong, Rebecca; Wee, Eng-Hoe; Lim, Boon-Hooi; Rengasamy, Shabesan Sit

    2015-03-29

    Motivation has long been associated with sports engagement. However, to date no research has been performed to understand the domain of motivation among ten-pin bowlers. The purpose of this study was to investigate different types of motivation (i.e., intrinsic vs. extrinsic) based on self-determination theory from the perspective of gender and the bowler type (competitive vs. casual). A total of 240 bowlers (104 male, 136 female; 152 competitive, 88 casual) with a mean age of 16.61 ± 0.78 years were recruited in Kuala Lumpur. The Sport Motivation Scale, a 28-item self-report questionnaire measuring seven subscales (i.e., intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, extrinsic motivation to identify regulation, extrinsic motivation for introjection regulation, extrinsic motivation to external regulation, and amotivation) was administered. Results showed significant differences (t=10.43, df=239, p=0.01) between total scores of intrinsic and extrinsic motivation among ten-pin bowlers. There were significant gender differences with respect to intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, and extrinsic motivation to identify regulation. However, no significant bowler type differences were found for either the intrinsic (t=-1.15, df=238, p=0.25) or extrinsic (t=-0.51, df=238, p=0.61) motivation dimensions. In conclusion, our study demonstrated substantial intrinsic motivation for gender effects, but no bowler type effects among adolescent ten-pin bowlers.

  13. Copper absorption from foods labelled intrinsically and extrinsically with Cu-65 stable isotope.

    Science.gov (United States)

    Harvey, L J; Dainty, J R; Beattie, J H; Majsak-Newman, G; Wharf, S G; Reid, M D; Fairweather-Tait, S J

    2005-03-01

    To determine copper absorption from copper containing foods labelled either intrinsically or extrinsically with a highly enriched Cu-65 stable isotope label. A longitudinal cross-over study. The study was conducted at the Institute of Food Research, Human Nutrition Unit, Norwich, UK. Subjects were recruited locally via advertisements placed around the Norwich Research Park. A total of 10 volunteers (nine female, one male) took part in the study, but not all volunteers completed each of the test meals. A highly enriched Cu-65 stable isotope label was administered to volunteers in the form of a reference dose or in breakfast test meals consisting of red wine, soya beans, mushrooms or sunflower seeds. Faecal monitoring and mass spectrometry techniques were used to estimate the relative quantities of copper absorbed from the different test meals. True copper absorption from the reference dose (54%) was similar to extrinsically labelled red wine (49%) and intrinsically labelled sunflower seeds (52%), but significantly higher than extrinsically labelled mushrooms (35%), intrinsically (29%) and extrinsically (15%) labelled soya beans and extrinsically labelled sunflower seed (32%) test meals. The use of Cu-65 extrinsic labels in copper absorption studies requires validation according to the food being examined; intrinsic and extrinsic labelling produced significantly different results for sunflower seeds.

  14. Bridging the gap between extrinsic and intrinsic motivation in the cognitive remediation of schizophrenia.

    Science.gov (United States)

    Silverstein, Steven M

    2010-09-01

    An important development in cognitive remediation of schizophrenia is a focus on motivation. However, following a distinction between the concepts of intrinsic motivation (IM) and extrinsic motivation, discussions of IM-based methods have downplayed or misrepresented the role that extrinsic rewards can, and actually do, serve to promote positive treatment outcomes in cognitive remediation. Therefore, the purpose of this article is to explore the rationale for using techniques incorporating extrinsic rewards into cognitive treatment of people with schizophrenia. To do this, evidence is presented on each of the following points: (1) there is a long history of research demonstrating that delivery of extrinsic reward is associated with positive outcomes in both behavioral and cognitive rehabilitation; (2) basic human brain systems respond strongly to tangible rewards, and this can directly enhance attention, working memory, and other cognitive functions; (3) nearly all data on the negative effects of extrinsic reward on IM have come from studies of healthy children and adults in school or work settings who have adequate IM for target tasks; these findings do not generalize well to cognitive remediation settings for people with schizophrenia, who often have abnormally low levels of IM and low base rates of attentive behaviors; and (4) in real-world situations, cognitive remediation interventions already utilize a combination of intrinsic and extrinsic reinforcers. Future studies are needed to clarify state and trait factors responsible for individual differences in the extent to which extrinsic rewards are necessary to set the conditions under which IM can develop.

  15. Intrinsic and Extrinsic Motivation Among Adolescent Ten-Pin Bowlers in Kuala Lumpur, Malaysia

    Directory of Open Access Journals (Sweden)

    Teo Eng-Wah

    2015-03-01

    Full Text Available Motivation has long been associated with sports engagement. However, to date no research has been performed to understand the domain of motivation among ten-pin bowlers. The purpose of this study was to investigate different types of motivation (i.e., intrinsic vs. extrinsic based on self-determination theory from the perspective of gender and the bowler type (competitive vs. casual. A total of 240 bowlers (104 male, 136 female; 152 competitive, 88 casual with a mean age of 16.61 ± 0.78 years were recruited in Kuala Lumpur. The Sport Motivation Scale, a 28-item self-report questionnaire measuring seven subscales (i.e., intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, extrinsic motivation to identify regulation, extrinsic motivation for introjection regulation, extrinsic motivation to external regulation, and amotivation was administered. Results showed significant differences (t=10.43, df=239, p=0.01 between total scores of intrinsic and extrinsic motivation among tenpin bowlers. There were significant gender differences with respect to intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, and extrinsic motivation to identify regulation. However, no significant bowler type differences were found for either the intrinsic (t=-1.15, df=238, p=0.25 or extrinsic (t=-0.51, df=238, p=0.61 motivation dimensions. In conclusion, our study demonstrated substantial intrinsic motivation for gender effects, but no bowler type effects among adolescent ten-pin bowlers.

  16. Craniocerebral trauma. Magnetic resonance imaging of diffuse axonal injury

    International Nuclear Information System (INIS)

    Mallouhi, A.

    2014-01-01

    Acceleration-deceleration rotational brain trauma is a common cause of disability or death in young adults and often leads to a focal destruction of axons. The resulting pathology, axonal shear injury is referred to as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are widely dispersed and have been observed in the surface and deep white matter. They are found near to and far from the impact site. When DAI is clinically suspected, magnetic resonance imaging (MRI) is the method of choice for further clarification, especially in patients where cranial computed tomography (CT) is inconspicuous. To investigate the presence of DAI after traumatic brain injury (TBI), a multimodal MRI approach is applied including the common structural and also functional imaging sequences. For structural MRI, fluid-attenuated inversion recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the sequences mainly used. The SWI technique is extremely sensitive to blood breakdown products, which appear as small signal voids at three locations, at the gray-white interface, in the corpus callosum and in the brain stem. Functional MRI comprises a group of constantly developing techniques that have great potential in optimal evaluation of the white matter in patients after craniocerebral trauma. These imaging techniques allow the visualization of changes associated with shear injuries, such as functional impairment of axons and decreased blood flow and abnormal metabolic activity of the brain parts affected. The multimodal MRI approach in patients with DAI results in a more detailed and differentiated representation of the underlying pathophysiological changes of the injured nerve tracts and helps to improve the diagnostic and prognostic accuracy of MRI. When DAI is suspected multimodal MRI should be performed as soon as possible after craniocerebral injury. (orig.) [de

  17. Polyethylene glycol restores axonal conduction after corpus callosum transection

    Directory of Open Access Journals (Sweden)

    Ravinder Bamba

    2017-01-01

    Full Text Available Polyethylene glycol (PEG has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA were used to measure mean firing rate (MFR and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05. These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  18. Polyethylene glycol restores axonal conduction after corpus callosum transection.

    Science.gov (United States)

    Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P

    2017-05-01

    Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups ( P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  19. International guidance activities

    International Nuclear Information System (INIS)

    Richardson, Allan C.B.

    1989-01-01

    International principles for setting Protective Action Guides (PAGs) are contained in two key documents that contain identical statements. One is Publication Number 40 of the ICRP, which was issued in 1985. The title is 'Protection of the Public in the Event of Major Radiation Accidents, Principles for Planning'. The other is the IAEA's Safety Series Publication Number 72, also issued in 1985, written by many of the same authors and titled, 'Principles for Establishing Intervention Levels'. The principles that were set forth in these documents were identical, were incomplete, and they are, unfortunately, the only principles that are now in effect, while proposed revisions go through one draft after another. There are several such draft revisions that are of significance. The most important is that of the ICRP. The basic guidance that applies to most planned exposure to radiation is ICRP Publication 26. That document has been under revision by the Commission for a number of years, and the new version will, for the first time, include recommendations for emergency response. They are now getting close to closure, and I think it should be a very much improved and useful document. But it isn't finished yet. Such guidance doesn't get developed in a vacuum, and there have been a couple of parallel efforts which have provided significant input to the ICRP, which is essentially a behind-closed-doors effort. These other efforts are more open. One of these is being carried out within the IAEA, which has convened annual meetings of national experts for a number of years in Vienna, to generate a replacement for Safety Series No. 72, mentioned earlier. There is a meeting scheduled this December to complete this effort; and, hopefully, we will reach closure at that meeting on at least the basic principles. The Nuclear Energy Agency (NEA) has also been at work. It has convened a group of experts from member nations that have been developing recommendations. There is an overlap

  20. RH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2006-01-01

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' It further states: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M and O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 Code of Federal Regulations (CFR) 1.8, 'Deliberate Misconduct.' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, 'Packaging and Transportation of Radioactive Material,' certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, 'Reporting of Defects and Noncompliance,' regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to these

  1. RH Packaging Program Guidance

    International Nuclear Information System (INIS)

    2008-01-01

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the 'RH-TRU 72-B cask') and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: 'each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application.' It further states: 'each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application.' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M and O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) 71.8, 'Deliberate Misconduct.' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, 'Packaging and Transportation of Radioactive Material,' certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, 'Reporting of Defects and Noncompliance,' regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous

  2. Prediction of Functional Outcome in Axonal Guillain-Barre Syndrome.

    Science.gov (United States)

    Sung, Eun Jung; Kim, Dae Yul; Chang, Min Cheol; Ko, Eun Jae

    2016-06-01

    To identify the factors that could predict the functional outcome in patients with the axonal type of Guillain-Barre syndrome (GBS). Two hundred and two GBS patients admitted to our university hospital between 2003 and 2014 were reviewed retrospectively. We defined a good outcome as being "able to walk independently at 1 month after onset" and a poor outcome as being "unable to walk independently at 1 month after onset". We evaluated the factors that differed between the good and poor outcome groups. Twenty-four patients were classified into the acute motor axonal neuropathy type. There was a statistically significant difference between the good and poor outcome groups in terms of the GBS disability score at admission, and GBS disability score and Medical Research Council sum score at 1 month after admission. In an electrophysiologic analysis, the good outcome group showed greater amplitude of median, ulnar, deep peroneal, and posterior tibial nerve compound muscle action potentials (CMAP) and greater amplitude of median, ulnar, and superficial peroneal sensory nerve action potentials (SNAP) than the poor outcome group. A lower GBS disability score at admission, high amplitude of median, ulnar, deep peroneal, and posterior tibial CMAPs, and high amplitude of median, ulnar, and superficial peroneal SNAPs were associated with being able to walk at 1 month in patients with axonal GBS.

  3. Axonal Control of the Adult Neural Stem Cell Niche

    Science.gov (United States)

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  4. Vesicular glutamate release from central axons contributes to myelin damage.

    Science.gov (United States)

    Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

    2018-03-12

    The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

  5. Retinal glia promote dorsal root ganglion axon regeneration.

    Directory of Open Access Journals (Sweden)

    Barbara Lorber

    Full Text Available Axon regeneration in the adult central nervous system (CNS is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.

  6. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  7. Pathophysiologic insights into motor axonal function in Kennedy disease.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2007-11-06

    Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

  8. Intrinsic and extrinsic motivational orientations in the competitive context: an examination of person-situation interactions.

