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Sample records for snb motoneuron development

  1. Development and regulation of response properties in spinal cord motoneurons

    DEFF Research Database (Denmark)

    Perrier, J F; Hounsgaard, J

    2000-01-01

    The intrinsic response properties of spinal motoneurons determine how converging premotor neuronal input is translated into the final motor command transmitted to muscles. From the patchy data available it seems that these properties and their underlying currents are highly conserved in terrestrial...... vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties...... mediated by L-type Ca2+ channels. This mature phenotype is reached gradually during development through phases in which A-type potassium channels and T-type calcium channels are transiently expressed. The intrinsic response properties of mature spinal motoneurons are subject to short-term adjustments via...

  2. HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

    Science.gov (United States)

    Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

    2017-11-29

    Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43 , is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding

  3. Development and regulation of response properties in spinal cord motoneurons

    DEFF Research Database (Denmark)

    Perrier, J F; Hounsgaard, J

    2000-01-01

    vertebrates in terms of both phylogeny and ontogeny. Spinal motoneurons in adults are remarkably similar in many respects ranging from the resting membrane potential to pacemaker properties. Apart from the axolotls, spinal motoneurons from all species investigated have latent intrinsic response properties...

  4. Developing electrical properties of postnatal mouse lumbar motoneurons

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    Jacques eDurand

    2015-09-01

    Full Text Available We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest input resistance and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained. The delayed onset firing type has the highest rheobase and the fastest action potential whereas the transient firing group has the lowest rheobase and the less mature action potential. We found 32% and 10 % of motoneurons with a transient firing at P3-P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3-P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis are the most preponderant at P6-P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis emerge at P8-P9. The emergence of type 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week

  5. Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

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    Julien Ackermann

    2011-04-01

    Full Text Available The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.

  6. Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

    Science.gov (United States)

    Nakanishi, S T; Whelan, P J

    2010-05-01

    During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

  7. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization......, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions...... and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K(+) current, cationic inward...

  8. Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

    2013-01-01

    The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) perform......, essential to keep the morbidity and economic costs low, while keeping the quality of the procedure high....

  9. Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of Survival motor neuron 1

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    Bateman Andrew

    2010-10-01

    Full Text Available Abstract Background Progranulin (PGRN encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD. This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43 molecular signature (FTLD-U. The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1. This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions Expression of

  10. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter

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    Eisen Judith S

    2008-07-01

    Full Text Available Abstract Background Expression of correct neurotransmitters is crucial for normal nervous system function. How neurotransmitter expression is regulated is not well-understood; however, previous studies provide evidence that both environmental signals and intrinsic differentiation programs are involved. One environmental signal known to regulate neurotransmitter expression in vertebrate motoneurons is Hepatocyte growth factor, which acts through the Met receptor tyrosine kinase and also affects other aspects of motoneuron differentiation, including axonal extension. Here we test the role of Met in development of motoneurons in embryonic zebrafish. Results We found that met is expressed in all early developing, individually identified primary motoneurons and in at least some later developing secondary motoneurons. We used morpholino antisense oligonucleotides to knock down Met function and found that Met has distinct roles in primary and secondary motoneurons. Most secondary motoneurons were absent from met morpholino-injected embryos, suggesting that Met is required for their formation. We used chemical inhibitors to test several downstream pathways activated by Met and found that secondary motoneuron development may depend on the p38 and/or Akt pathways. In contrast, primary motoneurons were present in met morpholino-injected embryos. However, a significant fraction of them had truncated axons. Surprisingly, some CaPs in met morpholino antisense oligonucleotide (MO-injected embryos developed a hybrid morphology in which they had both a peripheral axon innervating muscle and an interneuron-like axon within the spinal cord. In addition, in met MO-injected embryos primary motoneurons co-expressed mRNA encoding Choline acetyltransferase, the synthetic enzyme for their normal neurotransmitter, acetylcholine, and mRNA encoding Glutamate decarboxylase 1, the synthetic enzyme for GABA, a neurotransmitter never normally found in these motoneurons, but

  11. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  12. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    International Nuclear Information System (INIS)

    Zhang, Yun; Wang, Jing; Chen, Guian; Fan, Dongsheng; Deng, Min

    2011-01-01

    Research highlights: → Nicotinamide inhibit Sirt1. → MASH1 and Ngn2 activation. → Increase the expression of HB9. → Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and βIII-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 μM) or inhibitor nicotinamide (100 μM). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  13. Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

    Science.gov (United States)

    Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

    2017-06-01

    Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

  14. The effects of model composition design choices on high-fidelity simulations of motoneuron recruitment and firing behaviors

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    Allen, John M.; Elbasiouny, Sherif M.

    2018-06-01

    Objective. Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results. Approach. We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations. The practices examined were the use of: (1) generic cell models to simulate different motoneuron types, (2) discrete property ranges for different motoneuron types, and (3) biological homogeneity of cell properties within motoneuron types. Main results. Our results show that each of these practices accentuates conditions of motoneuron recruitment based on the size principle, and minimizes conditions of mixed and reversed recruitment orders, which have been observed in animal and human recordings. Specifically, strict motoneuron orderly size recruitment occurs, but in a compressed range, after which mixed and reverse motoneuron recruitment occurs due to the overlap in electrical properties of different motoneuron types. Additionally, these practices underestimate the motoneuron firing rates and force data simulated by existing models. Significance. Our results indicate that current modeling practices increase conditions of motoneuron recruitment based on the size principle, and decrease conditions of mixed and reversed recruitment order, which, in turn, impacts the predictions made by existing models on motoneuron recruitment, firing rate, and force. Additionally, mixed and reverse motoneuron recruitment generated higher muscle force than orderly size motoneuron recruitment in these simulations and represents one potential scheme to increase muscle efficiency. The examined model

  15. Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics

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    Seredick Steve D

    2012-11-01

    Full Text Available Abstract Background Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons. Results Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology. Conclusions Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.

  16. Hybrid transport and diffusion modeling using electron thermal transport Monte Carlo SNB in DRACO

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    Chenhall, Jeffrey; Moses, Gregory

    2017-10-01

    The iSNB (implicit Schurtz Nicolai Busquet) multigroup diffusion electron thermal transport method is adapted into an Electron Thermal Transport Monte Carlo (ETTMC) transport method to better model angular and long mean free path non-local effects. Previously, the ETTMC model had been implemented in the 2D DRACO multiphysics code and found to produce consistent results with the iSNB method. Current work is focused on a hybridization of the computationally slower but higher fidelity ETTMC transport method with the computationally faster iSNB diffusion method in order to maximize computational efficiency. Furthermore, effects on the energy distribution of the heat flux divergence are studied. Work to date on the hybrid method will be presented. This work was supported by Sandia National Laboratories and the Univ. of Rochester Laboratory for Laser Energetics.

  17. Where Would the EUR/CHF Exchange Rate be Without the SNB's Minimum Exchange Rate Policy?

    DEFF Research Database (Denmark)

    Hanke, Michael; Poulsen, Rolf; Weissensteiner, Alex

    2015-01-01

    Since its announcement made on September 6, 2011, the Swiss National Bank (SNB) has been pursuing the goal of a minimum EUR/CHF exchange rate of 1.20, promising to intervene on currency markets to prevent the exchange rate from falling below this level.We use a compound option pricing approach...

