WorldWideScience

Sample records for term axon maintenance

  1. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    " pockets. The total number of axons in the sural nerve was unchanged, but a greater proportion was unmyelinated. In addition, we observed large-diameter axons that were in a 1:1 relationship with Schwann cells, surrounded by a basal lamina but not myelinated. There was no evidence of DRG or Schwann cell...... death; the markers of different DRG cell populations and cutaneous innervation were unchanged. These anatomical changes were reflected in a slowing of conduction velocity at the lower end of the A-fiber conduction velocity range and a new population of more rapidly conducting C-fibers that are likely...

  2. 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.

  3. ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons.

    Science.gov (United States)

    Franco, D Lorena; Rezával, Carolina; Cáceres, Alfredo; Schinder, Alejandro F; Ceriani, M Fernanda

    2010-06-01

    Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that are accompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishment and maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration. 2010 Elsevier Inc. All rights reserved.

  4. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...

  5. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Martin Veronica

    2008-04-01

    Full Text Available Abstract Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the

  6. Effect of Long-Term Cannabis Use on Axonal Fibre Connectivity

    Science.gov (United States)

    Zalesky, Andrew; Solowij, Nadia; Yucel, Murat; Lubman, Dan I.; Takagi, Michael; Harding, Ian H.; Lorenzetti, Valentina; Wang, Ruopeng; Searle, Karissa; Pantelis, Christos; Seal, Marc

    2012-01-01

    Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The…

  7. Maintenance Issues in Long Term Operation of Nuclear Power Plant

    International Nuclear Information System (INIS)

    Contri, P.; Bieth, M.; Rieg, C.

    2006-01-01

    Due to current social and economical framework, in last years many nuclear power plant owners started a program for the Long Term Operation (LTO)/PLEX (Plant Life Extension) of their older nuclear facilities. This process has many nuclear safety implications, other than strategic and political ones. The need for tailoring the available safety assessment tools to such applications has become urgent in recent years and triggered many research actions. The review of regular maintenance and ageing management programs are tools widely used in LTO/PLEX context in many Countries. However, most of these tools are rather general and in many cases they need reshaping in an LTO/PLEX framework before application, with focus to the safety implications of the LTO/PLEX. Many Countries and plants radically modified their maintenance rules towards a condition based approach as a precondition for the implementation of LTO/PLEX programs. In 2004 a network of European Organisations operating Nuclear Power Plants, SENUF, under the coordination of the JRC-IE, carried out an extensive questionnaire on maintenance practice in their facilities aiming at capturing the aspects of the maintenance programs where research is mostly needed. This paper uses some results of the questionnaire, which was not oriented to LTO/PLEX, to draw some conclusions on how the current maintenance programs could support a potential LTO/PLEX, among the other programs running at NPPs. In this sense, it is spin-off of the SENUF WG on maintenance. The paper aims at identifying the technical attributes of the maintenance programs more directly affecting the decision for a long-term safe operation of a nuclear facility, the issues related to their implementation and safety review. The paper includes an analysis of the questionnaire circulated among the SENUF participants and a discussion on the implications of optimised maintenance programs in existing plants. Some examples at WWER plants taken by sources other than

  8. Maintenance management during long-term stop of JRR-3

    International Nuclear Information System (INIS)

    Matsui, Yutaka; Suwa, Masayuki; Wada, Shigeru

    2016-01-01

    JRR-3 has been continuing its stop state for more than 5 years as of FY2015 after stopping the use operation of the reactor in November 2010. Different responses are required in the maintenance management for operation resumption, compared with those in normal operation. This paper introduces part of the maintenance managements that are performed during long-term stop. The water qualities of primary coolant and secondary coolant are controlled by measuring pH and conductivity, and the prevention of crevice corrosion of equipment is performed. In the management of pumps for coolant circulation, vibration measurement is performed to confirm that there are no signs of abnormality. As the management of the core structure, the bend measurement of beryllium reflector is performed to confirm that there is no hindrance to operation resumption, and the visual inspection of high burnup fuel elements is performed to confirm that abnormality has not occurred. As for the management of monitoring equipment, the equipment required in shutdown period is subjected to calibration work, and the equipment required in operation period is subjected to soundness check based on the results of cooling system operation. As the functional maintenance of the cooling system, cooling system operating test and 10-day continuous operation of the cooling system are monthly performed to confirm the soundness of equipment. In addition, the competence maintenance and capacity improvement of operators are performed through the cooling system operation and reactor simulator training. (A.O.)

  9. 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.

  10. 2003 Long-Term Surveillance and Maintenance Program Report

    International Nuclear Information System (INIS)

    2004-01-01

    are part of long-term site management. In response to post-closure care requirements set forth in UMTRCA, DOE Headquarters established the Long-Term Surveillance and Maintenance (LTS&M) Program in 1988 at the DOE office in Grand Junction, Colorado. The program assumed long-term management responsibility for sites remediated under UMTRCA and other programs. Since its inception, the LTS&M Program has evolved in response to changing stakeholder needs, improvements in technology, and the addition of more DOE sites as remediation is completed. The mission of the LTS&M Program was to fulfill DOE's responsibility to implement all activities necessary to ensure regulatory compliance and to protect the public and the environment from long-lived wastes associated with the nation's nuclear energy, weapons, and research activities. Key components of the LTS&M Program included stakeholder participation, site monitoring and maintenance, records and information management, and research and technology transfer. This report presents summaries of activities conducted in 2003 in fulfillment of the LTS&M Program mission. On December 15, 2003, DOE established the Office of Legacy Management (LM) to allow for optimum management of DOE's legacy responsibilities. Offices are located in Washington, DC, Grand Junction, Colorado, Morgantown, West Virginia, and Pittsburgh, Pennsylvania, to perform long-term site management, land management, site transition support, records management, and other related tasks. All activities formerly conducted under the LTS&M Program have been incorporated into the Office of Land and Site Management (LM-50), as well as management of remedies involving ground water and surface water contaminated by former processing activities

  11. 2003 Long-Term Surveillance and Maintenance Program Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-07-01

    are part of long-term site management. In response to post-closure care requirements set forth in UMTRCA, DOE Headquarters established the Long-Term Surveillance and Maintenance (LTS&M) Program in 1988 at the DOE office in Grand Junction, Colorado. The program assumed long-term management responsibility for sites remediated under UMTRCA and other programs. Since its inception, the LTS&M Program has evolved in response to changing stakeholder needs, improvements in technology, and the addition of more DOE sites as remediation is completed. The mission of the LTS&M Program was to fulfill DOE’s responsibility to implement all activities necessary to ensure regulatory compliance and to protect the public and the environment from long-lived wastes associated with the nation’s nuclear energy, weapons, and research activities. Key components of the LTS&M Program included stakeholder participation, site monitoring and maintenance, records and information management, and research and technology transfer. This report presents summaries of activities conducted in 2003 in fulfillment of the LTS&M Program mission. On December 15, 2003, DOE established the Office of Legacy Management (LM) to allow for optimum management of DOE’s legacy responsibilities. Offices are located in Washington, DC, Grand Junction, Colorado, Morgantown, West Virginia, and Pittsburgh, Pennsylvania, to perform long-term site management, land management, site transition support, records management, and other related tasks. All activities formerly conducted under the LTS&M Program have been incorporated into the Office of Land and Site Management (LM–50), as well as management of remedies involving ground water and surface water contaminated by former processing activities.

  12. Leisure-time activity is an important determinant of long-term weight maintenance after weight loss in the Sibutramine Trial on Obesity Reduction and Maintenance (STORM trial)

    DEFF Research Database (Denmark)

    van Baak, M. A.; van Mil, E.; Astrup, A.

    2003-01-01

    The success rate of long-term maintenance of weight loss in obese patients is usually low. To improve the success rate, determinants of long-term weight maintenance must be identified.......The success rate of long-term maintenance of weight loss in obese patients is usually low. To improve the success rate, determinants of long-term weight maintenance must be identified....

  13. 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

  14. 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.

  15. Site transition framework for long-term surveillance and maintenance

    International Nuclear Information System (INIS)

    2014-01-01

    This document provides a framework for all U.S. Department of Energy (DOE) facilities and sites where DOE may have anticipated long-term surveillance and maintenance (LTSM) responsibilities. It is a tool to help facilitate a smooth transition from remediation to LTSM, providing a systematic process for affected parties to utilize in analyzing the baseline to understand and manage the actions from EM mission completion through a site's transition into LTSM. The framework is not meant to provide an exhaustive list of the specific requirement and information that are needed. Sites will have unique considerations that may not be adequately addressed by this tool, and it is anticipated that a team comprised of the transferring and receiving organization will use judgment in utilizing this augmenting with other DOE guidance. However the framework should be followed to the extent possible at each site; and adapted to accommodate unique site-specific requirements, needs, and documents. Since the objective of the tool is facilitate better understanding of the conditions of the site and the actions required for transfer, the transition team utilizing the checklist is expected to consult with management of both the receiving and transferring organization to verify that major concerns are addressed. Ideally, this framework should be used as early in the remediation process as possible. Subsequent applications of the Site Transition Framework (STF) to the site should be conducted periodically and used to verify that all appropriate steps have been or will be taken to close-out the site and that actions by both organization are identified to transfer the site to LTSM. The requirements are provided herein

  16. Site transition framework for long-term surveillance and maintenance

    Energy Technology Data Exchange (ETDEWEB)

    None

    2014-04-01

    This document provides a framework for all U.S. Department of Energy (DOE) facilities and sites where DOE may have anticipated long-term surveillance and maintenance (LTSM) responsibilities. It is a tool to help facilitate a smooth transition from remediation to LTSM, providing a systematic process for affected parties to utilize in analyzing the baseline to understand and manage the actions from EM mission completion through a site’s transition into LTSM. The framework is not meant to provide an exhaustive list of the specific requirement and information that are needed. Sites will have unique considerations that may not be adequately addressed by this tool, and it is anticipated that a team comprised of the transferring and receiving organization will use judgment in utilizing this augmenting with other DOE guidance. However the framework should be followed to the extent possible at each site; and adapted to accommodate unique site-specific requirements, needs, and documents. Since the objective of the tool is facilitate better understanding of the conditions of the site and the actions required for transfer, the transition team utilizing the checklist is expected to consult with management of both the receiving and transferring organization to verify that major concerns are addressed. Ideally, this framework should be used as early in the remediation process as possible. Subsequent applications of the Site Transition Framework (STF) to the site should be conducted periodically and used to verify that all appropriate steps have been or will be taken to close-out the site and that actions by both organization are identified to transfer the site to LTSM. The requirements are provided herein.

  17. Short and long term maintenance strategy for reactor vessel head penetrations

    International Nuclear Information System (INIS)

    Teissier, A.; Heuze, A.

    1995-01-01

    This paper presents elements based on : surveys, operating inspection, theoretical studies, safety analysis, laboratory results, that enabled to determine maintenance options and short and long term strategies for processing on reactor vessel head leaks. (TEC). 1 tab

  18. How visual short-term memory maintenance modulates subsequent visual aftereffects.

    Science.gov (United States)

    Saad, Elyana; Silvanto, Juha

    2013-05-01

    Prolonged viewing of a visual stimulus can result in sensory adaptation, giving rise to perceptual phenomena such as the tilt aftereffect (TAE). However, it is not known if short-term memory maintenance induces such effects. We examined how visual short-term memory (VSTM) maintenance modulates the strength of the TAE induced by subsequent visual adaptation. We reasoned that if VSTM maintenance induces aftereffects on subsequent encoding of visual information, then it should either enhance or reduce the TAE induced by a subsequent visual adapter, depending on the congruency of the memory cue and the adapter. Our results were consistent with this hypothesis and thus indicate that the effects of VSTM maintenance can outlast the maintenance period.

  19. The right hippocampus participates in short-term memory maintenance of object-location associations

    NARCIS (Netherlands)

    Piekema, C.; Kessels, R.P.C.; Mars, R.B.; Petersson, K.M.; Fernandez, G.S.E.

    2006-01-01

    Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance.

  20. The right hippocampus participates in short-term memory maintenance of object-location associations.

    NARCIS (Netherlands)

    Piekema, C.; Kessels, R.P.C.; Mars, R.B.; Petersson, K.M.; Fernandez, G.S.E.

    2006-01-01

    Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance.

  1. 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...

  2. Long-term development of nuclear maintenance service provider in Slovenia

    International Nuclear Information System (INIS)

    Androjna, A.; Racic, Z.; Balazic, D.

    2004-01-01

    In recent years, most utilities have been facing a challenge of optimizing maintenance costs, while maintaining or improving equipment reliability. As the equipment ages and maintenance skills within the plant staff may decline due to a generation exchange, the challenge becomes even stronger. Consequently, many plants are looking for possible solutions through partnering with maintenance service providers. The fact that there is only one nuclear power plant in Slovenia hinders the development of local maintenance contractors to some extent. Additionally, they have to face everincreasing technical and organizational requirements while a longer fuel cycle and shorter outage durations result in a narrower annual scope of outage activities. In such circumstances, it may be very difficult for local maintenance service providers to retain and improve skills and qualifications in the long run. Even more so, since they also face the need to rejuvenate their staff and the interest of subcontractors to participate diminishes. The paper presents a case on long-term development issues as experienced by NUMIP, the leading Slovenian nuclear maintenance service provider. Above all, we would like to contribute to a better understanding of efficient local maintenance support. NUMIP's future strategic options are explored in light of possible partnering relationship with the nuclear power plant, based on trust, win-win attitude and continuous improvement. Long-term benefits of the proposed partnering are indicated for both parties, the nuclear power plant and the local maintenance service provider. (author)

  3. Distinct electrophysiological indices of maintenance in auditory and visual short-term memory.

    Science.gov (United States)

    Lefebvre, Christine; Vachon, François; Grimault, Stephan; Thibault, Jennifer; Guimond, Synthia; Peretz, Isabelle; Zatorre, Robert J; Jolicœur, Pierre

    2013-11-01

    We compared the electrophysiological correlates for the maintenance of non-musical tones sequences in auditory short-term memory (ASTM) to those for the short-term maintenance of sequences of coloured disks held in visual short-term memory (VSTM). The visual stimuli yielded a sustained posterior contralateral negativity (SPCN), suggesting that the maintenance of sequences of coloured stimuli engaged structures similar to those involved in the maintenance of simultaneous visual displays. On the other hand, maintenance of acoustic sequences produced a sustained negativity at fronto-central sites. This component is named the Sustained Anterior Negativity (SAN). The amplitude of the SAN increased with increasing load in ASTM and predicted individual differences in the performance. There was no SAN in a control condition with the same auditory stimuli but no memory task, nor one associated with visual memory. These results suggest that the SAN is an index of brain activity related to the maintenance of representations in ASTM that is distinct from the maintenance of representations in VSTM. © 2013 Elsevier Ltd. All rights reserved.

  4. Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

    Science.gov (United States)

    Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

    2014-10-01

    Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

  5. Designing remote monitoring systems for long term maintenance and reliability

    International Nuclear Information System (INIS)

    Davis, G.E.; Johnson, G.L.; Schrader, F.D.; Stone, M.A.; Wilson, E.F.

    2001-01-01

    Full text: As part of the effort to modernize safeguards equipment, the IAEA is continuing to acquire and install equipment for upgrading obsolete surveillance systems with digital technology; and providing remote-monitoring capabilities where and when economically justified. Remote monitoring is expected to reduce inspection effort, particularly at storage facilities and reactor sites. Remote monitoring technology will not only involve surveillance, but will also include seals, sensors, and other unattended measurement equipment. LLNL's experience with the Argus Security System offers lessons for the design, deployment, and maintenance of remote monitoring systems. Argus is an integrated security system for protection of high-consequence U.S. Government assets, including nuclear materials. Argus provides secure transmission of sensor data, administrative data, and video information to support intrusion detection and access control functions. LLNL developed and deployed the Argus system on its own site in 1988. Since that time LLNL has installed, maintained, and upgraded Argus systems at several Department of Energy and Department of Defense sites in the US as well as at the original LLNL site. Argus has provided high levels of reliability and integrity, as well as reducing overall lifecycle cost through incremental improvements to hardware and software. This philosophy permits expansion of functional capability, hardware upgrade and software upgrade without system outages and with minimum outage of local functions. This presentation will describe Argus design strategies and lessons learned from the Argus program as they apply to the design, development, and maintenance of a remote monitoring network. Hardware failures, software failures, and communication outages are expected and must be addressed by astute selection of system architecture. A combination of redundancy, diversity, and effective functional allocation between field and system level components should

  6. Protein kinase M ζ and the maintenance of long-term memory.

    Science.gov (United States)

    Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

    2016-10-01

    Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Long term substitution treatment (maintenance treatment of opioid dependent persons

    Directory of Open Access Journals (Sweden)

    Wirl, Charlotte

    2007-03-01

    Full Text Available Health political background: Methadone substitution treatment in Germany is introduced in 1988 in the framework of a scientific pilot study in North Rhein Westphalia. Recent statistics show that by now a broad offer of substitution treatment exists. From 1 June 2002 to 31 December 2003 113,000 substitution treatments have been recorded as being started of which around 56,000 have been recorded as ongoing treatments by 1 December 2003. Scientific background: Substitution treatment (treatment of opioid-dependent persons using substitution substances is one part of addiction treatment. Its goals are harm reduction and the stabilisation of opioid dependent persons. Integration of opioid-dependent persons in a treatment-setting, reduction of consumption of psychoactive substances, reduction of risk behaviour (primarily related to infectious diseases, decrease of mortality and improvements concerning the social, psychic and physic situation are seen as a success of substitution treatment as maintenance therapy. Research questions: The aim of this HTA report is to investigate which indicators can be used to evaluate the effectiveness of substitution treatment. Based on these indicators an evaluation of the medical, social and economical benefit of substitution treatment - also in relation to abstinence oriented treatment - is carried out. Methods: A systematic literature search was performed in 31 international databases which yielded 2451 articles with publication date between 1995 and February 2005. Results: After a twofold selection process 32 publications were included for assessment and 276 publications were used as background literature. Despite serious restrictions due to selection bias and dropout in most studies focusing on substitution treatment, reduction of consumption of illegal opioids, reduction of risk behaviour, criminal behaviour, mortality and incidence of HIV can be seen as an empirically proven success of substitution treatment

  8. 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.

  9. Management of remanent lifetime. Short-term benefits of the maintenance evaluation and improvement programme

    International Nuclear Information System (INIS)

    Sainero Garcia, J.

    1993-01-01

    Remanent Lifetime Management, which is scientifically based on knowing the degradatory phenomena associated with aging, today allows us to optimize plant life through a long-term maintenance strategy combining preventive maintenance and condition monitoring programmes. Within a project for Remanent Lifetime Management (RLM), the determination of methods of control and mitigation of degradations due to aging depends on the programme of Maintenance Evaluation and Improvement (MEI). This programme, underpinned by the analysis of degradatory phenomena to which plant components are subjected, evaluates current maintenance practices and defines the complementary actions which would facilitate establishment of a long-term strategy to control aging. Together with this main objective of the RLM project, the MEI programme achieves short-term benefits since, right from the beginning, it offers solutions to mitigate and guard against degradations in crucial plant components, and generally sets out a programme to control aging. The MEI programme further serves as a tool to reach the final objectives of the new 10CFR50.65 rule, 'Requirements for Maintenance Programs for NPPs'. The MEI always offers the option should the Utility Owner decide to extend plant life. (author)

  10. Long-Term Surveillance and Maintenance Plan for the Gnome-Coach, New Mexico, Site

    Energy Technology Data Exchange (ETDEWEB)

    Kreie, Ken [USDOE Office of Legacy Management, Grand Junction, CO (United States); Findlay, Rick [Navarro Research and Engineering, Inc., Grand Junction, CO (United States)

    2016-06-08

    The U.S. Department of Energy (DOE) Office of Legacy Management (LM) prepared this Long-Term Surveillance and Maintenance Plan (LTSMP) for the Gnome-Coach, New Mexico, Site (the Gnome site). The Gnome site is approximately 25 miles east of Carlsbad in Eddy County, New Mexico (Figure 1). The site was the location of a 3-kiloton-yield underground nuclear test and radioisotope groundwater tracer test. The tests resulted in residual contamination and post-detonation features that require long-term oversight. Long-term responsibility for the site was transferred from the DOE National Nuclear Security Administration Nevada Site Office to LM on October 1, 2006. Responsibilities include surveillance, monitoring, and maintenance of institutional controls (ICs) as part of the long-term stewardship of the site. Long-term stewardship is designed to ensure protection of human health and the environment.

  11. Applying Psychological Theories to Promote Long-Term Maintenance of Health Behaviors

    Science.gov (United States)

    Joseph, Rodney P.; Daniel, Casey L.; Thind, Herpreet; Benitez, Tanya J.; Pekmezi, Dori

    2014-01-01

    Behavioral health theory provides a framework for researchers to design, implement, and evaluate the effects of health promotion programs. However, limited research has examined theories used in interventions to promote long-term maintenance of health behaviors. The purpose of this review was to evaluate the available literature and identify prominent behavioral health theories used in intervention research to promote maintenance of health behaviors. We reviewed theories used in intervention research assessing long-term maintenance (≥ 6 months post-intervention) of physical activity, weight loss, and smoking cessation. Five prominent behavioral theories were referenced by the 34 studies included in the review: Self-Determination Theory, Theory of Planned Behavior, Social Cognitive Theory, Transtheoretical Model, and Social Ecological Model. Descriptions and examples of applications of these theories are provided. Implications for future research are discussed. PMID:28217036

  12. Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

    Science.gov (United States)

    Wachholtz, Amy; Gonzalez, Gerardo

    2014-12-01

    Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's opioid maintenance compared to active methadone patients (p opioid naïve control group participants (p's opioid abstinence increased (R = .37; p opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Determining a functional responsibility allocation between public and private parties in a long-term maintenance contract for waterworks

    NARCIS (Netherlands)

    Brommet, O.D.; Schoenmaker, R.; Hertogh, M.J.C.M.; Kleijn van Willigen, G.R.; Chen, Y.; Bakker, Jaap; Frangopol, Dan M.; van Breugel, Klaas

    2017-01-01

    A proper allocation of risks and responsibilities is vital for the success of long-term maintenance contracts. This paper focuses on a method to identify an adequate allocation of responsibilities for the maintenance of waterworks. The Dutch agency recently started outsourcing the maintenance of

  14. A Novel Short-Term Maintenance Strategy for Power Transmission and Transformation Equipment Based on Risk-Cost-Analysis

    Directory of Open Access Journals (Sweden)

    Hang Yang

    2017-11-01

    Full Text Available Current studies on preventive condition-based maintenance of power transmission and transformation equipment mainly focus on mid-term or long-term maintenance, and cannot meet the requirements of short-term especially temporary maintenance. In order to solve the defects of the present preventive maintenance strategies, according to the engineering application and based on risk-cost analysis, a short-term maintenance strategy is proposed in this manuscript. For the equipment working in bad health condition, its active maintenance costs and operation risk costs are evaluated, respectively. Then the latest maintenance time is calculated in accordance with the principle that its operation risk costs are no higher than active maintenance costs. Utilizing the latest maintenance time, the best maintenance time is calculated by setting the maximum relative earnings of postponing maintenance as the target, which provides the operation staffs with comprehensive maintenance-decision support. In the end, different cases on the IEEE 24-bus system are simulated. The effectiveness and advantages of the proposed strategy are demonstrated by the simulation results.

  15. Long-term weight-loss maintenance in obese patients with knee osteoarthritis

    DEFF Research Database (Denmark)

    Christensen, Pia; Henriksen, Marius; Bartels, Else Marie

    2017-01-01

    Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear.Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight...

  16. Transcriptional Correlates of Memory Maintenance Following Long-Term Sensitization of "Aplysia Californica"

    Science.gov (United States)

    Conte, Catherine; Herdegen, Samantha; Kamal, Saman; Patel, Jency; Patel, Ushma; Perez, Leticia; Rivota, Marissa; Calin-Jageman, Robert J.; Calin-Jageman, Irina E.

    2017-01-01

    We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of "Aplysia californica" using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a…

  17. Attention modulates maintenance of representations in visual short-term memory.

    Science.gov (United States)

    Kuo, Bo-Cheng; Stokes, Mark G; Nobre, Anna Christina

    2012-01-01

    Recent studies have shown that selective attention is of considerable importance for encoding task-relevant items into visual short-term memory (VSTM) according to our behavioral goals. However, it is not known whether top-down attentional biases can continue to operate during the maintenance period of VSTM. We used ERPs to investigate this question across two experiments. Specifically, we tested whether orienting attention to a given spatial location within a VSTM representation resulted in modulation of the contralateral delay activity (CDA), a lateralized ERP marker of VSTM maintenance generated when participants selectively encode memory items from one hemifield. In both experiments, retrospective cues during the maintenance period could predict a specific item (spatial retrocue) or multiple items (neutral retrocue) that would be probed at the end of the memory delay. Our results revealed that VSTM performance is significantly improved by orienting attention to the location of a task-relevant item. The behavioral benefit was accompanied by modulation of neural activity involved in VSTM maintenance. Spatial retrocues reduced the magnitude of the CDA, consistent with a reduction in memory load. Our results provide direct evidence that top-down control modulates neural activity associated with maintenance in VSTM, biasing competition in favor of the task-relevant information.

  18. Olfactory short-term memory encoding and maintenance - an event-related potential study.

    Science.gov (United States)

    Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

    2014-09-01

    This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Mobile robotics for CANDU reactor maintenance: case studies and near-term improvements

    International Nuclear Information System (INIS)

    Lipsett, M. G.; Rody, K.H.

    1995-01-01

    Although robotics researchers have been promising that robotics would soon be performing tasks in hazardous environments, the reality has yet to live up to the hype. The presently available crop of robots suitable for deployment in industrial situations are remotely operated, requiring skilled users. This talk describes cases where mobile robots have been used successfully in CANDU stations, discusses the difficulties in using mobile robots for reactor maintenance, and provides near-term goals for achievable improvements in performance and usefulness. (author)

  20. I have already a LTMC (Long Term Maintenance Contract) what now

    International Nuclear Information System (INIS)

    Liste Alba, D.

    2010-01-01

    More and more usual, LTMCs (Long Term Maintenance Contracts) mean in the practice a real challenge for those responsible of their implementation and execution. So by the owner as by the contractor sides, great deal of patience is required, as well as common sense and professionalism to complete them successfully. In a summarized way, through this article is reviewed the LTMC experience of in a plant of combined cycle, during the early years of exploitation. (Author)

  1. Stochastic short-term maintenance scheduling of GENCOs in an oligopolistic electricity market

    International Nuclear Information System (INIS)

    Fotouhi Ghazvini, Mohammad Ali; Canizes, Bruno; Vale, Zita; Morais, Hugo

    2013-01-01

    Highlights: ► Decision making under uncertainty. ► Stochastic Mixed Integer Quadratic Programming applied to short-term maintenance scheduling. ► Outage scheduling in Oligopolistic electricity markets. ► Generation companies maintenance scheduling. -- Abstract: In the proposed model, the independent system operator (ISO) provides the opportunity for maintenance outage rescheduling of generating units before each short-term (ST) time interval. Long-term (LT) scheduling for 1 or 2 years in advance is essential for the ISO and the generation companies (GENCOs) to decide their LT strategies; however, it is not possible to be exactly followed and requires slight adjustments. The Cournot-Nash equilibrium is used to characterize the decision-making procedure of an individual GENCO for ST intervals considering the effective coordination with LT plans. Random inputs, such as parameters of the demand function of loads, hourly demand during the following ST time interval and the expected generation pattern of the rivals, are included as scenarios in the stochastic mixed integer program defined to model the payoff-maximizing objective of a GENCO. Scenario reduction algorithms are used to deal with the computational burden. Two reliability test systems were chosen to illustrate the effectiveness of the proposed model for the ST decision-making process for future planned outages from the point of view of a GENCO.

  2. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  3. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Science.gov (United States)

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2012-01-01

    Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  4. 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.

  5. 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.

  6. Periodontal and periimplant maintenance: a critical factor in long-term treatment success.

    Science.gov (United States)

    Shumaker, Nicholas D; Metcalf, Brett T; Toscano, Nicholas T; Holtzclaw, Dan J

    2009-09-01

    Periodontal maintenance (PM) is a critical factor in the long-term success of both periodontal and dental implant therapy. Studies have shown both modern periodontal and dental implant therapies are effective in maintaining natural teeth and replacing lost teeth, respectively. However, without a regular program of clinical reevaluation, plaque control, oral hygiene instruction, and reassessment of biomechanical factors, the benefits of treatment often are lost and inflammatory disease in the form of recurrent periodontitis or periimplantitis may result. This article reviews the goals, types, and appropriate frequency of PM in periodontal and dental implant therapy, as well as the incidence and etiology of periimplant disease and strategies for management when recurrent disease develops during the maintenance phase of treatment.

  7. Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Kim D Allen

    Full Text Available Long-term memory (LTM formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose polymerase-1 (PARP-1, are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosylation (PAR dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP ribose molecules (pADPr after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA and extracellular signal-regulated kinase (ERK--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I, responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.

  8. 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.

  9. 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

  10. Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

    Science.gov (United States)

    Takamura, Shiki

    2018-01-01

    Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that

  11. Selection of multiple cued items is possible during visual short-term memory maintenance.

    Science.gov (United States)

    Matsukura, Michi; Vecera, Shaun P

    2015-07-01

    Recent neuroimaging studies suggest that maintenance of a selected object feature held in visual short-term/working memory (VSTM/VWM) is supported by the same neural mechanisms that encode the sensory information. If VSTM operates by retaining "reasonable copies" of scenes constructed during sensory processing (Serences, Ester, Vogel, & Awh, 2009, p. 207, the sensory recruitment hypothesis), then attention should be able to select multiple items represented in VSTM as long as the number of these attended items does not exceed the typical VSTM capacity. It is well known that attention can select at least two noncontiguous locations at the same time during sensory processing. However, empirical reports from the studies that examined this possibility are inconsistent. In the present study, we demonstrate that (1) attention can indeed select more than a single item during VSTM maintenance when observers are asked to recognize a set of items in the manner that these items were originally attended, and (2) attention can select multiple cued items regardless of whether these items are perceptually organized into a single group (contiguous locations) or not (noncontiguous locations). The results also replicate and extend the recent finding that selective attention that operates during VSTM maintenance is sensitive to the observers' goal and motivation to use the cueing information.

  12. Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.