    Science.gov (United States)

    Abuhamdeh, Sami; Csikszentmihalyi, Mihaly

    2009-10-01

    The current study examined Intrinsic Motivation Orientation and Extrinsic Motivation Orientation (Work Preference Inventory; Amabile, Hill, Hennessey, & Tighe, 1994) as potential trait-level moderators of the way Internet chess players responded to the intrinsic and extrinsic rewards of the chess games they played. On the basis of the defining characteristics of these 2 types of motivational orientations, we predicted that (a) Intrinsic Motivation Orientation would be associated with a stronger curvilinear relationship between challenge and enjoyment and (b) Extrinsic Motivation Orientation would be associated with a heightened affective responsivity to competitive outcome (i.e., winning vs. losing). Results supported the predictions. Implications of the findings are discussed.

  9. Plowshare radiation protection guidance

    International Nuclear Information System (INIS)

    Parker, H.M.

    1969-01-01

    The recommendations of the ICRP and the NCRP were developed primarily for occupational radiation exposures. They were later modified and applied to non-occupational exposures of populations. These, with appropriate interpretations, can be used to provide Plowshare radiation protection guidance. Exposures from Plowshare operations will tend to be acute, arising from radionuclides of relatively short half-life, but will have some chronic aspects due to small amounts of long-lived radionuclides generated. In addition, the neutron activation process of Plowshare technology will produce radionuclides not commonly encountered in routine nuclear energy programs. How these radionuclides contribute to personnel exposure is known for only a few situations that may not be representative of Plowshare exposure. Further complications arise from differences in radionuclide deposition and physiological sensitivity among individuals of different ages and states of health in the exposed population. All parameters necessary to evaluate such exposures are not available, even for good quantitative approximations, resulting in the need for interpretive experience. (author)

  10. Plowshare radiation protection guidance

    Energy Technology Data Exchange (ETDEWEB)

    Parker, H M [Environmental and Life Sciences Division, Battelle Memorial Institute, Pacific Northwest Laboratory, Richland, WA (United States)

    1969-07-01

    The recommendations of the ICRP and the NCRP were developed primarily for occupational radiation exposures. They were later modified and applied to non-occupational exposures of populations. These, with appropriate interpretations, can be used to provide Plowshare radiation protection guidance. Exposures from Plowshare operations will tend to be acute, arising from radionuclides of relatively short half-life, but will have some chronic aspects due to small amounts of long-lived radionuclides generated. In addition, the neutron activation process of Plowshare technology will produce radionuclides not commonly encountered in routine nuclear energy programs. How these radionuclides contribute to personnel exposure is known for only a few situations that may not be representative of Plowshare exposure. Further complications arise from differences in radionuclide deposition and physiological sensitivity among individuals of different ages and states of health in the exposed population. All parameters necessary to evaluate such exposures are not available, even for good quantitative approximations, resulting in the need for interpretive experience. (author)

  11. NGST fine guidance sensor

    Science.gov (United States)

    Rowlands, Neil; Hutchings, John; Murowinski, Richard G.; Alexander, Russ

    2003-03-01

    Instrumentation for the Next Generation Space Telescope (NGST) is currently in the Phase A definition stage. We have developed a concept for the NGST Fine Guidance Sensor or FGS. The FGS is a detector array based imager which resides in the NGST focal plane. We report here on tradeoff studies aimed at defining an overall configuration of the FGS which will meet the performance and interface requirements. A key performance requirement is a noise equivalent angle of 3 milli-arcseconds to be achieved with 95% probability for any pointing of the observatory in the celestial sphere. A key interface requirement is compatibility with the architecture of the Integrated Science Instrument Module (ISIM). The concept developed consists of two independent and redundant FGS modules, each with a 4' x 2' field of view covered by two 2048 x 2048 infrared detector arrays, providing 60 milli-arcsecond sampling. Performance modeling supporting the choice of this architecture and the trade space considered is presented. Each module has a set of readout electronics which perform star detection, pixel-by-pixel correction, and in fine guiding mode, centroid calculation. These readout electronics communicate with the ISIM Command &Data Handling Units where the FGS control software is based. Rationale for this choice of architecture is also presented.

  12. In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging.

    Science.gov (United States)

    Cao, Xu; Wang, Haiqiong; Wang, Zhao; Wang, Qingyao; Zhang, Shuang; Deng, Yuanping; Fang, Yanshan

    2017-10-01

    Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochondria or axonal degeneration. Further, unlike in in vitro cultured neurons, we found that mitophagy rarely occurred in intact axons in vivo, even in aged animals. Furthermore, blocking overall mitophagy by knockdown of the core autophagy genes Atg12 or Atg17 had little effect on the turnover of axonal mitochondria or axonal integrity, suggesting that mitophagy is not required for axonal maintenance; this is regardless of whether the mitophagy is PINK1-Parkin dependent or independent. In contrast, downregulation of mitochondrial fission-fusion genes caused age-dependent axonal degeneration. Moreover, Opa1 expression in the fly head was significantly decreased with age, which may underlie the accumulation of fragmented mitochondria in aged axons. Finally, we showed that adult-onset, neuronal downregulation of the fission-fusion, but not mitophagy genes, dramatically accelerated features of aging. We propose that axonal mitochondria are maintained independently of mitophagy and that mitophagy-independent mechanisms such as fission-fusion may be central to the maintenance of axonal mitochondria and neural integrity during normal aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

    Science.gov (United States)

    Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

    2017-09-27

    Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the

  14. Intrinsic and extrinsic rewards in a nonformal environmental education program.

    Science.gov (United States)

    Price, Emily A; Vining, Joanne; Saunders, Carol D

    2009-09-01

    Humans are surrounded by threats to the environment, many of their own making. The severity of environmental problems will not decrease unless action is taken to develop and encourage greater environmentally responsible behavior (ERB) in the general populace. Environmental education (EE) is one method for strengthening precursors to ERB such as knowledge and attitudes, but research on the connection is currently unclear. In this paper we present the results of a study investigating the role played by rewards in encouraging ERB precursors for adults and children involved in a zoo-based Nature Swap program. We used semistructured interviews to question 91 participants, including 38 children, 38 adult guardians, and 15 staff members regarding the importance of rewards in the program. We content analyzed the interviews to identify and describe major themes and then coded them. We found that adult guardians and Play Partners perceived intrinsic and extrinsic rewards as aiding in maintaining motivation and interest in the nonformal Nature Swap program. In addition, both children and adult companion participants in the program mentioned strengthened precursors to ERB. Overall we found that adult companions perceived that children who participated in the program spent more quality time outdoors and had a heightened awareness of their surroundings as a result of program-based rewards. Implications for other EE and conservation education programs are discussed.

  15. Enabling complex genetic circuits to respond to extrinsic environmental signals.

    Science.gov (United States)

    Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

    2017-07-01

    Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Rethinking the extrinsic incubation period of malaria parasites.

    Science.gov (United States)

    Ohm, Johanna R; Baldini, Francesco; Barreaux, Priscille; Lefevre, Thierry; Lynch, Penelope A; Suh, Eunho; Whitehead, Shelley A; Thomas, Matthew B

    2018-03-12

    The time it takes for malaria parasites to develop within a mosquito, and become transmissible, is known as the extrinsic incubation period, or EIP. EIP is a key parameter influencing transmission intensity as it combines with mosquito mortality rate and competence to determine the number of mosquitoes that ultimately become infectious. In spite of its epidemiological significance, data on EIP are scant. Current approaches to estimate EIP are largely based on temperature-dependent models developed from data collected on parasite development within a single mosquito species in the 1930s. These models assume that the only factor affecting EIP is mean environmental temperature. Here, we review evidence to suggest that in addition to mean temperature, EIP is likely influenced by genetic diversity of the vector, diversity of the parasite, and variation in a range of biotic and abiotic factors that affect mosquito condition. We further demonstrate that the classic approach of measuring EIP as the time at which mosquitoes first become infectious likely misrepresents EIP for a mosquito population. We argue for a better understanding of EIP to improve models of transmission, refine predictions of the possible impacts of climate change, and determine the potential evolutionary responses of malaria parasites to current and future mosquito control tools.

  17. Dynamic Changes of Neuroskeletal Proteins in DRGs Underlie Impaired Axonal Maturation and Progressive Axonal Degeneration in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Hideki Kamiya

    2009-01-01

    Full Text Available We investigated mechanisms underlying progressive axonal dysfunction and structural deficits in type 1 BB/Wor-rats from 1 week to 10 month diabetes duration. Motor and sensory conduction velocities were decreased after 4 and 6 weeks of diabetes and declined further over the remaining 9 months. Myelinated sural nerve fibers showed progressive deficits in fiber numbers and sizes. Structural deficits in unmyelinated axonal size were evident at 2 month and deficits in number were present at 4 mo. These changes were preceded by decreased availability of insulin, C-peptide and IGF-1 and decreased expression of neurofilaments and β-III-tubulin. Upregulation of phosphorylating stress kinases like Cdk5, p-GSK-3β, and p42/44 resulted in increased phosphorylation of neurofilaments. Increasing activity of p-GSK-3β correlated with increasing phosphorylation of NFH, whereas decreasing Cdk5 correlated with diminishing phosphorylation of NFM. The data suggest that impaired neurotrophic support results in sequentially impaired synthesis and postranslational modifications of neuroskeletal proteins, resulting in progressive deficits in axonal function, maturation and size.

  18. General RMP Guidance - Appendix D: OSHA Guidance on PSM

    Science.gov (United States)

    OSHA's Process Safety Management (PSM) Guidance on providing complete and accurate written information concerning process chemicals, process technology, and process equipment; including process hazard analysis and material safety data sheets.

  19. CAREER GUIDANCE EXPERIENCE ABROAD

    Directory of Open Access Journals (Sweden)

    Sergey N. Tolstoguzov

    2015-01-01

    Full Text Available The aim of this paper is to describe the experience of careeroriented activities carried out with students of schools in developed and developing countries. Career Guidance in Russia, despite the vast experience of its implementation, is experiencing serious difficulties. In this regard, it is important to take into account the international experience career-oriented activities, such as in the developed countries of North America and the European Union as well as in several Asian countries with rapidly growing economies and a large demographic potential, taking into account the best variants for the Russian education system. Methods. The experience of career-oriented work undertaken with pupils of the USA, Canada, Israel, France, UK, Germany, Denmark, Sweden, Japan, Singapore, China and India is shown on the basis of the comparative analysis of different publications and information sources. The author has made an attempt to generalize the principles of psycho-pedagogical and administrative assistance in professional self-determination of senior pupils abroad. Scientific novelty. The approaches to career-oriented activities in countries with different levels of economic development are compared for the first time. Some principles are revealed. Firstly, the higher the income level per capita in the country, the greater attention is given to vocational guidance. The politics in the developed countries is based on interests of the individual: children’s acquaintance with the world of professions begins already at younger school and the moment of definitive selfdetermination is postponed till the end of their senior stage of education; the possibility of direction change of professional preparation in case of detection of discrepancy of qualities of the pupil to originally selected profile is provided. Career-oriented activity in developing countries, on the contrary, is rigidly coordinated to requirements of economy and a labour market

  20. RH Packaging Program Guidance

    International Nuclear Information System (INIS)

    Washington TRU Solutions, LLC

    2003-01-01

    The purpose of this program guidance document is to provide technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the SARP and/or C of C shall govern. The C of C states: ''...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, ''Operating Procedures,'' of the application.'' It further states: ''...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, ''Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M and O) contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC approved, users need to be familiar with 10 CFR (section) 71.11, ''Deliberate Misconduct.'' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. This document details the instructions to be followed to operate, maintain, and test the RH-TRU 72-B packaging. This Program Guidance standardizes instructions for all users. Users shall follow these instructions. Following these instructions assures that operations are safe and meet the requirements of the SARP. This document is available on the Internet at: ttp://www.ws/library/t2omi/t2omi.htm. Users are responsible for ensuring they are using the current revision and change notices. Sites may prepare their own document using the word

  1. The continuum of behavior guidance.

    Science.gov (United States)

    Nelson, Travis

    2013-01-01

    Behavior guidance is a continuum of techniques, basic and advanced, fundamental to the provision of quality dental care for pediatric patients. This practice must be individualized, pairing the correct method of behavior guidance with each child. To select the appropriate technique, the clinician must have a thorough understanding of each aspect of the continuum and anticipate parental expectations, child temperament, and the technical procedures necessary to complete care. By effectively using techniques within the continuum of behavior guidance, a healing relationship with the family is maintained while addressing dental disease and empowering the child to receive dental treatment throughout their lifetime. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Regulatory guidance for license renewal

    International Nuclear Information System (INIS)

    Thoma, John A.