  18. ICF target 2D modeling using Monte Carlo SNB electron thermal transport in DRACO

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    Chenhall, Jeffrey; Cao, Duc; Moses, Gregory

    2016-10-01

    The iSNB (implicit Schurtz Nicolai Busquet multigroup diffusion electron thermal transport method is adapted into a Monte Carlo (MC) transport method to better model angular and long mean free path non-local effects. The MC model was first implemented in the 1D LILAC code to verify consistency with the iSNB model. Implementation of the MC SNB model in the 2D DRACO code enables higher fidelity non-local thermal transport modeling in 2D implosions such as polar drive experiments on NIF. The final step is to optimize the MC model by hybridizing it with a MC version of the iSNB diffusion method. The hybrid method will combine the efficiency of a diffusion method in intermediate mean free path regions with the accuracy of a transport method in long mean free path regions allowing for improved computational efficiency while maintaining accuracy. Work to date on the method will be presented. This work was supported by Sandia National Laboratories and the Univ. of Rochester Laboratory for Laser Energetics.

  19. Identified ankle extensor and flexor motoneurons display different firing profiles in the neonatal rat

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    Cotel, Florence; Antri, Myriam; Barthe, Jean-Yves

    2009-01-01

    population of flexor motoneurons solely exhibited the type II profile, characterized by a frequency-current (F-I) relationship with a clockwise hysteresis. In contrast, in addition to this type II profile, the other three profiles of repetitive firing (type I, III and IV) were observed in extensor...... postnatal development, a significant part of the population of extensor motoneurons, but not flexors, are able to produce self-sustained discharges known to involve the activation of persistent inward currents....

  20. 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.

  1. 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.

  2. Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation.

    Science.gov (United States)

    Usui, Noriyoshi; Watanabe, Keisuke; Ono, Katsuhiko; Tomita, Koichi; Tamamaki, Nobuaki; Ikenaka, Kazuhiro; Takebayashi, Hirohide

    2012-03-01

    Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

  3. Design process for applying the nonlocal thermal transport iSNB model to a Polar-Drive ICF simulation

    Science.gov (United States)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques; Collins, Timothy

    2014-10-01

    A design process is presented for the nonlocal thermal transport iSNB (implicit Schurtz, Nicolai, and Busquet) model to provide reliable nonlocal thermal transport in polar-drive ICF simulations. Results from the iSNB model are known to be sensitive to changes in the SNB ``mean free path'' formula, and the latter's original form required modification to obtain realistic preheat levels. In the presented design process, SNB mean free paths are first modified until the model can match temperatures from Goncharov's thermal transport model in 1D temperature relaxation simulations. Afterwards the same mean free paths are tested in a 1D polar-drive surrogate simulation to match adiabats from Goncharov's model. After passing the two previous steps, the model can then be run in a full 2D polar-drive simulation. This research is supported by the University of Rochester Laboratory for Laser Energetics.

  4. Preparation of highly infective Leishmania promastigotes by cultivation on SNB-9 biphasic medium

    Czech Academy of Sciences Publication Activity Database

    Grekov, Igor; Svobodová, M.; Nohýnková, E.; Lipoldová, Marie

    2011-01-01

    Roč. 87, č. 3 (2011), s. 273-277 ISSN 0167-7012 R&D Projects: GA MŠk(CZ) LC06009; GA ČR GA310/08/1697 Institutional research plan: CEZ:AV0Z50520514 Keywords : Leishmania * SNB-9 * biphasic culture medium * parasite infectivity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.086, year: 2011

  5. Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

    International Nuclear Information System (INIS)

    Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

    2009-01-01

    Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.

  6. The 25 MW Super Near Boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces Base

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, H.W.; Paquette, S.; Boucher, P.J. [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-12-15

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95 {sup o} C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100 {sup o} C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor's core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  7. The 25 MW super near boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces base

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, H.W.; Paquette, S.; Boucher, P.J., E-mail: bonin-h@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-07-01

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95{sup o}C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100{sup o}C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor’s core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  8. The 25 MW super near boiling nuclear reactor (SNB25) for supplying co-generation energy to an Arctic Canadian Forces base

    International Nuclear Information System (INIS)

    Bonin, H.W.; Paquette, S.; Boucher, P.J.

    2014-01-01

    Nuclear energy represents a better alternative for the supply of heat and electricity to the Canadian Forces bases in the Arctic (CFS Alert and CFB Nanisivik). In this context, the Super Near-Boiling 25-MWth reactor (SNB25) has been designed as a small unpressurized LWR that displays inherent safety and is intended to run in automatic mode. The reactor employs TRISO fuel particles (20% enrichment) in zirconium-sheathed fuel rods, and is light water cooled and moderated with a normal output temperature is 95 o C at atmospheric pressure. Control is via 133 control rods and six adjustable radial reflector plates. The design work used the probabilistic simulation code MCNP 5 and the deterministic code WIMS-AECL Version 3.1, permitting a code-to-code comparison of the results. Inherent safety was confirmed and is mostly due to the large negative void reactivity coefficient of -5.17 mk per % void. A kinetic model that includes thermal-hydraulics calculations was developed to determine the reactor's behaviour in transient states, and the results further confirm the inherent safety. Large power excursions temperatures that could compromise structural integrity cannot be produced. If the coolant/moderator temperature exceeds the saturation temperature of 100 o C, the coolant begins to boil and the large negative void coefficient causes the reactor to become subcritical in 0.84 seconds. The SNB25 reactor’s core life exceeds 12 years between refuellings. A group of 4 SNB25 reactors meets both the heating and electricity requirements of a base like CFB Nanisivik via a hot water network and through an organic Rankine cycle conversion plant. (author)

  9. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

    DEFF Research Database (Denmark)

    Enríquez Denton, M; Wienecke, Jacob; Zhang, Mengliang

    2012-01-01

    time, the likely amplifying processes at work in respiratory motoneurones. In phrenic motoneurones, which control the most important respiratory muscle, the diaphragm, we found that the mechanism most favoured by investigations in other motoneurones, the activation of persistent inward currents via...

  10. Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes

    Directory of Open Access Journals (Sweden)

    Kyoung-in Cho

    2017-05-01

    Full Text Available The pathogenic drivers of sporadic and familial motor neuron disease (MND, such amyotrophic lateral sclerosis (ALS, are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of Ranbp2 in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and

  11. Mechanochemical synthesis of 1-stanna-2,3-dicarba-closo-dodecaborane SnB9C2H11

    International Nuclear Information System (INIS)

    Volkov, V.V.; Myakishev, K.G.; Solomatina, L.Ya.