    Science.gov (United States)

    Kato, M; Ishimaru, S; Seki, M; Yoshida, K; Shiraishi, Y; Chiba, K; Kakiuchi, N; Sato, Y; Ueno, H; Tanaka, H; Inukai, T; Tomizawa, D; Hasegawa, D; Osumi, T; Arakawa, Y; Aoki, T; Okuya, M; Kaizu, K; Kato, K; Taneyama, Y; Goto, H; Taki, T; Takagi, M; Sanada, M; Koh, K; Takita, J; Miyano, S; Ogawa, S; Ohara, A; Tsuchida, M; Manabe, A

    2017-03-01

    In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

  13. Brain Activation during Associative Short-Term Memory Maintenance is Not Predictive for Subsequent Retrieval

    Directory of Open Access Journals (Sweden)

    Heiko eBergmann

    2015-09-01

    Full Text Available Performance on working memory (WM tasks may partially be supported by long-term memory (LTM processing. Hence, brain activation recently being implicated in WM may actually have been driven by (incidental LTM formation. We examined which brain regions actually support successful WM processing, rather than being confounded by LTM processes, during the maintenance and probe phase of a WM task. We administered a four-pair (faces and houses associative delayed-match-to-sample (WM task using event-related fMRI and a subsequent associative recognition LTM task, using the same stimuli. This enabled us to analyze subsequent memory effects for both the WM and the LTM test by contrasting correctly recognized pairs with incorrect pairs for either task. Critically, with respect to the subsequent WM effect, we computed this analysis exclusively for trials that were forgotten in the subsequent LTM recognition task. Hence, brain activity associated with successful WM processing was less likely to be confounded by incidental LTM formation. The subsequent LTM effect, in contrast, was analyzed exclusively for pairs that previously had been correctly recognized in the WM task, disclosing brain regions involved in successful LTM formation after successful WM processing. Results for the subsequent WM effect showed no significantly activated brain areas for WM maintenance, possibly due to an insensitivity of fMRI to mechanisms underlying active WM maintenance. In contrast, a correct decision at WM probe was linked to activation in the retrieval success network (anterior and posterior midline brain structures. The subsequent LTM analyses revealed greater activation in left dorsolateral prefrontal cortex and posterior parietal cortex in the early phase of the maintenance stage. No supra-threshold activation was found during the WM probe. Together, we obtained clearer insights in which brain regions support successful WM and LTM without the potential confound of the

  14. Brain activation during associative short-term memory maintenance is not predictive for subsequent retrieval.

    Science.gov (United States)

    Bergmann, Heiko C; Daselaar, Sander M; Beul, Sarah F; Rijpkema, Mark; Fernández, Guillén; Kessels, Roy P C

    2015-01-01

    Performance on working memory (WM) tasks may partially be supported by long-term memory (LTM) processing. Hence, brain activation recently being implicated in WM may actually have been driven by (incidental) LTM formation. We examined which brain regions actually support successful WM processing, rather than being confounded by LTM processes, during the maintenance and probe phase of a WM task. We administered a four-pair (faces and houses) associative delayed-match-to-sample (WM) task using event-related functional MRI (fMRI) and a subsequent associative recognition LTM task, using the same stimuli. This enabled us to analyze subsequent memory effects for both the WM and the LTM test by contrasting correctly recognized pairs with incorrect pairs for either task. Critically, with respect to the subsequent WM effect, we computed this analysis exclusively for trials that were forgotten in the subsequent LTM recognition task. Hence, brain activity associated with successful WM processing was less likely to be confounded by incidental LTM formation. The subsequent LTM effect, in contrast, was analyzed exclusively for pairs that previously had been correctly recognized in the WM task, disclosing brain regions involved in successful LTM formation after successful WM processing. Results for the subsequent WM effect showed no significantly activated brain areas for WM maintenance, possibly due to an insensitivity of fMRI to mechanisms underlying active WM maintenance. In contrast, a correct decision at WM probe was linked to activation in the "retrieval success network" (anterior and posterior midline brain structures). The subsequent LTM analyses revealed greater activation in left dorsolateral prefrontal cortex and posterior parietal cortex in the early phase of the maintenance stage. No supra-threshold activation was found during the WM probe. Together, we obtained clearer insights in which brain regions support successful WM and LTM without the potential confound of

  15. Appropriate zinc addition management into PWR primary coolant after the plant long-term maintenance

    International Nuclear Information System (INIS)

    Hirose, Atsushi; Matsui, Ryo; Imamura, Haruki; Takahashi, Akira; Shimizu, Yuichi; Kogawa, Noritaka; Nagamine, Kunitaka

    2014-01-01

    Zinc addition into the PWR primary coolant is known as an effective method to reduce the radioactivity build up. The reduction effect has been confirmed by actual plant experience of the Genkai Nuclear Power Plant Unit 1 to 4 and the Sendai Nuclear Power Plant Unit 1 to 2 which are operated by Kyushu Electric Power Co. in Japan. Zinc addition is suspended at shut-down, and is resumed after heat up or arrival at full power. In usual maintenance, the period when zinc addition is not applied is short; thus it is considered that suspension of zinc addition does not have practical influence on the corrosion and the radioactivity buildup in the oxide layer of surface for the primary equipment and piping. On the other hand, in case the maintenance period is much longer, the new oxide which does not contain zinc has grown, and then the structure of the oxide layer may be changed. Therefore, it is considered that zinc addition suspension in long-term period has possibilities to deteriorate the dose reduction effect. In order to verify the effect of long-term suspension of zinc addition upon oxide layer, the lab experiment was carried out using TT690 alloy which is the constitution material of the steam generator tubes under the conditions of long-term and the subsequent resuming operations. After the experiment, the specimens were analyzed by IMA and chemical analysis. These measurement results suggest the difference of the oxide layer is little or none between long-term suspension of zinc addition and short-term suspension of zinc suspension. Hence it is considered that influence of long-term maintenance on the oxide layer is small. Furthermore, in this study, in order to evaluate the influence of the suspension of zinc addition in the operation period, specimens of oxide film formed with zinc were carried out the corrosion test in the simulated RCS condition without zinc. These measurement results indicate the effect of reduction of the activity build up will become less

  16. 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...

  17. Long-term safety of the maintenance and decommissioning waste of the encapsulation plant

    International Nuclear Information System (INIS)

    Nummi, O.; Kylloenen, J.; Eurajoki, T.

    2012-12-01

    This report, Long-term safety of the maintenance and decommissioning waste of the encapsulation plant, presents the disposal concept for the low and intermediate level waste (L/ILW) that is generated during the operation and decommissioning of the encapsulation plant, and assesses the long-term safety of the disposal of the waste. Radioactive waste originates from the spent nuclear fuel transferred and dried in the encapsulation plant. Radioactive waste accumulates also in the maintenance of the components and systems of the encapsulation plant. The waste is collected, exempted from control if possible and treated for final disposal if necessary. The waste is disposed of in the L/ILW hall which is currently planned to be located at a depth of -180 meters along the access tunnel to the repository for spent fuel. The main engineered barrier in the L/ILW hall is a concrete basin that encases the dried liquid waste. The safety concept of L/ILW disposal is based on the slow release of radioactivity from the L/ILW hall and its limited transport through the bedrock into biosphere. The release and transport of the radioactivity is described by the assessment scenarios, which include expected evolution and unlikely events affecting the long-term safety. The scenarios act as guidelines according to which the conceptual and mathematical models are formed. The long-term safety of the L/ILW hall is assessed using deterministic and probabilistic modeling. Special issues such as human intrusion and radiation effects on other biota are also assessed. The most significant contributor to the dose rates is the short-lived radionuclide 90 Sr followed by long-lived nuclides 129 I and 108 mAg. The annual doses to the public, and release rates of radioactive substances stay below the regulatory constraints in all analyzed scenarios. (orig.)

  18. The Role of Actin Cytoskeleton in Dendritic Spines in the Maintenance of Long-Term Memory.

    Science.gov (United States)

    Basu, Sreetama; Lamprecht, Raphael

    2018-01-01

    Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such alterations induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. This is especially intriguing as the half-life of most of the proteins that underlie such changes is usually in the range of hours to days and these proteins may change their location over time. In this review we describe studies that indicate the involvement of dendritic spines in memory formation and its maintenance. These studies show that learning leads to changes in the number and morphology of spines. Disruption in spines morphology or manipulations that lead to alteration in their number after consolidation are associated with impairment in memory maintenance. We further ask how changes in dendritic spines morphology, induced by learning and reputed to encode memory, are maintained to preserve long-term memory. We propose a mechanism, based on studies described in the review, whereby the actin cytoskeleton and its regulatory proteins involved in the initial alteration in spine morphology induced by learning are also essential for spine structural stabilization that maintains long-term memory. In this model glutamate receptors and other synaptic receptors activation during learning leads to the creation of new actin cytoskeletal scaffold leading to changes in spines morphology and memory formation. This new actin cytoskeletal scaffold is preserved beyond actin and its regulatory proteins turnover and dynamics by active stabilization of the level and activity of actin regulatory proteins within these memory spines.

  19. Long-term weight loss maintenance for obesity: a multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    Montesi L

    2016-02-01

    Full Text Available Luca Montesi,1 Marwan El Ghoch,2 Lucia Brodosi,1 Simona Calugi,2 Giulio Marchesini,1 Riccardo Dalle Grave2 1Unit of Metabolic Diseases, S Orsola-Malpighi Hospital, “Alma Mater Studiorum” University, Bologna, Italy; 2Department of Eating and Weight Disorders, Villa Garda Hospital, Verona, Italy Abstract: The long-term weight management of obesity remains a very difficult task, associated with a high risk of failure and weight regain. However, many people report that they have successfully managed weight loss maintenance in the long term. Several factors have been associated with better weight loss maintenance in long-term observational and randomized studies. A few pertain to the behavioral area (eg, high levels of physical activity, eating a low-calorie, low-fat diet; frequent self-monitoring of weight, a few to the cognitive component (eg, reduced disinhibition, satisfaction with results achieved, confidence in being able to lose weight without professional help, and a few to personality traits (eg, low novelty seeking and patient–therapist interaction. Trials based on the most recent protocols of lifestyle modification, with a prolonged extended treatment after the weight loss phase, have also shown promising long-term weight loss results. These data should stimulate the adoption of a lifestyle modification-based approach for the management of obesity, featuring a nonphysician lifestyle counselor (also called “lifestyle trainer” or “healthy lifestyle practitioner” as a pivotal component of the multidisciplinary team. The obesity physicians maintain a primary role in engaging patients, in team coordination and supervision, in managing the complications associated with obesity and, in selected cases, in the decision for drug treatment or bariatric surgery, as possible more intensive, add-on interventions to lifestyle treatment. Keywords: obesity, lifestyle modification, cognitive behavior therapy, multidisciplinary treatment

  20. Long-term weight-loss maintenance in obese patients with knee osteoarthritis: a randomized trial.

    Science.gov (United States)

    Christensen, Pia; Henriksen, Marius; Bartels, Else M; Leeds, Anthony R; Meinert Larsen, Thomas; Gudbergsen, Henrik; Riecke, Birgit F; Astrup, Arne; Heitmann, Berit L; Boesen, Mikael; Christensen, Robin; Bliddal, Henning

    2017-09-01

    Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear. Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y. Design: The design was a randomized trial with participants aged >50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m 2 )] ≥30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data. Results: A total of 153 participants (means ± SDs: BMI: 33.3 ± 4.6; age: 63.8 ± 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN ( n = 76) or RE ( n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95% CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35). Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These

  1. Design and implementation of an interactive website to support long-term maintenance of weight loss.

    Science.gov (United States)

    Stevens, Victor J; Funk, Kristine L; Brantley, Phillip J; Erlinger, Thomas P; Myers, Valerie H; Champagne, Catherine M; Bauck, Alan; Samuel-Hodge, Carmen D; Hollis, Jack F

    2008-01-25

    For most individuals, long-term maintenance of weight loss requires long-term, supportive intervention. Internet-based weight loss maintenance programs offer considerable potential for meeting this need. Careful design processes are required to maximize adherence and minimize attrition. This paper describes the development, implementation and use of a Web-based intervention program designed to help those who have recently lost weight sustain their weight loss over 1 year. The weight loss maintenance website was developed over a 1-year period by an interdisciplinary team of public health researchers, behavior change intervention experts, applications developers, and interface designers. Key interactive features of the final site include social support, self-monitoring, written guidelines for diet and physical activity, links to appropriate websites, supportive tools for behavior change, check-in accountability, tailored reinforcement messages, and problem solving and relapse prevention training. The weight loss maintenance program included a reminder system (automated email and telephone messages) that prompted participants to return to the website if they missed their check-in date. If there was no log-in response to the email and telephone automated prompts, a staff member called the participant. We tracked the proportion of participants with at least one log-in per month, and analyzed log-ins as a result of automated prompts. The mean age of the 348 participants enrolled in an ongoing randomized trial and assigned to use the website was 56 years; 63% were female, and 38% were African American. While weight loss data will not be available until mid-2008, website use remained high during the first year with over 80% of the participants still using the website during month 12. During the first 52 weeks, participants averaged 35 weeks with at least one log-in. Email and telephone prompts appear to be very effective at helping participants sustain ongoing website use

  2. 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)

  3. Location-specific effects of attention during visual short-term memory maintenance.

    Science.gov (United States)

    Matsukura, Michi; Cosman, Joshua D; Roper, Zachary J J; Vatterott, Daniel B; Vecera, Shaun P

    2014-06-01

    Recent neuroimaging studies suggest that early sensory areas such as area V1 are recruited to actively maintain a selected feature of the item held in visual short-term memory (VSTM). These findings raise the possibility that visual attention operates in similar manners across perceptual and memory representations to a certain extent, despite memory-level and perception-level selections are functionally dissociable. If VSTM operates by retaining "reasonable copies" of scenes constructed during sensory processing (Serences et al., 2009, p. 207, the sensory recruitment hypothesis), then it is possible that selective attention can be guided by both exogenous (peripheral) and endogenous (central) cues during VSTM maintenance. Yet, the results from the previous studies that examined this issue are inconsistent. In the present study, we investigated whether attention can be directed to a specific item's location represented in VSTM with the exogenous cue in a well-controlled setting. The results from the four experiments suggest that, as observed with the endogenous cue, the exogenous cue can efficiently guide selective attention during VSTM maintenance. The finding is not only consistent with the sensory recruitment hypothesis but also validates the legitimacy of the exogenous cue use in past and future studies. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  4. Novel environments enhance the induction and maintenance of long-term potentiation in the dentate gyrus.

    Science.gov (United States)

    Davis, Cyndy D; Jones, Floretta L; Derrick, Brian E

    2004-07-21

    The induction of long-term potentiation (LTP) in the hippocampal formation can be modulated by different behavioral states. However, few studies have addressed modulation of LTP during behavioral states in which the animal is likely acquiring new information. Here, we demonstrate that both the induction and the longevity of LTP in the dentate gyrus are enhanced when LTP is induced during the initial exploration of a novel environment. These effects are independent from locomotor activity, changes in brain temperature, and theta rhythm. Previous exposure to the novel environment attenuated this enhancement, suggesting that the effects of novelty habituate with familiarity. LTP longevity also was enhanced when induced in familiar environments containing novel objects. Together, these data indicate that both LTP induction and maintenance are enhanced when LTP is induced while rats investigate novel stimuli. We suggest that novelty initiates a transition of the hippocampal formation to a mode that is particularly conducive to synaptic plasticity, a process that could allow for new learning while preserving the stability of previously stored information. In addition, LTP induced in novel environments elicited a sustained late LTP. This suggests that a single synaptic population can display distinct profiles of LTP maintenance and that this depends on the animal's behavioral state during its induction. Furthermore, the duration of LTP enhanced by novelty parallels the time period during which the hippocampal formation is thought necessary for memory, consistent with the view that dentate LTP is of a duration sufficient to sustain memory in the hippocampal formation.

  5. Long-Term Body Weight Maintenance among StrongWomen–Healthy Hearts Program Participants

    Directory of Open Access Journals (Sweden)

    Rebecca A. Seguin

    2017-01-01

    Full Text Available Background. The repeated loss and regain of body weight, referred to as weight cycling, may be associated with negative health complications. Given today’s obesity epidemic and related interventions to address obesity, it is increasingly important to understand contexts and factors associated with weight loss maintenance. This study examined BMI among individuals who had previously participated in a 12-week, evidence-based, nationally disseminated nutrition and physical activity program designed for overweight and obese middle-aged and older women. Methods. Data were collected using follow-up surveys. Complete height and weight data were available for baseline, 12-week program completion (post-program and follow-up (approximately 3 years later for 154 women (response rate = 27.5%; BMI characteristics did not differ between responders and nonresponders. Results. Mean BMI decreased significantly from baseline to post-program (−0.5, P<0.001 and post-program to follow-up (−0.7, P<0.001. Seventy-five percent of survey respondents maintained or decreased BMI post-program to follow-up. Self-efficacy and social support for healthy eating behaviors (but not physical activity were associated with BMI maintenance or additional weight loss. Conclusions. These findings support the durability of weight loss following participation in a relatively short-term intervention.

  6. 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

  7. Feature-based and object-based attention orientation during short-term memory maintenance.

    Science.gov (United States)

    Ku, Yixuan

    2015-12-01

    Top-down attention biases the short-term memory (STM) processing at multiple stages. Orienting attention during the maintenance period of STM by a retrospective cue (retro-cue) strengthens the representation of the cued item and improves the subsequent STM performance. In a recent article, Backer et al. (Backer KC, Binns MA, Alain C. J Neurosci 35: 1307-1318, 2015) extended these findings from the visual to the auditory domain and combined electroencephalography to dissociate neural mechanisms underlying feature-based and object-based attention orientation. Both event-related potentials and neural oscillations explained the behavioral benefits of retro-cues and favored the theory that feature-based and object-based attention orientation were independent. Copyright © 2015 the American Physiological Society.

  8. Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults.

    Science.gov (United States)

    Waters, D L; Vawter, R; Qualls, C; Chode, S; Armamento-Villareal, R; Villareal, D T

    2013-01-01

    To determine if long-term weight loss with associated improvement in physical and metabolic health can be maintained after lifestyle intervention in frail, obese older adults. Thirty-month follow-up pilot study of a 1-year lifestyle intervention trial. Community. Sixteen frail, obese (body mass index=36±2 kg/m2) older (71±1 yr.) adults. Body weight and composition, physical function, markers of the metabolic syndrome, glucose and insulin response to an oral glucose tolerance test, bone mineral density (BMD), liver and renal function tests, and food diaries. At 30-month follow-up, weight (101.5±3.8 vs. 94.5±3.9 kg) and BMI (36.0 ±1.7 vs. 33.5±1.7 kg/m2) remained significantly below baseline (all plean mass (24.1±1.0 vs. 24.1±1.1kg, all p>0.05) occurred between 12 months (end of trial) and 30 months. Improvements in the physical performance test (PPT 27±0.7 vs. 30.2±0.6), insulin sensitivity (4.1±0.8 vs. 3.0±0.6), and insulin area under the curve (12484±2042 vs. 9270±1139 min.mg/dl) remained at 30 months compared to baseline (all pmaintenance of clinically important weight loss is possible in frail, obese older adults. Weight maintenance appears to be achieved through continued caloric restriction. Larger, long-term studies are needed to follow up on these findings and investigate mechanisms and behaviors underlying maintenance of weight loss and physical function.

  9. Maintenance-based prognostics of nuclear plant equipment for long-term operation

    Energy Technology Data Exchange (ETDEWEB)

    Welz, Zachary; Coble, Jamie; Upadhyaya, Belle; Hines, Wes [University of Tennessee, Knoxville (United States)

    2017-08-15

    While industry understands the importance of keeping equipment operational and well maintained, the importance of tracking maintenance information in reliability models is often overlooked. Prognostic models can be used to predict the failure times of critical equipment, but more often than not, these models assume that all maintenance actions are the same or do not consider maintenance at all. This study investigates the influence of integrating maintenance information on prognostic model prediction accuracy. By incorporating maintenance information to develop maintenance-dependent prognostic models, prediction accuracy was improved by more than 40% compared with traditional maintenance-independent models. This study acts as a proof of concept, showing the importance of utilizing maintenance information in modern prognostics for industrial equipment.

  10. 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.

  11. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 regulates axon integrity in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Amy N Hicks

    Full Text Available Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder. Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2. Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2(blad/blad mutants. Examination of the brains of E18.5 Nmnat2(blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2(blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG. In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

  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. Successful long-term weight loss maintenance in a rural population

    Directory of Open Access Journals (Sweden)

    Milsom VA

    2011-11-01

    Full Text Available Vanessa A Milsom1,2, Kathryn M Ross Middleton2, Michael G Perri21Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USABackground: Few investigations of successful long-term weight loss beyond two years have been conducted, and none has examined weight changes in medically underserved rural populations of older adults. The purpose of this study was to assess long-term weight loss maintenance 3.5 years after the completion of an initial six-month lifestyle intervention for obesity among women aged 50–75 years residing in rural communities.Methods: One hundred and ten obese women with a mean (± standard deviation age of 60.08 ± 6.17 years and mean body mass index of 36.76 ± 5.10 kg/m2 completed an in-person assessment during which their weight and adherence to behavioral weight management strategies were evaluated.Results: Participants showed a mean weight reduction of 10.17% ± 5.0% during the initial six-month intervention and regained 6.95% ± 9.44% from the completion of treatment to follow-up assessment 3.5 years later. A substantial proportion of participants (41.80% were able to maintain weight reductions of 5% or greater from baseline to follow-up. "Successful" participants (those who maintained losses of 5% or greater at follow-up reported weighing themselves, self-monitoring their intake and calories, planning meals in advance, and choosing lower calorie foods with greater frequency than "unsuccessful" participants (those who lost less than 5%.Conclusion: Collectively, these findings indicate that a large proportion of participants were able to maintain clinically significant weight losses for multiple years after treatment, and that self-monitoring was a key component of successful long-term weight management.Keywords: obesity, weight loss, weight maintenance, lifestyle intervention, rural, health disparities

  14. Transmodal comparison of auditory, motor, and visual post-processing with and without intentional short-term memory maintenance.

    Science.gov (United States)

    Bender, Stephan; Behringer, Stephanie; Freitag, Christine M; Resch, Franz; Weisbrod, Matthias

    2010-12-01

    To elucidate the contributions of modality-dependent post-processing in auditory, motor and visual cortical areas to short-term memory. We compared late negative waves (N700) during the post-processing of single lateralized stimuli which were separated by long intertrial intervals across the auditory, motor and visual modalities. Tasks either required or competed with attention to post-processing of preceding events, i.e. active short-term memory maintenance. N700 indicated that cortical post-processing exceeded short movements as well as short auditory or visual stimuli for over half a second without intentional short-term memory maintenance. Modality-specific topographies pointed towards sensory (respectively motor) generators with comparable time-courses across the different modalities. Lateralization and amplitude of auditory/motor/visual N700 were enhanced by active short-term memory maintenance compared to attention to current perceptions or passive stimulation. The memory-related N700 increase followed the characteristic time-course and modality-specific topography of the N700 without intentional memory-maintenance. Memory-maintenance-related lateralized negative potentials may be related to a less lateralised modality-dependent post-processing N700 component which occurs also without intentional memory maintenance (automatic memory trace or effortless attraction of attention). Encoding to short-term memory may involve controlled attention to modality-dependent post-processing. Similar short-term memory processes may exist in the auditory, motor and visual systems. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Jie-Li Li

    2018-04-01

    Full Text Available We aimed to quantitatively synthesize data from randomized controlled trials (RCTs concerning maintenance for multiple myeloma (MM. We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS but not overall survival (OS. Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR = 0.59, 95% Confidence Interval (CI = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001. NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

  16. 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.

  17. Successful long-term weight loss maintenance in a rural population.

    Science.gov (United States)

    Milsom, Vanessa A; Middleton, Kathryn M Ross; Perri, Michael G

    2011-01-01

    Few investigations of successful long-term weight loss beyond two years have been conducted, and none has examined weight changes in medically underserved rural populations of older adults. The purpose of this study was to assess long-term weight loss maintenance 3.5 years after the completion of an initial six-month lifestyle intervention for obesity among women aged 50-75 years residing in rural communities. One hundred and ten obese women with a mean (± standard deviation) age of 60.08 ± 6.17 years and mean body mass index of 36.76 ± 5.10 kg/m(2) completed an in-person assessment during which their weight and adherence to behavioral weight management strategies were evaluated. Participants showed a mean weight reduction of 10.17% ± 5.0% during the initial six- month intervention and regained 6.95% ± 9.44% from the completion of treatment to follow-up assessment 3.5 years later. A substantial proportion of participants (41.80%) were able to maintain weight reductions of 5% or greater from baseline to follow-up. "Successful" participants (those who maintained losses of 5% or greater at follow-up) reported weighing themselves, self-monitoring their intake and calories, planning meals in advance, and choosing lower calorie foods with greater frequency than "unsuccessful" participants (those who lost less than 5%). Collectively, these findings indicate that a large proportion of participants were able to maintain clinically significant weight losses for multiple years after treatment, and that self-monitoring was a key component of successful long-term weight management.

  18. Successful long-term maintenance of Mansonella perstans in an in vitro culture system

    Directory of Open Access Journals (Sweden)

    Abdel Jelil Njouendou

    2017-11-01

    Full Text Available Abstract Background Approximately 114 million people are infected with Mansonella perstans in large proportions of Africa. In contrast to other filariae that infect humans, M. perstans-infected individuals show no distinct pathology or specific clinical picture, indicating a well-tuned adaptation to the host. In addition, since M. perstans adult worms reside in serous cavities which are difficult to access, research has been hindered and there is a paucity of knowledge about the biology of M. perstans, especially the development of the different life stages as well as M. perstans-driven immune responses. Thus in this study, an in vitro culture system was developed which allows an in-depth analysis of M. perstans. Results Culicoides species were caught in Ediki (Kumba, Southwest Region within Cameroon following a blood meal on a microfilaremic donor that had 1500 microfilariae/ml of peripheral blood and kept in captivity for 12 days at 23 °C. In a pilot experiment, 15 infective larvae were obtained from the midges and co-cultured with a confluent monolayer of monkey kidney epithelial cells (LLC-MK2 in DMEM medium supplemented with 10% FBS for up to 77 days. The resulting survival rates of 33% revealed that the cell-conditioned medium was suitable for long-term maintenance of M. perstans worms. To confirm these preliminary observations, 249 infective larvae were cultured for 50 days and their development was monitored daily and microscopically graded for motility. In total, 170 (68.3% filariae survived and 124 (49.8% larvae moulted between days 21–30 to become L5 stage larvae which were motile and showed continuous vigorous movement. Conclusion We have established an in vitro culture system for the generation and long-term maintenance of viable M. perstans worms. This technique will be an important tool to study parasite biology and development, the role in host immunity, and might be helpful to discover novel treatment strategies against

  19. Long-term maintenance of the sea urchin Paracentrotus lividus in culture

    Directory of Open Access Journals (Sweden)

    Paola Cirino

    2017-08-01

    Full Text Available The common sea urchin Paracentrotus lividus (Lamarck, 1816 is an important commercial species in the Mediterranean Sea for the consumption of its gonads (roe. This species has also long been used as an animal model in developmental biology and as an indicator in the assessment of environmental quality. In recent decades, the exploitation of this marine resource has become increasingly intensive, causing the depletion of wild stocks. The ripple effect observed in the laboratory use of this species has been the growing difficulty in finding valiant mature animals in the wild. We focused on the long-term maintenance of wild P. lividus and on the essential question of diet to maintain the animals and improve gonad development. The use of practical ration blocks which are nutrient-rich and show stability, easy storage and handling, resulted reduction in labor requirement and time for feeding streamlining the feeding practice. A significantly higher gonad production and a prolonged period of reproduction were obtained compared to wild caught individuals over the same period of time.

  20. Visual short-term memory: activity supporting encoding and maintenance in retinotopic visual cortex.

    Science.gov (United States)

    Sneve, Markus H; Alnæs, Dag; Endestad, Tor; Greenlee, Mark W; Magnussen, Svein

    2012-10-15

    Recent studies have demonstrated that retinotopic cortex maintains information about visual stimuli during retention intervals. However, the process by which transient stimulus-evoked sensory responses are transformed into enduring memory representations is unknown. Here, using fMRI and short-term visual memory tasks optimized for univariate and multivariate analysis approaches, we report differential involvement of human retinotopic areas during memory encoding of the low-level visual feature orientation. All visual areas show weaker responses when memory encoding processes are interrupted, possibly due to effects in orientation-sensitive primary visual cortex (V1) propagating across extrastriate areas. Furthermore, intermediate areas in both dorsal (V3a/b) and ventral (LO1/2) streams are significantly more active during memory encoding compared with non-memory (active and passive) processing of the same stimulus material. These effects in intermediate visual cortex are also observed during memory encoding of a different stimulus feature (spatial frequency), suggesting that these areas are involved in encoding processes on a higher level of representation. Using pattern-classification techniques to probe the representational content in visual cortex during delay periods, we further demonstrate that simply initiating memory encoding is not sufficient to produce long-lasting memory traces. Rather, active maintenance appears to underlie the observed memory-specific patterns of information in retinotopic cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Long-Term Surveillance and Maintenance Records: Maintaining Access to the Knowledge - 13122

    International Nuclear Information System (INIS)

    Montgomery, John; Gueretta, Jeanie; McKinney, Ruth; Anglim, Cliff

    2013-01-01

    The U.S. Department of Energy (DOE) Office of Legacy Management (LM) is an integral part of DOE's strategy to ensure that legacy liabilities of former nuclear weapons production sites are properly managed following the completion of environmental cleanup activities. In the area of environmental legacy management, records management is crucial to the protection of health, environmental, and legal interests of the Department and the public. LM is responsible for maintaining long-term surveillance and maintenance (LTS and M) records in performance of its mission. Maintaining access to the knowledge contained in these record collections is one of LM's primary responsibilities. To fulfill this responsibility, LM established a consolidated records management facility, the LM Business Center (LMBC), to house physical media records and electronic records. A new electronic record keeping system (ERKS) was needed to replace an obsolete system while helping to ensure LM is able to meet ongoing responsibilities to maintain access to knowledge and control the life cycle management of records. (authors)

  2. A risk based model supporting long term maintenance and reinvestment strategy decision making

    Energy Technology Data Exchange (ETDEWEB)

    Sand, Kjell; Montard, Julien; Tremoen, Tord H.