    1991-01-01

    The proposed 10 CFR Part 54 rule proceduralizes the process for license renewal by identifying both the administrative and technical requirements for a renewal application. To amplify and support this regulation, written guidance has been provided in the form of a draft Regulatory Guide (DG 1009) and a draft Standard Review Plan for License Renewal (NUREG 1299). This guidance is scheduled to be finalized in 1992. Similar guidance will be provided for the proposed revisions to 10 CFR Part 51 concerning the environmental aspects of license renewal. (author)

  3. European Educational Research Quality Indicators (EERQI): A first prototype framework of intrinsic and extrinsic indicators

    NARCIS (Netherlands)

    Mooij, Ton

    2011-01-01

    Mooij, T. (2011, 15-16 March). European Educational Research Quality Indicators (EERQI): A first prototype framework of intrinsic and extrinsic indicators. Paper presented at the final EERQI conference, Brussels, University Foundation.

  4. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    Science.gov (United States)

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  5. The detrimental effects of extrinsic reinforcement on “Intrinsic motivation”

    Science.gov (United States)

    Dickinson, Alyce M.

    1989-01-01

    Extrinsic consequences have been criticized on the grounds that they decrease intrinsic motivation or internally initiated behavior. Two popular rationales for this criticism, Lepper's overjustification hypothesis (1981) and Deci's motivational theory (Deci & Ryan, 1985), are reviewed and the criticism is then redefined behaviorally. “Intrinsically controlled” behavior is defined as behavior maintained by response-produced reinforcers, and the question concerning extrinsic consequences is thus restated as follows: When behavior is maintained by response-produced stimuli, does extrinsic reinforcement decrease the reinforcing value of those stimuli? The empirical support for this detrimental effect is summarized briefly, and several possible explanations for the phenomenon are offered. Research results that reflect on the effect's generality and social significance are discussed next, with the conclusion that the effect is transient and not likely to occur at all if extrinsic rewards are reinforcing, noncompetitive, based on reasonable performance standards, and delivered repetitively. PMID:22478013

  6. Self-Perception of Intrinsic and Extrinsic Motivation: Effects on Institutionalized Mentally Retarded Adolescents

    Science.gov (United States)

    Lee, Dong Yul; And Others

    1977-01-01

    The self-perception theory which predicts that the introduction of extrinsic rewards for behavior that was intrinsically rewarding may decrease overall motivation was tested on 44 mildly retarded institutionalized adolescents. (Author/CL)

  7. Axonal Spheroid Accumulation In the Brainstem and Spinal Cord of A Young Angus Cow with Ataxia.

    Science.gov (United States)

    Hanshaw, D M; Finnie, J W; Manavis, J; Kessell, A E

    2015-08-01

    An 18-month-old Angus cow presented with rapidly developing ataxia and subsequently died. The finding of large numbers of axonal spheroids in brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in distribution, was consistent with a histopathological diagnosis of neuroaxonal dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid precursor protein, suggesting that interruption to axonal flow was important in their genesis. The topographical distribution of axonal spheroids in the brain and spinal cord in this bovine case closely resembled that found in the ovine neurodegenerative disorder termed NAD, in which axonal swellings are the major pathological feature. This appears to be the first reported case of this type of NAD in cattle. The aetiology of the spheroidal aggregations in this case was not determined. There was no evidence from the case history or neuropathology to indicate whether the axonal spheroids in this case involved an acquired or heritable aetiology. © 2015 Australian Veterinary Association.

  8. Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.

    Science.gov (United States)

    Ma, Marek

    2013-12-01

    Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed. © 2013.

  9. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso...... their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient...

  10. Reanalysis of the EMC charm production data with extrinsic and intrinsic charm at NLO

    International Nuclear Information System (INIS)

    Harris, B.W.; Vogt, R.

    1996-01-01

    A calculation of the next-to-leading order exclusive extrinsic charm quark differential distributions in deeply inelastic electroproduction has recently been completed. Using these results we compare the NLO extrinsic contributions to the charm structure function F 2 (x,Q 2 ,m c 2 ) with the corresponding NLO intrinsic contributions. The results of this analysis are compared with the EMC DIS charm quark data and evidence for an intrinsic charm component in the proton is found. (orig.)

  11. Distinguishing subtypes of extrinsic motivation among people with mild to borderline intellectual disability

    OpenAIRE

    Frielink, N.; Schuengel, C.; Embregts, P.J.C.M.

    2017-01-01

    Background According to self-determination theory, motivation is ordered in types, including amotivation, extrinsic motivation and intrinsic motivation. Self-determination theory defines four subtypes of extrinsic motivation: external motivation, introjected motivation, identified motivation and integrated motivation. Although it has been argued theoretically that the different types of motivation are universally applicable, Reid et al. (2009) proposed a dichotomy of broad subtypes of extrins...

  12. A comparison of South African and German extrinsic and intrinsic motivation

    OpenAIRE

    Snelgar, Robin; Shelton, Stacy A.; Giesser, Anne

    2017-01-01

    Background: Various researchers have identified a trend of individuals shifting their preference from extrinsic to intrinsic motivation. The authors aimed to research this phenomenon specifically within the context of two different cultures as to date, this had not been done. This research explored the differing levels of extrinsic and intrinsic motivation in Germans and South Africans. Aim: The main objective of this study was to investigate similarities and differences concerning extrins...

  13. A validity generalization procedure to test relations between intrinsic and extrinsic motivation and influence tactics.

    Science.gov (United States)

    Barbuto, John E; Moss, Jennifer A

    2006-08-01

    The relations of intrinsic and extrinsic motivation with use of consultative, legitimating, and pressure influence tactics were examined using validity generalization procedures. 5 to 7 field studies with cumulative samples exceeding 800 were used to test each relationship. Significance was found for relation between agents' intrinsic motivation and their use of consultative influence tactics and agents' extrinsic motivation and their use of legitimating influence tactics.

  14. The relationship between extrinsic motivation, job satisfaction and life satisfaction amongst employees in a public organisation

    OpenAIRE

    Mafini, Chengedzai; Dlodlo, Nobukhosi

    2014-01-01

    Orientation: There is much research on extrinsic motivation, job satisfaction and life satisfaction in organisations. However, empirical evidence on how such factors affect employees in public organisations in developing countries is lacking. Research purpose: To examine the relationships between extrinsic motivation, job satisfaction and life satisfaction amongst employees in a public organisation. Motivation for the study: Labour strife is an endemic phenomenon in South Africa’s publ...

  15. The Effect Of Extrinsic Motivation On Adversity Quotient In Patients With HIV/AIDS

    OpenAIRE

    Nursalam, Nursalam; Misutarno, Misutarno; Puspitawati, Yulia Dewi

    2017-01-01

    Introduction: Patients with HIV/AIDS may have various types of psychological responses. It was very difficult situation for them. Difficulty can measured by using Adversity Quotient. As a nurse, we can give extrinsic motivation to bring back the patient HIV/AIDS’s quality of life. The objective of this study was to identify the presence effect of extrinsic motivation on Adversity Quotient in patients with HIV/AIDS in Infectious Disease Intermediateatery Treatment Unit, Dr. Soetomo Hospital, S...

  16. The Effect of Extrinsic Motivation on Adversity Quotient in Patients with Hiv/aids

    OpenAIRE

    Nursalam, Nursalam; Misutarno, Misutarno; Puspitawati, Yulia Dewi

    2008-01-01

    Introduction: Patients with HIV/AIDS may have various types of psychological responses. It was very difficult situation for them. Difficulty can measured by using Adversity Quotient. As a nurse, we can give extrinsic motivation to bring back the patient HIV/AIDS’s quality of life. The objective of this study was to identify the presence effect of extrinsic motivation on Adversity Quotient in patients with HIV/AIDS in Infectious Disease Intermediateatery Treatment Unit, Dr. Soetomo Hospital, S...

  17. The detrimental effects of extrinsic reinforcement on “Intrinsic motivation”

    OpenAIRE

    Dickinson, Alyce M.

    1989-01-01

    Extrinsic consequences have been criticized on the grounds that they decrease intrinsic motivation or internally initiated behavior. Two popular rationales for this criticism, Lepper's overjustification hypothesis (1981) and Deci's motivational theory (Deci & Ryan, 1985), are reviewed and the criticism is then redefined behaviorally. “Intrinsically controlled” behavior is defined as behavior maintained by response-produced reinforcers, and the question concerning extrinsic consequences is thu...

  18. SPLC Sustainable Purchasing Guidance Profile

    Science.gov (United States)

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  19. CDM Convective Forecast Planning guidance

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The CDM Convective Forecast Planning (CCFP) guidance product provides a foreast of en-route aviation convective hazards. The forecasts are updated every 2 hours and...

  20. Guidance at the educational marketplace

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    in educational policies and institutions. As educational systems have expanded and, further, have been restructured with the expansion of choice opportunities since the 1980s, guidance has become prioritized as a form of counseling or coaching, which can support students. Thus, guidance has become an important...... `agent´ on the educational "market´, assisting (potential) students into and around the `marketplace´. Consequently, guidance is also an important `agent´ for educational institutions that increasingly use marketing strategies to promote themselves on the market to attract and hold on to their “customers......” in order for the institutions to increase their ´market value´, `sales” and “turnover”. Thus, the expansion of guidance is nurtured by the expansion of the logic of marketization and consumerism. Drawing on Foucauldian perspectives in educational research, which highlight the expansion of powerful...

  1. REGENERATIVE GROWTH OF CORTICOSPINAL TRACT AXONS VIA THE VENTRAL COLUMN AFTER SPINAL CORD INJURY IN MICE

    OpenAIRE

    Steward, Oswald; Zheng, Binhai; Tessier-Lavigne, Marc; Hofstadter, Maura; Sharp, Kelli; Yee, Kelly Matsudaira

    2008-01-01

    Studies that have assessed regeneration of corticospinal tract (CST) axons in mice following genetic modifications or other treatments have tacitly assumed that there is little if any regeneration of CST axons in normal mice in the absence of some intervention. Here, we document a previously unrecognized capability for regenerative growth of CST axons in normal mice that involves growth past the lesion via the ventral column. Mice received dorsal hemisection injuries at thoracic level 6–7, wh...

  2. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

    OpenAIRE

    Jablonka, Sibylle; Beck, Marcus; Lechner, Barbara Dorothea; Mayer, Christine; Sendtner, Michael

    2007-01-01

    Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced f...

  3. Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

  4. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Science.gov (United States)

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  5. The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

    Directory of Open Access Journals (Sweden)

    Giulio Caravagna

    Full Text Available After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii a model of enzymatic futile cycle and (iii a genetic toggle switch. In (ii and (iii we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

  6. Influential Effects of Intrinsic-Extrinsic Incentive Factors on Management Performance in New Energy Enterprises.

    Science.gov (United States)

    Wang, Ping; Lu, Zhengnan; Sun, Jihong

    2018-02-08

    Background : New energy has become a key trend for global energy industry development. Talent plays a very critical role in the enhancement of new energy enterprise competitiveness. As a key component of talent, managers have been attracting more and more attention. The increase in job performance relies on, to a certain extent, incentive mechanism. Based on the Two-factor Theory, differences in influences and effects of different incentives on management performance have been checked in this paper from an empirical perspective. Methods : This paper selects the middle and low level managers in new energy enterprises as research samples and classifies the managers' performance into task performance, contextual performance and innovation performance. It uses manager performance questionnaires and intrinsic-extrinsic incentive factor questionnaires to investigate and study the effects and then uses Amos software to analyze the inner link between the intrinsic-extrinsic incentives and job performance. Results : Extrinsic incentives affect task performance and innovation performance positively. Intrinsic incentives impose active significant effects on task performance, contextual performance, and innovation performance. The intrinsic incentive plays a more important role than the extrinsic incentive. Conclusions : Both the intrinsic-extrinsic incentives affect manager performance positively and the intrinsic incentive plays a more important role than the extrinsic incentive. Several suggestions to management should be given based on these results.