    1990-01-01

    The possibility of synthesis of 1-stanna-2, 3-dicarba-dodecaborane (2), SnB 9 C 2 H 11 by the mechanical activation of solid mixtures of CsB 9 C 2 H 12 , NaH and SnCl 2 has been studied. These solid phase mechano-chemical reactions were performed in vacuum vibration mills without any liquid solvents at room temperature. Crystalline SnB 9 C 2 H 11 was produced by sublimation in vacuum at 140 deg C. Yioeld of the sublimate was 3-6%

  12. Gain control mechanisms in spinal motoneurons

    Directory of Open Access Journals (Sweden)

    Michael David Johnson

    2014-07-01

    Full Text Available Motoneurons provide the only conduit for motor commands to reach muscles. For many years, motoneurons were in fact considered to be little more than passive wires. Systematic studies in the past 25 years however have clearly demonstrated that the intrinsic electrical properties of motoneurons are under strong neuromodulatory control via multiple sources. The discovery of potent neuromodulation from the brainstem and its ability to change the gain of motoneurons shows that the passive view of the motor output stage is no longer tenable. A mechanism for gain control at the motor output stage makes good functional sense considering our capability of generating an enormous range of forces, from very delicate (e.g. putting in a contact lens to highly forceful (emergency reactions. Just as sensory systems need gain control to deal with a wide dynamic range of inputs, so to might motor output need gain control to deal with the wide dynamic range of the normal movement repertoire. Two problems emerge from the potential use of the brainstem monoaminergic projection to motoneurons for gain control. First, the projection is highly diffuse anatomically, so that independent control of the gains of different motor pools is not feasible. In fact, the system is so diffuse that gain for all the motor pools in a limb likely increases in concert. Second, if there is a system that increases gain, probably a system to reduce gain is also needed. In this review, we summarize recent studies that show local inhibitory circuits within the spinal cord, especially reciprocal and recurrent inhibition, have the potential to solve both of these problems as well as constitute another source of gain modulation.

  13. Implantable optical-electrode device for stimulation of spinal motoneurons

    International Nuclear Information System (INIS)

    Matveev, M V; Erofeev, A I; Zakharova, O A; Vlasova, O L; Pyatyshev, E N; Kazakin, A N

    2016-01-01

    Recent years, optogenetic method of scientific research has proved its effectiveness in the nerve cell stimulation tasks. In our article we demonstrate an implanted device for the spinal optogenetic motoneurons activation. This work is carried out in the Laboratory of Molecular Neurodegeneration of the Peter the Great St. Petersburg Polytechnic University, together with Nano and Microsystem Technology Laboratory. The work of the developed device is based on the principle of combining fiber optic light stimulation of genetically modified cells with the microelectrode multichannel recording of neurons biopotentials. The paper presents a part of the electrode implant manufacturing technique, combined with the optical waveguide of ThorLabs (USA). (paper)

  14. GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving Drosophila.

    Science.gov (United States)

    Gowda, Swetha B M; Paranjpe, Pushkar D; Reddy, O Venkateswara; Thiagarajan, Devasena; Palliyil, Sudhir; Reichert, Heinrich; VijayRaghavan, K

    2018-02-27

    Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available in Drosophila to investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed an algorithm for automated analysis of leg motion to characterize the walking parameters of wild-type flies from high-speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walking Drosophila Our findings indicate that targeted down-regulation of the GABA A receptor Rdl (Resistance to Dieldrin) in leg motoneurons results in a dramatic reduction of walking speed and step length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together, these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving Drosophila . Copyright © 2018 the Author(s). Published by PNAS.

  15. Exploring the limits of the ``SNB'' multi-group diffusion nonlocal model

    Science.gov (United States)

    Brodrick, Jonathan; Ridgers, Christopher; Kingham, Robert

    2014-10-01

    A correct treatment of nonlocal transport in the presence of steep temperature gradients found in laser and inertial fusion plasmas has long been highly desirable over the use of an ad-hoc flux limiter. Therefore, an implementation of the ``SNB'' nonlocal model (G P Schurtz, P D Nicolaï & M Busquet, Phys. Plas. 7, 4238 (2000)) has been benchmarked against a fully-implicit kinetic code: IMPACT. A variety of scenarios, including relaxation of temperature sinusoids and Gaussians in addition to continuous laser heating have been investigated. Results highlight the effect of neglecting electron inertia (∂f1/∂ t) as well as question the feasibility of a nonlocal model that does not continuously track the evolution of the distribution function. Deviations from the Spitzer electric fields used in the model across steep gradients are also investigated. Regimes of validity for such a model are identified and discussed, and possible improvements to the model are suggested.

  16. 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.

  17. Functional expression of T-type Ca2+ channels in spinal motoneurons of the adult turtle.

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    Full Text Available Voltage-gated Ca2+ (CaV channels are transmembrane proteins comprising three subfamilies named CaV1, CaV2 and CaV3. The CaV3 channel subfamily groups the low-voltage activated Ca2+ channels (LVA or T-type a significant role in regulating neuronal excitability. CaV3 channel activity may lead to the generation of complex patterns of action potential firing such as the postinhibitory rebound (PIR. In the adult spinal cord, these channels have been found in dorsal horn interneurons where they control physiological events near the resting potential and participate in determining excitability. In motoneurons, CaV3 channels have been found during development, but their functional expression has not yet been reported in adult animals. Here, we show evidence for the presence of CaV3 channel-mediated PIR in motoneurons of the adult turtle spinal cord. Our results indicate that Ni2+ and NNC55-0396, two antagonists of CaV3 channel activity, inhibited PIR in the adult turtle spinal cord. Molecular biology and biochemical assays revealed the expression of the CaV3.1 channel isotype and its localization in motoneurons. Together, these results provide evidence for the expression of CaV3.1 channels in the spinal cord of adult animals and show also that these channels may contribute to determine the excitability of motoneurons.

  18. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  19. Modeling motoneuron firing properties: dependency on size and calcium dynamics

    NARCIS (Netherlands)

    van der Heyden, M. J.; Hilgevoord, A. A.; Bour, L. J.; Ongerboer de Visser, B. W.

    1994-01-01

    The origin of functional differences between motoneurons of varying size was investigated by employing a one-compartmental motoneuron model containing a slow K+ conductance dependent on the intracellular calcium concentration. The size of the cell was included as an explicit parameter. Simulations

  20. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

    Science.gov (United States)

    Enríquez Denton, M; Wienecke, J; Zhang, M; Hultborn, H; Kirkwood, P A

    2012-01-01

    The role of persistent inward currents (PICs) in cat respiratory motoneurones (phrenic inspiratory and thoracic expiratory) was investigated by studying the voltage-dependent amplification of central respiratory drive potentials (CRDPs), recorded intracellularly, with action potentials blocked with the local anaesthetic derivative, QX-314. Decerebrate unanaesthetized or barbiturate-anaesthetized preparations were used. In expiratory motoneurones, plateau potentials were observed in the decerebrates, but not under anaesthesia. For phrenic motoneurones, no plateau potentials were observed in either state (except in one motoneurone after the abolition of the respiratory drive by means of a medullary lesion), but all motoneurones showed voltage-dependent amplification of the CRDPs, over a wide range of membrane potentials, too wide to result mainly from PIC activation. The measurements of the amplification were restricted to the phase of excitation, thus excluding the inhibitory phase. Amplification was found to be greatest for the smallest CRDPs in the lowest resistance motoneurones and was reduced or abolished following intracellular injection of the NMDA channel blocker, MK-801. Plateau potentials were readily evoked in non-phrenic cervical motoneurones in the same (decerebrate) preparations. We conclude that the voltage-dependent amplification of synaptic excitation in phrenic motoneurones is mainly the result of NMDA channel modulation rather than the activation of Ca2+ channel mediated PICs, despite phrenic motoneurones being strongly immunohistochemically labelled for CaV1.3 channels. The differential PIC activation in different motoneurones, all of which are CaV1.3 positive, leads us to postulate that the descending modulation of PICs is more selective than has hitherto been believed. PMID:22495582

  1. Human motoneurone excitability is depressed by activation of serotonin 1A receptors with buspirone

    DEFF Research Database (Denmark)

    D'Amico, Jessica M; Butler, Annie A; Héroux, Martin E

    2017-01-01

    that activation of 5-HT1Areceptors depresses human motoneurone excitability. Such a depression could contribute to decreased motoneurone output during fatiguing exercise if there is high serotonergic drive to the motoneurones. ABSTRACT: Intense serotonergic drive in the turtle spinal cord results in serotonin...... motoneurone output. Such a mechanism could potentially contribute to fatigue with exercise....