    2010-02-15

    This Technical Report is a product from the project Risk-Based Distribution System Asset Management (short: RISK DSAM) - Work Package 3 Risk exposure on company/strategic level. In the report a concept for portfolio distribution system asset management is presented. The approach comprises four main steps: 1. Decide the asset base. 2. Divide the asset base into relevant archetypes. 3. Develop or select relevant maintenance and reinvestment strategies for the different archetypes. 4. Estimate risks and costs for each archetype for the relevant strategies. For the different steps guidelines are given and a proposal for implementation of the concept is given in terms of a proposed IT system architecture.To evaluate the feasibility of such a concept, a prototype was developed in by using Visual Basic macros in Excel using real technical data from a small DSO. The experience from using the prototype shows that the concept is realistic. All assets are included and depending of the ambition of the risk analysis both simple simulation models and more advanced might be embedded. Presentations of the concept for a utility engineers have receive positive feedback indicating that the concept is regarded as a practical way to develop risk based asset management strategies for the asset fleet. It should be noted that the concept should be applied on a company strategic level and is thus not designed to be applied for a specific project or asset decisions. For this, more detailed models with area specific information, topology etc. are needed. (Author)

  3. Long-Term Surveillance and Maintenance Records: Maintaining Access to the Knowledge - 13122

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, John; Gueretta, Jeanie [U.S. Department of Energy Office of Legacy Management, 99 Research Park Road Morgantown, WV 26505 (United States); McKinney, Ruth; Anglim, Cliff [Source One Management, Inc. (United States)

    2013-07-01

    The U.S. Department of Energy (DOE) Office of Legacy Management (LM) is an integral part of DOE's strategy to ensure that legacy liabilities of former nuclear weapons production sites are properly managed following the completion of environmental cleanup activities. In the area of environmental legacy management, records management is crucial to the protection of health, environmental, and legal interests of the Department and the public. LM is responsible for maintaining long-term surveillance and maintenance (LTS and M) records in performance of its mission. Maintaining access to the knowledge contained in these record collections is one of LM's primary responsibilities. To fulfill this responsibility, LM established a consolidated records management facility, the LM Business Center (LMBC), to house physical media records and electronic records. A new electronic record keeping system (ERKS) was needed to replace an obsolete system while helping to ensure LM is able to meet ongoing responsibilities to maintain access to knowledge and control the life cycle management of records. (authors)

  4. Long-term Maintenance of Fungal Cultures on Perlite in Cryovials – an Alternative for Agar Slants

    Czech Academy of Sciences Publication Activity Database

    Homolka, Ladislav; Lisá, Ludmila

    2008-01-01

    Roč. 53, č. 6 (2008), s. 534-536 ISSN 0015-5632 R&D Projects: GA MŠk LC06066 Institutional research plan: CEZ:AV0Z50200510 Keywords : basidiomycete * perlite * long-term maintenance Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  5. 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

    maintenance of axon integrity. We demonstrate the role of the periodic spectrin-dependent cytoskeleton in axons and show that loss of αII spectrin from PNS axons causes preferential degeneration of large-diameter myelinated axons. We show that nodal αII spectrin is found at greater densities in large-diameter myelinated axons, suggesting that nodes are particularly vulnerable domains requiring a specialized cytoskeleton to protect against axon degeneration. Copyright © 2017 the authors 0270-6474/17/3711323-12$15.00/0.

  6. 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.

  7. 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.

  8. Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague.

    Directory of Open Access Journals (Sweden)

    Amy J Vogler

    2017-09-01

    Full Text Available Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the

  9. Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague.

    Science.gov (United States)

    Vogler, Amy J; Andrianaivoarimanana, Voahangy; Telfer, Sandra; Hall, Carina M; Sahl, Jason W; Hepp, Crystal M; Centner, Heather; Andersen, Genevieve; Birdsell, Dawn N; Rahalison, Lila; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Rajerison, Minoarisoa

    2017-09-01

    Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period. We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period. Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated

  10. Translational research: bridging the gap between long-term weight loss maintenance research and practice.

    Science.gov (United States)

    Akers, Jeremy D; Estabrooks, Paul A; Davy, Brenda M

    2010-10-01

    The number of US adults classified as overweight or obese has dramatically increased in the past 25 years, resulting in a significant body of research addressing weight loss and weight loss maintenance. However, little is known about the potential of weight loss maintenance interventions to be translated into actual practice settings. Thus, the purpose of this article is to determine the translation potential of published weight loss maintenance intervention studies by determining the extent to which they report information across the reach, efficacy/effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. A secondary purpose is to provide recommendations for research based on these findings. To identify relevant research articles, a literature search was conducted using four databases; 19 weight loss maintenance intervention studies were identified for inclusion. Each article was evaluated using the RE-AIM Coding Sheet for Publications to determine the extent to which dimensions related to internal and external validity were reported. Approximately half of the articles provided information addressing three RE-AIM dimensions, yet only a quarter provided information addressing adoption and maintenance. Significant gaps were identified in understanding external validity, and metrics that could facilitate the translation of these interventions from research to practice are presented. Based upon this review, it is unknown how effective weight loss maintenance interventions could be in real-world situations, such as clinical or community practice settings. Future studies should be planned to address how weight loss maintenance intervention programs will be adopted and maintained, with special attention to costs for participants and for program implementation. Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  11. Routine maintenance: safety term based work selection; Selecao de trabalho baseado no prazo seguro

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, Albair de; Filho, Antnio S.; Brendler, Fabiano E.; Adamatti, Gilberto A.; Naruto, Itiro; Araujo, Luiz C.F.; Puerari, Roberto [PETROBRAS, Rio de Janeiro, RJ (Brazil)

    2004-07-01

    This work has objective to present the experience of improvement of routine maintenance system in some refineries of the PETROBRAS system, with the purpose to increase the efficiency in the Industrial Maintenance Management (cost), Utilization and HSE (Health, Safety and Environment), key of success of a petroleum company. The new system is based on the implantation of the culture of work selection in the safe period, through elaboration of new maintenance procedure, with emphasis in decisions shared between Operation and Maintenance Team, resulting in reduction of emergencies, making possible contract of services of maintenance for packages and improved allocation of resources. This work treat about improvement of the system in use, in view of that it has already taken in consideration the consequence of fail in the maintenance with participation of the operators. Besides of these challenge, this modification was made without causing riots in the process of implantation of SAP. As main result, financial profits had got better of resources with increase of safety, considering that they are analyzed in a way it that systematized potential risks. (author)

  12. Solid Waste Management Units And Areas Of Concern Annual Long-Term Monitoring & Maintenance Report For Calendar Year 2016.

    Energy Technology Data Exchange (ETDEWEB)

    Dotson, Patrick Wells [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Little, Bonnie Colleen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    Long-term controls were maintained at 21 Solid Waste Management Units (SWMUs) and Areas of Concern (AOCs) in accordance with the requirements of the “Long-Term Monitoring and Maintenance Plan for SWMUs and AOCs Granted Corrective Action Complete with Controls” in Attachment M of the Resource Conservation and Recovery Act Facility Operating Permit, which took effect February 26, 2015. Maintenance and controls at these SWMUs and AOCs are described and documented in this report. Conditions requiring maintenance or repair activities were not identified for any of the inspected SWMUs or AOCs. Based upon the inspections performed and site conditions observed, the administrative and physical institutional controls in place at the SWMUs and AOCs are effectively providing continued protection of human health and the environment. This report does not present monitoring and maintenance activities for SWMU 76, the Mixed Waste Landfill; those activities adhere to the approved MWL LTMM Plan, Section 4.8.1 requiring a separate annual report which will be submitted to the NMED by June 30, 2017.

  13. Identification of factors promoting ex vivo maintenance of mouse hematopoietic stem cells by long-term single-cell quantification.

    Science.gov (United States)

    Kokkaliaris, Konstantinos D; Drew, Erin; Endele, Max; Loeffler, Dirk; Hoppe, Philipp S; Hilsenbeck, Oliver; Schauberger, Bernhard; Hinzen, Christoph; Skylaki, Stavroula; Theodorou, Marina; Kieslinger, Matthias; Lemischka, Ihor; Moore, Kateri; Schroeder, Timm

    2016-09-01

    The maintenance of hematopoietic stem cells (HSCs) during ex vivo culture is an important prerequisite for their therapeutic manipulation. However, despite intense research, culture conditions for robust maintenance of HSCs are still missing. Cultured HSCs are quickly lost, preventing their improved analysis and manipulation. Identification of novel factors supporting HSC ex vivo maintenance is therefore necessary. Coculture with the AFT024 stroma cell line is capable of maintaining HSCs ex vivo long-term, but the responsible molecular players remain unknown. Here, we use continuous long-term single-cell observation to identify the HSC behavioral signature under supportive or nonsupportive stroma cocultures. We report early HSC survival as a major characteristic of HSC-maintaining conditions. Behavioral screening after manipulation of candidate molecules revealed that the extracellular matrix protein dermatopontin (Dpt) is involved in HSC maintenance. DPT knockdown in supportive stroma impaired HSC survival, whereas ectopic expression of the Dpt gene or protein in nonsupportive conditions restored HSC survival. Supplementing defined stroma- and serum-free culture conditions with recombinant DPT protein improved HSC clonogenicity. These findings illustrate a previously uncharacterized role of Dpt in maintaining HSCs ex vivo. © 2016 by The American Society of Hematology.

  14. 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.

  15. Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

    Science.gov (United States)

    Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

    2014-01-01

    Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

  16. 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.

  17. 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.

  18. 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".

  19. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila

    Science.gov (United States)

    Duncan, Jason E.; Lytle, Nikki K.; Zuniga, Alfredo; Goldstein, Lawrence S. B.

    2013-01-01

    Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai) gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila . The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila , which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila , we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport. PMID:23840848

  20. Long-Term Weight Maintenance after a 17-Week Weight Loss Intervention with or without a One-Year Maintenance Program: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tuula Pekkarinen

    2015-01-01

    Full Text Available Background. Weight lost by obese patients is almost always regained over time. Extended treatment may improve maintenance, but solid evidence is lacking. Purpose. We determined effectiveness of maintenance therapy after a weight loss program. Methods. Together 201 patients (mean age 47 years and BMI 42 kg/m2, 71% women were randomly assigned to either a 17-week weight loss program followed by a one-year maintenance program or to a weight loss program without subsequent maintenance intervention. The weight loss program included behavior modification and a very-low-calorie diet, and maintenance program behavior modification. The primary outcome measure was percentage of patients with 5% or more weight loss at the end of maintenance (week 69 and one year later (week 121. Secondary outcomes were weight related changes in lifestyle and quality of life. Results. At week 69, 52% of the patients with and 44% of those without maintenance program had lost weight ≥5%, P=0.40, and, at week 121, 33% and 34%, P=0.77, respectively. At week 121 secondary outcomes did not differ between the groups among those successfully followed up. Conclusions. This one-year maintenance program was not effective in preventing weight regain in severely obese patients. Trial Registration. This trial is registered under clinicaltrials.gov Identifier: NCT00590655.

  1. Synaptic Mechanisms of Induction and Maintenance of Long-Term Sensitization Memory in Aplysia

    OpenAIRE

    Glanzman, DL

    2013-01-01

    The marine snail Aplysia californica exhibits a simple defensive withdrawal reflex that can undergo several forms of learning. In particular, the reflex can exhibit long-term sensitization (LTS), a form of nonassociative memory. LTS is mediated by long-term facilitation (LTF) of the monosynaptic connection between the sensory and motor neurons that mediate the withdrawal reflex. LTS and LTF represent one of the best understood model systems of long-term memory extent. Furthermore, discoveries...

  2. Long-term maintenance of human induced pluripotent stem cells by automated cell culture system.

    Science.gov (United States)

    Konagaya, Shuhei; Ando, Takeshi; Yamauchi, Toshiaki; Suemori, Hirofumi; Iwata, Hiroo

    2015-11-17

    Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem (iPS) cells, are regarded as new sources for cell replacement therapy. These cells can unlimitedly expand under undifferentiated conditions and be differentiated into multiple cell types. Automated culture systems enable the large-scale production of cells. In addition to reducing the time and effort of researchers, an automated culture system improves the reproducibility of cell cultures. In the present study, we newly designed a fully automated cell culture system for human iPS maintenance. Using an automated culture system, hiPS cells maintained their undifferentiated state for 60 days. Automatically prepared hiPS cells had a potency of differentiation into three germ layer cells including dopaminergic neurons and pancreatic cells.

  3. Initial Weight Loss after Restrictive Bariatric Procedures May Predict Mid-Term Weight Maintenance: Results From a 12-Month Pilot Trial

    OpenAIRE

    Nikolić, Marko; Kruljac, Ivan; Kirigin, Lora; Mirošević, Gorana; Ljubičić, Neven; Nikolić, Borka Pezo; Bekavac-Bešlin, Miroslav; Budimir, Ivan; Vrkljan, Milan

    2015-01-01

    Background: Bariatric procedures are effective options for weight loss (WL) in the morbidly obese. However, some patients fail to lose any weight after bariatric surgery, and mid-term weight maintenance is variable. The aim of this study was to investigate whether initial WL could predict mid-term weight maintenance. ----- Methods: Eighty patients were enrolled, of whom 44 were treated with the BioEnterics Intragastric Balloon (BIB), 21 with laparoscopic adjustable gastric lap-banding (LAGB),...

  4. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

    Science.gov (United States)

    Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

    2013-02-01

    Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. Involvement of protein kinase Mζ in the maintenance of long-term memory for taste aversion learning in young chicks.

    Science.gov (United States)

    Tiunova, A A; Bezryadnov, D V; Anokhin, K V

    2015-03-01

    The effects of an inhibitor of protein kinase Mζ on long-term memory were studied using the model of taste aversion in newborn chicks. Memory was impaired by intracerebral injection of 10 or 20 nmol of ζ-inhibiting peptide 24 h after training. Memory impairment was found 2 h after peptide administration, and repeated examination 24 h after treatment showed no recovery. Memory impairment was not observed 24 h after inhibitor administration if the testing 2 h after treatment was not performed. The results indicate the contribution of protein kinase Mζ in the maintenance of long-term memory in the avian brain. These data confirm the hypothesis of several authors that inhibition of protein kinase Mζ does not abolish memory, but rather interacts with processes of memory retrieval and/or reconsolidation.

  7. Interventional radiology in the provision and maintenance of long-term central venous access

    International Nuclear Information System (INIS)

    Lyon, S.M.; Given, M.; Marshall, N.L.

    2008-01-01

    Establishing and maintaining venous access forms an increasing proportion of the workload in interventional radiology. Several patient groups require medium-term to long-term venous catheters for a variety of purposes, including chemotherapy, long-term antimicrobials, parenteral nutrition, short-term access for haemodialysis or exhausted haemodialysis. Often, these catheters are required for treatment and frequent blood testing, which can quickly exhaust the peripheral veins. Venous access devices include implantable catheters (ports), tunnelled catheters and peripherally inserted central catheters, which have different functions, advantages and limitations. Imaging-guided placement is the preferred method of insertion in many institutions because of higher success rates and radiologists are well suited to address catheter complications.

  8. Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity.

    Science.gov (United States)

    Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel

    2017-03-08

    Multiple kinase activations contribute to long-term synaptic plasticity, a cellular mechanism mediating long-term memory. The sensorimotor synapse of Aplysia expresses different forms of long-term facilitation (LTF)-nonassociative and associative LTF-that require the timely activation of kinases, including protein kinase C (PKC). It is not known which PKC isoforms in the sensory neuron or motor neuron L7 are required to sustain each form of LTF. We show that different PKMs, the constitutively active isoforms of PKCs generated by calpain cleavage, in the sensory neuron and L7 are required to maintain each form of LTF. Different PKMs or calpain isoforms were blocked by overexpressing specific dominant-negative constructs in either presynaptic or postsynaptic neurons. Blocking either PKM Apl I in L7, or PKM Apl II or PKM Apl III in the sensory neuron 2 d after 5-hydroxytryptamine (5-HT) treatment reversed persistent nonassociative LTF. In contrast, blocking either PKM Apl II or PKM Apl III in L7, or PKM Apl II in the sensory neuron 2 d after paired stimuli reversed persistent associative LTF. Blocking either classical calpain or atypical small optic lobe (SOL) calpain 2 d after 5-HT treatment or paired stimuli did not disrupt the maintenance of persistent LTF. Soon after 5-HT treatment or paired stimuli, however, blocking classical calpain inhibited the expression of persistent associative LTF, while blocking SOL calpain inhibited the expression of persistent nonassociative LTF. Our data suggest that different stimuli activate different calpains that generate specific sets of PKMs in each neuron whose constitutive activities sustain long-term synaptic plasticity. SIGNIFICANCE STATEMENT Persistent synaptic plasticity contributes to the maintenance of long-term memory. Although various kinases such as protein kinase C (PKC) contribute to the expression of long-term plasticity, little is known about how constitutive activation of specific kinase isoforms sustains long-term

  9. Maintenance of tactile short-term memory for locations is mediated by spatial attention.

    Science.gov (United States)

    Katus, Tobias; Andersen, Søren K; Müller, Matthias M

    2012-01-01

    According to the attention-based rehearsal hypothesis, maintenance of spatial information is mediated by covert orienting towards memorized locations. In a somatosensory memory task, participants simultaneously received bilateral pairs of mechanical sample pulses. For each hand, sample stimuli were randomly assigned to one of three locations (fingers). A subsequent visual retro-cue determined whether the left or right hand sample was to be memorized. The retro-cue elicited lateralized activity reflecting the location of the relevant sample stimulus. Sensory processing during the retention period was probed by task-irrelevant pulses randomized to locations at the cued and uncued hand. The somatosensory N140 was enhanced for probes delivered to the cued hand, relative to uncued. Probes presented shortly after the retro-cue showed greatest attentional modulations. This suggests that transient contributions from retrospective selection overlapped with the sustained effect of attention-based rehearsal. In conclusion, focal attention shifts within tactile mnemonic content occurred after retro-cues and guided sensory processing during retention. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. The role of long-term familiarity and attentional maintenance in short-term memory for timbre.

    Science.gov (United States)

    Siedenburg, Kai; McAdams, Stephen

    2017-04-01

    We study short-term recognition of timbre using familiar recorded tones from acoustic instruments and unfamiliar transformed tones that do not readily evoke sound-source categories. Participants indicated whether the timbre of a probe sound matched with one of three previously presented sounds (item recognition). In Exp. 1, musicians better recognised familiar acoustic compared to unfamiliar synthetic sounds, and this advantage was particularly large in the medial serial position. There was a strong correlation between correct rejection rate and the mean perceptual dissimilarity of the probe to the tones from the sequence. Exp. 2 compared musicians' and non-musicians' performance with concurrent articulatory suppression, visual interference, and with a silent control condition. Both suppression tasks disrupted performance by a similar margin, regardless of musical training of participants or type of sounds. Our results suggest that familiarity with sound source categories and attention play important roles in short-term memory for timbre, which rules out accounts solely based on sensory persistence.

  11. New maintenance strategy of Tokyo Electric Power Company and Fukushima Dai-ichi Nuclear Power Plant for effective ageing management and safe long-term operation

    International Nuclear Information System (INIS)

    Inagaki, Takeyuki; Yamashita, Norimichi

    2009-01-01

    Fukushima Dai-ichi Nuclear Power Plant is the oldest among three nuclear power plants owned and operated by Tokyo Electric Power Company, which consists of six boiling water reactor units. The commercial operation of Unit 1 was commenced in 1971 (37 years old) and Unit 6 in 1978 (29 years old). Currently ageing degradations of systems, structures and components are managed through maintenance programs, component replacement/refurbishment programs and long-term maintenance plans. The long-term maintenance plans are established through ageing management component replacement/refurbishment programs reviews performed before the 30th year of operation and they are for safe and reliable operation after 30 years (long-term operation). However the past maintenance actions and past component replacement/refurbishment programs were not always proactive and past operational experience and maintenance practices suggest that effective/proactive ageing management programs be introduced in earlier stage of the plant operation. In this circumstance, Tokyo Electric Power Company and Fukushima Dai-ichi Nuclear Power Plant are setting up a new maintenance strategy that includes 1) improving the normal maintenance programs by using ageing degradation data, 2) effective use of information on internal/external operational experience and maintenance practices related to ageing, and 3) proactive component/equipment refurbishment programs during a refreshment outage for safe and reliable long-term operation. To accomplish the goal of this strategy, strengthening engineering capability of plant staff members is a crucial required for the plant. The objective of this paper is to briefly explain main results ageing management reviews, past and current significant ageing issues and management programs against them, and the new maintenance strategy established by Tokyo Electric Power Company and Fukushima Dai-ichi Nuclear Power Plant. (author)

  12. 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

  13. Efficacy of Adalimumab as a long term maintenance therapy in ulcerative colitis.

    LENUS (Irish Health Repository)

    McDermott, Edel

    2013-03-01

    Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF-alpha. There are limited data with regard to its efficacy in ulcerative colitis. We report experience of adalimumab in ulcerative colitis in a single centre with a focus on the ability of this agent to maintain response and avoid colectomy in the medium to long-term.

  14. The Role of Attention in the Maintenance of Feature Bindings in Visual Short-term Memory

    Science.gov (United States)

    Johnson, Jeffrey S.; Hollingworth, Andrew; Luck, Steven J.

    2008-01-01

    This study examined the role of attention in maintaining feature bindings in visual short-term memory. In a change-detection paradigm, participants attempted to detect changes in the colors and orientations of multiple objects; the changes consisted of new feature values in a feature-memory condition and changes in how existing feature values were…

  15. Protecting visual short-term memory during maintenance : Attentional modulation of target and distractor representations

    NARCIS (Netherlands)

    Vissers, M.E.; Gulbinaite, R.; van den Bos, T.; Slagter, H.A.

    2017-01-01

    In the presence of distraction, attentional filtering is a key predictor of efficient information storage in visual short-term memory (VSTM). Yet, the role of attention in distractor filtering, and the extent to which attentional filtering continues to protect information during post-perceptual

  16. 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.

  17. Barriers to and facilitators of long term weight loss maintenance in adult UK people: A thematic analysis

    Directory of Open Access Journals (Sweden)

    Himanshu Gupta

    2014-01-01

    Full Text Available Adult obesity and overweight is affecting every region of the world and is described as one of today′s most significant and neglected public health problems. The problem has taken the shape of an epidemic not only because the prevalence of obesity has witnessed a dramatic progress in a short period of time, but also because obesity has paved the way for increased risks for morbidity and mortality associated with it. It has been predicted that about half of the adult men and more than a quarter of adult women would be obese by 2030 in the UK and this figure could rise up to 50% in 2050 for whole of the adult UK population. Although a modest 5-10% weight loss maintained in the long term can significantly decrease health risk, few people engage in weight loss activities. Against this background, this review paper aims to investigate the reasons helping and/or hindering adults in the UK maintain weight loss in the long term; using online and organizational data sources and thematically analyzing the data. Self-body perception, enhanced self-confidence, social support, self-motivation, incentives and rewards, increased physical activity levels and healthy eating habits facilitated people in maintaining weight loss in the long term and overall quality of life. Extreme weather conditions, natural phenomena such as accidents, injuries and ill-health, work commitments, inability for time management and to resist the temptation for food constrained the successful long-term weight loss maintenance.

  18. 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.

  19. Long term weight maintenance after advice to consume low carbohydrate, higher protein diets--a systematic review and meta analysis.

    Science.gov (United States)

    Clifton, P M; Condo, D; Keogh, J B

    2014-03-01

    Meta analysis of short term trials indicates that a higher protein, lower carbohydrate weight loss diet enhances fat mass loss and limits lean mass loss compared with a normal protein weight loss diet. Whether this benefit persists long term is not clear. We selected weight loss studies in adults with at least a 12 month follow up in which a higher percentage protein/lower carbohydrate diet was either planned or would be expected for either weight loss or weight maintenance. Studies were selected regardless of the success of the advice but difference in absolute and percentage protein intake at 12 months was used as a moderator in the analysis. Data was analysed using Comprehensive Meta analysis V2 using a random effects analysis. As many as 32 studies with 3492 individuals were analysed with data on fat and lean mass, glucose and insulin from 18 to 22 studies and lipids from 28 studies. A recommendation to consume a lower carbohydrate, higher protein diet in mostly short term intensive interventions with long term follow up was associated with better weight and fat loss but the effect size was small-standardised means of 0.14 and 0.22, p = 0.008 and p fat mass (0.9 vs. 0.3 kg). Fasting triglyceride and insulin were also lower with high protein diets with effect sizes of 0.17 and 0.22, p = 0.003 and p = 0.042 respectively. Other lipids and glucose were not different. The short term benefit of higher protein diets appears to persist to a small degree long term. Benefits are greater with better compliance to the diet. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. 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.

  1. 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

  2. Long-term preventive maintenance of instrumentation control equipment for PWR plants

    International Nuclear Information System (INIS)

    Sugitani, S.; Nanba, M.

    2006-01-01

    Since the PWR plants in Japan have been operated more than 30 years, main instrumentation control equipment of analog systems has been renewed to digital control systems. Renewal works had to be done in short period within periodical inspection term and for several facilities. The Mitsubishi LTD group had been provided with these market needs by its digital control system (MELTAC-NplusR 3) applicable to main instrumentation control equipment for primary and secondary systems and had already finished the renewal for practical plants. (T. Tanaka)

  3. 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.

  4. Long-Term Surveillance and Maintenance Plan for the U.S. Department of Energy Amchitka, Alaska, Site

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-09-01

    This Long-Term Surveillance and Maintenance Plan describes how the U.S. Department of Energy (DOE) intends to fulfill its mission to maintain protection of human health and the environment at the Amchitka, Alaska, Site1. Three underground nuclear tests were conducted on Amchitka Island. The U.S. Department of Defense, in conjunction with the U.S. Atomic Energy Commission (AEC), conducted the first nuclear test (Long Shot) to provide data that would improve the United States' capability of detecting underground nuclear explosions. The second nuclear test (Milrow) was a weapons-related test conducted by AEC as a means to study the feasibility of detonating a much larger device. The final nuclear test (Cannikin), the largest United States underground test, was a weapons-related test. Surface disturbances associated with these tests have been remediated. However, radioactivity remains deep below the surface, contained in and around the test cavities, for which no feasible remediation technology has been identified. In 2006, the groundwater model (Hassan et al. 2002) was updated using 2005 data collected by the Consortium for Risk Evaluation with Stakeholder Participation. Model simulation results indicate there is no breakthrough or seepage of radionuclides into the marine environment within 2,000 years. The Amchitka conceptual model is reasonable; the flow and transport simulation is based on the best available information and data. The simulation results are a quantitative prediction supported by the best available science and technology. This Long-Term Surveillance and Maintenance Plan is an additional step intended for the protection of human health and the environment. This plan may be modified from time to time in the future consistent with the mission to protect human health

  5. Long-term maintenance of pediatric asthma: focus on budesonide/formoterol inhalation aerosol

    Directory of Open Access Journals (Sweden)

    Peter N Huynh

    2010-02-01

    Full Text Available Peter N Huynh1, Lyne G Scott1, Kenny YC Kwong21Division of Allergy-Immunology, Department of Pediatrics, Los Angeles County, University of Southern California Medical Center, Los Angeles, CA, USA; 2Division of Allergy-Immunology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USAAbstract: Current national and international asthma guidelines recommend treatment of children with asthma towards achieving and maintaining asthma control. These guidelines provide more stringent recommendations to increase therapy for patients with uncontrolled asthma in order to reduce asthma-related morbidity and mortality. Newer combination agents such as budesonide and formoterol have been shown to be safe and effective in treatment of asthma in children. Use of long-term controller agents like this in combination with improved compliance and treatment of co-morbid conditions have been successful in this endeavor. This review discusses control of pediatric asthma with focus on the use of budesonide in combination with formoterol.Keywords: asthma, control, children, budesonide, formoterol, long-term

  6. Evaluation of waste management options in view of long-term maintenance-free landfills

    International Nuclear Information System (INIS)

    Brunner, P.H.; Doeberl, G.; Huber, R.; Eder, M.; Pierrard, R.; Schoenbaeck, W.; Fruehwirth, W.; Hutterer, H.; Woeginger, H.

    2001-01-01

    The present case study compares and evaluates different waste management options with special consideration to their long-term implications. Multiple scenarios of these options were created and investigated as to which of term best fulfilled the goals of the Austrian waste management act (Abfallwirtschaftgesetz, AWG). Serving as a basis for this study, an elaborated model of the Austrian waste management, as described in GUA and IFIP (1998, 'Management of Household and Household-like Waste in Austria'), was used. Alterations to the GUA and IFIP study were done in order to best fulfill the needs of this assessment. Household and household-like waste, as well as municipal sewage sludge have been defined as the system input. The following list of scenarios were investigated against an up-dated status-quo (P0): M1 maximum landfilling of untreated waste; M2a maximum incineration without any after treatment; M2b maximum incineration with cement stabilization of the residual material; M2c maximum high temperature process; M3a maximum mechanical-biological treatment with the light fraction from sorting and splitting processed in a fluidized-bed furnace; M3b maximum mechanical-biological treatment with the light fraction from sorting and splitting processed in a rotary kiln for use in the cement industry; M3c maximum mechanical-biological treatment with the high caloric heavy fraction after decomposition processed in a fluidized-bed furnace; M3d maximum mechanical-biological treatment with the high caloric heavy fraction after decomposition processed in a rotary kiln for use in the cement industry. In order to oblige to the precautionary principle of the AWG, each of the scenarios were investigated, with regards to the short, middle, and long-term landfills behaviors of the deposited residual material. The macro-economical Cost-Benefit-Analysis (CBA) was used in the assessment. Additionally a so-called 'modified-Cost-Effect-Analysis' (MCEA) was developed. Unlike the

  7. Formation and Maintenance of Robust Long-Term Information Storage in the Presence of Synaptic Turnover.

    Directory of Open Access Journals (Sweden)

    Michael Fauth

    2015-12-01

    Full Text Available A long-standing problem is how memories can be stored for very long times despite the volatility of the underlying neural substrate, most notably the high turnover of dendritic spines and synapses. To address this problem, here we are using a generic and simple probabilistic model for the creation and removal of synapses. We show that information can be stored for several months when utilizing the intrinsic dynamics of multi-synapse connections. In such systems, single synapses can still show high turnover, which enables fast learning of new information, but this will not perturb prior stored information (slow forgetting, which is represented by the compound state of the connections. The model matches the time course of recent experimental spine data during learning and memory in mice supporting the assumption of multi-synapse connections as the basis for long-term storage.