  7. The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

    Science.gov (United States)

    Caravagna, Giulio; Mauri, Giancarlo; d'Onofrio, Alberto

    2013-01-01

    After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i) the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii) a model of enzymatic futile cycle and (iii) a genetic toggle switch. In (ii) and (iii) we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

  8. Intrinsic to extrinsic phonon lifetime transition in a GaAs–AlAs superlattice

    International Nuclear Information System (INIS)

    Hofmann, F; Garg, J; Chen, G; Maznev, A A; Nelson, K A; Jandl, A; Bulsara, M; Fitzgerald, E A

    2013-01-01

    We have measured the lifetimes of two zone-center longitudinal acoustic phonon modes, at 320 and 640 GHz, in a 14 nm GaAs/2 nm AlAs superlattice structure. By comparing measurements at 296 and 79 K we separate the intrinsic contribution to phonon lifetime determined by phonon–phonon scattering from the extrinsic contribution due to defects and interface roughness. At 296 K, the 320 GHz phonon lifetime has approximately equal contributions from intrinsic and extrinsic scattering, whilst at 640 GHz it is dominated by extrinsic effects. These measurements are compared with intrinsic and extrinsic scattering rates in the superlattice obtained from first-principles lattice dynamics calculations. The calculated room-temperature intrinsic lifetime of longitudinal phonons at 320 GHz is in agreement with the experimentally measured value of 0.9 ns. The model correctly predicts the transition from predominantly intrinsic to predominantly extrinsic scattering; however the predicted transition occurs at higher frequencies. Our analysis indicates that the ‘interfacial atomic disorder’ model is not entirely adequate and that the observed frequency dependence of the extrinsic scattering rate is likely to be determined by a finite correlation length of interface roughness. (paper)

  9. Extrinsic response enhancement at the polymorphic phase boundary in piezoelectric materials

    Energy Technology Data Exchange (ETDEWEB)

    Ochoa, Diego A.; García, José E., E-mail: jose.eduardo.garcia@upc.edu [Department of Physics, Universitat Politècnica de Catalunya - BarcelonaTech, Barcelona 08034 (Spain); Esteves, Giovanni; Jones, Jacob L. [Department of Materials Science and Engineering, North Carolina State University, Raleigh, North Carolina 27696 (United States); Rubio-Marcos, Fernando; Fernández, José F. [Department of Electroceramics, Instituto de Cerámica y Vidrio - CSIC, Madrid 28049 (Spain)

    2016-04-04

    Polymorphic phase boundaries (PPBs) in piezoelectric materials have attracted significant interest in recent years, in particular, because of the unique properties that can be found in their vicinity. However, to fully harness their potential as micro-nanoscale functional entities, it is essential to achieve reliable and precise control of their piezoelectric response, which is due to two contributions known as intrinsic and extrinsic. In this work, we have used a (K,Na)NbO{sub 3}-based lead-free piezoceramic as a model system to investigate the evolution of the extrinsic contribution around a PPB. X-ray diffraction measurements are performed over a wide range of temperatures in order to determine the structures and transitions. The relevance of the extrinsic contribution at the PPB region is evaluated by means of nonlinear dielectric response measurements. Though it is widely appreciated that certain intrinsic properties of ferroelectric materials increase as PPBs are approached, our results demonstrate that the extrinsic contribution also maximizes. An enhancement of the extrinsic contribution is therefore also responsible for improving the functional properties at the PPB region. Rayleigh's law is used to quantitatively analyze the nonlinear response. As a result, an evolution of the domain wall motion dynamics through the PPB region is detected. This work demonstrates that the extrinsic contribution at a PPB may have a dynamic role in lead-free piezoelectric materials, thereby exerting a far greater influence on their functional properties than that considered to date.

  10. Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.

    Science.gov (United States)

    Wachter, Franziska; Grunert, Michaela; Blaj, Cristina; Weinstock, David M; Jeremias, Irmela; Ehrhardt, Harald

    2013-04-17

    The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling. We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity. In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.

  11. Intrinsic to extrinsic phonon lifetime transition in a GaAs-AlAs superlattice.

    Science.gov (United States)

    Hofmann, F; Garg, J; Maznev, A A; Jandl, A; Bulsara, M; Fitzgerald, E A; Chen, G; Nelson, K A

    2013-07-24

    We have measured the lifetimes of two zone-center longitudinal acoustic phonon modes, at 320 and 640 GHz, in a 14 nm GaAs/2 nm AlAs superlattice structure. By comparing measurements at 296 and 79 K we separate the intrinsic contribution to phonon lifetime determined by phonon-phonon scattering from the extrinsic contribution due to defects and interface roughness. At 296 K, the 320 GHz phonon lifetime has approximately equal contributions from intrinsic and extrinsic scattering, whilst at 640 GHz it is dominated by extrinsic effects. These measurements are compared with intrinsic and extrinsic scattering rates in the superlattice obtained from first-principles lattice dynamics calculations. The calculated room-temperature intrinsic lifetime of longitudinal phonons at 320 GHz is in agreement with the experimentally measured value of 0.9 ns. The model correctly predicts the transition from predominantly intrinsic to predominantly extrinsic scattering; however the predicted transition occurs at higher frequencies. Our analysis indicates that the 'interfacial atomic disorder' model is not entirely adequate and that the observed frequency dependence of the extrinsic scattering rate is likely to be determined by a finite correlation length of interface roughness.

  12. Influential Effects of Intrinsic-Extrinsic Incentive Factors on Management Performance in New Energy Enterprises

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2018-02-01

    Full Text Available Background: New energy has become a key trend for global energy industry development. Talent plays a very critical role in the enhancement of new energy enterprise competitiveness. As a key component of talent, managers have been attracting more and more attention. The increase in job performance relies on, to a certain extent, incentive mechanism. Based on the Two-factor Theory, differences in influences and effects of different incentives on management performance have been checked in this paper from an empirical perspective. Methods: This paper selects the middle and low level managers in new energy enterprises as research samples and classifies the managers’ performance into task performance, contextual performance and innovation performance. It uses manager performance questionnaires and intrinsic-extrinsic incentive factor questionnaires to investigate and study the effects and then uses Amos software to analyze the inner link between the intrinsic-extrinsic incentives and job performance. Results: Extrinsic incentives affect task performance and innovation performance positively. Intrinsic incentives impose active significant effects on task performance, contextual performance, and innovation performance. The intrinsic incentive plays a more important role than the extrinsic incentive. Conclusions: Both the intrinsic-extrinsic incentives affect manager performance positively and the intrinsic incentive plays a more important role than the extrinsic incentive. Several suggestions to management should be given based on these results.

  13. Resistance to abrasion of extrinsic porcelain esthetic characterization techniques.

    Science.gov (United States)

    Chi, Woo J; Browning, William; Looney, Stephen; Mackert, J Rodway; Windhorn, Richard J; Rueggeberg, Frederick

    2017-01-01

    groups. In this study, the novel external characterization technique (stain+LFP: Group SL) did not significantly enhance the wear resistance against toothbrush abrasion. Instead, the average wear of the applied extrinsic porcelain was 2 to 3 times more than Group S (stain only) and Group GS (glaze over stain). Application of a glaze layer over the colorants (Group GS) showed a significant improvement on wear resistance. Despite its superior physical properties, the leucite reinforced ceramic core (Group C) showed 2 to 4 times more wear when compared with other test groups. A conventional external esthetic characterization technique of applying a glaze layer over the colorants (Group GS) significantly enhanced the surface wear resistance to toothbrush abrasion when compared with other techniques involving application of colorants only (Group S) or mixture of colorant and LFP (Group SL). The underlying core ceramic had significantly less wear resistance compared with all externally characterized specimens. The novel esthetic characterization technique showed more wear and less color stability, and is thus not advocated as the "best" method for surface characterization. Application of a glaze layer provides a more wear-resistant surface from toothbrush abrasion when adjusting or extrinsically characterizing leucite reinforced ceramic restorations. Without the glaze layer, the restoration is subjected to a 2 to 4 times faster rate and amount of wear leading to possible shade mismatch.

  14. [Anterior guidance in complete dentures].

    Science.gov (United States)

    Dubreuil, J; Trevelo, A

    1990-01-01

    Although the anterior guidance in complete dentures is not really a guide, the arrangement of the anterior maxillary and mandibular prosthetic teeth, defines a propulsive line called the virtual anterior guidance, a part from the cinematic criterias. The influence of this guide on cuspal movement is superior, in all mandibular points, to the influence of the condylar pathway. If this line is not respected, the practitioner may have to do excessive grindings during occlusal adjustments.

  15. Extrinsic Calibration for Vehicle-based Mobile Mapping System

    Directory of Open Access Journals (Sweden)

    SHI Limei

    2015-01-01

    Full Text Available Having the advantage of 360° imaging and rotation invariance, panoramic camera has gradually been used in mobile mapping systems(MMS. Calibration is an essential requirement to make sure that MMS can get high quality geo-information. This paper presents a way to address the extrinsic calibration for vehicle-based MMS composed of panoramic camera and Position and Orientation System (POS. Firstly, control points in the natural scene are set up, whose spatial coordinates are measured with high precision. Secondly, a panoramic spherical model is constructed and panoramic image can be projected to this model by means of spherical reverse transformation projection. Then, localize and select the control points in 3D spherical panoramic view but not in panoramic distorted image directly, the spherical coordinates of control points in panoramic image are gotten. After points correspondence is established, make use of direct geo-reference positioning equation and coordinate transformation, the translation and rotation parameters of panoramic camera relative to POS are computed. Experiments are conducted separately in space city calibration site located in Beijing and the Binhai New Area in Tianjin using our approach. Test results are listed as follows. When the GPS signal are of good quality, absolute positioning mean square error of a point is 10.3 cm in two-dimension plane and 16.5 cm in height direction; Otherwise, it is 35.4 cm in two-dimension plane and 54.8 cm in height direction. The max relative error of distance measurement is about 5 cm over a short distance (distance<3 km, which is not obviously affected by the GPS signal quality.

  16. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Christian Witzel

    2015-01-01

    Full Text Available Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection. ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005 and the number of arborizing axons (21% vs. 16% P = 0.008 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  17. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

    Science.gov (United States)

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

    2016-01-01

    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

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

    Science.gov (United States)

    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

  19. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Jan Jessen Krut

    Full Text Available Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL (marker of neuronal injury, neopterin (intrathecal immunoactivation and CSF/Plasma albumin ratio (blood-brain barrier integrity were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200, HIV-associated dementia (HAD (n = 14 and on combinations antiretroviral treatment (cART (n = 85, and healthy controls (n = 204. 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation.While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups.Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further

  20. Axon-Schwann cell interaction in the squid nerve fibre.

    Science.gov (United States)

    Villegas, J

    1972-09-01

    The electrical properties of Schwann cells and the effects of neuronal impulses on their membrane potential have been studied in the giant nerve fibre of the squid.1. The behaviour of the Schwann cell membrane to current injection into the cell was ohmic. No impulse-like responses were observed with displacements of 35 mV in the membrane potential. The resistance of the Schwann cell membrane was found to be approximately 10(3) Omega cm(2).2. A long-lasting hyperpolarization is observed in the Schwann cells following the conduction of impulse trains by the axon. Whereas the propagation of a single impulse had little effect, prolonged stimulation of the fibre at 250 impulses/sec was followed by a hyperpolarization of the Schwann cell that gradually declined over a period of several minutes.3. The prolonged effects of nerve impulse trains on the Schwann cell were similar to those produced by depolarizing current pulses applied to the axon by the voltage-clamp technique. Thus, a series of depolarizing pulses in the axon was followed by a long-lasting hyperpolarization of the Schwann cells. In contrast, the application of a series of hyperpolarizing 100 mV pulses at a frequency of 1/sec had no apparent effects.4. Changes in the external potassium concentration did not reproduce the long-lasting effects of nerve excitation.5. The hyperpolarizing effects of impulse trains were abolished by the incubation of the nerve fibre in a sea-water solution containing trypsin.6. These findings are discussed in relation to the possible mechanisms that might be responsible for the long-lasting hyperpolarizations of the Schwann cells.