  2. Feedback Signal from Motoneurons Influences a Rhythmic Pattern Generator.

    Science.gov (United States)

    Rotstein, Horacio G; Schneider, Elisa; Szczupak, Lidia

    2017-09-20

    Motoneurons are not mere output units of neuronal circuits that control motor behavior but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia, dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons). The study was performed in isolated ganglia where manipulation of the activity of specific motoneurons was performed in the course of fictive crawling ( crawling ). In this study, the membrane potential of CV was manipulated while crawling was monitored through the rhythmic activity of DE-3. Matching behavioral observations that show that elongation dominates the rhythmic pattern, the electrophysiological activity of CV motoneurons dominates the cycle. Brief excitation of CV motoneurons during crawling episodes resets the rhythmic activity of DE-3, indicating that CV feeds back to the rhythmic pattern generator. CV hyperpolarization accelerated the rhythm to an extent that depended on the magnitude of the cycle period, suggesting that CV exerted a positive feedback on the unit(s) of the pattern generator that controls the elongation phase. A simple computational model was implemented to test the consequences of such feedback. The simulations indicate that the duty cycle of CV depended on the strength of the positive feedback between CV and the pattern generator circuit. SIGNIFICANCE STATEMENT Rhythmic movements of animals are controlled by neuronal networks that have been conceived as hierarchical structures. At the basis of this hierarchy, we find the motoneurons, few neurons at the top control global aspects of the behavior (e.g., onset, duration); and within these two ends, specific neuronal circuits control

  3. Divisive gain modulation of motoneurons by inhibition optimizes muscular control

    DEFF Research Database (Denmark)

    Vestergaard, Mikkel; Berg, Rune W.

    2015-01-01

    unclear whether the motoneuron gain, i.e., the slope of the transformation between synaptic input and spiking output, is also modulated to reduce variability in force. To address this issue, we use turtle hindlimb scratching as a model for fine motor control, since this behavior involves precise limb...... movement to rub the location of somatic nuisance touch. We recorded intracellularly from motoneurons in a reduced preparation where the limbs were removed to increase mechanical stability and the motor nerve activity served as a surrogate for muscle force. We found that not only is the gain of motoneurons...

  4. Ca++ dependent bistability induced by serotonin in spinal motoneurons

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1985-01-01

    The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly...... to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude...... that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons....

  5. Neural control of phrenic motoneuron discharge

    Science.gov (United States)

    Lee, Kun-Ze; Fuller, David D.

    2011-01-01

    Phrenic motoneurons (PMNs) provide a synaptic relay between bulbospinal respiratory pathways and the diaphragm muscle. PMNs also receive propriospinal inputs, although the functional role of these interneuronal projections has not been established. Here we review the literature regarding PMN discharge patterns during breathing and the potential mechanisms that underlie PMN recruitment. Anatomical and neurophysiological studies indicate that PMNs form a heterogeneous pool, with respiratory-related PMN discharge and recruitment patterns likely determined by a balance between intrinsic MN properties and extrinsic synaptic inputs. We also review the limited literature regarding PMN bursting during respiratory plasticity. Differential recruitment or rate modulation of PMN subtypes may underlie phrenic motor plasticity following neural injury and/or respiratory stimulation; however this possibility remains relatively unexplored. PMID:21376841

  6. Fatigue diminishes motoneuronal excitability during cycling exercise.

    Science.gov (United States)

    Weavil, Joshua C; Sidhu, Simranjit K; Mangum, Tyler S; Richardson, Russell S; Amann, Markus

    2016-10-01

    Exercise-induced fatigue influences the excitability of the motor pathway during single-joint isometric contractions. This study sought to investigate the influence of fatigue on corticospinal excitability during cycling exercise. Eight men performed fatiguing constant-load (80% W peak ; 241 ± 13 W) cycling to exhaustion during which the percent increase in quadriceps electromyography (ΔEMG; vastus lateralis and rectus femoris) was quantified. During a separate trial, subjects performed two brief (∼45 s) nonfatiguing cycling bouts (244 ± 15 and 331 ± 23W) individually chosen to match the ΔEMG across bouts to that observed during fatiguing cycling. Corticospinal excitability during exercise was quantified by transcranial magnetic, electric transmastoid, and femoral nerve stimulation to elicit motor-evoked potentials (MEP), cervicomedullary evoked potentials (CMEP), and M waves in the quadriceps. Peripheral and central fatigue were expressed as pre- to postexercise reductions in quadriceps twitch force (ΔQ tw ) and voluntary quadriceps activation (ΔVA). Whereas nonfatiguing cycling caused no measureable fatigue, fatiguing cycling resulted in significant peripheral (ΔQ tw : 42 ± 6%) and central (ΔVA: 4 ± 1%) fatigue. During nonfatiguing cycling, the area of MEPs and CMEPs, normalized to M waves, similarly increased in the quadriceps (∼40%; P fatiguing cycling. As a consequence, the ratio of MEP to CMEP was unchanged during both trials (P > 0.5). Therefore, although increases in muscle activation promote corticospinal excitability via motoneuronal facilitation during nonfatiguing cycling, this effect is abolished during fatigue. We conclude that the unaltered excitability of the corticospinal pathway from start of intense cycling exercise to exhaustion is, in part, determined by inhibitory influences on spinal motoneurons obscuring the facilitating effects of muscle activation.

  7. Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis.

    Directory of Open Access Journals (Sweden)

    Juliane Bremer

    2016-11-01

    Full Text Available During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator.

  8. 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.

  9. Nonlocal electron transport: direct and Greens function solution and comparison of our model with the SNB model

    Science.gov (United States)

    Colombant, Denis; Manheimer, Wallace; Schmitt, Andrew J.

    2013-10-01

    At least two models, ours and SNB (Schurtz-Nicolai-Busquet), and two methods of solution, direct numerical solution (DS) and Greens function (GF) are being used in multi-dimensional radiation hydrodynamics codes. We present results of a laser target implosion using both methods of solution. Although our model and SNB differ in some physical content, direct comparisons have been non-existent up to now. However a paper by Marocchino et al. has recently presented the results of two nanosecond-time-scale test problems, showing that the preheat calculated by the two models are different by about three orders of magnitude. We have rerun these problems and we find much less difference between the two than they do. One can show analytically that the results should be quite similar and are about an order of magnitude less than the maximum, and two orders of magnitude more than the minimum preheating in. We have been able to trace the somewhat different results back to the different physical assumptions made in each model. Work supported by DoE-NNSA and ONR.