  8. Flexible endoscopy for pediatric tracheobronchial metallic stent placement, maintenance and long-term outcomes

    Science.gov (United States)

    2018-01-01

    Objectives To assess the placement, surveillance management and long-term outcomes of the tracheobronchial (TB) balloon expandable metallic stent (BEMS) managed by therapeutic flexible endoscopy (TFE). Methods This is a retrospective review and analysis of all computerized medical records and related flexible endoscopy videos of pediatric patients who received TB BEMS during 20 years period, from January 1997 to December 2016. TFE techniques with forceps debridement, balloon dilatation and laser ablation were used to implant stents, perform regular surveillance, maintain their functions, and expand the diameters of BEMS. Short-length (30cm-36cm) endoscopes of OD 3.2mm to 5.0mm coupled with the noninvasive ventilation, without ventilation bag, mask or airway tube, supported the whole procedures. Results 146 BEMS were implanted in 87 consecutive children, including 84 tracheal, 15 carinal and 47 bronchial stents. At the time of placement, the mean age was 35.6 ± 54.6 month-old (range 0.3–228) and the mean body weight was 13.9 ± 10.6 kg (range 2.2–60). Surveillance period was 9.4 ± 6.7 years (range, 0.3–18.0). Satisfactory clinical improvements were noted immediately in all but two patients. Seventy-two (82.8%) patients were still alive with stable respiratory status, except two patients necessitating TFE management every two months. Fifty-one stents, including 35 tracheal and 16 bronchial ones, were successfully retrieved mainly with rigid endoscopy. Implanted stents could be significantly (stent diameters were positively correlated to the implanted duration. Altogether, 33 stents expired (15 patients), 51 were retrieved (40 patients), and 62 remained and functioning well (38 patients), with their mean duration of 7.4 ± 9.5, 34.9 ± 36.3 and 82.3 ± 62.5 months, respectively. Conclusion In pediatric patients, TFE with short-length scopes coupled with this NIV support has provided a safe, feasible and effective modality in placing and subsequently managing

  9. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    Science.gov (United States)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  10. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.

    Science.gov (United States)

    Farías, Ginny G; Guardia, Carlos M; De Pace, Raffaella; Britt, Dylan J; Bonifacino, Juan S

    2017-04-04

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

  11. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

    Science.gov (United States)

    Farías, Ginny G.; Guardia, Carlos M.; De Pace, Raffaella; Britt, Dylan J.; Bonifacino, Juan S.

    2017-01-01

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes. PMID:28320970

  12. Functional interplay of top-down attention with affective codes during visual short-term memory maintenance.

    Science.gov (United States)

    Kuo, Bo-Cheng; Lin, Szu-Hung; Yeh, Yei-Yu

    2018-06-01

    Visual short-term memory (VSTM) allows individuals to briefly maintain information over time for guiding behaviours. Because the contents of VSTM can be neutral or emotional, top-down influence in VSTM may vary with the affective codes of maintained representations. Here we investigated the neural mechanisms underlying the functional interplay of top-down attention with affective codes in VSTM using functional magnetic resonance imaging. Participants were instructed to remember both threatening and neutral objects in a cued VSTM task. Retrospective cues (retro-cues) were presented to direct attention to the hemifield of a threatening object (i.e., cue-to-threat) or a neutral object (i.e., cue-to-neutral) during VSTM maintenance. We showed stronger activity in the ventral occipitotemporal cortex and amygdala for attending threatening relative to neutral representations. Using multivoxel pattern analysis, we found better classification performance for cue-to-threat versus cue-to-neutral objects in early visual areas and in the amygdala. Importantly, retro-cues modulated the strength of functional connectivity between the frontoparietal and early visual areas. Activity in the frontoparietal areas became strongly correlated with the activity in V3a-V4 coding the threatening representations instructed to be relevant for the task. Together, these findings provide the first demonstration of top-down modulation of activation patterns in early visual areas and functional connectivity between the frontoparietal network and early visual areas for regulating threatening representations during VSTM maintenance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Factors associated with long-term weight-loss maintenance following bariatric surgery in adolescents with severe obesity.

    Science.gov (United States)

    Ryder, J R; Gross, A C; Fox, C K; Kaizer, A M; Rudser, K D; Jenkins, T M; Ratcliff, M B; Kelly, A S; Kirk, S; Siegel, R M; Inge, T H

    2018-01-01

    Bariatric surgery produces robust weight loss, however, factors associated with long-term weight-loss maintenance among adolescents undergoing Roux-en-Y gastric bypass surgery are unknown. Fifty adolescents (mean±s.d. age and body mass index (BMI)=17.1±1.7 years and 59±11 kg m -2 ) underwent Roux-en-Y gastric bypass surgery, had follow-up visits at 1 year and at a visit between 5 and 12 years following surgery (Follow-up of Adolescent Bariatric Surgery at 5 Plus years (FABS-5+) visit; mean±s.d. 8.1±1.6 years). A non-surgical comparison group (n=30; mean±s.d. age and BMI=15.3±1.7 years and BMI=52±8 kg m -2 ) was recruited to compare weight trajectories over time. Questionnaires (health-related and eating behaviors, health responsibility, impact of weight on quality of life (QOL), international physical activity questionnaire and dietary habits via surgery guidelines) were administered at the FABS-5+ visit. Post hoc, participants were split into two groups: long-term weight-loss maintainers (n=23; baseline BMI=58.2 kg m -2 ; 1-year BMI=35.8 kg m -2 ; FABS-5+ BMI=34.9 kg m -2 ) and re-gainers (n=27; baseline BMI=59.8 kg m -2 ; 1-year BMI=36.8 kg m -2 ; FABS-5+ BMI=48.0 kg m -2 ) to compare factors which might contribute to differences. Data were analyzed using generalized estimating equations adjusted for age, sex, baseline BMI, baseline diabetes status and length of follow-up. The BMI of the surgical group declined from baseline to 1 year (-38.5±6.9%), which, despite some regain, was largely maintained until FABS-5+ (-29.6±13.9% change). The BMI of the comparison group increased from baseline to the FABS-5+ visit (+10.3±20.6%). When the surgical group was split into maintainers and re-gainers, no differences in weight-related and eating behaviors, health responsibility, physical activity/inactivity, or dietary habits were observed between groups. However, at FABS-5+, maintainers had greater overall QOL scores than re

  15. Management of remanent lifetime. Short-term benefits of the maintenance evaluation and improvement programme; Gestion de la vida remanente de instalaciones industriales. Extension de vida

    Energy Technology Data Exchange (ETDEWEB)

    Sainero Garcia, J [Empresarios Agrupados, Madrid (Spain)

    1993-12-15

    Remanent Lifetime Management, which is scientifically based on knowing the degradatory phenomena associated with aging, today allows us to optimize plant life through a long-term maintenance strategy combining preventive maintenance and condition monitoring programmes. Within a project for Remanent Lifetime Management (RLM), the determination of methods of control and mitigation of degradations due to aging depends on the programme of Maintenance Evaluation and Improvement (MEI). This programme, underpinned by the analysis of degradatory phenomena to which plant components are subjected, evaluates current maintenance practices and defines the complementary actions which would facilitate establishment of a long-term strategy to control aging. Together with this main objective of the RLM project, the MEI programme achieves short-term benefits since, right from the beginning, it offers solutions to mitigate and guard against degradations in crucial plant components, and generally sets out a programme to control aging. The MEI programme further serves as a tool to reach the final objectives of the new 10CFR50.65 rule, 'Requirements for Maintenance Programs for NPPs'. The MEI always offers the option should the Utility Owner decide to extend plant life. (author)

  16. 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.

  17. Effect of short-term low-protein diet supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis patients.

    Science.gov (United States)

    Li, Haiming; Long, Quan; Shao, Chunhai; Fan, Hong; Yuan, Li; Huang, Bihong; Gu, Yong; Lin, Shanyan; Hao, Chuanming; Chen, Jing

    2011-01-01

    To evaluate the effects of short-term restriction of dietary protein intake (DPI) supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis (MHD) patients. Forty MHD patients with uncontrolled hyperphosphatemia were randomized to either low DPI with keto acid-supplemented (sLP) or normal DPI (NP) group for 8 weeks. After 8 weeks, the sLP group was shifted to NP for another 8 weeks. Low-protein diet (LPD) was individualized with total caloric intake 30-35 kcal/kg/day, protein intake of 0.8 g/kg/day and phosphate intake of 500 mg/day. Keto acids were supplied in a dosage of 12 pills per day. Calcium phosphorous metabolism index and nutritional index (serum albumin, total protein, somatometric measurements, 3-day diaries and Mini-Nutritional Assessment score) were recorded. C-reactive protein, CO(2) combining power and Kt/V were measured to evaluate the inflammation, metabolic acidosis and dialysis adequacy, respectively. Serum phosphorus level and calcium-phosphate product were significantly decreased at the end of the first 8 weeks in the sLP group compared to the basal value and the NP group (p keto acids could decrease hyperphosphatemia and calcium-phosphate product, while keeping stable nutritional status among MHD patients. Copyright © 2010 S. Karger AG, Basel.

  18. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.

    Science.gov (United States)

    Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T; Wangsawihardja, Felix; Ricci, Anthony J; Mustapha, Mirna

    2016-01-01

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1(dw)) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1(dw) mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1(dw) IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1(dw) IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1(dw) IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Human biomonitoring after chemical incidents and during short-term maintenance work as a tool for exposure analysis and assessment.

    Science.gov (United States)

    Bader, M; Van Weyenbergh, T; Verwerft, E; Van Pul, J; Lang, S; Oberlinner, C

    2014-12-15

    Human biomonitoring (HBM) is frequently used for the analysis and assessment of exposure to chemicals under routine working conditions. In recent years, HBM has also been applied to monitor the exposure of the general population, and of emergency responders in the aftermath of chemical incidents. Two examples of targeted HBM programs in the chemical industry are described and discussed in this paper: (1) analysis and assessment of the exposure of firefighters and chemical workers after the spill of p-chloroaniline from a burning chemical barrel, and (2) biomonitoring of maintenance workers potentially exposed to benzene during regular turnarounds. The results of these investigations underline that human biomonitoring contributes substantially to comprehensive exposure analyses, human health risk assessments and communication. In addition, regular HBM surveillance and feedback can assist in the continuous improvement of workplace safety measures and exposure control. In conclusion, data on accidental or short-term exposure to hazardous chemicals are an important source of information for the further development of limit and assessment values, the validation of biomarkers and of targeted HBM programs for both routine monitoring and disaster management. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Long-term in vitro system for maintenance and amplification of root-knot nematodes in Cucumis sativus roots

    Directory of Open Access Journals (Sweden)

    Fernando E. eDíaz-Manzano

    2016-02-01

    Full Text Available Root-knot nematodes (RKN are polyphagous plant-parasitic roundworms that produce large crop losses, representing a relevant agricultural pest worldwide. After infection, they induce swollen root structures called galls containing giant cells (GCs indispensable for nematode development. Among efficient control methods are biotechnology-based strategies that require a deep knowledge of underlying molecular processes during the plant-nematode interaction. Methods of achieving this knowledge include the application of molecular biology techniques such as transcriptomics (massive sequencing or microarray hybridization, proteomics or metabolomics. These require aseptic experimental conditions, as undetected contamination with other microorganisms could compromise the interpretation of the results. Herein, we present a simple, efficient and long-term method for nematode amplification on cucumber roots grown in vitro. Amplification of juveniles (J2 from the starting inoculum is around 40-fold. The method was validated for three Meloidogyne species (M. javanica, M. incognita and M. arenaria, producing viable and robust freshly hatched J2s. These can be used for further in vitro infection of different plant species such as Arabidopsis, tobacco and tomato, as well as enough J2s to maintain the population. The method allowed maintenance of around 90 Meloidogyne spp. generations (one every two months from a single initial female over 15 years.

  1. Maintenance of class III trifurcated molars versus implant placement in regenerated extraction sockets: long-term results of 2 cases.

    Science.gov (United States)

    Zafiropoulos, Gregory-George K; di Prisco, Manuela Occipite; Deli, Giorgio; Hoffmann, Oliver

    2011-03-01

    Studies to date have reached differing conclusions regarding the long-term prognosis of teeth with class III furcation involvement. Replacement of such teeth with implants could be an alternative. This report compares the treatment outcomes of 2 cases with similar disease progression: 1 treated by implant therapy and 1 maintained with nonsurgical periodontal treatment. Two patients with advanced chronic periodontitis and class III furcation involvement of all molars were treated. Case 1 received a conservative periodontal and antibiotic treatment, followed by 15 years of maintenance. In case 2, the molars were extracted and replaced with implants, and the implants were observed for 7 years. Clinical attachment level (CAL), probing attachment level (PAL), bleeding on probing, plaque index, and periodontal pathogens were recorded. Despite good compliance of case 1, periodontal pathogens were not eliminated and tissue destruction was not halted. The PAL outcomes of case 2 improved over time; mean PAL loss reached 0.35 mm/y in the first 3 years and then decreased to 0.01 mm/y. While CAL outcomes did not change in case 2, case 1 showed increased CAL loss after 8 years. Based on the limited findings of this case report, extraction of molars with class III furcation involvement and subsequent implant placement may render a better predictability of treatment outcomes than nonsurgical periodontal therapy in the cases of infection with periodontal pathogens.

  2. Long-term maintenance therapy for vulvar lichen sclerosus: the results of a randomized study comparing topical vitamin E with an emollient.

    Science.gov (United States)

    Virgili, Annarosa; Minghetti, Sara; Borghi, Alessandro; Corazza, Monica

    2013-04-01

    The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids. To compare the effect of topical vitamin E with that of an emollient in reducing the risk of VLS relapse over a 52-week maintenance treatment. 156 patients with VLS were enrolled in a 12-week active treatment phase on topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase in which patients were randomized to apply either an emollient or topical vitamin E once daily. 80 patients entered the maintenance phase. At 52 weeks, for the vitamin E maintenance group, the cumulative crude relapse rate was 27.8% and the cumulative modified crude relapse rate was 55.6%. For the emollient maintenance group, the cumulative crude relapse rate was 22.7% and the cumulative modified crude relapse rate was 50.0%. The median time to relapse was 20 weeks for the vitamin E group and 18.7 weeks for the emollient group. Once VLS has been stabilized with topical corticosteroids, long-term treatment with both vitamin E and emollients may be considered in maintain LS remission.

  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. 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

  5. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

    Directory of Open Access Journals (Sweden)

    Giovanni Morelli

    2018-05-01

    Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

  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. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

    Science.gov (United States)

    Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

    2015-01-01

    Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

  8. Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system.

    Science.gov (United States)

    de Boysson, Hubert; Parienti, Jean-Jacques; Arquizan, Caroline; Boulouis, Grégoire; Gaillard, Nicolas; Régent, Alexis; Néel, Antoine; Detante, Olivier; Touzé, Emanuel; Aouba, Achille; Bienvenu, Boris; Guillevin, Loïc; Naggara, Olivier; Zuber, Mathieu; Pagnoux, Christian

    2017-10-01

    We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  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. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Parmenion P. Tsitsopoulos

    2017-11-01

    risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI.

  16. Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

    Science.gov (United States)

    Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

    2016-03-01

    Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. The complexity of self-regulating food intake in weight loss maintenance. A qualitative study among short- and long-term weight loss maintainers

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Sniethotta, Falko F.; Sainsbury, Kirby

    2018-01-01

    Rationale Whether self-regulation of food intake in weight loss maintenance (WLM) differs between being a short-term maintainer (having maintained without regaining less than 12 months) and a long-term maintainer (having maintained without regaining at least 12 months) is under-researched. Object......Rationale Whether self-regulation of food intake in weight loss maintenance (WLM) differs between being a short-term maintainer (having maintained without regaining less than 12 months) and a long-term maintainer (having maintained without regaining at least 12 months) is under......-researched. Objective The aim of this study was to explore the self-regulatory strategies and self-efficacy beliefs applied by short- and long-term maintainers to the complex set of behaviours comprising food intake in WLM, and to obtain a better understanding of their challenges in the various food-intake processes...... in WLM. Method Individual interviews (14 female/4 male) were conducted with nine Danish short- and nine long-term weight loss maintainers. The Health Action Process Approach (HAPA) was applied post-hoc to organise data and support analyses, since the approach focuses on both the cognitions (e.g., self...

  18. 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.

  19. 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.

  20. Modern electronic maintenance principles

    CERN Document Server

    Garland, DJ

    2013-01-01

    Modern Electronic Maintenance Principles reviews the principles of maintaining modern, complex electronic equipment, with emphasis on preventive and corrective maintenance. Unfamiliar subjects such as the half-split method of fault location, functional diagrams, and fault finding guides are explained. This book consists of 12 chapters and begins by stressing the need for maintenance principles and discussing the problem of complexity as well as the requirements for a maintenance technician. The next chapter deals with the connection between reliability and maintenance and defines the terms fai

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. Long-term effect of the combined use of powered toothbrush and triclosan dentifrice in periodontal maintenance patients.

    Science.gov (United States)

    Bogren, Anna; Teles, Ricardo P; Torresyap, Gay; Haffajee, Anne D; Socransky, Sigmund S; Jönsson, Kerstin; Wennström, Jan L

    2008-02-01

    To test the hypothesis of a superior clinical and microbiological effect of the combined use of powered toothbrush+triclosan-containing dentifrice compared with manual toothbrush+regular fluoride-containing dentifrice in periodontal maintenance patients. A total of 128 periodontitis subjects involved in recall programmes were randomized to use either powered toothbrush with triclosan-dentifrice (test) or manual toothbrush and standard dentifrice (control). Supportive periodontal treatment was provided at baseline and every 6 months. Plaque, bleeding on probing (BoP), probing pocket depth (PPD) and relative attachment level (RAL) were scored at baseline, 1, 2 and 3 years. Subgingival plaque samples were taken and analysed for their content of 40 bacterial species at each examination interval. All analyses were performed by "intention-to-treat" protocol. Both groups showed significant reduction in BoP, PPD and in mean total counts of the 40 bacterial species between baseline and 3 years, while plaque score and RAL remained almost unchanged. No significant differences between the two prevention programmes were found for any of the clinical outcome variables or in mean counts of the various bacterial species. The study failed to demonstrate superior clinical and microbiological effects of powered toothbrush+triclosan dentifrice compared with manual toothbrush+standard fluoride-dentifrice in periodontitis-susceptible patients on regular maintenance therapy.

  6. Laboratory equipment maintenance contracts.

    Science.gov (United States)

    Boudreau, D A; Scheer, W D; Catrou, P G

    1985-12-01

    The increasing level of technical sophistication and complexity found in clinical laboratory instrumentation today more than ever demands careful attention to maintenance service needs. The time-worn caution for careful definition of requirements for acquisition of a system should also carry over to acquisition of maintenance service. Guidelines are presented for specifications of terms and conditions for maintenance service from the perspective of the laboratorian in the automated clinical laboratory.

  7. Long-term effects of 1-year maintenance training on physical functioning and health status in patients with COPD: A randomized controlled study

    DEFF Research Database (Denmark)

    Ringbaek, Thomas; Brondum, Eva; Martinez, Gerd

    2010-01-01

    PURPOSE: To examine whether maintenance training (MT) for 1 year improved the long-term effects of a 7-week chronic obstructive pulmonary disease (COPD) rehabilitation program. METHODS: After a 7-week outpatient rehabilitation program, 96 patients with COPD were randomized to either an MT group (n...... study period. Primary effect parameters were Endurance Shuttle Walk Test (ESWT) time and health status (St. George's Respiratory Questionnaire, SGRQ). Secondary effect parameters were adherence to supervised training, dropout rates, and hospitalization. RESULTS: Compared with the control group, the MT...... or hospital admissions, compared with unsupervised daily training at home. The effect of the MT was closely related to adherence to the program....

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Maintenance of smoking cessation in the postpartum period: which interventions work best in the long-term?

    Science.gov (United States)

    Su, Anny; Buttenheim, Alison M

    2014-04-01

    Smoking during pregnancy has been linked to a variety of adverse outcomes for both maternal and child health. Decades of studies have sought to increase cessation antepartum and reduce relapse postpartum. A number of effective interventions exist to significantly reduce smoking rates during pregnancy; however, less is known about how to prevent relapse in the postpartum period. This review investigates interventions to prevent relapse in the long-term postpartum period. We focus specifically on nonspontaneous quitters (individuals who quit smoking as a result of an external intervention) to reveal differences in long-term response to interventions for this population compared to spontaneous quitters. A systematic literature search yielded 32 relevant studies of pharmacological, behavioral, and incentives-based interventions. Results were compiled, analyzed, and compared in order to evaluate success factors in maintaining cessation postpartum. Though intervention groups showed consistently higher quit rates during pregnancy than control groups, none of the intervention types were effective at preventing relapse in the longer-term postpartum period. One study maintained significantly higher abstinence in the longer-term period postpartum using a mix of behavioral and incentives strategies. Additional research in this area is needed to identify optimal intervention strategies to reduce long-term postpartum relapse, particularly for nonspontaneous quitters.

  15. Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas.

    Science.gov (United States)

    Hamidi, Sofiane; Letourneur, Didier; Aid-Launais, Rachida; Di Stefano, Antonio; Vainchenker, William; Norol, Françoise; Le Visage, Catherine

    2014-04-01

    Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (prelease TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (pstress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that could be further combined with mechanical stress to promote sarcomere formation at terminal stages of differentiation.

  16. Towards an integrative model of visual short-term memory maintenance: Evidence from the effects of attentional control, load, decay, and their interactions in childhood.

    Science.gov (United States)

    Shimi, Andria; Scerif, Gaia

    2017-12-01

    Over the past decades there has been a surge of research aiming to shed light on the nature of capacity limits to visual short-term memory (VSTM). However, an integrative account of this evidence is currently missing. We argue that investigating parameters constraining VSTM in childhood suggests a novel integrative model of VSTM maintenance, and that this in turn informs mechanisms of VSTM maintenance in adulthood. Over 3 experiments with 7-year-olds and young adults (total N=206), we provide evidence for multiple cognitive processes interacting to constrain VSTM performance. While age-related increases in storage capacity are undisputable, we replicate the finding that attentional processes control what information will be encoded and maintained in VSTM in the face of increased competition. Therefore, a central process to the current model is attentional refreshment, a mechanism that it is thought to reactivate and strengthen the signal of the visual representations. Critically, here we also show that attentional influences on VSTM are further constrained by additional factors, traditionally studied to the exclusion of each other, such as memory load and temporal decay. We propose that these processes work synergistically in an elegant manner to capture the adult-end state, whereas their less refined efficiency and modulations in childhood account for the smaller VSTM capacity that 7-year-olds demonstrate compared to older individuals. We conclude that going beyond the investigation of single cognitive mechanisms, to their interactions, holds the promise to understand both developing and fully developed maintenance in VSTM. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down

    Science.gov (United States)

    Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

    2016-01-01

    Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190

  18. Maintenance methods

    International Nuclear Information System (INIS)

    Sanchis, H.; Aucher, P.

    1990-01-01

    The maintenance method applied at the Hague is summarized. The method was developed in order to solve problems relating to: the different specialist fields, the need for homogeneity in the maintenance work, the equipment diversity, the increase of the materials used at the Hague's new facilities. The aim of the method is to create a knowhow formalism, to facilitate maintenance, to ensure the running of the operations and to improve the estimation of the maintenance cost. One of the method's difficulties is the demonstration of the profitability of the maintenance operations [fr

  19. [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

  20. 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

  1. 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

  2. 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

  3. Industrial Maintenance Strategies

    International Nuclear Information System (INIS)

    Sajjad Akbar

    2006-01-01

    Industrial plants have become more complex due to technological advancement. This has made the task of maintenance more difficult. The maintenance costs in terms of resources and downtime loss are so high that maintenance function has become a critical factor in a plant's profitability. Industry should devote as much forethought to the management of maintenance function as to production. Maintenance has grown from an art to a precise, technical engineering science. Planning, organizing scheduling and control of maintenance using modern techniques pays dividends in the form of reduced costs and increased reliability. The magnitude and the dimension of maintenance have multiplied due to development in the engineering technologies. Production cost and capacities are directly affected by the breakdown time. Total operating cost including the maintenance cost plays an important role in replacement dimension. The integrated system approach would bring forth the desired results of high maintenance standards. The standards once achieved and sustained, would add to the reliability of the plan and relieve heavy stresses and strains on the engineering logistic support. (author)

  4. Development and beyond: Strategy for long-term maintenance of an online laser diffraction particle size method in a spray drying manufacturing process.

    Science.gov (United States)

    Medendorp, Joseph; Bric, John; Connelly, Greg; Tolton, Kelly; Warman, Martin

    2015-08-10

    The purpose of this manuscript is to present the intended use and long-term maintenance strategy of an online laser diffraction particle size method used for process control in a spray drying process. A Malvern Insitec was used for online particle size measurements and a Malvern Mastersizer was used for offline particle size measurements. The two methods were developed in parallel with the Mastersizer serving as the reference method. Despite extensive method development across a range of particle sizes, the two instruments demonstrated different sensitivities to material and process changes over the product lifecycle. This paper will describe the procedure used to ensure consistent alignment of the two methods, thus allowing for continued use of online real-time laser diffraction as a surrogate for the offline system over the product lifecycle. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Walsh, M.; Faurschou, M.; Berden, A.

    2014-01-01

    BACKGROUND AND OBJECTIVES: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine...... after 3-6 months or after 12 months of cyclophosphamide treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time...

  6. Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia

    OpenAIRE

    Pearce, Kaycey; Cai, Diancai; Roberts, Adam C; Glanzman, David L

    2017-01-01

    eLife digest The formation of long-term memory depends on new proteins being made in the brain. These new proteins are used partly to build the new connections among neurons that essentially store the memory, and must be made within a critical period of time. Experiments on animals have found that new proteins must be made during or shortly after training to form a stable memory; if protein synthesis is blocked during this period, the memory will not be stabilized (a process also known as mem...

  7. Long-Term Weight-Loss Maintenance by a Meal Replacement Based Weight Management Program in Primary Care.

    Science.gov (United States)

    Kruschitz, Renate; Wallner-Liebmann, Sandra; Lothaller, Harald; Luger, Maria; Ludvik, Bernhard

    2017-01-01

    Structured obesity treatment programs at primary care level are becoming increasingly important. However, evidence from current treatment approaches in the long term is lacking. In view of this fact we evaluated a standardized, meal replacement-based weight loss program (myLINE®; AENGUS, Graz, Austria) according to the currently applicable guidelines. Data of overweight and obese individuals (n = 70) who participated at least 36 months in the program were analyzed. Data were collected at baseline (T0) as well as after 1, 3, 6, 12, 24, and 36 (T1-T36) months. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis. Compared to T0, a maximum weight, BMI, fat mass, absolute body cell mass (BCM) reduction and an increase of relative BCM could be seen at T6. Subsequently, the findings reveal a significant reduction of body weight and body fat and a satisfying development of body cell mass during the observation period of 36 months. The evaluated program complies with national and international guidelines for the therapy of obesity in adults and is efficient and meaningful for a long-term therapeutic use in primary care.. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

  8. Long-Term Weight-Loss Maintenance by a Meal Replacement Based Weight Management Program in Primary Care

    Directory of Open Access Journals (Sweden)

    Renate Kruschitz

    2017-04-01

    Full Text Available Objective: Structured obesity treatment programs at primary care level are becoming increasingly important. However, evidence from current treatment approaches in the long term is lacking. In view of this fact we evaluated a standardized, meal replacement-based weight loss program (myLINE®; AENGUS, Graz, Austria according to the currently applicable guidelines. Methods: Data of overweight and obese individuals (n = 70 who participated at least 36 months in the program were analyzed. Data were collected at baseline (T0 as well as after 1, 3, 6, 12, 24, and 36 (T1-T36 months. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis. Results: Compared to T0, a maximum weight, BMI, fat mass, absolute body cell mass (BCM reduction and an increase of relative BCM could be seen at T6. Subsequently, the findings reveal a significant reduction of body weight and body fat and a satisfying development of body cell mass during the observation period of 36 months. Conclusion: The evaluated program complies with national and international guidelines for the therapy of obesity in adults and is efficient and meaningful for a long-term therapeutic use in primary care..

  9. Serotonin induces memory-like, rapamycin-sensitive hyperexcitability in sensory axons of aplysia that contributes to injury responses.

    Science.gov (United States)

    Weragoda, Ramal M S; Walters, Edgar T

    2007-09-01

    The induction of long-term facilitation (LTF) of synapses of Aplysia sensory neurons (SNs) by serotonin (5-HT) has provided an important mechanistic model of memory, but little is known about other long-term effects of 5-HT on sensory properties. Here we show that crushing peripheral nerves results in long-term hyperexcitability (LTH) of the axons of these nociceptive SNs that requires 5-HT activity in the injured nerve. Serotonin application to a nerve segment induces local axonal (but not somal) LTH that is inhibited by 5-HT-receptor antagonists. Blockade of crush-induced axonal LTH by an antagonist, methiothepin, provides evidence for mediation of this injury response by 5-HT. This is the first demonstration in any axon of neuromodulator-induced LTH, a phenomenon potentially important for long-lasting pain. Methiothepin does not reduce axonal LTH induced by local depolarization, so 5-HT is not required for all forms of axonal LTH. Serotonin-induced axonal LTH is expressed as reduced spike threshold and increased repetitive firing, whereas depolarization-induced LTH involves only reduced threshold. Like crush- and depolarization-induced LTH, 5-HT-induced LTH is blocked by inhibiting protein synthesis. Blockade by rapamycin, which also blocks synaptic LTF, is interesting because the eukaryotic protein kinase that is the target of rapamycin (TOR) has a conserved role in promoting growth by stimulating translation of proteins required for translation. Rapamycin sensitivity suggests that localized increases in translation of proteins that promote axonal conduction and excitability at sites of nerve injury may be regulated by the same signals that increase translation of proteins that promote neuronal growth.

  10. Long-term maintenance of weight loss with sibutramine in a GP setting following a specialist guided very-low-calorie diet: a double-blind, placebo-controlled, parallel group study

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M. H.