  1. Excitability properties of motor axons in adults with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Cliff S. Klein

    2015-06-01

    Full Text Available Cerebral Palsy (CP is a permanent disorder caused by a lesion to the developing brain that significantly impairs motor function. The neurophysiological mechanisms underlying motor impairment are not well understood. Specifically, few have addressed whether motoneuron or peripheral axon properties are altered in CP, even though disruption of descending inputs to the spinal cord may cause them to change. In the present study, we have compared nerve excitability properties in seven adults with CP and fourteen healthy controls using threshold tracking techniques by stimulating the median nerve at the wrist and recording the compound muscle action potential (CMAP over the abductor pollicis brevis. The excitability properties in the CP subjects were found to be abnormal. Early and late depolarizing and hyperpolarizing threshold electrotonus was significantly larger (i.e., fanning out, and resting current-threshold (I/V slope was smaller, in CP compared to control. In addition resting threshold and rheobase tended to be larger in CP. According to a modeling analysis of the data, an increase in leakage current under or through the myelin sheath, i.e., the Barrett-Barrett conductance (GBB, combined with a slight hyperpolarization of the resting membrane potential, best explained the group differences in excitability properties. There was a trend for those with greater impairment in gross motor function to have more abnormal axon properties. The findings indicate plasticity of motor axon properties far removed from the site of the lesion. We suspect that this plasticity is caused by disruption of descending inputs to the motoneurons at an early age around the time of their injury.

  2. Mechanisms of hyperpolarization in regenerated mature motor axons in cat

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2004-01-01

    We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...

  3. Understanding the Function of Tuberous Sclerosis Complex Genes in Neural Development: Roles in Synapse Assembly and Axon Guidance

    Science.gov (United States)

    2012-02-01

    physiological levels (Jan and Jan, 1976; Gramates and Budnik, 1999; Ruiz-Canada and Budnik, 2006; Schuster, 2006). The Drosophila...Gherbesi N, Thomas U, Gundelfinger E, Gramates LS, et al. 2007. Postsynaptic membrane addition depends on the discs-large-interacting t-SNARE gtaxin. J...Neurosci 27:1033–1044. Gramates LS, Budnik V. 1999. Assembly and maturation of the Drosophila larval neuromuscular junction. Int Rev Neurobiol 43

  4. Differential expression of anti-angiogenic factors and guidance genes in the developing macula.

    Science.gov (United States)

    Kozulin, Peter; Natoli, Riccardo; O'Brien, Keely M Bumsted; Madigan, Michele C; Provis, Jan M

    2009-01-01

    The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color vision. The spatial resolution provided by the neural retina at the macula is optimized by stereotyped retinal blood vessel and ganglion cell axon patterning, which radiate away from the macula and reduce shadowing of macular photoreceptors. However, the genes that mediate these specializations, and the reasons for the vulnerability of the macula to degenerative disease, remain obscure. The aim of this study was to identify novel genes that may influence retinal vascular patterning and definition of the foveal avascular area. We used RNA from human fetal retinas at 19-20 weeks of gestation (WG; n=4) to measure differential gene expression in the macula, a region nasal to disc (nasal) and in the surrounding retina (surround) by hybridization to 12 GeneChip microarrays (HG-U133 Plus 2.0). The raw data was subjected to quality control assessment and preprocessing, using GC-RMA. We then used ANOVA analysis (Partek) Genomic Suite 6.3) and clustering (DAVID website) to identify the most highly represented genes clustered according to "biological process." The neural retina is fully differentiated at the macula at 19-20 WG, while neuronal progenitor cells are present throughout the rest of the retina. We therefore excluded genes associated with the cell cycle, and markers of differentiated neurons, from further analyses. Significantly regulated genes (pmacula versus surround" and "macula versus nasal." KEGG pathway clustering of the filtered gene lists identified 25 axon guidance-related genes that are differentially regulated in the macula. Furthermore, we found significant upregulation of three anti-angiogenic factors in the macula: pigment epithelium derived factor (PEDF), natriuretic peptide precurusor B (NPPB), and collagen type IValpha2. Differential expression of several members of the ephrin and semaphorin axon guidance gene families, PEDF, and NPPB was verified by

  5. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport

    Science.gov (United States)

    Freundt, Eric C.; Maynard, Nate; Clancy, Eileen K.; Roy, Shyamali; Bousset, Luc; Sourigues, Yannick; Covert, Markus; Melki, Ronald; Kirkegaard, Karla; Brahic, Michel

    2012-01-01

    Objective The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Results Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey. PMID:23109146

  6. Quality in career guidance: The Danish case

    DEFF Research Database (Denmark)

    Plant, Peter

    2011-01-01

    Quality assurance systems are introduced in career guidance to monitor, control and develop guidance interventions. The Danish case represents at centrally driven, top-down approach......Quality assurance systems are introduced in career guidance to monitor, control and develop guidance interventions. The Danish case represents at centrally driven, top-down approach...

  7. Recollection and unitization in associating actors with extrinsic and intrinsic motions.

    Science.gov (United States)

    Kersten, Alan W; Earles, Julie L; Berger, Johanna D

    2015-04-01

    Four experiments provide evidence for a distinction between 2 different kinds of motion representations. Extrinsic motions involve the path of an object with respect to an external frame of reference. Intrinsic motions involve the relative motions of the parts of an object. This research suggests that intrinsic motions are represented conjointly with information about the identities of the actors who perform them, whereas extrinsic motions are represented separately from identity information. Experiment 1 demonstrated that participants remembered which actor had performed a particular intrinsic motion better than they remembered which actor had performed a particular extrinsic motion. Experiment 2 replicated this effect with incidental encoding of actor information, suggesting that encoding intrinsic motions leads one to automatically encode identity information. The results of Experiments 3 and 4 were fit by Yonelinas's (1999) source-memory model to quantify the contributions of familiarity and recollection to memory for the actors who carried out the intrinsic and extrinsic motions. Successful performance with extrinsic motion items in Experiment 3 required participants to remember in which scene contexts an actor had appeared, whereas successful performance in Experiment 4 required participants to remember the exact path taken by an actor in each scene. In both experiments, discrimination of old and new combinations of actors and extrinsic motions relied strongly on recollection, suggesting independent but associated representations of actors and extrinsic motions. In contrast, participants discriminated old and new combinations of actors and intrinsic motions primarily on the basis of familiarity, suggesting unitized representations of actors and intrinsic motions. (c) 2015 APA, all rights reserved).

  8. Bimanual motor coordination controlled by cooperative interactions in intrinsic and extrinsic coordinates.

    Science.gov (United States)

    Sakurada, Takeshi; Ito, Koji; Gomi, Hiroaki

    2016-01-01

    Although strong motor coordination in intrinsic muscle coordinates has frequently been reported for bimanual movements, coordination in extrinsic visual coordinates is also crucial in various bimanual tasks. To explore the bimanual coordination mechanisms in terms of the frame of reference, here we characterized implicit bilateral interactions in visuomotor tasks. Visual perturbations (finger-cursor gain change) were applied while participants performed a rhythmic tracking task with both index fingers under an in-phase or anti-phase relationship in extrinsic coordinates. When they corrected the right finger's amplitude, the left finger's amplitude unintentionally also changed [motor interference (MI)], despite the instruction to keep its amplitude constant. Notably, we observed two specificities: one was large MI and low relative-phase variability (PV) under the intrinsic in-phase condition, and the other was large MI and high PV under the extrinsic in-phase condition. Additionally, using a multiple-interaction model, we successfully decomposed MI into intrinsic components caused by motor correction and extrinsic components caused by visual-cursor mismatch of the right finger's movements. This analysis revealed that the central nervous system facilitates MI by combining intrinsic and extrinsic components in the condition with in-phases in both intrinsic and extrinsic coordinates, and that under-additivity of the effects is explained by the brain's preference for the intrinsic interaction over extrinsic interaction. In contrast, the PV was significantly correlated with the intrinsic component, suggesting that the intrinsic interaction dominantly contributed to bimanual movement stabilization. The inconsistent features of MI and PV suggest that the central nervous system regulates multiple levels of bilateral interactions for various bimanual tasks. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and

  9. Distinct neural control of intrinsic and extrinsic muscles of the hand during single finger pressing.

    Science.gov (United States)

    Dupan, Sigrid S G; Stegeman, Dick F; Maas, Huub

    2018-06-01

    Single finger force tasks lead to unintended activation of the non-instructed fingers, commonly referred to as enslaving. Both neural and mechanical factors have been associated with this absence of finger individuality. This study investigates the amplitude modulation of both intrinsic and extrinsic finger muscles during single finger isometric force tasks. Twelve participants performed single finger flexion presses at 20% of maximum voluntary contraction, while simultaneously the electromyographic activity of several intrinsic and extrinsic muscles associated with all four fingers was recorded using 8 electrode pairs in the hand and two 30-electrode grids on the lower arm. The forces exerted by each of the fingers, in both flexion and extension direction, were recorded with individual force sensors. This study shows distinct activation patterns in intrinsic and extrinsic hand muscles. Intrinsic muscles exhibited individuation, where the agonistic and antagonistic muscles associated with the instructed fingers showed the highest activation. This activation in both agonistic and antagonistic muscles appears to facilitate finger stabilisation during the isometric force task. Extrinsic muscles show an activation independent from instructed finger in both agonistic and antagonistic muscles, which appears to be associated with stabilisation of the wrist, with an additional finger-dependent modulation only present in the agonistic extrinsic muscles. These results indicate distinct muscle patterns in intrinsic and extrinsic hand muscles during single finger isometric force pressing. We conclude that the finger specific activation of intrinsic muscles is not sufficient to fully counteract enslaving caused by the broad activation of the extrinsic muscles. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Intrinsic and Extrinsic Motivation Among Adolescent Ten-Pin Bowlers in Kuala Lumpur, Malaysia

    Science.gov (United States)

    Teo, Eng-Wah; Khoo, Selina; Wong, Rebecca; Wee, Eng-Hoe; Lim, Boon-Hooi; Rengasamy, Shabesan Sit

    2015-01-01

    Motivation has long been associated with sports engagement. However, to date no research has been performed to understand the domain of motivation among ten-pin bowlers. The purpose of this study was to investigate different types of motivation (i.e., intrinsic vs. extrinsic) based on self-determination theory from the perspective of gender and the bowler type (competitive vs. casual). A total of 240 bowlers (104 male, 136 female; 152 competitive, 88 casual) with a mean age of 16.61 ± 0.78 years were recruited in Kuala Lumpur. The Sport Motivation Scale, a 28-item self-report questionnaire measuring seven subscales (i.e., intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, extrinsic motivation to identify regulation, extrinsic motivation for introjection regulation, extrinsic motivation to external regulation, and amotivation) was administered. Results showed significant differences (t=10.43, df=239, p=0.01) between total scores of intrinsic and extrinsic motivation among ten-pin bowlers. There were significant gender differences with respect to intrinsic motivation to know, intrinsic motivation to accomplish, intrinsic motivation to experience stimulation, and extrinsic motivation to identify regulation. However, no significant bowler type differences were found for either the intrinsic (t=−1.15, df=238, p=0.25) or extrinsic (t=−0.51, df=238, p=0.61) motivation dimensions. In conclusion, our study demonstrated substantial intrinsic motivation for gender effects, but no bowler type effects among adolescent ten-pin bowlers. PMID:25964827

  11. THE EFFECT OF EXTRINSIC MOTIVATION ON ADVERSITY QUOTIENT IN PATIENTS WITH HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Nursalam Nursalam

    2017-07-01

    Full Text Available Introduction: Patients with HIV/AIDS may have various types of psychological responses. It was very difficult situation for them. Difficulty can measured by using Adversity Quotient. As a nurse, we can give extrinsic motivation to bring back the patient HIV/AIDS’s quality of life. The objective of this study was to identify the presence effect of extrinsic motivation on Adversity Quotient in patients with HIV/AIDS in Infectious Disease Intermediateatery Treatment Unit, Dr. Soetomo Hospital, Surabaya. Method: This study was used a quasy experimental purposive sampling design. The population was taken from ambulatory patients. There were 16 respondents who met to the inclusion criteria. The independent variable was extrinsic motivation and dependent variable was Adversity Quotient. Data were collected by using questionnaire and interview, then analyzed by using Wilcoxon Signed Rank Test and Mann Whitney U Test with significance level p=0.05. Result: The result revealed that there was an effect of extrinsic motivation on Adversity Quotient of patients with HIV/AIDS (p=0.017. The extrinsic motivation was found to have an effect on control response (p=0.027 and origin response (p=0.028, there was no influence of extrinsic motivation on ownership response (p=0.334, reach (p=0.129 and endurance (p=0.161. Discussion: It can be concluded that the extrinsic motivation with intervention of social support has a positive effect on the improvement of Adversity Quotient in patients with HIV/AIDS. Further studies should measure the effectiveness of Adversity Quotient training on acceptance response in patients with HIV/AIDS.