  10. The effects of aging on hypoglossal motoneurons in rats.

    Science.gov (United States)

    Schwarz, Emilie C; Thompson, Jodi M; Connor, Nadine P; Behan, Mary

    2009-03-01

    Aging can result in a loss of neuronal cell bodies and a decrease in neuronal size in some regions of the brain and spinal cord. Motoneuron loss in the spinal cord is thought to contribute to the progressive decline in muscle mass and strength that occurs with age (sarcopenia). Swallowing disorders represent a large clinical problem in elderly persons; however, age-related alterations in cranial motoneurons that innervate muscles involved in swallowing have been understudied. We aimed to determine if age-related alterations occurred in the hypoglossal nucleus in the brainstem. If present, these changes might help explain alterations at the neuromuscular junction and changes in the contractile properties of tongue muscle that have been reported in older rats. We hypothesized that with increasing age there would be a loss of motoneurons and a reduction in neuronal size and the number of primary dendrites associated with each hypoglossal motoneuron. Neurons in the hypoglossal nucleus were visualized with the neuronal marker NeuN in young (9-10 months), middle-aged (24-25 months), and old (32-33 months) male F344/BN rats. Hypoglossal motoneurons were retrograde-labeled with injections of Cholera Toxin beta into the genioglossus muscle of the tongue and visualized using immunocytochemistry. Results indicated that the number of primary dendrites of hypoglossal motoneurons decreased significantly with age, while no age-associated changes were found in the number or size of hypoglossal motoneurons. Loss of primary dendrites could reduce the number of synaptic inputs and thereby impair function.

  11. Perineuronal Nets in Spinal Motoneurones: Chondroitin Sulphate Proteoglycan around Alpha Motoneurones

    Directory of Open Access Journals (Sweden)

    Sian F. Irvine

    2018-04-01

    Full Text Available Perineuronal nets (PNNs are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones, PNNs using Wisteria floribunda agglutinin (WFA and chondroitin sulphate proteoglycans (CSPGs, including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns. CSPG-positive PNNs surrounded ~70–80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15–30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1 aggrecan labels spinal PNNs better than WFA, and (2 there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

  12. 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...

  13. Electrical stimulation of transplanted motoneurons improves motor unit formation

    Science.gov (United States)

    Liu, Yang; Grumbles, Robert M.

    2014-01-01

    Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

  14. Comparative Analysis of NOAA REFM and SNB3GEO Tools for the Forecast of the Fluxes of High-Energy Electrons at GEO

    Science.gov (United States)

    Balikhin, M. A.; Rodriguez, J. V.; Boynton, R. J.; Walker, S. N.; Aryan, Homayon; Sibeck, D. G.; Billings, S. A.

    2016-01-01

    Reliable forecasts of relativistic electrons at geostationary orbit (GEO) are important for the mitigation of their hazardous effects on spacecraft at GEO. For a number of years the Space Weather Prediction Center at NOAA has provided advanced online forecasts of the fluence of electrons with energy >2 MeV at GEO using the Relativistic Electron Forecast Model (REFM). The REFM forecasts are based on real-time solar wind speed observations at L1. The high reliability of this forecasting tool serves as a benchmark for the assessment of other forecasting tools. Since 2012 the Sheffield SNB3GEO model has been operating online, providing a 24 h ahead forecast of the same fluxes. In addition to solar wind speed, the SNB3GEO forecasts use solar wind density and interplanetary magnetic field B(sub z) observations at L1. The period of joint operation of both of these forecasts has been used to compare their accuracy. Daily averaged measurements of electron fluxes by GOES 13 have been used to estimate the prediction efficiency of both forecasting tools. To assess the reliability of both models to forecast infrequent events of very high fluxes, the Heidke skill score was employed. The results obtained indicate that SNB3GEO provides a more accurate 1 day ahead forecast when compared to REFM. It is shown that the correction methodology utilized by REFM potentially can improve the SNB3GEO forecast.

  15. Comparative analysis of NOAA REFM and SNB3GEO tools for the forecast of the fluxes of high-energy electrons at GEO

    Science.gov (United States)

    Balikhin, M. A.; Rodriguez, J. V.; Boynton, R. J.; Walker, S. N.; Aryan, H.; Sibeck, D. G.; Billings, S. A.

    2016-01-01

    Reliable forecasts of relativistic electrons at geostationary orbit (GEO) are important for the mitigation of their hazardous effects on spacecraft at GEO. For a number of years the Space Weather Prediction Center at NOAA has provided advanced online forecasts of the fluence of electrons with energy >2 MeV at GEO using the Relativistic Electron Forecast Model (REFM). The REFM forecasts are based on real-time solar wind speed observations at L1. The high reliability of this forecasting tool serves as a benchmark for the assessment of other forecasting tools. Since 2012 the Sheffield SNB3GEO model has been operating online, providing a 24 h ahead forecast of the same fluxes. In addition to solar wind speed, the SNB3GEO forecasts use solar wind density and interplanetary magnetic field Bz observations at L1.The period of joint operation of both of these forecasts has been used to compare their accuracy. Daily averaged measurements of electron fluxes by GOES 13 have been used to estimate the prediction efficiency of both forecasting tools. To assess the reliability of both models to forecast infrequent events of very high fluxes, the Heidke skill score was employed. The results obtained indicate that SNB3GEO provides a more accurate 1 day ahead forecast when compared to REFM. It is shown that the correction methodology utilized by REFM potentially can improve the SNB3GEO forecast.

  16. Modulation of the intrinsic properties of motoneurons by serotonin

    DEFF Research Database (Denmark)

    Perrier, Jean-François; Rasmussen, Hanne Borger; Christensen, Rasmus Kordt

    2013-01-01

    Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts...... a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle...

  17. 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.

  18. Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

    Science.gov (United States)

    Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

    2011-12-01

    Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. On a method to detect long-latency excitations and inhibitions of single hand muscle motoneurons in man.

    Science.gov (United States)

    Awiszus, F; Feistner, H; Schäfer, S S

    1991-01-01

    The peri-stimulus-time histogram (PSTH) analysis of stimulus-related neuronal spike train data is usually regarded as a method to detect stimulus-induced excitations or inhibitions. However, for a fairly regularly discharging neuron such as the human alpha-motoneuron, long-latency modulations of a PSTH are difficult to interpret as PSTH modulations can also occur as a consequence of a modulated neuronal autocorrelation. The experiments reported here were made (i) to investigate the extent to which a PSTH of a human hand-muscle motoneuron may be contaminated by features of the autocorrelation and (ii) to develop methods that display the motoneuronal excitations and inhibitions without such contamination. Responses of 29 single motor units to electrical ulnar nerve stimulation below motor threshold were investigated in the first dorsal interosseous muscle of three healthy volunteers using an experimental protocol capable of demonstrating the presence of autocorrelative modulations in the neuronal response. It was found for all units that the PSTH as well as the cumulative sum (CUSUM) derived from these responses were severely affected by the presence of autocorrelative features. On the other hand, calculating the CUSUM in a slightly modified form yielded--for all units investigated--a neuronal output feature sensitive only to motoneuronal excitations and inhibitions induced by the afferent volley. The price that has to be paid to arrive at such a modified CUSUM (mCUSUM) was a high computational effort prohibiting the on-line availability of this output feature during the experiment. It was found, however, that an interspike interval superposition plot (IISP)--easily obtainable during the experiment--is also free of autocorrelative features.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

    Science.gov (United States)

    Mantilla, Carlos B.; Bailey, Jeffrey P.; Zhan, Wen-Zhi; Sieck, Gary C.

    2012-01-01

    Following cervical spinal cord injury at C2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10 μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability. PMID:22227062

  1. Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

    DEFF Research Database (Denmark)

    Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

    2012-01-01

    A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

  2. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  3. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  4. Serotonin differentially modulates the intrinsic properties of spinal motoneurons from the adult turtle

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; Cotel, Florence

    2007-01-01

    turtle. In agreement with previous studies, we had found that 5-HT applied to the extracellular medium promoted a voltage sensitive plateau potential. However, we also reported that this effect was only observed in half of the motoneurons; 5-HT inhibited the firing of the other half of the motoneurons...