    2005-01-01

    Objective: Very-low-calorie diets (VLCDs) are used to promote short-term weight loss in obese patients. However, long-term maintenance of weight loss is generally poor. We assessed the efficacy and safety of sibutramine in maintaining weight loss achieved in obese patients by means of a 3-month

  11. Ditch network maintenance in peatland forest as a private investment: short- and long-term effects on financial performance at stand level

    Directory of Open Access Journals (Sweden)

    T. Penttilä

    2008-03-01

    Full Text Available In Finland, most of the suitable peatland has now been ditched for forestry purposes, and ditch network maintenance (DNM is carried out on 70,000–80,000 hectares of land each year. We examined the financial performance of DNM operations on 44 sample plots representing two medium-quality site types located within two different climatic regions in northern Finland. We applied a simulation approach in which actual measurements of trees growing on sample plots were fed into a stand simulator (MOTTI which predicted stand development with and without DNM. The financial assessments involved calculating short-term and long-term effects of DNM by applying, respectively, ROI (return on investment and NPV (net present value analyses. The results indicated that the financial performance of DNM, particularly in the short term, was highly dependent on the availability of government subsidies. Without the DNM subsidy, the return on investment was between 1.6% and 3.7%; whereas with government subsidy it ranged from 3.8% to 8.4%. In the long run, the net present value was ca. 4–14% higher for stands with DNM than for those without.

  12. Protein-pacing caloric-restriction enhances body composition similarly in obese men and women during weight loss and sustains efficacy during long-term weight maintenance

    DEFF Research Database (Denmark)

    Arciero, Paul J; Edmonds, Rohan; He, Feng

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in ob......Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein....../day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P......-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men...

  13. Long-term effects of low calcium dialysates on the serum calcium levels during maintenance hemodialysis treatments: A systematic review and meta-analysis.

    Science.gov (United States)

    Yoshikawa, Masahiro; Takase, Osamu; Tsujimura, Taro; Sano, Etsuko; Hayashi, Matsuhiko; Takato, Tsuyoshi; Hishikawa, Keiichi

    2018-03-28

    Hypercalcemia and hyperparathyroidism in patients receiving maintenance hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal concentration remains controversial. Here, we conducted a systematic review and a meta-analysis of seven randomized controlled trials examining a total of 622 patients to investigate the optimal concentration for MHD for 6 months or longer. The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52 mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38), respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three studies showed that a low concentration was preferred for lowering arterial calcifications or atherosclerosis in different arteries, but one study showed that coronary arterial calcifications increased with a low concentration. Two studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed that a dialysate with a low Ca concentration lowered the serum Ca levels in patients receiving long-term MHD, but further studies are needed to determine the optimal Ca concentration in terms of CVD and MBD.

  14. Mouse Intermittent Hypoxia Mimicking Apnea of Prematurity: Effects on Myelinogenesis and Axonal Maturation

    Science.gov (United States)

    CAI, JUN; TUONG, CHI MINH; ZHANG, YIPING; SHIELDS, CHRISTOPHER B.; GUO, GANG; FU, HUI; GOZAL, DAVID

    2014-01-01

    Premature babies are at high risk for both infantile apnea and long-term neurobehavioral deficits. Recent studies suggest that diffuse structural changes in brain white matter are a positive predictor of poor cognitive outcomes. Since oligodendrocyte maturation, myelination, axon development and synapse formation mainly occur in the 3rd trimester of gestation and 1st postnatal year, infantile apnea could lead to and/or exaggerate white matter impairments in preterm neonates. Therefore, we investigated oligodendroglia and axon development in a neonatal mouse model of intermittent hypoxia between postnatal days 2 to 10. During critical phases of central nervous system development, intermittent hypoxia induced hypomyelination in the corpus callosum, striatum, fornix and cerebellum, but not the pons or spinal cord. Intermittent hypoxia-elicited alterations in myelin-forming processes were reflected by decreased expression of myelin proteins, including MBP, PLP, MAG and CNPase, possibly due to arrested maturation of oligodendrocytes. Ultra-structural abnormalities were apparent in the myelin sheath and axon. Immature oligodendrocytes were more vulnerable to neonatal intermittent hypoxia exposures than developing axons, suggesting that hypomyelination may contribute, at least partially, to axonal deficits. Insufficient neurofilament synthesis with anomalous components of neurofilament subunits, β-tubulin and MAP2 isoforms indicated immaturity of axons in intermittent hypoxia-exposed mouse brains. In addition, down-regulation of Synapsin I, Synaptophysin and Gap-43 phosphorylation suggested a potential stunt in axonogenesis and synaptogenesis. The region-selective and complex impairment in brain white matter induced by intermittent hypoxia was further associated with electrophysiological changes that may underlie long-term neurobehavioral sequelae. PMID:21953180

  15. 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

  16. The long-term use of soap does not affect the pH-maintenance mechanism of human skin.

    Science.gov (United States)

    Takagi, Y; Kaneda, K; Miyaki, M; Matsuo, K; Kawada, H; Hosokawa, H

    2015-05-01

    The pH at the surface of healthy human skin is around 5. Cleansing the skin with soap increases the pH of the skin, which then returns to a more acidic pH within a few hours. However, the effects of skin cleansing with soap over a long time on the pH regulatory system is still unclear. We compared the pH of the skin between users of a soap-based cleanser and of a mild-acidic cleanser prior to and following the cleansing. This study had two groups of subjects, one group who had used a soap-based cleanser for more than 5 years and the other group who had used a mild-acidic cleanser for more than 5 years. The pH on the inner forearm of each subject was measured prior to and for 6 h after cleansing with a soap bar. There were no differences between the pH of the skin these two groups prior to cleansing, immediately after cleansing or in the pH recovery rate for 6 h. These results suggest that long-term continuous use of a soap-based cleanser does not affect the pH-maintaining mechanism of human skin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Context-specific differences in fronto-parieto-occipital effective connectivity during short-term memory maintenance.

    Science.gov (United States)

    Kundu, Bornali; Chang, Jui-Yang; Postle, Bradley R; Van Veen, Barry D

    2015-07-01

    Although visual short-term memory (VSTM) performance has been hypothesized to rely on two distinct mechanisms, capacity and filtering, the two have not been dissociated using network-level causality measures. Here, we hypothesized that behavioral tasks challenging capacity or distraction filtering would both engage a common network of areas, namely dorsolateral prefrontal cortex (dlPFC), superior parietal lobule (SPL), and occipital cortex, but would do so according to dissociable patterns of effective connectivity. We tested this by estimating directed connectivity between areas using conditional Granger causality (cGC). Consistent with our prediction, the results indicated that increasing mnemonic load (capacity) increased the top-down drive from dlPFC to SPL, and cGC in the alpha (8-14Hz) frequency range was a predominant component of this effect. The presence of distraction during encoding (filtering), in contrast, was associated with increased top-down drive from dlPFC to occipital cortices directly and from SPL to occipital cortices directly, in both cases in the beta (15-25Hz) range. Thus, although a common anatomical network may serve VSTM in different contexts, it does so via specific functions that are carried out within distinct, dynamically configured frequency channels. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. Maintenance optimization after RCM

    International Nuclear Information System (INIS)

    Doyle, E.K.; Lee, C.-G.; Cho, D.

    2005-01-01

    Variant forms of RCM (Reliability Centered Maintenance) have been the maintenance optimizing tools of choice in industry for the last 20 years. Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy whereby decisions are based on statistical analysis of historical failure data are now being evaluated. The evaluation includes a requirement to demonstrate that earlier optimization projects have long term positive impacts. This proved to be a significant challenge. Eventually a methodology was developed using Crowe/AMSAA (Army Materials Systems Analysis Activity) plots to justify expenditures on further optimization efforts. (authors)

  1. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

    Science.gov (United States)

    Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

    2016-01-01

    Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Preventative Maintenance.

    Science.gov (United States)

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  3. 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.

  4. Integrated maintenance program (IMP)

    International Nuclear Information System (INIS)

    Zemdegs, R.T.; Chout, Q.B.

    1998-01-01

    the station's maintenance effectiveness and reduce maintenance costs including RCM4, callup overhauls, analysis of equipment and system failure history to name a few. It has become apparent that there is no single D o-All m aintenance strategy. What is needed is an integrated program combining the benefits of a variety of problem-specific strategies. Such a program should address both the short term and long term station requirements. The impact of the Integrated Maintenance Program (IMP) is expected to be high. In the short term, IMP will upgrade the call-up management system to provide accurate classification, effective monitoring and reporting, and develop a documented rationale (PMO) for each Preventive Maintenance task. To the greatest extent possible, IMP will utilize on-condition (predictive) maintenance and result in the elimination of replacement of many obsolete or ineffective preventive maintenance call-ups. The IMP described in this paper, will improve maintenance effectiveness, equipment reliability and have cost benefits to Ontario Hydro. In doing so it will reduce the cost of maintenance and improve system availability and reliability. (author)

  5. 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.

  6. 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.

  7. 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.

  8. Lifetime oriented maintenance planning in the Netherlands

    NARCIS (Netherlands)

    Straub, A.

    2003-01-01

    In this paper we set up a framework for lifetime oriented maintenance planning as an outcome and input for strategic housing stock management. The maintenance planning holds maintenance activities and costs in the longer term. We consider the maintenance planning as a tool to calculate and implement

  9. 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.

  10. Maintenance Mentor

    National Research Council Canada - National Science Library

    Jacobs, John

    2003-01-01

    Maintenance Mentor (MXM) is a research effort conducted by a joint AFRL/HESR and Northrop Grumman Information Technology team to identify the basic, high-level requirements necessary for improving flight line diagnostic capabilities...

  11. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    Science.gov (United States)

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-07-30

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p 50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.

  12. Maintenance of C sinks sustains enhanced C assimilation during long-term exposure to elevated [CO2] in Mojave Desert shrubs.

    Science.gov (United States)

    Aranjuelo, Iker; Ebbets, Allison L; Evans, R Dave; Tissue, David T; Nogués, Salvador; van Gestel, Natasja; Payton, Paxton; Ebbert, Volker; Adams, Williams W; Nowak, Robert S; Smith, Stanley D

    2011-10-01

    During the first few years of elevated atmospheric [CO(2)] treatment at the Nevada Desert FACE Facility, photosynthetic downregulation was observed in desert shrubs grown under elevated [CO(2)], especially under relatively wet environmental conditions. Nonetheless, those plants maintained increased A (sat) (photosynthetic performance at saturating light and treatment [CO(2)]) under wet conditions, but to a much lesser extent under dry conditions. To determine if plants continued to downregulate during long-term exposure to elevated [CO(2)], responses of photosynthesis to elevated [CO(2)] were examined in two dominant Mojave Desert shrubs, the evergreen Larrea tridentata and the drought-deciduous Ambrosia dumosa, during the eighth full growing season of elevated [CO(2)] treatment at the NDFF. A comprehensive suite of physiological processes were collected. Furthermore, we used C labeling of air to assess carbon allocation and partitioning as measures of C sink activity. Results show that elevated [CO(2)] enhanced photosynthetic performance and plant water status in Larrea, especially during periods of environmental stress, but not in Ambrosia. δ(13)C analyses indicate that Larrea under elevated [CO(2)] allocated a greater proportion of newly assimilated C to C sinks than Ambrosia. Maintenance by Larrea of C sinks during the dry season partially explained the reduced [CO(2)] effect on leaf carbohydrate content during summer, which in turn lessened carbohydrate build-up and feedback inhibition of photosynthesis. δ(13)C results also showed that in a year when plant growth reached the highest rates in 5 years, 4% (Larrea) and 7% (Ambrosia) of C in newly emerging organs were remobilized from C that was assimilated and stored for at least 2 years prior to the current study. Thus, after 8 years of continuous exposure to elevated [CO(2)], both desert perennials maintained their photosynthetic capacities under elevated [CO(2)]. We conclude that C storage, remobilization

  13. Instrumentation maintenance

    International Nuclear Information System (INIS)

    Mack, D.A.

    1976-09-01

    It is essential to any research activity that accurate and efficient measurements be made for the experimental parameters under consideration for each individual experiment or test. Satisfactory measurements in turn depend upon having the necessary instruments and the capability of ensuring that they are performing within their intended specifications. This latter requirement can only be achieved by providing an adequate maintenance facility, staffed with personnel competent to understand the problems associated with instrument adjustment and repair. The Instrument Repair Shop at the Lawrence Berkeley Laboratory is designed to achieve this end. The organization, staffing and operation of this system is discussed. Maintenance policy should be based on studies of (1) preventive vs. catastrophic maintenance, (2) records indicating when equipment should be replaced rather than repaired and (3) priorities established to indicate the order in which equipment should be repaired. Upon establishing a workable maintenance policy, the staff should be instructed so that they may provide appropriate scheduled preventive maintenance, calibration and corrective procedures, and emergency repairs. The education, training and experience of the maintenance staff is discussed along with the organization for an efficient operation. The layout of the various repair shops is described in the light of laboratory space and financial constraints

  14. Myelin-associated proteins labelled by slow axonal transport

    International Nuclear Information System (INIS)

    Giorgi, P.P.; DuBois, H.

    1981-01-01

    This paper deals with the problem of protein metabolism and provides evidence that the neuronal contribution to myelin metabolism may be restricted to lipids only. On the other hand this line of research led to the partial characterization of a group of neuronal proteins probably involved in axo-glial interactions subserving the onset of myelination and the structural maintenance of the mature myelin sheath. Intraocular injection of radioactive amino acids allows the study of the anterograde transport of labelled proteins along retinofugal fibres which are well myelinated. Myelin extracted from the optic nerve and tract under these conditions also contains labelled proteins. Three hypotheses are available to explain this phenomenon. To offer an explanation for this phenomenon the work was planned as follows. a) Characterization of the spatio-temporal pattern of labelling of myelin, in order to define the experimental conditions (survival time and region of the optic pathway to be studied) necessary to obtain maximal labelling. b) Characterization (by gel electrophoresis) of the myelin-associated proteins which become labelled by axonal transport, in order to work on a consistent pattern of labelling. c) Investigation of the possible mechanism responsible for the labelling of myelin-associated proteins. (Auth.)

  15. 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.

  16. A fast and robust method for automated analysis of axonal transport.

    Science.gov (United States)

    Welzel, Oliver; Knörr, Jutta; Stroebel, Armin M; Kornhuber, Johannes; Groemer, Teja W

    2011-09-01

    Cargo movement along axons and dendrites is indispensable for the survival and maintenance of neuronal networks. Key parameters of this transport such as particle velocities and pausing times are often studied using kymograph construction, which converts the transport along a line of interest from a time-lapse movie into a position versus time image. Here we present a method for the automatic analysis of such kymographs based on the Hough transform, which is a robust and fast technique to extract lines from images. The applicability of the method was tested on simulated kymograph images and real data from axonal transport of synaptophysin and tetanus toxin as well as the velocity analysis of synaptic vesicle sharing between adjacent synapses in hippocampal neurons. Efficiency analysis revealed that the algorithm is able to detect a wide range of velocities and can be used at low signal-to-noise ratios. The present work enables the quantification of axonal transport parameters with high throughput with no a priori assumptions and minimal human intervention.

  17. 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

  18. 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...

  19. 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.

  20. A phantom axon setup for validating models of action potential recordings.

    Science.gov (United States)

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  1. 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....

  2. Managed maintenance, the next step in power plant maintenance

    International Nuclear Information System (INIS)

    Butterworth, G.; Anderson, T.M.

    1984-01-01

    The Westinghouse Nuclear Services Integration Division managed maintenance services are described. Essential to the management and control of a total plant maintenance programme is the development of a comprehensive maintenance specification. During recent years Westinghouse has jointly developed total plant engineering-based maintenance specifications with a number of utilities. The process employed and the experience to date are described. To efficiently implement the maintenance programme Westinghouse has developed a computer software program specifically designed for day to day use at the power plant by maintenance personnel. This program retains an equipment maintenance history, schedules maintenance activities, issues work orders and performs a number of sophisticated analyses of the maintenance backlog and forecast, equipment failure rates, etc. The functions of this software program are described and details of Westinghouse efforts to support the utilities in reducing outage times through development of predefined outage plans for critical report maintenance activities are given. Also described is the experience gained in the training of specialized maintenance personnel, employing competency-based training techniques and equipment mock-ups, and the benefits experienced, in terms of improved quality and productivity of maintenance performed. The success experienced with these methods has caused Westinghouse to expand the use of these training techniques to the more routine skill areas of power plant maintenance. A significant reduction in the operating costs of nuclear power plants will only be brought about by a significant improvement in the quality of maintenance. Westinghouse intends to effect this change by expanding its international service capabilities and to make major investments in order to promote technological developments in the area of power plant maintenance. (author)

  3. 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.

  4. 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

  5. Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

    Science.gov (United States)

    Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

    2017-10-24

    Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. 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

  7. 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

  8. 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

  9. Residual life management. Maintenance improvement

    International Nuclear Information System (INIS)

    Sainero Garcia, J.; Hevia Ruperez, F.

    1995-01-01

    The terms Residual Life Management, Life Cycle Management and Long-Term Management are synonymous with a concept which aims to establish efficient maintenance for the profitable and safe operation of a power plant for as long as possible. A Residual Life Management programme comprises a number of stages, of which Maintenance Evaluation focuses on how power plant maintenance practices allow the mitigation and control of component ageing. with this objective in mind, a methodology has been developed for the analysis of potential degradative phenomena acting on critical components in terms of normal power plant maintenance practices. This methodology applied to maintenance evaluation enables the setting out of a maintenance programme based on the Life Management concept, and the programme's subsequent up-dating to allow for new techniques and methods. Initial applications have shown that although, in general terms, power plant maintenance is efficient, the way in which Residual Life Management is approached requires changes in maintenance practices. These changes range from modifications to existing inspection and surveillance methods or the establishment of new ones, to the monitoring of trends or the performance of additional studies, the purpose of which is to provide an accurate evaluation of the condition of the installations and the possibility of life extension. (Author)

  10. Mouse Intermittent Hypoxia Mimicking Apnea of Prematurity: Effects on Myelinogenesis and Axonal Maturation

    OpenAIRE

    CAI, JUN; TUONG, CHI MINH; ZHANG, YIPING; SHIELDS, CHRISTOPHER B.; GUO, GANG; FU, HUI; GOZAL, DAVID

    2011-01-01

    Premature babies are at high risk for both infantile apnea and long-term neurobehavioral deficits. Recent studies suggest that diffuse structural changes in brain white matter are a positive predictor of poor cognitive outcomes. Since oligodendrocyte maturation, myelination, axon development and synapse formation mainly occur in the 3rd trimester of gestation and 1st postnatal year, infantile apnea could lead to and/or exaggerate white matter impairments in preterm neonates. Therefore, we inv...

  11. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  12. 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.

  13. 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...

  14. 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

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium

    Directory of Open Access Journals (Sweden)

    Kirsten E. Lyke

    2018-02-01

    Full Text Available Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP Malian children, aged 4–8 years, are protected from malaria compared to matched schistosomiasis-negative (SN children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4–14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6 months later, following cessation of malaria transmission. CD4+ T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17A responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children (P < 0.0001. At the time of malaria infection, 12/24 SN children and 15/23 SP children (P = 0.29 stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children (P = 0.009 at the convalescent timepoint. 46.2% of cytokine-producing CD4+ T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2–59.5% of responses derived from CD45RA−CD62L− effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.

  20. 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.

  1. Maintenance for life management

    International Nuclear Information System (INIS)

    Hevia, F.

    1997-01-01

    Life Management is based on the detection, monitoring and control of long-term degradation that affects individual plant components and important populations. Experience has shown that in many cases current maintenance practices do not attend to ageing directly; instead they deal with the consequences when it is already too late, when good Life Management is no longer practical. This has brought about the need for specific Maintenance Evaluation and Improvement Programmes to adjust to the basic objective of Life Management which is to project against, monitor and mitigate ageing that can affect the safe and profitable operating life of the facility. New regulatory requirements for ageing monitoring and effective maintenance to ensure safety (Maintenance Rule) have made it even more necessary to implement the Maintenance Evaluation Programme to cope with ageing, and to integrate that tasks in both programmes to optimise effort and use of tools. This paper presents a brief description of the objectives and methodologies of these Programmes which has been applied to plants around the world and in Spain at the Garona and Vandellos II plants in Spain as part of the PIE project for developing a Remanent Life Evaluation System for nuclear power plants. (Author)

  2. Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder with or without Agoraphobia? A Randomized Controlled Clinical Trial

    Science.gov (United States)

    White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

    2013-01-01

    Objective: We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method: Participants were all patients (N = 379) who…

  3. Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study

    NARCIS (Netherlands)

    van Oers, Marinus H. J.; van Glabbeke, Martine; Giurgea, Livia; Klasa, Richard; Marcus, Robert E.; Wolf, Max; Kimby, Eva; van 't Veer, Mars; Vranovsky, Andrej; Holte, Harald; Hagenbeek, Anton

    2010-01-01

    Purpose In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the

  4. A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity.

    Science.gov (United States)

    Kassmann, Celia M; Quintes, Susanne; Rietdorf, Jens; Möbius, Wiebke; Sereda, Michael Werner; Nientiedt, Tobias; Saher, Gesine; Baes, Myriam; Nave, Klaus-Armin

    2011-07-21

    Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Opportune maintenance and predictive maintenance decision support

    OpenAIRE

    Thomas , Edouard; Levrat , Eric; Iung , Benoît; Cocheteux , Pierre

    2009-01-01

    International audience; Conventional maintenance strategies on a single component are being phased out in favour of more predictive maintenance actions. These new kinds of actions are performed in order to control the global performances of the whole industrial system. They are anticipative in nature, which allows a maintenance expert to consider non-already-planned maintenance actions. Two questions naturally emerge: when to perform a predictive maintenance action; how a maintenance expert c...

  6. 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.

  7. Network maintenance

    CERN Multimedia

    GS Department

    2009-01-01

    A site-wide network maintenance operation has been scheduled for Saturday 28 February. Most of the network devices of the general purpose network will be upgraded to a newer software version, in order to improve our network monitoring capabilities. This will result in a series of short (2-5 minutes) random interruptions everywhere on the CERN sites throughout the day. This upgrade will not affect the Computer Centre itself, Building 613, the Technical Network and the LHC experiments, dedicated networks at the pits. For further details of this intervention, please contact Netops by phone 74927 or e-mail mailto:Netops@cern.ch. IT/CS Group

  8. Network maintenance

    CERN Multimedia

    IT Department

    2009-01-01

    A site wide network maintenance has been scheduled for Saturday 28 February. Most of the network devices of the General Purpose network will be upgraded to a newer software version, in order to improve our network monitoring capabilities. This will result in a series of short (2-5 minutes) random interruptions everywhere on the CERN sites along this day. This upgrade will not affect: the Computer centre itself, building 613, the Technical Network and the LHC experiments dedicated networks at the pits. Should you need more details on this intervention, please contact Netops by phone 74927 or email mailto:Netops@cern.ch. IT/CS Group

  9. Nanostructured self-assembling peptides as a defined extracellular matrix for long-term functional maintenance of primary hepatocytes in a bioartificial liver modular device

    Directory of Open Access Journals (Sweden)

    Giri S

    2013-04-01

    Full Text Available Shibashish Giri,1 Ulf-Dietrich Braumann,2,3 Priya Giri,1,3 Ali Acikgöz,1,4 Patrick Scheibe,3,5 Karen Nieber,6 Augustinus Bader1 1Department of Cell Techniques and Applied Stem Cell Biology, Center for Biotechnology and Biomedicine (BBZ, 2Institute for Medical Informatics, Statistics, and Epidemiology (IMISE, University of Leipzig, Leipzig, Germany; 3Interdisciplinary Center for Bioinformatics (IZBI, University of Leipzig, Leipzig, Germany; 4Klinikum St Georg, Leipzig, Germany; 5Translational Center for Regenerative Medicine (TRM Leipzig, 6Department of Pharmacology for Natural Sciences, Institute of Pharmacy, University of Leipzig, Leipzig, Germany Abstract: Much effort has been directed towards the optimization of the capture of in vivo hepatocytes from their microenvironment. Some methods of capture include an ex vivo cellular model in a bioreactor based liver module, a micropatterned module, a microfluidic 3D chip, coated plates, and other innovative approaches for the functional maintenance of primary hepatocytes. However, none of the above methods meet US Food and Drug Administration (FDA guidelines, which recommend and encourage that the duration of a toxicity assay of a drug should be a minimum of 14 days, to a maximum of 90 days for a general toxicity assay. Existing innovative reports have used undefined extracellular matrices like matrigel, rigid collagen, or serum supplementations, which are often problematic, unacceptable in preclinical and clinical applications, and can even interfere with experimental outcomes. We have overcome these challenges by using integrated nanostructured self-assembling peptides and a special combination of growth factors and cytokines to establish a proof of concept to mimic the in vivo hepatocyte microenvironment pattern in vitro for predicting the in vivo drug hepatotoxicity in a scalable bioartificial liver module. Hepatocyte functionality (albumin, urea was measured at days 10, 30, 60, and 90 and we

  10. 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...

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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

  16. Neuroimmune processes associated with Wallerian degeneration support neurotrophin-3-induced axonal sprouting in the injured spinal cord.

    Science.gov (United States)

    Chen, Qin; Shine, H David

    2013-10-01

    Lesions of the spinal cord cause two distinctive types of neuroimmune responses, a response at the lesion site that leads to additional tissue destruction and a more subtle response, termed Wallerian degeneration (WD), that occurs distal to the lesion site. We have evidence that the neuroimmune response associated with WD may support tissue repair. Previously, we found that overexpression of neurotrophin-3 (NT-3) induced axonal growth in the spinal cord after a unilateral corticospinal tract (CST) lesion, but only if the immune system was intact and activated. We reasoned that a neuroimmune response associated with WD was involved in this neuroplasticity. To test this, we compared NT-3-induced axonal sprouting in athymic nude rats that lack functional T cells with rats with functional T cells and in nude rats grafted with CD4(+) T cells or CD8(+) T cells. There was no sprouting in nude rats and in nude rats grafted with CD8(+) T cells. However, nude rats grafted with CD4(+) T cells mounted a sprouting response. To determine which CD4(+) subtype, type 1 T helper (Th1) or type 2 T helper (Th2) cells, was responsible, we grafted Th1 and Th2 cells into nude rats and tested whether they would support sprouting. Axonal sprouting was greater in rats grafted with Th2 cells, demonstrating that the Th2 subtype was responsible for supporting axonal sprouting. These data suggest that WD activates Th2 cells that, along with the direct effects of NT-3 on CST axons, act to support axonal sprouting in the lesioned spinal cord. Copyright © 2013 Wiley Periodicals, Inc.

  17. 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

  18. 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.

  19. 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.

  20. Optimizing preventive maintenance with maintenance templates

    International Nuclear Information System (INIS)

    Dozier, I.J.

    1996-01-01

    Rising operating costs has caused maintenance professionals to rethink their strategy for preventive maintenance (PM) programs. Maintenance Templates are pre-engineered PM task recommendations for a component type based on application of the component. Development of the maintenance template considers the dominant failure cause of the component and the type of preventive maintenance that can predict or prevent the failure from occurring. Maintenance template development also attempts to replace fixed frequency tasks with condition monitoring tasks such as vibration analysis or thermography. For those components that have fixed frequency PM intervals, consideration is given to the maintenance drivers such as criticality, environment and usage. This helps to maximize the PM frequency intervals and maximize the component availability. Maintenance Templates have been used at PECO Energy's Limerick Generating Station during the Reliability Centered Maintenance (RCM) Process to optimize their PM program. This paper describes the development and uses of the maintenance templates

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

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    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.

  2. Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity

    Science.gov (United States)

    Svitkina, Tatyana M.

    2016-01-01

    The axon initial segment (AIS) is a specialized structure in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in neurons is ideal for its two major functions: it serves as the site of action potential firing and helps to maintain neuron polarity. It has become increasingly clear that the AIS cytoskeleton is fundamental to AIS functions. In this review, we discuss current understanding of the AIS cytoskeleton with particular interest in its unique architecture and role in maintenance of neuron polarity. The AIS cytoskeleton is divided into two parts, submembrane and cytoplasmic, based on localization, function, and molecular composition. Recent studies using electron and subdiffraction fluorescence microscopy indicate that submembrane cytoskeletal components (ankyrin G, βIV-spectrin, and actin filaments) form a sophisticated network in the AIS that is conceptually similar to the polygonal/triangular network of erythrocytes, with some important differences. Components of the AIS cytoplasmic cytoskeleton (microtubules, actin filaments, and neurofilaments) reside deeper within the AIS shaft and display structural features distinct from other neuronal domains. We discuss how the AIS submembrane and cytoplasmic cytoskeletons contribute to different aspects of AIS polarity function and highlight recent advances in understanding their AIS cytoskeletal assembly and stability. PMID:27493806

  3. 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

  4. 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.

  5. Radiosensitivity of stromal cells responsible for in vitro maintenance of hemopoietic stem cells in continuous, long-term marrow culture. [/sup 137/Cs; Mice

    Energy Technology Data Exchange (ETDEWEB)

    Tavassoli, M

    1982-05-01

    Marrow stromal cells are generally thought to be radioresistant. However, when the marrow was irradiated in vivo or in vitro before its use for the continuous longterm marrow culture, doses of radiation as low as 500 rad interfered with the establishment of the adherent stromal layer. Moreover, when the stromal layer was permitted to establish, similar doses of radiation interfered with its potential to support the proliferation and maintenance of the hemopoietic stem cell. Thus, marrow stromal cells appear to be more radiosensitive than hitherto thought. The type of damage may vary, however, according to the dose of radiation. Small doses may interfere with such functions as adhesion or cell division while larger doses may completely destroy the cell.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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)

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. Maintenance Business Plans.

    Science.gov (United States)

    Adams, Matt

    2002-01-01

    Discusses maintenance business plans, statements which provide accountability for facilities maintenance organizations' considerable budgets. Discusses the plan's components: statement of plan objectives, macro and detailed description of the facility assets, maintenance function descriptions, description of key performance indicators, milestone…

  19. Maintenance Management Update.

    Science.gov (United States)

    Sternloff, Robert E.

    1987-01-01

    Current trends in park maintenance are overviewed, including maintenance impact statements, avoidance of cost through efficient use and national resource conservation, horticultural accomplishments that influence maintenance management, and vandalism prevention. (CB)

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder.

    Science.gov (United States)

    Findling, Robert L; Mankoski, Raymond; Timko, Karen; Lears, Katherine; McCartney, Theresa; McQuade, Robert D; Eudicone, James M; Amatniek, Joan; Marcus, Ronald N; Sheehan, John J

    2014-01-01

    To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients. This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse. Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%). In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Small-Scale Die-Offs in Woodrats Support Long-Term Maintenance of Plague in the U.S. Southwest.