  12. Intrinsic and extrinsic spin-orbit torques from first principles

    International Nuclear Information System (INIS)

    Geranton, Guillaume

    2017-01-01

    This thesis attempts to shed light on the microscopic mechanisms underlying the current-induced magnetic torques in ferromagnetic heterostructures. We have developed first principles methods aiming at the accurate and effcient calculation of the so-called spin-orbit torques (SOTs) in magnetic thin films. The emphasis of this work is on the impurity-driven extrinsic SOTs. The main part of this thesis is dedicated to the development of a formalism for the calculation of the SOTs within the Korringa-Kohn-Rostoker (KKR) method. The impurity-induced transitions rates are obtained from first principles and their effect on transport properties is treated within the Boltzmann formalism. The developed formalism provides a mean to compute the SOTs beyond the conventional constant relaxation time approximation. We first apply our formalism to the investigation of FePt/Pt and Co/Cu bilayers in the presence of defects and impurities. Our results hint at a crucial dependence of the torque on the type of disorder present in the films, which we explain by a complex interplay of several competing Fermi surface contributions to the SOT. Astonishingly, specific defect distributions or doping elements lead respectively to an increase or a sign change of the torque, which can not be explained on the basis of simple models. We also compute the intrinsic SOT induced by electrical and thermal currents within the full potential linearized augmented plane-wave method. Motivated by recent experimental works, we then investigate the microscopic origin of the SOT in a Ag_2Bi-terminated Ag film grown on ferromagnetic Fe(110). We find that the torque in that system can not be explained solely by the spin-orbit coupling in the Ag_2Bi alloy, and instead results from the spin-orbit coupling in all regions of the film.Finally, we predict a large SOT in Fe/Ge bilayers and suggest that semiconductor substrates might be a promising alternative to heavy metals for the development of SOT-based magnetic

  13. Intrinsic and extrinsic spin-orbit torques from first principles

    Energy Technology Data Exchange (ETDEWEB)

    Geranton, Guillaume

    2017-09-01

    This thesis attempts to shed light on the microscopic mechanisms underlying the current-induced magnetic torques in ferromagnetic heterostructures. We have developed first principles methods aiming at the accurate and effcient calculation of the so-called spin-orbit torques (SOTs) in magnetic thin films. The emphasis of this work is on the impurity-driven extrinsic SOTs. The main part of this thesis is dedicated to the development of a formalism for the calculation of the SOTs within the Korringa-Kohn-Rostoker (KKR) method. The impurity-induced transitions rates are obtained from first principles and their effect on transport properties is treated within the Boltzmann formalism. The developed formalism provides a mean to compute the SOTs beyond the conventional constant relaxation time approximation. We first apply our formalism to the investigation of FePt/Pt and Co/Cu bilayers in the presence of defects and impurities. Our results hint at a crucial dependence of the torque on the type of disorder present in the films, which we explain by a complex interplay of several competing Fermi surface contributions to the SOT. Astonishingly, specific defect distributions or doping elements lead respectively to an increase or a sign change of the torque, which can not be explained on the basis of simple models. We also compute the intrinsic SOT induced by electrical and thermal currents within the full potential linearized augmented plane-wave method. Motivated by recent experimental works, we then investigate the microscopic origin of the SOT in a Ag{sub 2}Bi-terminated Ag film grown on ferromagnetic Fe(110). We find that the torque in that system can not be explained solely by the spin-orbit coupling in the Ag{sub 2}Bi alloy, and instead results from the spin-orbit coupling in all regions of the film.Finally, we predict a large SOT in Fe/Ge bilayers and suggest that semiconductor substrates might be a promising alternative to heavy metals for the development of SOT

  14. Spatiotemporal expression of repulsive guidance molecules (RGMs and their receptor neogenin in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Dianne M A van den Heuvel

    Full Text Available Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5 family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development.

  15. Nociceptive DRG neurons express muscle lim protein upon axonal injury.

    Science.gov (United States)

    Levin, Evgeny; Andreadaki, Anastasia; Gobrecht, Philipp; Bosse, Frank; Fischer, Dietmar

    2017-04-04

    Muscle lim protein (MLP) has long been regarded as a cytosolic and nuclear muscular protein. Here, we show that MLP is also expressed in a subpopulation of adult rat dorsal root ganglia (DRG) neurons in response to axonal injury, while the protein was not detectable in naïve cells. Detailed immunohistochemical analysis of L4/L5 DRG revealed ~3% of MLP-positive neurons 2 days after complete sciatic nerve crush and maximum ~10% after 4-14 days. Similarly, in mixed cultures from cervical, thoracic, lumbar and sacral DRG ~6% of neurons were MLP-positive after 2 days and maximal 17% after 3 days. In both, histological sections and cell cultures, the protein was detected in the cytosol and axons of small diameter cells, while the nucleus remained devoid. Moreover, the vast majority could not be assigned to any of the well characterized canonical DRG subpopulations at 7 days after nerve injury. However, further analysis in cell culture revealed that the largest population of MLP expressing cells originated from non-peptidergic IB4-positive nociceptive neurons, which lose their ability to bind the lectin upon axotomy. Thus, MLP is mostly expressed in a subset of axotomized nociceptive neurons and can be used as a novel marker for this population of cells.

  16. Profiling biomarkers of traumatic axonal injury: From mouse to man.

    Science.gov (United States)

    Manivannan, Susruta; Makwana, Milan; Ahmed, Aminul Islam; Zaben, Malik

    2018-05-18

    Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points. Copyright © 2018. Published by Elsevier B.V.

  17. Bridging the gap: axonal fusion drives rapid functional recovery of the nervous system

    Directory of Open Access Journals (Sweden)

    Jean-Sébastien Teoh

    2018-01-01

    Full Text Available Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair. This inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to patients. Compared to humans, a number of species possess far greater regenerative capabilities, and can therefore provide important insights into how our own nervous systems can be repaired. In particular, several invertebrate species have been shown to rapidly initiate regeneration post-injury, allowing separated axon segments to re-join. This process, known as axonal fusion, represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original structure. Our recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged neurons. Moreover, we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion, and discovered that the level of axonal fusion can be enhanced by promoting a neuron's intrinsic growth potential. A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting.

  18. Noninvasive Detection and Differentiation of Axonal Injury/Loss, Demyelination, and Inflammation

    Science.gov (United States)

    2014-10-01

    phosphorylated neurofilament primary antibody (SMI-31; 1:1000, Covance , US) to stain non-injured axons, and in rabbit anti-myelin basic protein (MBP) primary...neurofilament antibody (SMI- 31; 1:1000, Covance , US) to stain non-injured axons or with rabbit anti-myelin basic protein (MBP) antibody (1:1000, Sigma Inc

  19. MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents.

    Science.gov (United States)

    Kawauchi, Daisuke; Kobayashi, Hiroaki; Sekine-Aizawa, Yoko; Fujita, Shinobu C; Murakami, Fujio

    2003-10-01

    Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.

  20. Interaction between the soma and the axon terminal of horizontal cells in carp retina

    NARCIS (Netherlands)

    Kamermans, M.; van Dijk, B. W.; Spekreijse, H.

    1990-01-01

    In teleost retina, the receptive fields of horizontal cell axon terminals have a larger space constant than the receptive fields of the horizontal cell somata. Generally this difference in receptive field size is attributed to the cell coupling which is assumed to be stronger in the horizontal axon

  1. Axon-somatic back-propagation in detailed models of spinal alpha motoneurons

    Directory of Open Access Journals (Sweden)

    Pietro eBalbi

    2015-02-01

    Full Text Available Antidromic action potentials following distal stimulation of motor axons occasionally fail to invade the soma of alpha motoneurons in spinal cord, due to their passing through regions of high non-uniformity.Morphologically detailed conductance-based models of cat spinal alpha motoneurons have been developed, with the aim to reproduce and clarify some aspects of the electrophysiological behavior of the antidromic axon-somatic spike propagation. Fourteen 3D morphologically detailed somata and dendrites of cat spinal alpha motoneurons have been imported from an open-access web-based database of neuronal morphologies, NeuroMorpho.org, and instantiated in neurocomputational models. An axon hillock, an axonal initial segment and a myelinated axon are added to each model.By sweeping the diameter of the axonal initial segment (AIS and the axon hillock, as well as the maximal conductances of sodium channels at the AIS and at the soma, the developed models are able to show the relationships between different geometric and electrophysiological configurations and the voltage attenuation of the antidromically travelling wave.In particular, a greater than usually admitted sodium conductance at AIS is necessary and sufficient to overcome the dramatic voltage attenuation occurring during antidromic spike propagation both at the myelinated axon-AIS and at the AIS-soma transitions.

  2. Structure and Function of an Actin-Based Filter in the Proximal Axon

    Directory of Open Access Journals (Sweden)

    Varuzhan Balasanyan

    2017-12-01

    Full Text Available Summary: The essential organization of microtubules within neurons has been described; however, less is known about how neuronal actin is arranged and the functional implications of its arrangement. Here, we describe, in live cells, an actin-based structure in the proximal axon that selectively prevents some proteins from entering the axon while allowing the passage of others. Concentrated patches of actin in proximal axons are present shortly after axonal specification in rat and zebrafish neurons imaged live, and they mark positions where anterogradely traveling vesicles carrying dendritic proteins halt and reverse. Patches colocalize with the ARP2/3 complex, and when ARP2/3-mediated nucleation is blocked, a dendritic protein mislocalizes to the axon. Patches are highly dynamic, with few persisting longer than 30 min. In neurons in culture and in vivo, actin appears to form a contiguous, semipermeable barrier, despite its apparently sparse distribution, preventing axonal localization of constitutively active myosin Va but not myosin VI. : Balasanyan et al. find dynamic patches of actin in proximal axons of live neurons, mature and newly differentiated, in culture and in vivo. Patches contribute to a filter that sequesters some proteins within the somatodendritic domain while allowing others to pass into the axon, leading to polarized localization of proteins.

  3. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

    Directory of Open Access Journals (Sweden)

    Giorgi Kharebava

    2015-12-01

    Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

  4. A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity.

    Directory of Open Access Journals (Sweden)

    Romain Cartoni

    Full Text Available Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons. Here, using a microfluidic culture system we compared neurons co-deleted for PTEN and SOCS3, an established model of high axonal regeneration capacity, to control neurons. We measured the axonal transport of three cargos (mitochondria, synaptic vesicles and late endosomes in regenerating axons and found that the transport of mitochondria, but not the other cargos, was increased in PTEN/SOCS3 co-deleted axons relative to controls. The results reported here suggest a pivotal role for this organelle during axonal regeneration.