  5. Irregular Firing and High-Conductance States in Spinal Motoneurons during Scratching and Swimming

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jorn; Alaburda, Aidas

    2016-01-01

    UNLABELLED: Intense synaptic transmission during scratch network activity increases conductance and induces irregular firing in spinal motoneurons. It is not known whether this high-conductance state is a select feature for scratching or a property that goes with spinal motor network activity...... in general. Here we compare conductance and firing patterns in spinal motoneurons during network activity for scratching and swimming in an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta elegans). The pattern and relative engagement of motoneurons are distinctly different...... in scratching and swimming. Nevertheless, we found increased synaptic fluctuations in membrane potential, irregular firing, and increased conductance in spinal motoneurons during scratch and swim network activity. Our finding indicates that intense synaptic activation of motoneurons is a general feature...

  6. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    2010-01-01

    Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

  7. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique....... This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST...

  8. Response properties of motoneurones in a slice preparation of the turtle spinal cord

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.; Mintz, I.

    1988-01-01

    1. Motoneurones in transverse sections of the turtle spinal cord were investigated in vitro with intracellular recording techniques. 2. Turtle motoneurones had a resting membrane potential of ‐60 to ‐80 mV, spike height of 90‐110 mV and were able to maintain rhythmic firing during depolarization......‐dependent inward rectification was selectively blocked by extracellular Cs+ at concentrations below 1 mM. 6. The results show that the response properties of spinal motoneurones of the turtle are closely similar to those known from mammals in vivo. The experiments confirm and extend the identification of the ionic...

  9. Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

    Science.gov (United States)

    Bayliss, D A; Viana, F; Talley, E M; Berger, A J

    1997-11-01

    Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

  10. A functional model and simulation of spinal motor pools and intrafascicular recordings of motoneuron activity in peripheral nerve

    Directory of Open Access Journals (Sweden)

    Mohamed N. Abdelghani

    2014-11-01

    Full Text Available Decoding motor intent from recorded neural signals is essential for the development of effective neural-controlled prostheses. To facilitate the development of online decoding algorithms we have developed a software platform to simulate neural motor signals recorded with peripheral nerve electrodes, such as longitudinal intrafascicular electrodes (LIFEs. The simulator uses stored motor intent signals to drive a pool of simulated motoneurons with various spike shapes, recruitment characteristics, and firing frequencies. Each electrode records a weighted sum of a subset of simulated motoneuron activity patterns. As designed, the simulator facilitates development of a suite of test scenarios that would not be possible with actual data sets because, unlike with actual recordings, in the simulator the individual contributions to the simulated composite recordings are known and can be methodically varied across a set of simulation runs. In this manner, the simulation tool is suitable for iterative development of real-time decoding algorithms prior to definitive evaluation in amputee subjects with implanted electrodes. The simulation tool was used to produce data sets that demonstrate its ability to capture some features of neural recordings that pose challenges for decoding algorithms.

  11. Serotonin‐induced bistability of turtle motoneurones caused by a nifedipine‐sensitive calcium plateau potential

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1989-01-01

    1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during...... of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after‐depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked....... It is concluded that serotonin induces a Ca2+‐dependent and nifedipine‐sensitive plateau potential in turtle motoneurones primarily by reducing a K+‐current responsible for the slow after‐hyperpolarization....

  12. Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition

    NARCIS (Netherlands)

    Nielsen, JB; Tijssen, MAJ; Hansen, NL; Crone, C; Petersen, NT; Brown, P; Van Dijk, JG; Rothwell, JC

    2002-01-01

    Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease)

  13. Absence of synergy for monosynaptic Group I inputs between abdominal and internal intercostal motoneurons

    DEFF Research Database (Denmark)

    Ford, T W; Meehan, Claire Francesca; Kirkwood, P A

    2014-01-01

    Internal intercostal and abdominal motoneurons are strongly coactivated during expiration. We investigated whether that synergy was paralleled by synergistic Group I reflex excitation. Intracellular recordings were made from motoneurons of the internal intercostal nerve of T8 in anesthetized cats...... that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role in controlling expiratory movements but, where present, support other motor acts....

  14. Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons.

    Science.gov (United States)

    Gill, Luther C; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-06-01

    Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a well-established model of SCI, unilateral spinal hemisection of the C2 segment of the cervical spinal cord (SH), provide novel information regarding the molecular and cellular mechanisms of functional recovery after SCI. Over time post-SH, gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. Conversely, recovery after SH is blunted by quenching endogenous BDNF with the fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by selective inhibition of TrkB kinase activity using a chemical-genetic approach in TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB receptors at phrenic motoneurons is highlighted by the blunting of recovery by siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons and by the enhancement of recovery evident following virally-induced increases in TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling regulates synaptic plasticity in various neuronal systems, including glutamatergic pathways. Glutamatergic neurotransmission constitutes the main inspiratory-related, excitatory drive to motoneurons, and following SH, spontaneous neuroplasticity is associated with increased expression of ionotropic N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity following cervical SCI is reviewed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Motoneuron survival is promoted by specific exercise in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Deforges, Séverine; Branchu, Julien; Biondi, Olivier; Grondard, Clément; Pariset, Claude; Lécolle, Sylvie; Lopes, Philippe; Vidal, Pierre-Paul; Chanoine, Christophe; Charbonnier, Frédéric

    2009-07-15

    Several studies using transgenic mouse models of familial amyotrophic lateral sclerosis (ALS) have reported a life span increase in exercised animals, as long as animals are submitted to a moderate-intensity training protocol. However, the neuroprotective potential of exercise is still questionable. To gain further insight into the cellular basis of the exercise-induced effects in neuroprotection, we compared the efficiency of a swimming-based training, a high-frequency and -amplitude exercise that preferentially recruits the fast motor units, and of a moderate running-based training, that preferentially triggers the slow motor units, in an ALS mouse model. Surprisingly, we found that the swimming-induced benefits sustained the motor function and increased the ALS mouse life span by about 25 days. The magnitude of this beneficial effect is one of the highest among those induced by any therapeutic strategy in this disease. We have shown that, unlike running, swimming significantly delays spinal motoneuron death and, more specifically, the motoneurons of large soma area. Analysis of the muscular phenotype revealed a swimming-induced relative maintenance of the fast phenotype in fast-twitch muscles. Furthermore, the swimming programme preserved astrocyte and oligodendrocyte populations in ALS spinal cord. As a whole, these data are highly suggestive of a causal relationship not only linking motoneuron activation and protection, but also motoneuron protection and the maintenance of the motoneuron surrounding environment. Basically, exercise-induced neuroprotective mechanisms provide an example of the molecular adaptation of activated motoneurons.

  16. The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones

    DEFF Research Database (Denmark)

    Saywell, S A; Anissimova, N P; Ford, T W

    2007-01-01

    of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5-T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones...... in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal...... intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 microV. The overall strength of the connection supports...