    Science.gov (United States)

    Kosoy, Michael; Reynolds, Pamela; Bai, Ying; Sheff, Kelly; Enscore, Russell E; Montenieri, John; Ettestad, Paul; Gage, Kenneth

    2017-09-01

    Our longitudinal study of plague dynamics was conducted in north-central New Mexico to identify which species in the community were infected with plague, to determine the spatial and temporal patterns of the dynamics of plague epizootics, and to describe the dynamics of Yersinia pestis infection within individual hosts. A total of 3156 fleas collected from 535 small mammals of 8 species were tested for Y. pestis DNA. Nine fleas collected from six southern plains woodrats (Neotoma micropus) and from one rock squirrel (Otospermophilus variegatus) were positive for the pla gene of Y. pestis. None of 127 fleas collected from 17 woodrat nests was positive. Hemagglutinating antibodies to the Y. pestis-specific F1 antigen were detected in 11 rodents of 6 species. All parts of the investigated area were subjected to local disappearance of woodrats. Despite the active die-offs, some woodrats always were present within the relatively limited endemic territory and apparently were never exposed to plague. Our observations suggest that small-scale die-offs in woodrats can support maintenance of plague in the active U.S. Southwestern focus.

  10. The complexity of self-regulating food intake in weight loss maintenance. A qualitative exploration among short- and long-term weight loss maintainers

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Sniethotta, Falko; Sainsbury, Kirby

    Objective: The aim of this study was to better understand whether self-regulation of food intake in WLM differs in the challenging transition from being a short-term maintainer (having maintained without regaining less than 12 months) to a long-term maintainer (having maintained without regaining....../storing, preparing/cooking, eating, and general barriers and resources in WLM. Post-hoc coding was applied based on self-regulation strategies and self-efficacy beliefs, and thematic analysis was also applied to identify additional themes. A content analysis approach using NVivo 11 highlighted the differences...... describe and understand the self-regulatory strategies related to food intake in WLM. Methods: Individual interviews (14 female/5 male) were conducted with 9 Danish short- and 10 long-term weight loss maintainers. Initial codes were based on five themes related to food intake: planning, shopping...

  11. CHANGES IN THE ELECTRICAL SURFACE CHARGE AND TRANSPLANTATION PROPERTIES OF TA3 ASCITES TUMOR CELLS DURING SHORT-TERM MAINTENANCE IN AN ISOTONIC SALT SOLUTION

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T. S.; Richards, W. R.; Kelly, L. S.

    1980-12-01

    TA3 ascites tumor cells maintained in vitro as a dilute suspension in 0.9% NaCl solution (physiological saline) were found to undergo time-dependent degenerative processes leading to alterations in both membrane characteristics and tumor transplantation properties. A 30% decrease in the negative cellular surface charge density occurred within 2 hr. when TA3 cells were incubated in a 0.9% NaCl solution at 23 °C. A similar reduction in negative surface charge density occurred within 0.5 hr. when the medium was maintained at 37 °C. This time-dependent reduction in surface charge was prevented when cellular metabolism was blocked either by maintaining the medium at 4 °C. or by adding 1 mM cyanide ion to a 23 °C medium. TA3 cells incubated as a dilute suspension in 0.9% NaCl solution at 23 °C also exhibited a large 9 time-dependent reduction in proliferative capacity in isogeneic LAF1/J hosts, as indicated by an increase in the tumor dose for 50% mortality (TD50). Lowering the temperature of the medium to 4 °C was observed to slow the onset of the degenerative processes that lead to a decreased transplantability of TA3 cells. The modification in growth properties of TA3 cells maintained in vitro was found to be attributable in part to an alteration in tumor histocompatibility. This effect was demonstrated by comparing the tumor growth kinetics and TD50 values in normal hosts versus hosts that had been immunosuppressed by whole-body irradiation. Following the in vitro maintenance of TA3 cells, nigrosin dye exclusion tests were performed as a means of assessing cell viability. Evidence obtained in this series of experiments indicated that vital staining is an inadequate criterion for judging either the extent of cell membrane damage or the loss of cellular proliferative capacity.

  12. 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)

  13. 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.

  14. 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.

  15. 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...

  16. 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...

  17. 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)

  18. 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.

  19. 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.

  20. 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.

  1. 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)

  2. 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

  3. Performance Improvement through Implementation of Lean Maintenance

    OpenAIRE

    S. Kolanjiappan; Dr. K. Maran

    2011-01-01

    Lean Maintenance is a relatively new term, invented in the last decade of the twentieth century, but the principles are well established in Total Productive Maintenance (TPM). Lean Maintenance—taking its lead from Lean Manufacturing—applies some new techniques to TPM concepts to render a more structured implementation path. Tracing its roots back to Henry Ford with modern refinements born in Japanese manufacturing, specifically the Toyota Production System (TPS). Lean seeks to eliminate a...

  4. A Situational Maintenance Model

    DEFF Research Database (Denmark)

    Luxhoj, James T.; Thorsteinsson, Uffe; Riis, Jens Ove

    1997-01-01

    An overview of trend in maintenance management and presentation of a situational model and an analytical tools for identification of managerial efforts in maintenance.......An overview of trend in maintenance management and presentation of a situational model and an analytical tools for identification of managerial efforts in maintenance....

  5. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

    Science.gov (United States)

    Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

    2013-11-11

    The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

  6. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    Science.gov (United States)

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

  7. 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.

  8. Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.

    Science.gov (United States)

    Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N

    2017-07-01

    The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Long-Term Maintenance of Therapeutic Gains Associated With Cognitive-Behavioral Therapy for Insomnia Delivered Alone or Combined With Zolpidem.

    Science.gov (United States)

    Beaulieu-Bonneau, Simon; Ivers, Hans; Guay, Bernard; Morin, Charles M

    2017-03-01

    To document the long-term sleep outcomes at 12 and 24 months after patients with chronic insomnia were treated with cognitive-behavioral therapy (CBT), either singly or combined with zolpidem medication. Participants were 160 adults with chronic insomnia. They were first randomized for a six-week acute treatment phase involving CBT alone or CBT combined with nightly zolpidem, and randomized for a six-month extended treatment phase involving CBT, no additional treatment, CBT combined with zolpidem as needed, or CBT with zolpidem tapered. This paper reports results of the 12- and 24-month follow-ups on the main outcome measures derived from the Insomnia Severity Index and sleep diaries. Clinical improvements achieved 6 months following the end of treatment were well-maintained in all four conditions, with insomnia remission rates ranging from 48% to 74% at the 12-month follow-up, and from 44% to 63% at the 24-month follow-up. Participants receiving CBT with zolpidem taper in the extended treatment phase had significantly better results than those receiving CBT with continued zolpidem as needed. The magnitude of improvements on sleep diary parameters was similar between conditions, with a slight advantage for the CBT with zolpidem taper condition. The addition of extended CBT did not alter the long-term outcome over improvements obtained during the initial 6-week CBT. The results suggest that CBT for insomnia, when delivered alone or in combination with medication, produce durable sleep improvements up to two years after completion of treatment. These long-term results indicate that even if a combined CBT plus medication approach provide an added benefit immediately after treatment, extending CBT while tapering medication produce better sustained improvements compared to continued use of medication as needed. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e

  10. Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

    1999-01-01

    In rat brainstem slices, we investigated the interaction between platelet-activating factor and group I metabotropic glutamate receptors in mediating long-term potentiation within the medial vestibular nuclei. We analysed the N1 field potential wave evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation. The group I metabotropic glutamate receptor antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic acid, prevented long-term potentiation induced by a platelet-activating factor analogue [1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3-phosphocholine], as well as the full development of potentiation, induced by high-frequency stimulation under the blocking agent for synaptosomal platelet-activating factor receptors (ginkolide B), at drug washout. However, potentiation directly induced by the group I glutamate metabotropic receptor agonist, (R,S)-3,5-dihydroxyphenylglycine, was reduced by ginkolide B. These findings suggest that platelet-activating factor, whether exogenous or released following potentiation induction, exerts its effect through presynaptic group I metabotropic glutamate receptors, mediating the increase of glutamate release. In addition, we found that this mechanism, which led to full potentiation through presynaptic group I metabotropic glutamate receptor activation, was inactivated soon after application of potentiation-inducing stimulus. In fact, the long-lasting block of the platelet-activating factor and metabotropic glutamate receptors prevented the full potentiation development and the induced potentiation progressively declined to null. Moreover, ginkolide B, given when high-frequency-dependent potentiation was established, only reduced it within 5 min after potentiation induction. We conclude that to fully develop vestibular long-term potentiation requires presynaptic events. Platelet-activating factor, released after the activation of postsynaptic mechanisms which induce potentiation, is necessary

  11. Maintenance of nuclear power plants

    International Nuclear Information System (INIS)

    Migaud, D.; Hutin, J.P.; Jouette, I.; Eymond, P.; Devie, P.; Cudelou, C.; Magnier, S.; Frydman, M.

    2016-01-01

    This document gathers different articles concerning the maintenance of the French nuclear power plants. The first article analyses the impact of the recent law on the energetic transition that sets the share of nuclear power at 50% of the electricity produced by 2025. A consequence may be the decommissioning of 17 to 20 reactors by 2025 and the huge maintenance program called 'Grand Carenage' whose aim is to extend operating life over 40 years will have to be re-considered in order to avoid useless expenses. The second article shows that in 2015 the French nuclear reactor fleet got very good results in terms of availability and safety. There were 49 scheduled outages and among them some ended ahead of time. The third article describes the specificities of the maintenance of a nuclear power plant, for instance the redundancy of some systems implies that maintenance has to deal with systems that have never functioned but must be ready to operate at any moment. Another specificity is the complexity of a nuclear power plant that implies an essential phase of preparation for maintenance operations. Because of safety requirements any maintenance operation has to be controlled, checked and may provide feedback. The fourth article presents the 'Grand Carenage' maintenance program that involves the following operations: the replacement of steam generators, the re-tubing of condensers, the replacement of the filtering drums used for cooling water, the testing of the reactor building, the hydraulic test of the primary circuit and the inspection of the reactor vessel. The fifth article focuses on the organization of the work-site for maintenance operations and the example of the Belleville-sur-Loire is described in the sixth article. Important maintenance operations like 'Grand Carenage' requires a strong collaboration with a network of specialized enterprises and as no reactor (except Flamanville EPR) is being built in France, maintenance

  12. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance.

    Science.gov (United States)

    Axelsson, P; Nyström, B; Lindhe, J

    2004-09-01

    The biofilm that forms and remains on tooth surfaces is the main etiological factor in caries and periodontal disease. Prevention of caries and periodontal disease must be based on means that counteract this bacterial plaque. To monitor the incidence of tooth loss, caries and attachment loss during a 30-year period in a group of adults who maintained a carefully managed plaque control program. In addition, a comparison was made regarding the oral health status of individuals who, in 1972 and 2002, were 51-65 years old. In 1971 and 1972, more than 550 subjects were recruited. Three hundred and seventy-five subjects formed a test group and 180 a control group. After 6 years of monitoring, the control group was discontinued but the participants in the test group was maintained in the preventive program and was finally re-examined after 30 years. The following variables were studied at Baseline and after 3, 6, 15 and 30 years: plaque, caries, probing pocket depth, probing attachment level and CPITN. Each patient was given a detailed case presentation and education in self-diagnosis. Once every 2 months during the first 2 years, once every 3-12 months during years 3-30, the participants received, on an individual need basis, additional education in self-diagnosis and self-care focused on proper plaque control measures, including the use of toothbrushes and interdental cleaning devices (brush, dental tape, toothpick). The prophylactic sessions that were handled by a dental hygienist also included (i) plaque disclosure and (ii) professional mechanical tooth cleaning including the use of a fluoride-containing dentifrice/paste. Few teeth were lost during the 30 years of maintenance; 0.4-1.8 in different age cohorts. The main reason for tooth loss was root fracture; only 21 teeth were lost because of progressive periodontitis or caries. The mean number of new caries lesions was 1.2, 1.7 and 2.1 in the three groups. About 80% of the lesions were classified as recurrent caries

  13. Preventive maintenance and reliability-centered maintenance

    International Nuclear Information System (INIS)

    Anderson, J.G.

    1989-01-01

    In the recent past, the primary function of the preventive maintenance program at a nuclear power plant was to maintain the operability and reliability of the plant. Reducing overall maintenance costs by performing effective preventive maintenance, instead of more costly and disruptive corrective maintenance, instead of more costly and disruptive corrective maintenance, was a secondary consideration. In today's operating environment, the preventive maintenance program must meet the test of cost-effectiveness as well as many new standards for performance that are being required by rate regulators. The preventive maintenance program must be able to withstand the challenge of independent audit to a new standard of technical adequacy and compliance with recommendations from component vendors. In this new environment, the standard that is being applied at the San Onofre nuclear generating station (SONGS) is that the preventive maintenance program must meet the test of cost-effectiveness, improve equipment performance, support increased plant availability, and (a) literally implement the recommendations of the vendor, (b) provide other compensation for the vendor recommendation, or (c) provide technical justification for the deviation. The subject of this paper is the way that reliability-centered maintenance (RCM) is helping SONGS meet these challenges

  14. 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

  15. 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.

  16. Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by the POU-Domain Protein Pdm3 in Drosophila Larvae.

    Science.gov (United States)

    Qian, Cheng Sam; Kaplow, Margarita; Lee, Jennifer K; Grueber, Wesley B

    2018-02-21

    Internal sensory neurons innervate body organs and provide information about internal state to the CNS to maintain physiological homeostasis. Despite their conservation across species, the anatomy, circuitry, and development of internal sensory systems are still relatively poorly understood. A largely unstudied population of larval Drosophila sensory neurons, termed tracheal dendrite (td) neurons, innervate internal respiratory organs and may serve as a model for understanding the sensing of internal states. Here, we characterize the peripheral anatomy, central axon projection, and diversity of td sensory neurons. We provide evidence for prominent expression of specific gustatory receptor genes in distinct populations of td neurons, suggesting novel chemosensory functions. We identify two anatomically distinct classes of td neurons. The axons of one class project to the subesophageal zone (SEZ) in the brain, whereas the other terminates in the ventral nerve cord (VNC). We identify expression and a developmental role of the POU-homeodomain transcription factor Pdm3 in regulating the axon extension and terminal targeting of SEZ-projecting td neurons. Remarkably, ectopic Pdm3 expression is alone sufficient to switch VNC-targeting axons to SEZ targets, and to induce the formation of putative synapses in these ectopic target zones. Our data thus define distinct classes of td neurons, and identify a molecular factor that contributes to diversification of axon targeting. These results introduce a tractable model to elucidate molecular and circuit mechanisms underlying sensory processing of internal body status and physiological homeostasis. SIGNIFICANCE STATEMENT How interoceptive sensory circuits develop, including how sensory neurons diversify and target distinct central regions, is still poorly understood, despite the importance of these sensory systems for maintaining physiological homeostasis. Here, we characterize classes of Drosophila internal sensory neurons (td

  17. Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

    Directory of Open Access Journals (Sweden)

    Michaela Fredrich

    2011-01-01

    Full Text Available The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM, were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43 into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

  18. Advanced maintenance research programs

    International Nuclear Information System (INIS)

    Marston, T.U.; Gelhaus, F.; Burke, R.

    1985-01-01

    The purpose of this paper is to provide the reader with an idea of the advanced maintenance research program at the Electric Power Research Institute (EPRI). A brief description of the maintenance-related activities is provided as a foundation for the advanced maintenance research projects. The projects can be divided into maintenance planning, preventive maintenance program development and implementation, predictive (or conditional) maintenance, and innovative maintenance techniques. The projects include hardware and software development, human factors considerations, and technology promotion and implementation. The advanced concepts include: the incorporation of artificial intelligence into outage planning; turbine and pump maintenance; rotating equipment monitoring and diagnostics with the aid of expert systems; and the development of mobile robots for nuclear power plant maintenance

  19. Maintenance analysis method and operational feedback: a comprehensive maintenance management

    International Nuclear Information System (INIS)

    Mathieu Riou; Victor Planchon

    2006-01-01

    Full text of publication follows: Current periodic inspections program carried out on the COGEMA LOGISTICS casks is required by regulations and approved by the competent Authority. Thus, Safety and casks conformity to the according certificate of approval are guaranteed. Nonetheless, based on experience it appeared that some maintenance operations did not seem relevant or were redundant. Then, it was decided to rethink completely our maintenance program to reach the following objectives: - Set up the 'a minima' required inspection operations required to guarantee Safety and conformity to the certificate of approval, - Optimize criteria and periodicities of inspections taking into account: operational feedback, routine inspections carried out for each transport, regulations, environmental impact (ALARA, waste reduction,...), cost-effectiveness (reduction of cask's immobilization period,...). - Set up a maintenance program in Safety Analysis Reports that: stands alone (no need to check the specification or the certificate of approval to have the complete list of inspections mandatory to guarantee Safety), gives objectives instead of means of controls. This approach needs then to be re-evaluated by the competent Authority. Study's scope has been limited to the TN TM 12 cask family which is intensely used. COGEMA LOGISTICS has a high operational feedback on these casks. After Authority agreement, and in accordance with its requirements, study will then be extended to the other casks belonging to the COGEMA LOGISTICS cask fleet. Actually, the term 'maintenance' is linked to 'Base maintenance' and 'Main maintenance' and implicitly means that the cask is immobilized for a given period. To emphasize the modifications, the term 'maintenance' is no longer used and is substituted by 'periodic upkeep'. By changing the name, COGEMA LOGISTICS wants to emphasize that: some operations can for instance be realized while the cask is unloaded, periodicities are thought in terms of

  20. 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

  1. Technical and organizational considerations for the long-term maintenance and development of digital brain atlases and web-based databases.

    Science.gov (United States)

    Ito, Kei

    2010-01-01

    Digital brain atlas is a kind of image database that specifically provide information about neurons and glial cells in the brain. It has various advantages that are unmatched by conventional paper-based atlases. Such advantages, however, may become disadvantages if appropriate cares are not taken. Because digital atlases can provide unlimited amount of data, they should be designed to minimize redundancy and keep consistency of the records that may be added incrementally by different staffs. The fact that digital atlases can easily be revised necessitates a system to assure that users can access previous versions that might have been cited in papers at a particular period. To inherit our knowledge to our descendants, such databases should be maintained for a very long period, well over 100 years, like printed books and papers. Technical and organizational measures to enable long-term archive should be considered seriously. Compared to the initial development of the database, subsequent efforts to increase the quality and quantity of its contents are not regarded highly, because such tasks do not materialize in the form of publications. This fact strongly discourages continuous expansion of, and external contributions to, the digital atlases after its initial launch. To solve these problems, the role of the biocurators is vital. Appreciation of the scientific achievements of the people who do not write papers, and establishment of the secure academic career path for them, are indispensable for recruiting talents for this very important job.

  2. Upgrade of maintenance technologies of Nuclear Power Plants

    International Nuclear Information System (INIS)

    Kamada, Kazuaki

    2005-01-01

    In order to enhance long-term safe and stable operation of Ikata Nuclear Power Plants (NPPs) in more efficient way, maintenance technology upgrade project was started aiming at establishment of simplified and efficient self-maintenance system with affiliated companies. Maintenance technique and supervisor qualification system was introduced after improvement and reinforcement of personnel education and training. Reflecting investigation of maintenance activities of US NPPs and productivity improvement in other industries, preventive maintenance optimization project had been performed such as introduction of key performance indicator (KPI), new system incorporating reliability-centered maintenance (RCM) and condition-based maintenance (CBM), and on-line monitoring and maintenance (OLM) based on risk assessment. Enterprise asset management (EAM) to establish information data base and total productive maintenance (TPM) action for every personnel to participate in self-maintenance was also introduced. (T. Tanaka)

  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. A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

    Directory of Open Access Journals (Sweden)

    Marta Koch

    2018-02-01

    Full Text Available Injury to the adult central nervous systems (CNS can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1, the de-ubiquitinating enzyme Fat Facets (Faf/Usp9x and the Jun N-Terminal Kinase (JNK pathway transcription factor Kayak (Kay/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.

  5. 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.

  6. Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices.

    Science.gov (United States)

    Sezdi, Mana

    2016-01-01

    A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices.

  7. Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Uemura N

    2018-01-01

    Full Text Available Naomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o. and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg. Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or

  8. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  9. 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.

  10. Maintenance work management system

    International Nuclear Information System (INIS)

    Kanai, T.; Takahashi, Y.; Takahashi, K.; Nishino, M.; Takeshige, R.

    2000-01-01

    The maintenance work management system supports the efficient drawing up of various documents for the maintenance work at nuclear power stations and the speeding up of the permission procedure. In addition, it improves the quality assurance of the safety and reliability of the maintenance work. Key merits of the system are: 1. Efficiently drawing up various documents for the maintenance work by using the stored data for the previous maintenance work and the pipe and instrument diagram (P and ID) data. 2. Supporting the management work for the completion of maintenance work safety by using the isolation information stored on the computer system. 3. Speeding up the permission procedure by electronic mail and electronic permission. 4. Displaying additional information such as the specifications of equipment, maintenance result, and maintenance plan by linking up with the database of another system. 5. Reducing the cost of hardware devices by using client/server network configurations of personal computers and a personal computer server. (author)

  11. Unsurfaced Road Maintenance Management

    Science.gov (United States)

    1992-12-01

    This draft manual describes an unsurfaced road maintenance management system for use on military installations. This system is available in either a manual or computerized mode (Micro PAVER). The maintenance standards prescribed should protect Govern...

  12. Winter maintenance performance measure.

    Science.gov (United States)

    2016-01-01

    The Winter Performance Index is a method of quantifying winter storm events and the DOTs response to them. : It is a valuable tool for evaluating the States maintenance practices, performing post-storm analysis, training : maintenance personnel...

  13. An Internet- and mobile-based tailored intervention to enhance maintenance of physical activity after cardiac rehabilitation: short-term results of a randomized controlled trial.

    Science.gov (United States)

    Antypas, Konstantinos; Wangberg, Silje C

    2014-03-11

    (Kolmogorov-Smirnov Z=0.823, P=.38, r=.17). At 3 months after discharge, the tailored intervention group (n=7) had a significantly higher median level of overall physical activity (median 5613.0, IQR 2828.0) than the control group (n=12, median 1356.0, IQR 2937.0; Kolmogorov-Smirnov Z=1.397, P=.02, r=.33). The median adherence was 45.0 (95% CI 0.0-169.8) days for the tailored group and 111.0 (95% CI 45.1-176.9) days for the control group; however, the difference was not significant (P=.39). There were no statistically significant differences between the 2 groups in stage of change, self-efficacy, social support, perceived tailoring, anxiety, or depression. Because of the small sample size and the high attrition rate at the follow-up visits, we cannot make conclusions regarding the efficacy of our approach, but the results indicate that the tailored version of the intervention may have contributed to the long-term higher physical activity maintained after cardiac rehabilitation by participants receiving the tailored intervention compared with those receiving the nontailored intervention. ClinicalTrials.gov: NCT01223170; http://clinicaltrials.gov/show/NCT01223170 (Archived by WebCite at http://www.webcitation.org/6Nch4ldcL).

  14. 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

  15. 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.

  16. 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.

  17. Competence within Maintenance

    OpenAIRE

    Nerland, Annette Smørholm

    2010-01-01

    Maintenance can be a contributing factor to unwanted events, as well as desired events and states. Human competence can be defined as the ability to perform a specific task, action or function successfully, and is therefore a key factor to proper execution of maintenance tasks. Hence,maintenance will have negative consequences if done wrong, and give positive results when done right. The purpose of this report is to study the many aspects of maintenance competence. Endeavoring to improve ...

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Asphalt in Pavement Maintenance.

    Science.gov (United States)

    Asphalt Inst., College Park, MD.

    Maintenance methods that can be used equally well in all regions of the country have been developed for the use of asphalt in pavement maintenance. Specific information covering methods, equipment and terminology that applies to the use of asphalt in the maintenance of all types of pavement structures, including shoulders, is provided. In many…

  4. Optimization of surface maintenance

    International Nuclear Information System (INIS)

    Oeverland, E.

    1990-01-01

    The present conference paper deals with methods of optimizing the surface maintenance of steel-made offshore installations. The paper aims at identifying important approaches to the problems regarding the long-range planning of an economical and cost effective maintenance program. The methods of optimization are based on the obtained experiences from the maintenance of installations on the Norwegian continental shelf. 3 figs

  5. Dukovany NPP maintenance management

    International Nuclear Information System (INIS)

    Siegel, F.

    2005-01-01

    Maintenance planning and management for the technological equipment of the Dukovany NPP are described. A Maintenance Control and Evaluation System has been developed and is in use to help manage the complex maintenance issue. Practical examples of outputs of the System, with a comprehensive use of the cost, reliability and safety related data, are presented. (author)

  6. Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

    Science.gov (United States)

    Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

    2008-05-05

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

  7. Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

    Science.gov (United States)

    Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

    2008-06-01

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

  8. Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

    Science.gov (United States)

    Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

    2008-01-01

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

  9. 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

  10. Absence of IL-1β positively affects neurological outcome, lesion development and axonal plasticity after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Boato Francesco

    2013-01-01

    Full Text Available Abstract Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI. We used an IL-1β deficiency model (IL-1βKO mice and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation, but also on the plasticity of central nervous system axons after injury.

  11. Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury.

    Science.gov (United States)

    Goganau, Ioana; Sandner, Beatrice; Weidner, Norbert; Fouad, Karim; Blesch, Armin

    2018-02-01

    Activity dependent plasticity is a key mechanism for the central nervous system (CNS) to adapt to its environment. Whether neuronal activity also influences axonal regeneration in the injured CNS, and whether electrical stimulation (ES) can activate regenerative programs in the injured CNS remains incompletely understood. Using KCl-induced depolarization, in vivo ES followed by ex-vivo neurite growth assays and ES after spinal cord lesions and cell grafting, we aimed to identify parameters important for ES-enhanced neurite growth and axonal regeneration. Using cultures of sensory neurons, neurite growth was analyzed after KCl-induced depolarization for 1-72h. Increased neurite growth was detected after short-term stimulation and after longer stimulation if a sufficient delay between stimulation and growth measurements was provided. After in vivo ES (20Hz, 2× motor threshold, 0.2ms, 1h) of the intact sciatic nerve in adult Fischer344 rats, sensory neurons showed a 2-fold increase in in vitro neurite length one week later compared to sham animals, an effect not observed one day after ES. Longer ES (7h) and repeated ES (7days, 1h each) also increased growth by 56-67% one week later, but provided no additional benefit. In vivo growth of dorsal column sensory axons into a graft of bone marrow stromal cells 4weeks after a cervical spinal cord lesion was also enhanced with a single post-injury 1h ES of the intact sciatic nerve and was also observed after repeated ES without inducing pain-like behavior. While ES did not result in sensory functional recovery, our data indicate that ES has time-dependent influences on the regenerative capacity of sensory neurons and might further enhance axonal regeneration in combinatorial approaches after SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. EPR design for maintenance

    International Nuclear Information System (INIS)

    Krugmann, U.

    1998-01-01

    Preventive maintenance is very important in achieving high plant availability. For the European Pressurized Reactor (EPR) preventive maintenance has been carefully addressed in the design stage. This is particularly necessary because of the traditionally different maintenance strategies employed in France and Germany. This paper emphasizes the following features introduced in the ERP design to minimize the duration of the refueling outage: (1) containment accessibility during power operation; (2) overall plant layout to facilitate inspections and maintenances within the containment; and (3) safety system design for enabling preventive maintenance during power operation. (author)

  13. Managing nuclear maintenance

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    For utilities operating nuclear powerplants, the rules of the game continue to change. Conflicting regulatory pressures and a tougher competitive environment will make management's job more complicated and difficult in the 1990s. Dealing with these pressures successfully requires greater attention to maintenance effectiveness. Utilities can help shape their future environment by developing a well-planned strategy to guide their actions. Parts of the strategy that are discussed include developing a sound maintenance philosophy, selecting a service company, radiation exposure, and managing spare parts. This article also addresses the Swedish experience in maintenance, German philosophy regarding maintenance and the current maintenance practices of the Electricite de France

  14. AIRCRAFT MAINTENANCE HANGAR

    Directory of Open Access Journals (Sweden)

    GEAMBASU Gabriel George

    2017-05-01

    Full Text Available The paper presents the maintenance process that is done on an airplane, at a certain period of time, or after a number of flight hours or cycles and describes the checks performed behind each inspection. The first part of research describes the aircraft maintenance process that has to be done after an updated maintenance manual according with aircraft type, followed by a short introduction about maintenance hangar. The second part of the paper presents a hangar design with a foldable roof and walls, which can be folded or extended, over an airplane when a maintenance process is done, or depending on weather condition.

  15. 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.

  16. Maintenance management systems

    International Nuclear Information System (INIS)

    Rohan, M. de

    1989-01-01

    This paper is concerned principally with Maintenance Management systems and their effective introduction into organisations. Maintenance improvement is basically a problem of managing the maintenance department in the broadest sense. Improvement does not only lie in the area of special techniques, systems or procedures; although they are valuable tools, but rather in a balanced attack, carefully guided by management. Over recent years, maintenance systems have received the major emphasis and in many instances the selection of the system has become a pre-occupation, whereas the importance of each maintenance function must be recognised and good management practices applied to all maintenance activities. The ingredients for success in the implementation of maintenance management systems are summarised as: having a management committee, clear objectives, project approach using project management techniques and an enthusiastic leader, user managed and data processing supported project, realistic budget and an understanding of the financial audit requirements. (author)

  17. Knowledge based maintenance

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, A [Hamburgische Electacitaets-Werke AG Hamburg (Germany)

    1998-12-31

    The establishment of maintenance strategies is of crucial significance for the reliability of a plant and the economic efficiency of maintenance measures. Knowledge about the condition of components and plants from the technical and business management point of view therefore becomes one of the fundamental questions and the key to efficient management and maintenance. A new way to determine the maintenance strategy can be called: Knowledge Based Maintenance. A simple method for determining strategies while taking the technical condition of the components of the production process into account to the greatest possible degree which can be shown. A software with an algorithm for Knowledge Based Maintenance leads the user during complex work to the determination of maintenance strategies for this complex plant components. (orig.)

  18. Knowledge based maintenance

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, A. [Hamburgische Electacitaets-Werke AG Hamburg (Germany)

    1997-12-31

    The establishment of maintenance strategies is of crucial significance for the reliability of a plant and the economic efficiency of maintenance measures. Knowledge about the condition of components and plants from the technical and business management point of view therefore becomes one of the fundamental questions and the key to efficient management and maintenance. A new way to determine the maintenance strategy can be called: Knowledge Based Maintenance. A simple method for determining strategies while taking the technical condition of the components of the production process into account to the greatest possible degree which can be shown. A software with an algorithm for Knowledge Based Maintenance leads the user during complex work to the determination of maintenance strategies for this complex plant components. (orig.)