  5. In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

    Science.gov (United States)

    Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

    2007-02-01

    Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

  6. Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

    Directory of Open Access Journals (Sweden)

    Yihao Zhang

    2017-02-01

    Full Text Available Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav, which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

  7. Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

    Science.gov (United States)

    Zhang, Yihao; Abiraman, Krithika; Li, He; Pierce, David M; Tzingounis, Anastasios V; Lykotrafitis, George

    2017-02-01

    Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav), which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

  8. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri

    2015-01-01

    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  9. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  10. Information architecture. Volume 3: Guidance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

  11. The relationship between extrinsic motivation, job satisfaction and life satisfaction amongst employees in a public organisation

    Directory of Open Access Journals (Sweden)

    Chengedzai Mafini

    2014-04-01

    Research purpose: To examine the relationships between extrinsic motivation, job satisfaction and life satisfaction amongst employees in a public organisation. Motivation for the study: Labour strife is an endemic phenomenon in South Africa’s public sector as evidenced by the high incidences of industrial action and labour turnover. This study contributes to this subject by identifying the extrinsic factors that could be optimised with a view to enhancing job and life satisfaction amongst government employees. Research approach, design and method: The study used the quantitative research survey approach: a questionnaire was administered to 246 employees in a South African public organisation. Extrinsic motivation factors were identified using principal components analysis. Mean score ranking was used to compare the relative importance of all factors. The conceptual framework was tested using Spearman’s rank correlation analysis and linear regression analysis. Main findings: Statistically significant relationships were observed between job satisfaction and four extrinsic motivation factors: remuneration, quality of work life, supervision and teamwork. The relationship with promotion was insignificant, but a statistically significant relationship was established with life satisfaction. Practical/managerial implications: The findings may be used to implement strategies for enhancing employee performance and industrial relations within public organisations. Contribution/value-add: The study provides evidence of the interplay between extrinsic motivation, job satisfaction and life satisfaction for public servants in developing countries.

  12. Life Goals and Well-Being: Are Extrinsic Aspirations Always Detrimental to Well-Being?

    Directory of Open Access Journals (Sweden)

    Ingrid Brdar

    2009-12-01

    Full Text Available Past research has revealed that relative importance a person places on extrinsic life goals as oposed to intrinsic ones is related to lower well-being. But sometimes it is more important why a goal is being pursued than the content of the goal. Materialistic aspirations will not decrease people's well-being if they help them to achieve basic financial security or some intrinsic goals. On the other hand, if social comparison or seeking power drives extrinsic orientation, these aspirations may be detrimental for well-being, since they do not satisfy satisfy our basic psychological needs. Research from Croatia and other, less rich countries suggest that extrinsic aspirations are not necessarily deterimental but may even contribute to well-being. This finding suggests that various factors can moderate the relationship between aspirations and well-being. Intrinsic life goals may probably be affordable only for people who are well off enough. The meaning of financial success in transitional and poor countries may not necesseraly be associated with purchase and consumption. On the contrary, it may bring opportunities and possibilities of self-expression and self-growth. Individualistic societies allow individuals to pursue their intrinsic goals while collectivistic cultures stress extrinsic ones. Although this extrinsic orientation may detract their well-being, the sense of individual well-being may not be as important to them as the survival of the group they belong to or so called social well-being.

  13. Predictors of employment in schizophrenia: The importance of intrinsic and extrinsic motivation.

    Science.gov (United States)

    Reddy, L Felice; Llerena, Katiah; Kern, Robert S

    2016-10-01

    Unemployment is a primary functional deficit for the majority of adults with schizophrenia. Research indicates that over two-thirds of adults living in the community with schizophrenia are unemployed. Despite effective programs to assist with job identification and placement, the ability to attain and maintain employment remains a pressing concern. A contributing factor that may be relevant but has received little attention in the work rehabilitation literature is motivation. People with schizophrenia show marked deficits in both intrinsic and extrinsic motivation but these deficits have not been directly examined in relation to work outcomes. The present study sought to examine the relationship between intrinsic and extrinsic motivation and work outcome among a sample of 65 adults with schizophrenia enrolled in a supported employment program. One-third of the participants in the study obtained work. Intrinsic motivation related to valuing and feeling useful in a work role significantly predicted who would obtain employment. Extrinsic motivation related to gaining rewards and avoiding obstacles showed a non-significant trend-level relationship such that workers had higher extrinsic motivation than nonworkers. These findings highlight the importance of considering both intrinsic and extrinsic motivation in work-related interventions and supported employment for individuals with schizophrenia. The results are discussed in terms of clinical implications for improving rehabilitation and occupational outcomes in schizophrenia. Published by Elsevier B.V.

  14. Copper-65-absorption by men fed intrinsically and extrinsically labeled whole wheat bread

    International Nuclear Information System (INIS)

    Johnson, P.E.; Lykken, G.I.

    1988-01-01

    Six men were fed a diet composed of conventional foods with all bread as whole wheat bread. Intrinsically labeled 65 Cu bread (containing 6.5 ppm Cu and 48 atom % 65 Cu) was substituted for unlabeled bread for 3 days, and stools were collected for 24 days. Extrinsically labeled bread was then substituted for 3 days and another 24-day stool collection made. 65 Cu excretion was measured by mass spectrometry. Mean Cu intake was 1.10 mg of Cu/day. Average Cu balance was /minus/0.06 /+-/ 0.08 mg/day. Average absorption of the intrinsic copper was 72.2 /+-/ 9.3% and of extrinsic Cu 64.2 /+-/ 5.8%. The ratio of extrinsic to intrinsic absorption was 0.906 /+-/ 0.164. Absorption of intrinsic and extrinsic tracers did not differ significantly (p > 0.05) by a paired t-test, and the ratio (E/I) was not significantly different from 1. Use of extrinsic Cu tracers to assess Cu absorption is supported by these results

  15. Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system.

    Science.gov (United States)

    Gordon, Tessa; Udina, Esther; Verge, Valerie M K; de Chaves, Elena I Posse

    2009-10-01

    Injured peripheral but not central nerves regenerate their axons but functional recovery is often poor. We demonstrate that prolonged periods of axon separation from targets and Schwann cell denervation eliminate regenerative capacity in the peripheral nervous system (PNS). A substantial delay of 4 weeks for all regenerating axons to cross a site of repair of sectioned nerve contributes to the long period of separation. Findings that 1h 20Hz bipolar electrical stimulation accelerates axon outgrowth across the repair site and the downstream reinnervation of denervated muscles in rats and human patients, provides a new and exciting method to improve functional recovery after nerve injuries. Drugs that elevate neuronal cAMP and activate PKA promote axon outgrowth in vivo and in vitro, mimicking the electrical stimulation effect. Rapid expression of neurotrophic factors and their receptors and then of growth associated proteins thereafter via cAMP, is the likely mechanism by which electrical stimulation accelerates axon outgrowth from the site of injury in both peripheral and central nervous systems.

  16. Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    María Alejandra eLopez-Verrilli

    2012-06-01

    Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

  17. The disruption of mitochondrial axonal transport is an early event in neuroinflammation

    DEFF Research Database (Denmark)

    Errea, Oihana; Moreno, Beatriz; Gonzalez-Franquesa, Alba

    2015-01-01

    in the cerebellar slice cultures was analyzed through high-resolution respirometry assays and quantification of adenosine triphosphate (ATP) production. RESULTS: Both conditions promoted an increase in the size and complexity of axonal mitochondria evident in electron microscopy images, suggesting a compensatory...... acutely impairs axonal mitochondrial transportation, which would promote an inappropriate delivery of energy throughout axons and, by this way, contribute to axonal damage. Thus, preserving axonal mitochondrial transport might represent a promising avenue to exploit as a therapeutic target...... response. Such compensation was reflected at the tissue level as increased respiratory activity of complexes I and IV and as a transient increase in ATP production in response to acute inflammation. Notably, time-lapse microscopy indicated that mitochondrial transport (mean velocity) was severely impaired...

  18. Golgi bypass for local delivery of axonal proteins, fact or fiction?

    Science.gov (United States)

    González, Carolina; Cornejo, Víctor Hugo; Couve, Andrés

    2018-04-06

    Although translation of cytosolic proteins is well described in axons, much less is known about the synthesis, processing and trafficking of transmembrane and secreted proteins. A canonical rough endoplasmic reticulum or a stacked Golgi apparatus has not been detected in axons, generating doubts about the functionality of a local route. However, axons contain mRNAs for membrane and secreted proteins, translation factors, ribosomal components, smooth endoplasmic reticulum and post-endoplasmic reticulum elements that may contribute to local biosynthesis and plasma membrane delivery. Here we consider the evidence supporting a local secretory system in axons. We discuss exocytic elements and examples of autonomous axonal trafficking that impact development and maintenance. We also examine whether unconventional post-endoplasmic reticulum pathways may replace the canonical Golgi apparatus. Copyright © 2018. Published by Elsevier Ltd.

  19. Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development.

    Science.gov (United States)

    Gale, Jenna R; Aschrafi, Armaz; Gioio, Anthony E; Kaplan, Barry B

    2018-04-01

    Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

  20. Intra-axonal Synthesis of SNAP25 Is Required for the Formation of Presynaptic Terminals

    Directory of Open Access Journals (Sweden)

    Andreia F.R. Batista

    2017-09-01

    Full Text Available Localized protein synthesis is a mechanism for developing axons to react acutely and in a spatially restricted manner to extracellular signals. As such, it is important for many aspects of axonal development, but its role in the formation of presynapses remains poorly understood. We found that the induced assembly of presynaptic terminals required local protein synthesis. Newly synthesized proteins were detectable at nascent presynapses within 15 min of inducing synapse formation in isolated axons. The transcript for the t-SNARE protein SNAP25, which is required for the fusion of synaptic vesicles with the plasma membrane, was recruited to presynaptic sites and locally translated. Inhibition of intra-axonal SNAP25 synthesis affected the clustering of SNAP25 and other presynaptic proteins and interfered with the release of synaptic vesicles from presynaptic sites. This study reveals a critical role for the axonal synthesis of SNAP25 in the assembly of presynaptic terminals.

  1. Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus

    DEFF Research Database (Denmark)

    Jensen, M B; Poulsen, F R; Finsen, B

    2000-01-01

    to 35 days after transection of the entorhino-hippocampal perforant path axonal projection. In situ hybridization analysis showed that anterograde axonal and terminal degeneration lead to upregulated oligodendrocyte MBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratum...... axonal and terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. Oligodendrocyte MBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratum radiatum, stratum pyramidale and stratum oriens...... of CA1, areas that were unaffected by perforant path transection. These results provide strong evidence that oligodendrocyte MBP gene expression can be regulated by axonal sprouting independently of microglial activation in the injured adult CNS....

  2. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

    Science.gov (United States)

    Jao, Li-En; Appel, Bruce; Wente, Susan R

    2012-04-01

    In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

  3. Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

    Science.gov (United States)

    Rhee, K; Kim, J-H; Jung, D H; Han, J W; Lee, Y C; Lee, S K; Shin, S K; Park, J C; Chung, H S; Park, J J; Youn, Y H; Park, H

    2016-04-01

    Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic. © 2015 International Society for Diseases of the Esophagus.

  4. Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats

    Science.gov (United States)

    Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

    2013-01-01

    The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

  5. Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets.

    Science.gov (United States)

    Keeler, Austin B; Suo, Dong; Park, Juyeon; Deppmann, Christopher D

    2017-07-01

    Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i.e. calcium signaling), which dampens axon growth and branching. Based on the notion that axons do not express functional levels of Coronin-1 prior to final target innervation, we developed an in vitro model for axon growth and branching along intermediate targets using Coro1a -/- neurons grown in NT3. We found that, similar to NGF-TrkA, NT3-TrkA is capable of inducing MAPK and PI3K in the presence or absence of Coronin-1. However, unlike NGF, NT3 does not induce calcium release from intracellular stores. Using a combination of pharmacology, knockout neurons and in vitro functional assays, we suggest that the NT3-TrkA complex uses Ras/MAPK and/or PI3K-AKT signaling to induce axon growth and inhibit axon branching along intermediate targets. However, in the presence of Coronin-1, these signaling pathways lose their ability to impact NT3 dependent axon growth or branching. This is consistent with a role for Coronin-1 as a molecular switch for axon behavior and suggests that Coronin-1 suppresses NT3 dependent axon behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Path Taken: Consequences of Attaining Intrinsic and Extrinsic Aspirations in Post-College Life.