  17. Knockdown of Laminin gamma-3 (Lamc3 impairs motoneuron guidance in the zebrafish embryo [version 1; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Alexander M. J. Eve

    2017-11-01

    Full Text Available Background: Previous work in the zebrafish embryo has shown that laminin γ-3 (lamc3 is enriched in endothelial cells marked by expression of fli1a, but the role of Lamc3 has been unknown. Methods: We use antisense morpholino oligonucleotides, and CRISPR/Cas9 mutagenesis of F0 embryos, to create zebrafish embryos in which lamc3 expression is compromised. Transgenic imaging, immunofluorescence, and in situ hybridisation reveal that Lamc3 loss-of-function affects the development of muscle pioneers, endothelial cells, and motoneurons. Results: Lamc3 is enriched in endothelial cells during zebrafish development, but it is also expressed by other tissues. Depletion of Lamc3 by use of antisense morpholino oligonucleotides perturbs formation of the parachordal chain and subsequently the thoracic duct, but Lamc3 is not required for sprouting of the cardinal vein. F0 embryos in which lamc3 expression is perturbed by a CRISPR/Cas9 approach also fail to form a parachordal chain, but we were unable to establish a stable lamc3 null line. Lamc3 is dispensable for muscle pioneer specification and for the expression of netrin-1a in these cells. Lamc3 knockdown causes netrin-1a up-regulation in the neural tube and there is increased Netrin-1 protein throughout the trunk of the embryo. Axonal guidance of rostral primary motoneurons is defective in Lamc3 knockdown embryos. Conclusions: We suggest that knockdown of Lamc3 perturbs migration of rostral primary motoneurons at the level of the horizontal myoseptum, indicating that laminin γ3 plays a role in motoneuron guidance.

  18. Plateau potentials in alpha‐motoneurones induced by intravenous injection of L‐dopa and clonidine in the spinal cat

    DEFF Research Database (Denmark)

    Conway, B. A.; Hultborn, H.; Kiehn, O.

    1988-01-01

    1. Intracellular recordings were made from lumbar alpha‐motoneurones in unanaesthetized decerebrate acute spinal cats. The response of motoneurones to direct current pulse injection or synaptic excitation was investigated following intravenous injection of L‐beta‐3,4‐dihydroxyphenylalanine (L....... It is demonstrated that plateau potentials in the motoneurones contribute to the late long‐lasting reflexes observed in L‐DOPA‐treated spinal cats. 7. It is concluded that L‐DOPA (and clonidine) change the response properties of the motoneurones in an analogous way to 5‐hydroxy‐DL‐tryptophan (5‐HTP...

  19. Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

    Science.gov (United States)

    Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

    2004-10-01

    Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

  20. Intense synaptic activity enhances temporal resolution in spinal motoneurons.

    Directory of Open Access Journals (Sweden)

    Rune W Berg

    Full Text Available In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.

  1. Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

    Science.gov (United States)

    Hayakawa, T; Takanaga, A; Maeda, S; Ito, H; Seki, M

    2000-11-01

    The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

  2. CAUDAL MEDULLARY PATHWAYS TO LUMBOSACRAL MOTONEURONAL CELL GROUPS IN THE CAT - EVIDENCE FOR DIRECT PROJECTIONS POSSIBLY REPRESENTING THE FINAL COMMON PATHWAY FOR LORDOSIS

    NARCIS (Netherlands)

    VANDERHORST, VGJM; HOLSTEGE, G

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  3. Caudal Medullary Pathways To Lumbosacral Motoneuronal Cell Groups In The Cat; Evidence For Direct Projections Possibly Representing The Final Common Pathway For Lordosis.

    NARCIS (Netherlands)

    VanderHorst, Veronique G.J.M.; Holstege, Gert

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  4. ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

    Science.gov (United States)

    Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

    2018-05-24

    Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

  5. Modulation of recurrent inhibition from knee extensors to ankle motoneurones during human walking

    DEFF Research Database (Denmark)

    Lamy, Jean-Charles; Iglesias, Caroline; Lackmy, Alexandra

    2008-01-01

    The neural control for muscle coordination during human locomotion involves spinal and supraspinal networks, but little is known about the exact mechanisms implicated. The present study focused on modulation of heteronymous recurrent inhibition from knee extensors to ankle motoneurones at different...... times in the gait cycle, when quadriceps (Quad) muscle activity overlaps that in tibialis anterior (TA) and soleus (Sol). The effects of femoral nerve stimulation on ankle motoneurones were investigated during treadmill walking and during tonic co-contraction of Quad and TA/Sol while standing. Recurrent...... inhibition of TA motoneurones depended on the level of background EMG, and was similar during walking and standing for matched background EMG levels. On the other hand, recurrent inhibition in Sol was reduced in early stance, with respect to standing, and enhanced in late stance. Reduced inhibition in Sol...

  6. The influence of increased membrane conductance on response properties of spinal motoneurons

    DEFF Research Database (Denmark)

    Grigonis, Ramunas; Guzulaitis, Robertas; Buisas, Rokas

    2016-01-01

    During functional spinal neural network activity motoneurons receive massive synaptic excitation and inhibition, and their membrane conductance increases considerably – they are switched to a high-conductance state. High-conductance states can substantially alter response properties of motoneurons....... In the present study we investigated how an increase in membrane conductance affects spike frequency adaptation, the gain (i.e., the slope of the frequency-current relationship) and the threshold for action potential generation. We used intracellular recordings from adult turtle motoneurons in spinal cord slices....... Membrane conductance was increased pharmacologically by extracellular application of the GABAA receptor agonist muscimol. Our findings suggest that an increase in membrane conductance of about 40–50% increases the magnitude of spike frequency adaptation, but does not change the threshold for action...

  7. Reciprocal Ia inhibition contributes to motoneuronal hyperpolarisation during the inactive phase of locomotion and scratching in the cat

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Stecina, Katinka; Meehan, Claire Francesca

    2011-01-01

    Despite decades of research, the classical idea that "reciprocal inhibition" is involved in the hyperpolarisation of motoneurones in their inactive phase during rhythmic activity is still under debate. Here, we investigated the contribution of reciprocal Ia inhibition to the hyperpolarisation...... of motoneurones during fictive locomotion (evoked either by electrical stimulation of the brainstem or by L-DOPA administration following a spinal transection at the cervical level) and fictive scratching (evoked by stimulation of the pinna) in decerebrate cats. Simultaneous extracellular recordings of Ia...... inhibitory interneurones and intracellular recordings of lumbar motoneurones revealed the interneurones to be most active when their target motoneurones were hyperpolarised (i.e. in the inactive phase of the target motoneurones). To date, these results are the most direct evidence that Ia inhibitory...

  8. Phrenic motoneurons: output elements of a highly organized intraspinal network.

    Science.gov (United States)

    Ghali, Michael George Zaki

    2018-03-01

    pontomedullary respiratory network generates the respiratory pattern and relays it to bulbar and spinal respiratory motor outputs. The phrenic motor system controlling diaphragm contraction receives and processes descending commands to produce orderly, synchronous, and cycle-to-cycle-reproducible spatiotemporal firing. Multiple investigators have studied phrenic motoneurons (PhMNs) in an attempt to shed light on local mechanisms underlying phrenic pattern formation. I and colleagues (Marchenko V, Ghali MG, Rogers RF. Am J Physiol Regul Integr Comp Physiol 308: R916-R926, 2015.) recorded PhMNs in unanesthetized, decerebrate rats and related their activity to simultaneous phrenic nerve (PhN) activity by creating a time-frequency representation of PhMN-PhN power and coherence. On the basis of their temporal firing patterns and relationship to PhN activity, we categorized PhMNs into three classes, each of which emerges as a result of intrinsic biophysical and network properties and organizes the orderly contraction of diaphragm motor fibers. For example, early inspiratory diaphragmatic activation by the early coherent burst generated by high-frequency PhMNs may be necessary to prime it to overcome its initial inertia. We have also demonstrated the existence of a prominent role for local intraspinal inhibitory mechanisms in shaping phrenic pattern formation. The objective of this review is to relate and synthesize recent findings with those of previous studies with the aim of demonstrating that the phrenic nucleus is a region of active local processing, rather than a passive relay of descending inputs.