  19. Creating Value by Integrating Logistic Trains Services and Maintenance Activities

    NARCIS (Netherlands)

    Busstra, Marten; van Dongen, Leonardus Adriana Maria

    2015-01-01

    NedTrain is the Netherlands Railway's subsidiary responsible for rolling stock maintenance. Train sets are brought in for short-term routine maintenance after set intervals of some 75 to 120 days. When a major defect occurs, train sets are allocated to one of the three maintenance depots and are

  20. Balancing preventive and corrective maintenance in Cernavoda Unit 1 NPP

    International Nuclear Information System (INIS)

    Riedel, M.; Marinescu, S.

    2000-01-01

    The paper presents a short reminder of Romania's Cernavoda NPP entering commercial operation and a brief description of the CANDU-6 project on which Unit 1 is based. The short term objectives of the maintenance management, the status of the existing maintenance programmes as well as future predictable maintenance programmes are outlined together with the Government plan to complete the balance of NPP. (author)

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. The Myriad Roles of Miro in the Nervous System: Axonal Transport of Mitochondria and Beyond

    Directory of Open Access Journals (Sweden)

    Bingwei eLu

    2014-10-01

    Full Text Available Mitochondrial rho GTPase (Miro is a mitochondrial outer membrane protein containing two GTPase domains and two helix-loop-helix Ca2+-binding domains called EF hands. Pioneering genetic studies in Drosophila first revealed a key function of Miro in regulating the axonal transport of mitochondria, during which Miro forms a multi-protein transport complex with Milton and Kinesin heavy chain (KHC to link trafficking mitochondria with the microtubule cytoskeleton. Recent studies showed that through binding to the EF hands of Miro and causing conformational changes of Miro and alteration of protein-protein interactions within the transport complex, Ca2+ can alter the engagement of mitochondria with the microtubule (MT/kinesin network, offering one mechanism to match mitochondrial distribution with neuronal activity. Despite the importance of the Miro/Milton/Kinesin complex in regulating mitochondrial transport in metazoans, not all components of the transport complex are conserved in lower organisms, and transport-independent functions of Miro are emerging. Here we review the diverse functions of the evolutionarily conserved Miro proteins that are relevant to the development, maintenance, and functioning of the nervous system and discuss the potential contribution of Miro dysfunction to the pathogenesis of diseases of the nervous system.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. 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

  12. 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...

  13. Project Surveillance and Maintenance Plan

    International Nuclear Information System (INIS)

    1985-09-01

    The Project Surveillance and Maintenance Plan (PSMP) describes the procedures that will be used by the US Department of Energy (DOE), or other agency as designated by the President to verify that inactive uranium tailings disposal facilities remain in compliance with licensing requirements and US Environmental Protection Agency (EPA) standards for remedial actions. The PSMP will be used as a guide for the development of individual Site Surveillance and Maintenance Plans (part of a license application) for each of the UMTRA Project sites. The PSMP is not intended to provide minimum requirements but rather to provide guidance in the selection of surveillance measures. For example, the plan acknowledges that ground-water monitoring may or may not be required and provides the [guidance] to make this decision. The Site Surveillance and Maintenance Plans (SSMPs) will form the basis for the licensing of the long-term surveillance and maintenance of each UMTRA Project site by the NRC. Therefore, the PSMP is a key milestone in the licensing process of all UMTRA Project sites. The Project Licensing Plan (DOE, 1984a) describes the licensing process. 11 refs., 22 figs., 8 tabs

  14. Random maintenance policies

    CERN Document Server

    Nakagawa, Toshio

    2014-01-01

    Exploring random maintenance models, this book provides an introduction to the implementation of random maintenance, and it is one of the first books to be written on this subject.  It aims to help readers learn new techniques for applying random policies to actual reliability models, and it provides new theoretical analyses of various models including classical replacement, preventive maintenance and inspection policies. These policies are applied to scheduling problems, backup policies of database systems, maintenance policies of cumulative damage models, and reliability of random redundant systems. Reliability theory is a major concern for engineers and managers, and in light of Japan’s recent earthquake, the reliability of large-scale systems has increased in importance. This also highlights the need for a new notion of maintenance and reliability theory, and how this can practically be applied to systems. Providing an essential guide for engineers and managers specializing in reliability maintenance a...

  15. Framework for Maintenance Planning

    DEFF Research Database (Denmark)

    Soares, C. Guedes; Duarte, J. Caldeira; Garbatov, Y.

    2010-01-01

    the design and during the whole life span of operational use, within an integrated framework founded on risk and reliability based techniques. The document addresses designers, decision makers and professionals responsible for or involved in establishing maintenance plans. The purpose of this document......The present document presents a framework for maintenance planning. Maintenance plays a fundamental role in counteracting degradation effects, which are present in all infrastructure and industrial products. Therefore, maintenance planning is a very critical aspect to consider both during...... is to present maintenance as an integrated approach that needs to be planned, designed, engineered, and controlled by proper qualitative and quantitative techniques. This document outlines the basic premises for maintenance planning and provides the general philosophies that can be followed and points to a best...

  16. Suncor maintenance and reliability

    Energy Technology Data Exchange (ETDEWEB)

    Little, S. [Suncor Energy, Calgary, AB (Canada)

    2006-07-01

    Fleet maintenance and reliability at Suncor Energy was discussed in this presentation, with reference to Suncor Energy's primary and support equipment fleets. This paper also discussed Suncor Energy's maintenance and reliability standard involving people, processes and technology. An organizational maturity chart that graphed organizational learning against organizational performance was illustrated. The presentation also reviewed the maintenance and reliability framework; maintenance reliability model; the process overview of the maintenance and reliability standard; a process flow chart of maintenance strategies and programs; and an asset reliability improvement process flow chart. An example of an improvement initiative was included, with reference to a shovel reliability review; a dipper trip reliability investigation; bucket related failures by type and frequency; root cause analysis of the reliability process; and additional actions taken. Last, the presentation provided a graph of the results of the improvement initiative and presented the key lessons learned. tabs., figs.

  17. 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

  18. 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.

  19. 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.

  20. Software evolution and maintenance

    CERN Document Server

    Tripathy, Priyadarshi

    2014-01-01

    Software Evolution and Maintenance: A Practitioner's Approach is an accessible textbook for students and professionals, which collates the advances in software development and provides the most current models and techniques in maintenance.Explains two maintenance standards: IEEE/EIA 1219 and ISO/IEC14764Discusses several commercial reverse and domain engineering toolkitsSlides for instructors are available onlineInformation is based on the IEEE SWEBOK (Software Engineering Body of Knowledge)

  1. Status of fusion maintenance

    International Nuclear Information System (INIS)

    Fuller, G.M.

    1984-01-01

    Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission

  2. Interactive videodisc in maintenance

    International Nuclear Information System (INIS)

    Zwingelstein, G.; Nguyen Van Nghi, B.

    1986-01-01

    After a recall of the videodisc characteristics, this paper presents its utilization by Electricite de France in the framework of training and maintenance. The SICMA (Interactive Communication System in Maintenance) developed and tested by Electricte de France is presented as also its utilization. It has been tested on the sites of Dampierre and Paluel in the cases of training and maintenance (deconnexion of drive rods of control elements); the conclusions of this experimentation are finally given. 4 refs [fr

  3. Turbine maintenance and modernization

    Energy Technology Data Exchange (ETDEWEB)

    Unga, E. [Teollisuuden Voima Oy, Olkiluoto (Finland)

    1998-12-31

    The disturbance-free operation of the turbine plant plays an important role in reaching good production results. In the turbine maintenance of the Olkiluoto nuclear power plant the lifetime and efficiency of turbine components and the lifetime costs are taken into account in determining the turbine maintenance and modernization/improvement program. The turbine maintenance program and improvement/modernization measures taken in the plant units are described in this presentation. (orig.)

  4. Turbine maintenance and modernization

    Energy Technology Data Exchange (ETDEWEB)

    Unga, E [Teollisuuden Voima Oy, Olkiluoto (Finland)

    1999-12-31

    The disturbance-free operation of the turbine plant plays an important role in reaching good production results. In the turbine maintenance of the Olkiluoto nuclear power plant the lifetime and efficiency of turbine components and the lifetime costs are taken into account in determining the turbine maintenance and modernization/improvement program. The turbine maintenance program and improvement/modernization measures taken in the plant units are described in this presentation. (orig.)

  5. A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update): Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores.

    Science.gov (United States)

    Yamamoto, Masaaki; Serizawa, Toru; Higuchi, Yoshinori; Sato, Yasunori; Kawagishi, Jun; Yamanaka, Kazuhiro; Shuto, Takashi; Akabane, Atsuya; Jokura, Hidefumi; Yomo, Shoji; Nagano, Osamu; Aoyama, Hidefumi

    2017-09-01

    The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease <3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93%, 91%, and 92%, respectively, at the 12th month after SRS; 91%, 89%, and 91%, respectively, at the 24th month; 89%, 88%, and 89%, respectively, at the 36th month; and 87%, 86%, and 89%, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95% confidence interval [CI], 0.437-1.172; P=.18; HR of group B vs group C, 1.280; 95% CI, 0.696-2.508; P=.43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.8-26.5 months), as of December 2014, 145 patients (12.1%) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7%, 8%, and 6%, respectively, at the 12th month after SRS; 10%, 11%, and 11%, respectively, at the 24th month; 11%, 11%, and 12%, respectively, at the 36th month; and 12%, 12%, and 13%, respectively, at the 48th month (HR of group A vs group B, 0.850; 95% CI, 0.592-1.220; P=.38; HR of group B vs group C, 1.052; 95% CI, 0.666-1.662, P=.83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1%) with

  6. Site Maintenance Plan: Part 2, Site Maintenance Action Plan for FY 1994

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, E.L.

    1994-06-01

    This Fiscal Year (FY) 1994 Site Maintenance Action Plan (SMAP) is Part II of the Site Maintenance Plan, and has been written by Westinghouse Hanford Company (WHC) to outline the requirements stated in DOE Order 4330.4B, Maintenance Management Program, Chapter 1, Paragraph 3.3.1. The SMAP provides an annual status of maintenance initiatives completed and planned, a summary of performance indicators, a summary of maintenance backlog, a listing of real property and capital equipment maintenance cost estimates that were used to create the FY 1996 infrastructure and maintenance budget input, and a listing of proposed line item and general plant projects. Additionally, assumptions for various Site programs are listed to bring the Site Maintenance Plan into focus with overall Site activities. The primary mission at Hanford is to clean up the Site. In this cleanup process WHC will provide scientific and technological expertise to meet global needs, and partnership with stakeholders in the region to develop regional economic diversification. Other missions at the Hanford Site include energy research and development, and waste management and disposal activities. Their primary mission has a 30-year projected life span and will direct the shutting down and cleanup of defense production facilities and the Fast Flux Test Facility. This long-term mission requires continuous maintenance and in many instances, replacement of existing basic infrastructure, support facilities, and utilities. Without adequate maintenance and capital funding these infrastructure, support facilities, and utilities will continue to deteriorate causing an increase in backlogged work.

  7. Site Maintenance Plan: Part 2, Site Maintenance Action Plan for FY 1994

    International Nuclear Information System (INIS)

    Fisk, E.L.

    1994-06-01

    This Fiscal Year (FY) 1994 Site Maintenance Action Plan (SMAP) is Part II of the Site Maintenance Plan, and has been written by Westinghouse Hanford Company (WHC) to outline the requirements stated in DOE Order 4330.4B, Maintenance Management Program, Chapter 1, Paragraph 3.3.1. The SMAP provides an annual status of maintenance initiatives completed and planned, a summary of performance indicators, a summary of maintenance backlog, a listing of real property and capital equipment maintenance cost estimates that were used to create the FY 1996 infrastructure and maintenance budget input, and a listing of proposed line item and general plant projects. Additionally, assumptions for various Site programs are listed to bring the Site Maintenance Plan into focus with overall Site activities. The primary mission at Hanford is to clean up the Site. In this cleanup process WHC will provide scientific and technological expertise to meet global needs, and partnership with stakeholders in the region to develop regional economic diversification. Other missions at the Hanford Site include energy research and development, and waste management and disposal activities. Their primary mission has a 30-year projected life span and will direct the shutting down and cleanup of defense production facilities and the Fast Flux Test Facility. This long-term mission requires continuous maintenance and in many instances, replacement of existing basic infrastructure, support facilities, and utilities. Without adequate maintenance and capital funding these infrastructure, support facilities, and utilities will continue to deteriorate causing an increase in backlogged work

  8. Analysis of maintenance strategies

    International Nuclear Information System (INIS)

    Laakso, K.; Simola, K.

    1998-01-01

    The main topics of the presentation include: (1) an analysis model and methods to evaluate maintenance action programs and the support decision to make changes in them and (2) to understand the maintenance strategies in a systems perspective as a basis for future developments. The subproject showed how systematic models for maintenance analysis and decision support, utilising computerised and statistical tool packages, can be taken into use for evaluation and optimisation of maintenance of active systems from the safety and economic point of view

  9. Remote Maintenance Monitoring System -

    Data.gov (United States)

    Department of Transportation — The Remote Maintenance and Monitoring System (RMMS) is a collection of subsystems that includes telecommunication components, hardware, and software, which serve to...

  10. Army Maintenance System Transformation

    National Research Council Canada - National Science Library

    Gilbertson, Frank V

    2006-01-01

    .... Used in conjunction with pertinent historical data and developed with Army transformation goals in mind, General Systems thinking can provide the framework for guiding maintenance transformation...

  11. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

  12. Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

    Directory of Open Access Journals (Sweden)

    Dávid Csabai

    2018-01-01

    Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

  13. Operations and maintenance plans for the TFTR

    International Nuclear Information System (INIS)

    Allen, H.L.; Fedor, B.J.

    1978-01-01

    Princeton University Plasma Physics Laboratory (PPPL) is constructing a Tokamak Fusion Test Reactor (TFTR) scheduled to begin operation for fusion research experiments in late 1981, first with hydrogen and deuterium plasmas and later, in the second phase, using tritium for high power fusion studies. This latter mode will introduce considerable complexity to operation and maintenance of the TFTR in terms of meeting requirements for tritium handling, adequate radiation shielding, and corrective and preventive maintenance procedures. In this paper we discuss plans for the installation and preoperational testing of the major subsystems of TFTR, proposed start-up and operating scenarios for the device and the system of operational control. In addition, the TFTR Maintenance Plan and related procedures for specific major maintenance tasks are described, including the use of remote handling equipment and remote manipulators. Each of these topics is addressed in terms of the current status of planning and development

  14. Smartphone-Enabled Health Coaching Intervention (iMOVE) to Promote Long-Term Maintenance of Physical Activity in Breast Cancer Survivors: Protocol for a Feasibility Pilot Randomized Controlled Trial.

    Science.gov (United States)

    Ritvo, Paul; Obadia, Maya; Santa Mina, Daniel; Alibhai, Shabbir; Sabiston, Catherine; Oh, Paul; Campbell, Kristin; McCready, David; Auger, Leslie; Jones, Jennifer Michelle

    2017-08-24

    Although physical activity has been shown to contribute to long-term disease control and health in breast cancer survivors, a majority of breast cancer survivors do not meet physical activity guidelines. Past research has focused on promoting physical activity components for short-term breast cancer survivor benefits, but insufficient attention has been devoted to long-term outcomes and sustained exercise adherence. We are assessing a health coach intervention (iMOVE) that uses mobile technology to increase and sustain physical activity maintenance in initially inactive breast cancer survivors. This pilot randomized controlled trial (RCT) is an initial step in evaluating the iMOVE intervention and will inform development of a full-scale pragmatic RCT. We will enroll 107 physically inactive breast cancer survivors and randomly assign them to intervention or control groups at the University Health Network, a tertiary cancer care center in Toronto, Canada. Participants will be women (age 18 to 74 years) stratified by age (55 years and older/younger than 55 years) and adjuvant hormone therapy (AHT) exposure (AHT vs no AHT) following breast cancer treatment with no metastases or recurrence who report less than 60 minutes of preplanned physical activity per week. Both intervention and control groups receive the 12-week physical activity program with weekly group sessions and an individualized, progressive, home-based exercise program. The intervention group will additionally receive (1) 10 telephone-based health coaching sessions, (2) smartphone with data plan, if needed, (3) supportive health tracking software (Connected Wellness, NexJ Health Inc), and (4) a wearable step-counting device linked to a smartphone program. We will be assessing recruitment rates; acceptability reflected in selective, semistructured interviews; and enrollment, retention, and adherence quantitative intervention markers as pilot outcome measures. The primary clinical outcome will be directly

  15. Smartphone-Enabled Health Coaching Intervention (iMOVE) to Promote Long-Term Maintenance of Physical Activity in Breast Cancer Survivors: Protocol for a Feasibility Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ritvo, Paul; Obadia, Maya; Santa Mina, Daniel; Alibhai, Shabbir; Sabiston, Catherine; Oh, Paul; Campbell, Kristin; McCready, David; Auger, Leslie

    2017-01-01

    Background Although physical activity has been shown to contribute to long-term disease control and health in breast cancer survivors, a majority of breast cancer survivors do not meet physical activity guidelines. Past research has focused on promoting physical activity components for short-term breast cancer survivor benefits, but insufficient attention has been devoted to long-term outcomes and sustained exercise adherence. We are assessing a health coach intervention (iMOVE) that uses mobile technology to increase and sustain physical activity maintenance in initially inactive breast cancer survivors. Objective This pilot randomized controlled trial (RCT) is an initial step in evaluating the iMOVE intervention and will inform development of a full-scale pragmatic RCT. Methods We will enroll 107 physically inactive breast cancer survivors and randomly assign them to intervention or control groups at the University Health Network, a tertiary cancer care center in Toronto, Canada. Participants will be women (age 18 to 74 years) stratified by age (55 years and older/younger than 55 years) and adjuvant hormone therapy (AHT) exposure (AHT vs no AHT) following breast cancer treatment with no metastases or recurrence who report less than 60 minutes of preplanned physical activity per week. Both intervention and control groups receive the 12-week physical activity program with weekly group sessions and an individualized, progressive, home-based exercise program. The intervention group will additionally receive (1) 10 telephone-based health coaching sessions, (2) smartphone with data plan, if needed, (3) supportive health tracking software (Connected Wellness, NexJ Health Inc), and (4) a wearable step-counting device linked to a smartphone program. Results We will be assessing recruitment rates; acceptability reflected in selective, semistructured interviews; and enrollment, retention, and adherence quantitative intervention markers as pilot outcome measures. The primary

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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

  18. Maintenance in nuclear production power plants

    International Nuclear Information System (INIS)

    Lozano, J. M.

    2010-01-01

    This article highlights the importance and quality of maintenance in the complete phases of development, in a sector which has been often questioned by the public opinion, and that is always subject to national and international standards. The aim of maintenance is to guarantee the production of electric power in a reliable, safe, economic and friendly environmentally way, assuring a long-term production. (Author)

  19. Operations and maintenance - Safety challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Liv [Oljedirektoratet, Stavanger (Norway)

    1999-07-01

    With the unsteady oil prices and the possible consequences of the deregulation of the European energy markets one may expect further optimization of operating and maintenance costs. One may also expect extended use of various risk-based optimization techniques such as RCM (Reliability Centered Maintenance) and RBI (Risk Based Inspection). This presentation addresses the need for further research and development in this area. Maintenance work is necessary, but it can also create risk. The accident statistics show many examples of this. The Norwegian petroleum industry's ability to learn from previous incidents is questioned. Maintenance staff must be well trained and possess the necessary routines. Technical documentation must be updated. Uncertainties with respect to future oil and gas prices combined with the effect of the deregulation of the European energy markets will lead to even more focus on cost-effective operations and maintenance. The need for long-term research and development is stressed. Risk based techniques such as RCM and RBI are extensively used in the defence industry and the nuclear industry, but applying them to the petroleum industry requires improved risk models. Ageing effects such as corrosion, erosion, fatigue etc. can be expected, but the capability to predict, monitor and control them should be improved. At present, not even the most sophisticated risk analysis can model ageing effects. The importance of efficient use of information technology (IT) is stressed. Improving the product quality and safety often requires new technology and so research and development is important. Close cooperation with the industry is required.

  20. 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.

  1. 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.

  2. 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.

  3. Maintenance of nuclear power plants

    International Nuclear Information System (INIS)

    Lashgari, Farbod.

    1995-01-01

    This paper is about maintenance of nuclear power plants. In part one, the outage management of nuclear power plants has described. Meaning of the outage and objectives of outage management is given in introduction. The necessity of a long-term outage strategy is shown in chapter one. The main parts of an outage are as follows: Planning; Preparation; Execution, Each of them and also post-outage review have been explained in the followed chapters. Part two deals with technical details of main primary components of nuclear power plant type WWER. After an introduction about WWER reactors, in each chapter first the general and detailed description of main primary components has given and then their maintenance schedules and procedures. Chapter about reactor and steam generator is related to both types of WWER-440 and WWER-1000, but chapter about reactor coolant pump has specified to WWER-1000 to be more in details.(author)

  4. Mining Surveillance and Maintenance Dollars

    International Nuclear Information System (INIS)

    MARTINEZ, R.

    2000-01-01

    Accelerating site cleanup to reduce facility risks to the workers, the public and the environment during a time of declining federal budgets represents a significant technical and economic challenge to U.S. Department of Energy (DOE) Operations Offices and their respective contractors. A significant portion of a facility's recurring annual expenses are associated with routine, long-term surveillance and maintenance (S and M) activities. However, ongoing S and M activities do nothing to reduce risks and basically spend money that could be reallocated towards facility deactivation. This paper discusses the background around DOE efforts to reduce surveillance and maintenance costs, one approach used to perform cost reviews, lessons learned from field implementation and what assistance is available to assist DOE sites in performing these evaluations

  5. Maintenance Trades Guidelines

    Science.gov (United States)

    Weidner, Theodore J.

    2008-01-01

    In 2002, APPA published "Maintenance Staffing Guidelines for Educational Facilities," the first building maintenance trades staffing guideline designed to assist educational facilities professionals with their staffing needs. addresses how facilities professionals can determine the appropriate size and mix of their organization. Contents…

  6. Maintenance improvement program

    International Nuclear Information System (INIS)

    Derbonne, D.R.; Plunkett, T.F.; Simpson, J.R.

    1989-01-01

    During fuel cycle 1 at River Bend station, considerable effort was expended to reduce corrective maintenance work orders (MWOs) to <1,000. This was done by complementing the plant staff with costly contract personnel. Coming out of the first refueling outage, most contract personnel were released. The change in MWO backlog started a steady rise. It became readily apparent that to avoid costly contract staff time, a maintenance improvement program (MIP) was necessary. The MIP Was primarily directed at two areas: crew efficiency improvements and improved preplanned MWO packages. The overall effect of the MIP was to achieve significant productivity improvements with reduced operation and maintenance cost by providing frequent accountability to all levels of maintenance supervision. The MIP also produced a feeling of pride among the maintenance department employees that had not really existed before. This was the best benefit of all

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. 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.

  5. BmRobo2/3 is required for axon guidance 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

    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.

  6. 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....

  7. Application and issues of online maintenance for equipment of nuclear power plants

    International Nuclear Information System (INIS)

    Higasa, Hisakazu

    2011-01-01

    The maintenance systems for long-term safety and repair costs reduction of equipment of nuclear power plants are stated. Planned maintenance contained the breakdown maintenance (BM) and the preventive maintenance, which consists of the time based maintenance (MBM) and the condition based maintenance (CBM). Explained are the characteristics of equipments, maintenance methods, maintenance solutions and the self-evaluation maintenance power, damage mechanism and solutions, and monitoring tools and application. Stated are the maintenance system and application of monitoring technology, periodical maintenance, application of diagnosis, vibration monitoring techniques, decision of vibration monitoring, and application of monitoring techniques for improvement of maintenance. Illustrated are realization of planned maintenance by reorganization of maintenance, a trend of maintenance of equipments, table of classified maintenance systems, change of maintenance program, maintenance data and investigation of damage mechanism, examples of self-evaluation maintenance power, examples of analysis of damage of parts of equipments, evaluation of rotating machines by vibration method, examples of results of diagnosis of bearing of rotating machines, online maintenance system of Asahi Kasei Engineering Corporation, degradation pattern of pomp, estimation of lifetime by total vibration and vibration on acceleration, and improvement of equipments. (S.Y.)

  8. Maintenance Process Strategic Analysis

    Science.gov (United States)

    Jasiulewicz-Kaczmarek, M.; Stachowiak, A.

    2016-08-01

    The performance and competitiveness of manufacturing companies is dependent on the availability, reliability and productivity of their production facilities. Low productivity, downtime, and poor machine performance is often linked to inadequate plant maintenance, which in turn can lead to reduced production levels, increasing costs, lost market opportunities, and lower profits. These pressures have given firms worldwide the motivation to explore and embrace proactive maintenance strategies over the traditional reactive firefighting methods. The traditional view of maintenance has shifted into one of an overall view that encompasses Overall Equipment Efficiency, Stakeholders Management and Life Cycle assessment. From practical point of view it requires changes in approach to maintenance represented by managers and changes in actions performed within maintenance area. Managers have to understand that maintenance is not only about repairs and conservations of machines and devices, but also actions striving for more efficient resources management and care for safety and health of employees. The purpose of the work is to present strategic analysis based on SWOT analysis to identify the opportunities and strengths of maintenance process, to benefit from them as much as possible, as well as to identify weaknesses and threats, so that they could be eliminated or minimized.

  9. 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

  10. 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.

  11. Program integration of predictive maintenance with reliability centered maintenance

    International Nuclear Information System (INIS)

    Strong, D.K. Jr; Wray, D.M.

    1990-01-01

    This paper addresses improving the safety and reliability of power plants in a cost-effective manner by integrating the recently developed reliability centered maintenance techniques with the traditional predictive maintenance techniques of nuclear power plants. The topics of the paper include a description of reliability centered maintenance (RCM), enhancing RCM with predictive maintenance, predictive maintenance programs, condition monitoring techniques, performance test techniques, the mid-Atlantic Reliability Centered Maintenance Users Group, test guides and the benefits of shared guide development

  12. Space station orbit maintenance

    Science.gov (United States)

    Kaplan, D. I.; Jones, R. M.

    1983-01-01

    The orbit maintenance problem is examined for two low-earth-orbiting space station concepts - the large, manned Space Operations Center (SOC) and the smaller, unmanned Science and Applications Space Platform (SASP). Atmospheric drag forces are calculated, and circular orbit altitudes are selected to assure a 90 day decay period in the event of catastrophic propulsion system failure. Several thrusting strategies for orbit maintenance are discussed. Various chemical and electric propulsion systems for orbit maintenance are compared on the basis of propellant resupply requirements, power requirements, Shuttle launch costs, and technology readiness.

  13. Nuclear power plants maintenance

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    Nuclear power plants maintenance now appears as an important factor contributing to the competitivity of nuclea energy. The articles published in this issue describe the way maintenance has been organized in France and how it led to an actual industrial activity developing and providing products and services. An information note about Georges Besse uranium enrichment plant (Eurodif) recalls that maintenance has become a main data not only for power plants but for all nuclear industry installations. (The second part of this dossier will be published in the next issue: vol. 1 January-February 1989) [fr

  14. Mobile network maintenance (GSM)

    CERN Multimedia

    IT Department

    2009-01-01

    Maintenance work will be carried out on the CERN mobile network infrastructure (GSM) on the 23 and 24 July from 6 p.m. to 6 a.m. in order to replace discontinued equipment and to increase the bandwidth capacity of the GSM mobile network. All CERN GSM emitters (40 units) will be moved one by one to the new infrastructure during the maintenance. The call of a user connected to an emitter at the time of its maintenance will be cut off. However, the general overlapping of the GSM radio coverage should mean that users are able immediately to call again should their call be interrupted. IT/CS/CS

  15. Initiating statistical maintenance optimization

    International Nuclear Information System (INIS)

    Doyle, E. Kevin; Tuomi, Vesa; Rowley, Ian

    2007-01-01

    Since the 1980 s maintenance optimization has been centered around various formulations of Reliability Centered Maintenance (RCM). Several such optimization techniques have been implemented at the Bruce Nuclear Station. Further cost refinement of the Station preventive maintenance strategy includes evaluation of statistical optimization techniques. A review of successful pilot efforts in this direction is provided as well as initial work with graphical analysis. The present situation reguarding data sourcing, the principle impediment to use of stochastic methods in previous years, is discussed. The use of Crowe/AMSAA (Army Materials Systems Analysis Activity) plots is demonstrated from the point of view of justifying expenditures in optimization efforts. (author)

  16. 40 CFR 63.9600 - What are my operation and maintenance requirements?

    Science.gov (United States)

    2010-07-01

    ... instructions for routine and long-term maintenance. (2) Corrective action procedures for bag leak detection... 40 Protection of Environment 14 2010-07-01 2010-07-01 false What are my operation and maintenance... and Maintenance Requirements § 63.9600 What are my operation and maintenance requirements? (a) As...

  17. 40 CFR 63.7300 - What are my operation and maintenance requirements?

    Science.gov (United States)

    2010-07-01

    ...-term maintenance. (3) Corrective action for all baghouses applied to pushing emissions. In the event a... 40 Protection of Environment 13 2010-07-01 2010-07-01 false What are my operation and maintenance... Battery Stacks Operation and Maintenance Requirements § 63.7300 What are my operation and maintenance...

  18. 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.

  19. Plant Maintenance. The Licensee's Viewpoint

    Energy Technology Data Exchange (ETDEWEB)

    Ungi, T. [Heysham 2 Power Station, Nuclear Electric LTD (United Kingdom)

    1997-07-01

    Plant maintenance is a very complex process which requires considerable effort from both within the maintenance process and also many support activities. It is important that the plant maintenance policy is translated into a maintenance programme which will define all relevant aspects of the maintenance. An aspect of this maintenance programme will be a maintenance catalogue which will define the maintenance activities to be carried out and at what frequencies. This paper is aimed at discussing the maintenance philosophy and resulting maintenance catalogues currently adopted in Nuclear Electric Ltd, and in particular at Heysham 2 Power Station. It goes on to consider whether these maintenance catalogues contain the optimum maintenance and if not should they be changed. If change is required, the process by which this change will be brought about is also discussed. (author)

  20. 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.