    Science.gov (United States)

    Niemiec, Christopher P; Ryan, Richard M; Deci, Edward L

    2009-06-01

    Life goals, or aspirations, organize and direct behavior over extended periods of time. The present study, guided by self-determination theory, examined the consequences of pursuing and attaining aspirations over a one-year period in a post-college sample. Results indicated that placing importance on either intrinsic or extrinsic aspirations related positively to attainment of those goals. Yet, whereas attainment of intrinsic aspirations related positively to psychological health, attainment of extrinsic aspirations did not; indeed, attainment of extrinsic aspirations related positively to indicators of ill-being. Also as predicted, the association between change in attainment of intrinsic aspirations and change in psychological health was mediated by change in the satisfaction of the basic psychological needs for autonomy, competence, and relatedness. Discussion focuses on the idea that not all goal attainment is beneficial; rather, attainment of aspirations with different contents relates differentially to psychological health.

  7. Intrinsic and extrinsic mechanical properties related to the differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Lee, Jin-Ho; Park, Hun-Kuk; Kim, Kyung Sook

    2016-05-06

    Diverse intrinsic and extrinsic mechanical factors have a strong influence on the regulation of stem cell fate. In this work, we examined recent literature on the effects of mechanical environments on stem cells, especially on differentiation of mesenchymal stem cells (MSCs). We provide a brief review of intrinsic mechanical properties of single MSC and examined the correlation between the intrinsic mechanical property of MSC and the differentiation ability. The effects of extrinsic mechanical factors relevant to the differentiation of MSCs were considered separately. The effect of nanostructure and elasticity of the matrix on the differentiation of MSCs were summarized. Finally, we consider how the extrinsic mechanical properties transfer to MSCs and then how the effects on the intrinsic mechanical properties affect stem cell differentiation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Intrinsic and extrinsic labeling for studies of manganese absorption in humans

    International Nuclear Information System (INIS)

    Davidsson, L.; Cederblad, A.; Hagebo, E.; Loennerdal, B.S.; Sandstroem, B.

    1988-01-01

    A dual-radioisotope method was used to simultaneously study whole-body manganese retention from a chicken liver based meal intrinsically labeled with 54 Mn and extrinsically labeled with 52 Mn. Manganese retention was monitored in a sensitive whole-body counter during approximately 30 d in six young adult women. Both radioisotopes were retained to a similar degree and excreted at identical rates. Retention at d 5 was 14.4 +/- 10.3 and 14.0 +/- 9.9% while retention at d 10 was 5.0 +/- 3.1 and 5.0 +/- 3.0% (X +/- SD) for 54 Mn and 52 Mn, respectively. From these results we conclude that the intrinsic and extrinsic Mn isotopes did form a common pool before absorption. The results can therefore be regarded as a direct validation of the use of extrinsic labeling for studies of Mn retention for estimating Mn absorption in man

  9. Not All Ideals are Equal: Intrinsic and Extrinsic Ideals in Relationships.

    Science.gov (United States)

    Rodriguez, Lindsey M; Hadden, Benjamin W; Knee, C Raymond

    2015-03-01

    The ideal standards model suggests that greater consistency between ideal standards and actual perceptions of one's relationship predicts positive relationship evaluations; however, no research has evaluated whether this differs across types of ideals. A self-determination theory perspective was derived to test whether satisfaction of intrinsic ideals buffers the importance of extrinsic ideals. Participants (N=195) in committed relationships directly and indirectly reported the extent to which their partner met their ideal on two dimensions: intrinsic (e.g., warm, intimate) and extrinsic (e.g., attractive, successful). Relationship need fulfillment and relationship quality were also assessed. Hypotheses were largely supported, such that satisfaction of intrinsic ideals more strongly predicted relationship functioning, and satisfaction of intrinsic ideals buffered the relevance of extrinsic ideals for outcomes.

  10. Extrinsic Contribution and Instability Properties in Lead-Based and Lead-Free Piezoceramics

    Directory of Open Access Journals (Sweden)

    José Eduardo García

    2015-11-01

    Full Text Available Piezoceramic materials generally exhibit a notable instability of their functional properties when they work under real external conditions. This undesirable effect, known as nonlinear behavior, is mostly associated with the extrinsic contribution to material response. In this article, the role of the ferroelectric domain walls’ motion in the nonlinear response in the most workable lead-based and lead-free piezoceramics is reviewed. Initially, the extrinsic origin of the nonlinear response is discussed in terms of the temperature dependence of material response. The influence of the crystallographic phase and of the phase boundaries on the material response are then reviewed. Subsequently, the impact of the defects created by doping in order to control the extrinsic contribution is discussed as a way of tuning material properties. Finally, some aspects related to the grain-size effect on the nonlinear response of piezoceramics are surveyed.

  11. No evidence for extrinsic post-zygotic isolation in a wild Saccharomyces yeast system.

    Science.gov (United States)

    Charron, Guillaume; Landry, Christian R

    2017-06-01

    Although microorganisms account for the largest fraction of Earth's biodiversity, we know little about how their reproductive barriers evolve. Sexual microorganisms such as Saccharomyces yeasts rapidly develop strong intrinsic post-zygotic isolation, but the role of extrinsic isolation in the early speciation process remains to be investigated. We measured the growth of F 1 hybrids between two incipient species of Saccharomyces paradoxus to assess the presence of extrinsic post-zygotic isolation across 32 environments. More than 80% of hybrids showed either partial dominance of the best parent or over-dominance for growth, revealing no fitness defects in F 1 hybrids. Extrinsic reproductive isolation therefore likely plays little role in limiting gene flow between incipient yeast species and is not a requirement for speciation. © 2017 The Author(s).

  12. Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice

    Directory of Open Access Journals (Sweden)

    Belén Mollá

    2017-08-01

    Full Text Available Friedreich’s ataxia (FRDA is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux. The homogenous distribution of axonal spheroids along the neurites supports the existence of continues focal damages. This lead us to propose for FRDA a model of distal axonopathy based on axonal focal damages. In addition, we observed the involvement of oxidative stress and dyshomeostasis of calcium in axonal spheroid formation generating axonal injury as a primary cause of pathophysiology. Axonal spheroids may be a consequence of calcium imbalance, thus we propose the quenching or removal extracellular Ca2+ to prevent spheroids formation. In our neuronal model, treatments with BAPTA and o-phenanthroline reverted the axonal dystrophy and the mitochondrial dysmorphic parameters. These results support the hypothesis that axonal pathology is reversible in FRDA by pharmacological manipulation of intracellular Ca2+ with Ca2+ chelators or metalloprotease inhibitors, preventing Ca2+-mediated axonal injury. Thus, the modulation of Ca2+ levels may be a relevant therapeutic target to develop early axonal protection and prevent dying-back neurodegeneration.

  13. DOE Waste Treatability Group Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, T.D.

    1995-01-01

    This guidance presents a method and definitions for aggregating U.S. Department of Energy (DOE) waste into streams and treatability groups based on characteristic parameters that influence waste management technology needs. Adaptable to all DOE waste types (i.e., radioactive waste, hazardous waste, mixed waste, sanitary waste), the guidance establishes categories and definitions that reflect variations within the radiological, matrix (e.g., bulk physical/chemical form), and regulated contaminant characteristics of DOE waste. Beginning at the waste container level, the guidance presents a logical approach to implementing the characteristic parameter categories as part of the basis for defining waste streams and as the sole basis for assigning streams to treatability groups. Implementation of this guidance at each DOE site will facilitate the development of technically defined, site-specific waste stream data sets to support waste management planning and reporting activities. Consistent implementation at all of the sites will enable aggregation of the site-specific waste stream data sets into comparable national data sets to support these activities at a DOE complex-wide level.

  14. Agent Based Individual Traffic Guidance

    DEFF Research Database (Denmark)

    Wanscher, Jørgen

    of the project were not previously considered. We define a special inseparable cost function and develop a solution complex capable of using this cost function. In relation to calibration and estimation of statistical models used for dynamic route guidance we worked with generating random number sequences...

  15. Consensus standard requirements and guidance

    International Nuclear Information System (INIS)

    Putman, V.L.

    1995-01-01

    This report presents information from the ANS Criticality Alarm System Workshop relating to the consensus standard requirements and guidance. Topics presented include: definition; nomenclature; requirements and recommendations; purpose of criticality alarms; design criteria; signal characteristics; reliability, dependability and durability; tests; and emergency preparedness and planning

  16. DOE Waste Treatability Group Guidance

    International Nuclear Information System (INIS)

    Kirkpatrick, T.D.

    1995-01-01

    This guidance presents a method and definitions for aggregating U.S. Department of Energy (DOE) waste into streams and treatability groups based on characteristic parameters that influence waste management technology needs. Adaptable to all DOE waste types (i.e., radioactive waste, hazardous waste, mixed waste, sanitary waste), the guidance establishes categories and definitions that reflect variations within the radiological, matrix (e.g., bulk physical/chemical form), and regulated contaminant characteristics of DOE waste. Beginning at the waste container level, the guidance presents a logical approach to implementing the characteristic parameter categories as part of the basis for defining waste streams and as the sole basis for assigning streams to treatability groups. Implementation of this guidance at each DOE site will facilitate the development of technically defined, site-specific waste stream data sets to support waste management planning and reporting activities. Consistent implementation at all of the sites will enable aggregation of the site-specific waste stream data sets into comparable national data sets to support these activities at a DOE complex-wide level

  17. The cholinergic ligand binding material of axonal membranes

    International Nuclear Information System (INIS)

    Mautner, H.G.; Coronado, R.; Jumblatt, J.E.

    1986-01-01

    Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

  18. Neurogenetics of slow axonal transport: from cells to animals.

    Science.gov (United States)

    Sadananda, Aparna; Ray, Krishanu

    2012-09-01

    Slow axonal transport is a multivariate phenomenon implicated in several neurodegenerative disorders. Recent reports have unraveled the molecular basis of the transport of certain slow component proteins, such as the neurofilament subunits, tubulin, and certain soluble enzymes such as Ca(2+)/calmodulin-dependent protein kinase IIa (CaM kinase IIa), etc., in tissue cultured neurons. In addition, genetic analyses also implicate microtubule-dependent motors and other housekeeping proteins in this process. However, the biological relevance of this phenomenon is not so well understood. Here, the authors have discussed the possibility of adopting neurogenetic analyses in multiple model organisms to correlate molecular level measurements of the slow transport phenomenon to animal behavior, thus facilitating the investigation of its biological efficacy.

  19. Neuron Morphology Influences Axon Initial Segment Plasticity123

    Science.gov (United States)

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  20. Dynein is the motor for retrograde axonal transport of organelles

    International Nuclear Information System (INIS)

    Schnapp, B.J.; Reese, T.S.

    1989-01-01

    Vesicular organelles in axons of nerve cells are transported along microtubules either toward their plus ends (fast anterograde transport) or toward their minus ends (retrograde transport). Two microtubule-based motors were previously identified by examining plastic beads induced to move along microtubules by cytosol fractions from the squid giant axon: (i) an anterograde motor, kinesin, and (ii) a retrograde motor, which is characterized here. The retrograde motor, a cytosolic protein previously termed HMW1, was purified from optic lobes and extruded axoplasm by nucleotide-dependent microtubule affinity and release; microtubule gliding was used as the assay of motor activity. The following properties of the retrograde motor suggest that it is cytoplasmic dynein: (i) sedimentation at 20-22 S with a heavy chain of Mr greater than 200,000 that coelectrophoreses with the alpha and beta subunits of axonemal dynein, (ii) cleavage by UV irradiation in the presence of ATP and vanadate, and (iii) a molecular structure resembling two-headed dynein from axonemes. Furthermore, bead movement toward the minus end of microtubules was blocked when axoplasmic supernatants were treated with UV/vanadate. Treatment of axoplasmic supernatant with UV/vanadate also blocks the retrograde movement of purified organelles in vitro without changing the number of anterograde moving organelles, indicating that dynein interacts specifically with a subgroup of organelles programmed to move toward the cell body. However, purified optic lobe dynein, like purified kinesin, does not by itself promote the movement of purified organelles along microtubules, suggesting that additional axoplasmic factors are necessary for retrograde as well as anterograde transport