  1. 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

  2. The axonal guidance receptor neogenin promotes acute inflammation.

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Laboratory simulation of maintenance activity

    International Nuclear Information System (INIS)

    Kantowitz, B.H.

    1988-01-01

    Laboratory research in highly controlled settings can augment, but not replace, studies in plant or training center locations. A laboratory simulation involves abstraction of the human information processing and social interactions required in prototypical maintenance tasks. A variety of independent variables can be studied quickly, efficiently, and at relatively low cost. Sources of human error can be identified in terms of models of human perception, cognition, action, attention, and social/organizational processes. This paper discusses research in progress at the Battelle Human Performance Laboratory. Both theoretical aspects and practical implications are considered. Directions for future human factors research are indicated

  5. Mobile robotics for CANDU maintenance

    International Nuclear Information System (INIS)

    Lipsett, M.G.; Rody, K.H.

    1996-01-01

    Although robotics researchers have been promising that robotics would soon be performing tasks in hazardous environments, the reality has yet to live up to the hype. The presently available crop of robots suitable for deployment in industrial situations are remotely operated, requiring skilled users. This talk describes cases where mobile robots have been used successfully in CANDU stations, discusses the difficulties in using mobile robots for reactor maintenance, and provides near-term goals for achievable improvements in performance and usefulness. (author) 5 refs., 2 ills

  6. 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

  7. Diffuse axonal injury at ultra-high field MRI.

    Directory of Open Access Journals (Sweden)

    Christoph Moenninghoff

    Full Text Available Diffuse axonal injury (DAI is a specific type of traumatic brain injury caused by shearing forces leading to widespread tearing of axons and small vessels. Traumatic microbleeds (TMBs are regarded as a radiological marker for DAI. This study aims to compare DAI-associated TMBs at 3 Tesla (T and 7 T susceptibility weighted imaging (SWI to evaluate possible diagnostic benefits of ultra-high field (UHF MRI.10 study participants (4 male, 6 female, age range 20-74 years with known DAI were included. All MR exams were performed with a 3 T MR system (Magnetom Skyra and a 7 T MR research system (Magnetom 7 T, Siemens AG, Healthcare Sector, Erlangen, Germany each in combination with a 32-channel-receive coil. The average time interval between trauma and imaging was 22 months. Location and count of TMBs were independently evaluated by two neuroradiologists on 3 T and 7 T SWI images with similar and additionally increased spatial resolution at 7 T. Inter- and intraobserver reliability was assessed using the interclass correlation coefficient (ICC. Count and diameter of TMB were evaluated with Wilcoxon signed rank test.Susceptibility weighted imaging revealed a total of 485 TMBs (range 1-190, median 25 at 3 T, 584 TMBs (plus 20%, range 1-262, median 30.5 at 7 T with similar spatial resolution, and 684 TMBs (plus 41%, range 1-288, median 39.5 at 7 T with 10-times higher spatial resolution. Hemorrhagic DAI appeared significantly larger at 7 T compared to 3 T (p = 0.005. Inter- and intraobserver correlation regarding the counted TMB was high and almost equal 3 T and 7 T.7 T SWI improves the depiction of small hemorrhagic DAI compared to 3 T and may be supplementary to lower field strengths for diagnostic in inconclusive or medicolegal cases.

  8. Axonal transport of proteoglycans to the goldfish optic tectum

    International Nuclear Information System (INIS)

    Ripellino, J.A.; Elam, J.S.

    1988-01-01

    The study addressed the question of whether 35 SO 4 labeled molecules that have been delivered to the goldfish optic nerve terminals by rapid axonal transport include soluble proteoglycans. For analysis, tectal homogenates were subfractionated into a soluble fraction (soluble after centrifugation at 105,000 g), a lysis fraction (soluble after treatment with hypotonic buffer followed by centrifugation at 105,000 g) and a final 105,000 g pellet fraction. The soluble fraction contained 25.7% of incorporated radioactivity and upon DEAE chromatography was resolved into a fraction of sulfated glycoproteins eluting at 0-0.32 M NaCl and containing 39.5% of total soluble label and a fraction eluting at 0.32-0.60 M NaCl containing 53.9% of soluble label. This latter fraction was included on columns of Sepharose CL-6B with or without 4 M guanidine and after pronase digestion was found to have 51% of its radioactivity contained in the glycosaminoglycans (GAGs) heparan sulfate and chondroitin (4 or 6) sulfate in the ratio of 70% to 30%. Mobility of both intact proteoglycans and constituent GAGs on Sepharose CL-6B indicated a size distribution that is smaller than has been observed for proteoglycans and GAGs from cultured neuronal cell lines. Similar analysis of lysis fraction, containing 11.5% of incorporated 35 SO 4 , showed a mixture of heparan sulfate and chondroitin sulfate containing proteoglycans, apparent free heparan sulfate and few, if any, sulfated glycoproteins. Overall, the results support the hypothesis that soluble proteoglycans are among the molecules axonally transported in the visual system

  9. Maintenance policy of the nuclear park

    International Nuclear Information System (INIS)

    Teisset, J.M.

    1995-01-01

    The nuclear installations maintenance policy of Electricite de France (EDF) follows three axes: first, controlling the aging of the production tool to warrant the safety and the functional reliability during the 40 years of installations service life. Second: optimizing the maintenance activities taking into account the safety goals, costs, security, dosimetry, duration of outages, and intervention conditions in the decisions. Third: developing a real partnership with contractors. EDF has decided to decentralize its maintenance operations towards each unit which is in charge of the organization of its own project. A better management of the contractor personnel has allowed to increase the performances of maintenance operations. The development of long-term agreements with contractors has permitted to reinforce the qualification, the responsibility and the efficiency of the personnel and to improve their means and tools. (J.S.). 1 photo

  10. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    Science.gov (United States)

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  11. Experts' meeting: Maintenance '83

    International Nuclear Information System (INIS)

    1983-01-01

    The brochure presents, in full wording, 20 papers read at the experts' meeting ''Maintenance '83'' in Wiesbaden. Most of the papers discuss reliability data (acquisition, evaluation, processing) of nearly all fields of industry. (RW) [de

  12. Excellence through maintenance mastering

    International Nuclear Information System (INIS)

    Lamarche, M.; Guillot, M.; Monier, M.

    1987-01-01

    To improve the overall availability factor of nuclear power plants you have to cut either the forced outage role and the planned outage time or you need to reduce simultaneously the failures and the efforts devoted to avoiding them. Among other results, this goal leads to a decrease in the number of real or anticipated problems. Electricite de France policy, in this matter, is to focus on decreasing the compoents' maintenance needs through a comprehensive modification program, targeted to eliminating the weak points as revealed by the operation. Thereby one may reach, for simple equipment, a nearly maintenance-free condition in which the only maintenance needed is surveillance, which provides assurance that everything is operating properly. A good example of this type of equipment is the family of static components, drums, and pipes whose corrective maintenance is almost nil when their initial condition is good

  13. Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

    Science.gov (United States)

    Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

    2017-03-01

    Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated

  14. Remote maintenance development

    International Nuclear Information System (INIS)

    Zook, C.R.

    1979-01-01

    The concept of remote maintenance as it pertains to nuclear fuel fabrication facilities is quite unique. The future may require completely remote facilities where maintenance will be performed by hybrid manipulators/robots. These units will be capable of being preprogrammed for automatic operation or manually operated with the operator becoming a part of the closed loop control system. These robots will mesh television, computer control, and direct force feedback manual control in a usable new concept of robotics

  15. Predictive maintenance primer

    International Nuclear Information System (INIS)

    Flude, J.W.; Nicholas, J.R.

    1991-04-01

    This Predictive Maintenance Primer provides utility plant personnel with a single-source reference to predictive maintenance analysis methods and technologies used successfully by utilities and other industries. It is intended to be a ready reference to personnel considering starting, expanding or improving a predictive maintenance program. This Primer includes a discussion of various analysis methods and how they overlap and interrelate. Additionally, eighteen predictive maintenance technologies are discussed in sufficient detail for the user to evaluate the potential of each technology for specific applications. This document is designed to allow inclusion of additional technologies in the future. To gather the information necessary to create this initial Primer the Nuclear Maintenance Applications Center (NMAC) collected experience data from eighteen utilities plus other industry and government sources. NMAC also contacted equipment manufacturers for information pertaining to equipment utilization, maintenance, and technical specifications. The Primer includes a discussion of six methods used by analysts to study predictive maintenance data. These are: trend analysis; pattern recognition; correlation; test against limits or ranges; relative comparison data; and statistical process analysis. Following the analysis methods discussions are detailed descriptions for eighteen technologies analysts have found useful for predictive maintenance programs at power plants and other industrial facilities. Each technology subchapter has a description of the operating principles involved in the technology, a listing of plant equipment where the technology can be applied, and a general description of the monitoring equipment. Additionally, these descriptions include a discussion of results obtained from actual equipment users and preferred analysis techniques to be used on data obtained from the technology. 5 refs., 30 figs

  16. Maintenance of scientific instruments

    International Nuclear Information System (INIS)

    Lucero, E.

    1986-01-01

    During the last years Colombia has increased the use of nuclear techniques, instruments and equipment in ambitious health programs, as well as in research centers, industry and education; this has resulted in numerous maintenance problems. As an alternative solution IAN has established a Central Maintenance Laboratory for nuclear instruments within an International Atomic Energy Agency program for eight Latin American and nine Asian Countries. Established strategies and some results are detailed in this writing

  17. Mechanical configuration and maintenance

    International Nuclear Information System (INIS)

    Brown, T.G.; Casini, G.; Churakov, G.F.

    1982-01-01

    The INTOR engineering design has been strongly influenced by considerations for assembly and maintenance. A maintenance philosophy was established at the outset of the conceptual design to insure that the tokamak configuration would be developed to accommodate maintenance requirements. The main features of the INTOR design are summarized in this paper with primary emphasis on the impact of maintenance considerations. The most apparent configuration design feature is the access provided for torus maintenance. Particular attention was given to the size and location of superconducting magnets and the location of vacuum boundaries. All of the poloidal field (PF) coils are placed outside of the bore of the toroidal field (TF) coils and located above and below an access opening between adjacent TF coils through which torus sectors are removed. A magnet structural configuration consisting of mechanically attached reinforcing members has been designed which facilitates the open access space for torus sector removal. For impurity control, a single null poloidal divertor was selected over a double null design in order to maintain sufficient access for pumping and maintenance of the collector. A double null divertor was found to severely limit access to the torus with the addition of divertor collectors and pumping at the top. For this reason, a single null concept was selected in spite of the more difficult design problems associated with the required asymmetric PF system and higher particle loadings

  18. 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.

  19. Principles of MONJU maintenance. Characteristic of MONJU maintenance and reflection of LWR maintenance experience to FBR

    International Nuclear Information System (INIS)

    Nakai, Satoru; Nishio, Ryuichi; Uchihashi, Masaya; Kaneko, Yoshihisa; Yamashita, Hironobu; Yamaguchi, Atsunori; Aoki, Takayuki

    2014-01-01

    A sodium cooled fast breeder reactor (FBR) has unique systems and components and different degradation mechanism from light water reactor (LWR) so that need to establish maintenance technology in accordance with its features. The examination of the FBR maintenance technology is carried out in the special committee for considering the maintenance for Monju established in the Japan Society of Maintenology (JSM). As a result of the study such as extraction of Monju maintenance feature, maintenance technology benchmark between Monju and LWR components and survey of LWR maintenance experience, it is clear that principles of maintenance are same as LWR, necessity of LWR maintenance experience reflection and points to be considered in Monju maintenance. The road map to establish a FBR maintenance technology in the technical aspect became clear and it is vital to acquire operation and maintenance experience of the plant to implement this road map, and to establish a fast reactor maintenance. (author)

  20. Glia-axon interactions and the regulation of the extracellular K+ in the peripheral nerve.

    Science.gov (United States)

    Jirounek, P; Robert, A; Kindler, E; Blazek, T

    1998-01-01

    Changes in membrane potential of both axons and Schwann cells were measured simultaneously during electrical activity and during the period of recovery in the rabbit vagus nerve by the use of the sucrose-gap apparatus. During low-frequency stimulation (0.5-1 Hz) the preparation developed a ouabain-sensitive hyperpolarization. This hyperpolarization increased when the inwardly rectifying K+ channels in Schwann cells were blocked with Ba2+, indicating that the hyperpolarization was generated by the electrogenic glial Na(+)-K+ pump. During trains at higher frequencies (15 Hz), the preparation depolarized, but after cessation of the stimulation it developed a posttetanic hyperpolarization (PTH). The PTH was also ouabain-sensitive and was strongly enhanced by Cs+ which is known to block the hyperpolarization-activated inward current (Ih) in axons but not in glial cells. These results show that the PTH reflects mainly the axonal electrogenic pump. Our results indicate that during activity the K+ released from the firing axons is removed from the extracellular space by Schwann cells and that after cessation of the stimulation the K+ surplus returns from Schwann cells back to axons. Both the glial and axonal K+ uptake is mediated by successive activation of the glial and axonal Na(+)-K+ pump. The nature of the signalling mechanisms that control the pumping rates of the respective pumps remain unknown.

  1. Characterization of axon formation in the embryonic stem cell-derived motoneuron.

    Science.gov (United States)

    Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

    2011-01-01

    The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

  2. Target-Derived Neurotrophins Coordinate Transcription and Transport of Bclw to Prevent Axonal Degeneration

    Science.gov (United States)

    Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.

    2013-01-01

    Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit. PMID:23516285

  3. A Communication Theoretical Modeling of Axonal Propagation in Hippocampal Pyramidal Neurons.

    Science.gov (United States)

    Ramezani, Hamideh; Akan, Ozgur B

    2017-06-01

    Understanding the fundamentals of communication among neurons, known as neuro-spike communication, leads to reach bio-inspired nanoscale communication paradigms. In this paper, we focus on a part of neuro-spike communication, known as axonal transmission, and propose a realistic model for it. The shape of the spike during axonal transmission varies according to previously applied stimulations to the neuron, and these variations affect the amount of information communicated between neurons. Hence, to reach an accurate model for neuro-spike communication, the memory of axon and its effect on the axonal transmission should be considered, which are not studied in the existing literature. In this paper, we extract the important factors on the memory of axon and define memory states based on these factors. We also describe the transition among these states and the properties of axonal transmission in each of them. Finally, we demonstrate that the proposed model can follow changes in the axonal functionality properly by simulating the proposed model and reporting the root mean square error between simulation results and experimental data.

  4. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

    Directory of Open Access Journals (Sweden)

    Coralie Fassier

    2013-01-01

    Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

  5. Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation.

    Science.gov (United States)

    Ward, Patricia J; Clanton, Scott L; English, Arthur W

    2018-02-01

    Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluate the precision and selectivity of system-specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light-sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons had regenerated successfully was greater following system-specific optical treatment, with no effect on the number of ChR2-negative neurons (whether motor or sensory neurons). We conclude that acute system-specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration-enhancing effect is likely cell autonomous. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

    Science.gov (United States)

    Hummel, T; Leifker, K; Klämbt, C

    2000-04-01

    In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

  7. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  8. Using the system maintenance datastore to characterize lifetime maintenance for PLiM

    International Nuclear Information System (INIS)

    Watson, P.; Dam, R.; Nickerson, J.

    2004-01-01

    A comprehensive Plant Life Management (PLiM) program involves evaluating a large amount of information. For any plant, there are numerous maintenance, surveillance and inspection programs for the important systems, structures and components. There is extensive industry experience on component failure modes, degradation mechanisms and recommended maintenance practices. This information forms the basis of the aging assessment work, through which improvements to these plant programs are identified. AECL has developed several tools to manage the quantities of information required in aging assessment studies, such as the SYSTMS (SYtematic approach for the development of STrategy for Maintenance and Surveillance) tool and the System Maintenance Datastore (SMD). The SMD has been developed to serve as a hub to a Systematic based Adaptive Maintenance Program (SAMP), by storing maintenance resource requirements for recommended maintenance tasks for use by the other processes in a SAMP. The SMD can be used to (a) quantify the savings or cost of optimising a maintenance program, (b) characterize and understand long term trends in condition-based maintenance due to component aging, (c) quantify the resource savings due to optimum timing of component replacement or general plant refurbishment, and (d) provide aging assessment cost information for input to plant asset evaluation. The SMD contains data for regular maintenance program tasks, plant condition assessment recommendations, and equipment refurbishment costs. A prototype SMD has been developed with data tables populated with information from operating CANDU stations. The SMD is now available to be used either with a SYSTMS evaluation or with a plant's database of maintenance tasks. (author)

  9. Building relationships for better maintenance.

    Science.gov (United States)

    Lee, Hackman Hon Yin; Scott, David

    2009-02-01

    Effective management of building maintenance is a vital ingredient in ensuring a high quality built environment for any building's occupiers. However, maintenance is not high on the list of priorities for most organisations. Communication between top management personnel looking at maintenance issues from a strategic standpoint and maintenance staff considering them at an operational level is often not as good as it should be. When planning maintenance activities maintenance personnel often draw too heavily on their technical experience and expertise without taking sufficient account of wider organisational objectives or consulting effectively with top management. Senior managers also regularly complain about lack of managerial input from maintenance departments. Such barriers contribute to communication difficulties between top management at a strategic level and maintenance personnel at an operational level. Identifying where the key differences lie in senior managers' and maintenance personnel's viewpoints on maintenance strategy can prove invaluable in achieving some convergence of opinions and optimising the efficiency of the overall building maintenance process.

  10. Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion.

    Science.gov (United States)

    Schaal, S M; Kitay, B M; Cho, K S; Lo, T P; Barakat, D J; Marcillo, A E; Sanchez, A R; Andrade, C M; Pearse, D D

    2007-01-01

    Schwann cell (SC) implantation alone has been shown to promote the growth of propriospinal and sensory axons, but not long-tract descending axons, after thoracic spinal cord injury (SCI). In the current study, we examined if an axotomy close to the cell body of origin (so as to enhance the intrinsic growth response) could permit supraspinal axons to grow onto SC grafts. Adult female Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3 KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral vector encoding enhanced green fluorescent protein (EGFP) were implanted within media into the injury epicenter; injury-only animals served as controls. Animals were tested weekly using the BBB score for 7 weeks postimplantation and received at end point tests for upper body strength: self-supported forelimb hanging, forearm grip force, and the incline plane. Following behavioral assessment, animals were anterogradely traced bilaterally from the reticular formation using BDA-Texas Red. Stereological quantification revealed a twofold increase in the numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in SC implanted animals, corroborating previous reports of their neuroprotective efficacy. Examination of labeled reticulospinal axon growth revealed that while rarely an axon was present within the lesion site of injury-only controls, numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This has not been observed following implantation of SCs alone into the injured thoracic spinal cord. Significant behavioral improvements over injury-only controls in upper limb strength, including an enhanced grip strength (a 296% increase) and an increased self-supported forelimb hanging, accompanied SC-mediated neuroprotection and reticulospinal axon growth. The current study further supports the neuroprotective efficacy of SC implants after SCI and demonstrates that SCs alone are capable of supporting

  11. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

    Directory of Open Access Journals (Sweden)

    Alexandre Dumoulin

    2018-04-01

    Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  12. Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.

    Science.gov (United States)

    Karten, Barbara; Vance, Dennis E; Campenot, Robert B; Vance, Jean E

    2003-02-07

    Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease.

  13. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

    Science.gov (United States)

    Dumoulin, Alexandre; Ter-Avetisyan, Gohar; Schmidt, Hannes; Rathjen, Fritz G

    2018-04-24

    Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  14. JRR-3 maintenance program utilizing accumulated maintenance data

    International Nuclear Information System (INIS)

    Izumo, Hironobu; Kato, Tomoaki; Kinase, Masami; Torii, Yoshiya; Murayama, Yoji

    2007-07-01

    JRR-3(Japan Research Reactor No.3) has been operated for more than 15 years after the modification, without significant troubles by carrying out maintenance such as the preventive maintenance (mainly time-based maintenance) for the safety-grade equipments and the breakdown maintenance for the non-safety-grade equipments. Unscheduled shutdowns causes by aged non-safety-grade equipments have been increasing, and the resources such as budgets have been decreasing year by year. In this situation, JRR-3 maintenance program was reviewed about safety, reliability and economic efficiency. This report offers the policy of the maintenance review and the future direction of maintenance programs. (author)

  15. RCM [reliability-centered maintenance] at Ginna: Preventive maintenance program optimization at year 20

    International Nuclear Information System (INIS)

    Edgar, E.C.

    1989-01-01

    The reliability-centered maintenance (RCM) program at Rochester Gas ampersand Electric Company's Ginna station is entering its second year. Of the 20 systems originally selected for evaluation, 10 are in various stages of completion, and recommendations resulting from the earliest systems studied are now being implemented. As expected, few major discoveries have been made in terms of preventive maintenance program failings or excesses. The performance of the now 20-yr-old plant has been excellent in recent years, and objectives focus more on ensuring continued high standards of safety, reliability, and economy than on maintenance program cost reduction

  16. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina

    2006-01-01

    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  17. Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Chan, J.H.M.; Tsui, E.Y.K.; Yuen, M.K.; Peh, W.C.G.; Fong, D.; Fok, K.F.; Leung, K.M.; Fung, K.K.L.

    2003-01-01

    Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury. (orig.)

  18. The Modern Approach to Industrial Maintenance Management

    Directory of Open Access Journals (Sweden)

    Vasile DEAC

    2010-01-01

    Full Text Available The maintenance activity isn’t a purpose in itself, it’s a necessity of which "the production suffers" and the financial agent “considers too expensive”. It often exists a conflict between the production units and the maintenance department, not only for a short term, but, sometimes, for a long term, imposing a rigorous definition of each person’s responsibilities. Considering the mutations in the industrial equipments’ technical complexity and the accidental failures’ catastrophic consequences from the economic and/or social point of view, it should be assigned a new dimension to the maintenance activity. One of the imperatives imposed to this action is represented by modern means of informing through the maintenance’s operational computerization.

  19. Ontology Maintenance using Textual Analysis

    Directory of Open Access Journals (Sweden)

    Yassine Gargouri

    2003-10-01

    Full Text Available Ontologies are continuously confronted to evolution problem. Due to the complexity of the changes to be made, a maintenance process, at least a semi-automatic one, is more and more necessary to facilitate this task and to ensure its reliability. In this paper, we propose a maintenance ontology model for a domain, whose originality is to be language independent and based on a sequence of text processing in order to extract highly related terms from corpus. Initially, we deploy the document classification technique using GRAMEXCO to generate classes of texts segments having a similar information type and identify their shared lexicon, agreed as highly related to a unique topic. This technique allows a first general and robust exploration of the corpus. Further, we apply the Latent Semantic Indexing method to extract from this shared lexicon, the most associated terms that has to be seriously considered by an expert to eventually confirm their relevance and thus updating the current ontology. Finally, we show how the complementarity between these two techniques, based on cognitive foundation, constitutes a powerful refinement process.

  20. Using systematic aging assessments to improve effectiveness of plant maintenance programs

    International Nuclear Information System (INIS)

    Watson, P.; Yang, J.X.; Dam, R.F.; Nickerson, J.H.

    2003-01-01

    Nuclear plant equipment aging assessment studies provided by AECL include life assessments, condition assessments or systematic assessments of maintenance. AECL has developed several tools to apply the results of aging assessment studies to improve the effectiveness of actual plant maintenance programs. The Systematic Assessment of Maintenance and the SYSTMS tool generate maintenance tasks for a system. The System Maintenance Datastore tool assesses the maintenance resources on a system basis, and can thus quantify the savings realized by optimizing the maintenance program. Long term trends in condition-based maintenance due to component aging can be predicted, and resource savings due to optimum timing of component replacement or general plant refurbishment can be quantified. The System based Adaptive Maintenance Process ensures the maintenance program is continually updated to reflect the latest plant equipment condition and maintenance strategy information. (author)

  1. Instrumentalization of eating improves weight loss maintenance in obesity

    DEFF Research Database (Denmark)

    Christensen, Bodil Just; Iepsen, Eva Pers Winning; Lundgren, Julie Rehné

    2017-01-01

    Aim: The purpose of this study was to identify psychosocial determinants for maintaining weight loss. Methods: 42 obese individuals who achieved a 12% weight loss before entering a 52-week weight maintenance program were interviewed qualitatively. Psychosocial factors related to weight loss...... weight loss maintenance was associated with an interplay between behavioral, affective and contextual changes. ‘Instrumentalization of eating behavior' seems to be an important element in long-term weight maintenance....

  2. Building Maintenance, Management, and Budgeting.

    Science.gov (United States)

    Pawsey, M. R.

    1982-01-01

    Australian methods and formulas for funding building maintenance and management are outlined and found to be haphazard. Discussed are: ultimate costs of deferred maintenance, major plant replacements, life cycle costing, types of maintenance programs (including full preventive maintenance), use of computer programs for planning, and organization…

  3. Measuring the performance of maintenance service outsourcing.

    Science.gov (United States)

    Cruz, Antonio Miguel; Rincon, Adriana Maria Rios; Haugan, Gregory L

    2013-01-01

    The aims of this paper are (1) to identify the characteristics of maintenance service providers that directly impact maintenance service quality, using 18 independent covariables; (2) to quantify the change in risk these covariables present to service quality, measured in terms of equipment turnaround time (TAT). A survey was applied to every maintenance service provider (n = 19) for characterization purposes. The equipment inventory was characterized, and the TAT variable recorded and monitored for every work order of each service provider (N = 1,025). Finally, the research team conducted a statistical analysis to accomplish the research objectives. The results of this study offer strong empirical evidence that the most influential variables affecting the quality of maintenance service performance are the following: type of maintenance, availability of spare parts in the country, user training, technological complexity of the equipment, distance between the company and the hospital, and the number of maintenance visits performed by the company. The strength of the results obtained by the Cox model built are supported by the measure of the Rp,e(2) = 0.57 with a value of Rp,e= 0.75. Thus, the model explained 57% of the variation in equipment TAT, with moderate high positive correlation between the dependent variable (TAT) and independent variables.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. The MERC maintenance system

    International Nuclear Information System (INIS)

    Izquierdo, J.J.; Chauvire, P.; Plessis, L.

    1991-01-01

    Maintenance in the modern commercial reprocessing plants is a subject of the highest priority in order to guarantee availability for the whole life of the plant. The design concept of the UP3 reprocessing plant at La Hague identified several categories of equipment according to their maintenance design principles. Among them, Standard Process Equipment such as pumps, valves, ejectors and filters which need periodic maintenance. These equipment items are designed in removable modular form to avoid the need to disconnect piping. Removal is performed under shielding and without breach of containment through the use of a transfer cask that is connected to the cell containing the equipment to be removed. This transfer cask is called MERC (Mobile Equipment Replacement Cask). Containment is preserved by an air-tight system consisting of coupled doors, with a special connecting gasket. This system can remove and replace failed equipment, without spreading contamination to work areas. (author)

  8. Reliability Centered Maintenance - Methodologies

    Science.gov (United States)

    Kammerer, Catherine C.

    2009-01-01

    Journal article about Reliability Centered Maintenance (RCM) methodologies used by United Space Alliance, LLC (USA) in support of the Space Shuttle Program at Kennedy Space Center. The USA Reliability Centered Maintenance program differs from traditional RCM programs because various methodologies are utilized to take advantage of their respective strengths for each application. Based on operational experience, USA has customized the traditional RCM methodology into a streamlined lean logic path and has implemented the use of statistical tools to drive the process. USA RCM has integrated many of the L6S tools into both RCM methodologies. The tools utilized in the Measure, Analyze, and Improve phases of a Lean Six Sigma project lend themselves to application in the RCM process. All USA RCM methodologies meet the requirements defined in SAE JA 1011, Evaluation Criteria for Reliability-Centered Maintenance (RCM) Processes. The proposed article explores these methodologies.

  9. Computer assisted procedure maintenance

    International Nuclear Information System (INIS)

    Bisio, R.; Hulsund, J. E.; Nilsen, S.

    2004-04-01

    The maintenance of operating procedures in a NPP is a tedious and complicated task. Through the whole life cycle of the procedures they will be dynamic, 'living' documents. Several aspects of the procedure must be considered in a revision process. Pertinent details and attributes of the procedure must be checked. An organizational structure must be created and responsibilities allotted for drafting, revising, reviewing and publishing procedures. Available powerful computer technology provides solutions within document management and computerisation of procedures. These solutions can also support the maintenance of procedures. Not all parts of the procedure life cycle are equally amenable to computerized support. This report looks at the procedure life cycle in todays NPPs and discusses the possibilities associated with introduction of computer technology to assist the maintenance of procedures. (Author)

  10. Lineage Selection and the Maintenance of Sex

    Science.gov (United States)

    de Vienne, Damien M.; Giraud, Tatiana; Gouyon, Pierre-Henri

    2013-01-01

    Sex predominates in eukaryotes, despite its short-term disadvantage when compared to asexuality. Myriad models have suggested that short-term advantages of sex may be sufficient to counterbalance its twofold costs. However, despite decades of experimental work seeking such evidence, no evolutionary mechanism has yet achieved broad recognition as explanation for the maintenance of sex. We explore here, through lineage-selection models, the conditions favouring the maintenance of sex. In the first model, we allowed the rate of transition to asexuality to evolve, to determine whether lineage selection favoured species with the strongest constraints preventing the loss of sex. In the second model, we simulated more explicitly the mechanisms underlying the higher extinction rates of asexual lineages than of their sexual counterparts. We linked extinction rates to the ecological and/or genetic features of lineages, thereby providing a formalisation of the only figure included in Darwin's “The origin of species”. Our results reinforce the view that the long-term advantages of sex and lineage selection may provide the most satisfactory explanations for the maintenance of sex in eukaryotes, which is still poorly recognized, and provide figures and a simulation website for training and educational purposes. Short-term benefits may play a role, but it is also essential to take into account the selection of lineages for a thorough understanding of the maintenance of sex. PMID:23825582

  11. Using Maintenance Rehearsal to Explore Recognition Memory

    Science.gov (United States)

    Humphreys, Michael S.; Maguire, Angela M.; McFarlane, Kimberley A.; Burt, Jennifer S.; Bolland, Scott W.; Murray, Krista L.; Dunn, Ryan

    2010-01-01

    We examined associative and item recognition using the maintenance rehearsal paradigm. Our intent was to control for mnemonic strategies; to produce a low, graded level of learning; and to provide evidence of the role of attention in long-term memory. An advantage for low-frequency words emerged in both associative and item recognition at very low…

  12. Maintenance</