  9. Peripheral fatigue limits endurance exercise via a sensory feedback-mediated reduction in spinal motoneuronal output.

    Science.gov (United States)

    Amann, Markus; Venturelli, Massimo; Ives, Stephen J; McDaniel, John; Layec, Gwenael; Rossman, Matthew J; Richardson, Russell S

    2013-08-01

    This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 (P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.

  10. The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones

    Science.gov (United States)

    Saywell, S A; Anissimova, N P; Ford, T W; Meehan, C F; Kirkwood, P A

    2007-01-01

    The descending control of respiratory-related motoneurones in the thoracic spinal cord remains the subject of some debate. In this study, direct connections from expiratory bulbospinal neurones to identified motoneurones were investigated using spike-triggered averaging and the strengths of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5–T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 μV. The overall strength of the connection supports previous measurements made by cross-correlation, but is about 10 times stronger than that reported in the only previous similar survey to use spike-triggered averaging. Calculations are presented to suggest that this input alone is sufficient to account for all the expiratory depolarization seen in the recorded motoneurones. However, extra sources of input, or amplification of this one, are likely to be necessary to produce a useful motoneurone output. PMID:17204500

  11. Segregation of glutamatergic and cholinergic transmission at the mixed motoneuron Renshaw cell synapse.

    OpenAIRE

    Lamotte d Incamps, B.; Bhumbra, G. S.; Foster, J. D.; Beato, M.; Ascher, P.

    2017-01-01

    In neonatal mice motoneurons excite Renshaw cells by releasing both acetylcholine (ACh) and glutamate. These two neurotransmitters activate two types of nicotinic receptors (nAChRs) (the homomeric α7 receptors and the heteromeric α*ß* receptors) as well as the two types of glutamate receptors (GluRs) (AMPARs and NMDARs). Using paired recordings, we confirm that a single motoneuron can release both transmitters on a single post-synaptic Renshaw cell. We then show that co-transmission is prese...

  12. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    . This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST......During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique...... conventional transcranial magnetic stimulation (TMS) and responses to peripheral nerve stimulation were recorded following the same fatigue protocol. The size of both the MEPs and the peripheral responses increased after the contraction and were in direct contrast to the decrease in size of the TST response...

  13. Comparative study on the analgesic effect of acute ipsilateral shoulder pain after open thoracotomy between preoperative ultrasound guided suprascapular nerve block (SNB) and intraoperative phrenic nerve infiltration (PNI) in cancer lung patients.

    Science.gov (United States)

    Elfokery, Bassel M; Tawfic, Sahar A; Abdelrahman, Abdelrahman M; Abbas, Dina N; Abdelghaffar, Ikramy M

    2018-03-01

    Acute ipsilateral shoulder pain (ISP) is a common complaint in patients after thoracotomy. The incidence ranges from 21% to 97%. Unfortunately, clinical studies did not put enough focus on ISP post thoracic surgery. This study was designed to compare the effectiveness of suprascapular nerve block (SNB) and phrenic nerve infiltration (PNI) for controlling ISP. One hundred and thirty-five lung cancer patients (135) scheduled for open-lung surgery were randomly allocated into three equal groups; control group: received thoracic epidural with general anesthesia, suprascapular group: (SNB) one hour before the operation with 10 ml bupivacaine plus thoracic epidural with general anesthesia and phrenic nerve group: (PNI) was performed by the operating surgeon with 10 ml bupivacaine plus thoracic epidural with general anesthesia. The visual analogue score (VAS) of ISP, rescue of ketorolac for break through shoulder pain, peak expiratory flow rate (PEFR) and arterial blood gases were measured every 6 h postoperatively for 48 h. The VAS, rescue doses of ketorolc and PEFR were significantly lower in the phrenic nerve group (P-value 0.05). PNI is more effective than SNB for ISP. Production and hosting by Elsevier B.V.

  14. Hypoglossal motoneurons in newborn mice receive respiratory drive from both sides of the medulla

    DEFF Research Database (Denmark)

    Tarras-Wahlberg, S; Rekling, J C

    2009-01-01

    Respiratory motor output in bilateral cranial nerves is synchronized, but the underlying synchronizing mechanisms are not clear. We used an in vitro slice preparation from newborn mice to investigate the effect of systematic transsections on respiratory activity in bilateral XII nerves. Complete...... in bilateral XII nerves. Hypoglossal motoneurons receive respiratory drive from both sides of the medulla, possibly mediated by contralaterally projecting dendrites....

  15. Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat.

    Science.gov (United States)

    Nielsen, J B; Conway, B A; Halliday, D M; Perreault, M-C; Hultborn, H

    2005-11-15

    The basic locomotor rhythm in the cat is generated by a neuronal network in the spinal cord. The exact organization of this network and its drive to the spinal motoneurones is unknown. The purpose of the present study was to use time (cumulant density) and frequency domain (coherence) analysis to examine the organization of the last order drive to motoneurones during fictive locomotion (evoked by application of nialamide and dihydroxyphenylalanine (DOPA)) in the spinal cat. In all cats, narrow central synchronization peaks (half-width synchronization was observed between the individual intracellular recordings and the ENGs recorded from nerves of the same pool and of close synergists. Recordings from 34 pairs of motoneurones (10 pairs belonged to the same motor pool, 11 pairs to close synergists and 13 pairs to antagonistic pools) failed to reveal any short-lasting synchronization. These data demonstrate that short-term synchronization during fictive locomotion is relatively weak and is restricted to close synergists. In addition, coherence analysis failed to identify any specific rhythmic component in the locomotor drive that could be associated with this synchronization. These results resemble findings obtained during human treadmill walking and imply that the spinal interneurones participating in the generation of the locomotor rhythm are themselves weakly synchronized. The restricted synchronization within the locomotor drive to motoneuronal pools may be a feature of the locomotor generating networks that is related to the ability of these networks to produce highly adaptive patterns of muscle activity during locomotion.

  16. Influence of proprioceptive feedback on the firing rate and recruitment of motoneurons

    Science.gov (United States)

    De Luca, C. J.; Kline, J. C.

    2012-02-01

    We investigated the relationships of the firing rate and maximal recruitment threshold of motoneurons recorded during isometric contraction with the number of spindles in individual muscles. At force levels above 10% of maximal voluntary contraction, the firing rate was inversely related to the number of spindles in a muscle, with the slope of the relationship increasing with force. The maximal recruitment threshold of motor units increased linearly with the number of spindles in the muscle. Thus, muscles with a greater number of spindles had lower firing rates and a greater maximal recruitment threshold. These findings may be explained by a mechanical interaction between muscle fibres and adjacent spindles. During low-level (0% to 10%) voluntary contractions, muscle fibres of recruited motor units produce force twitches that activate nearby spindles to respond with an immediate excitatory feedback that reaches maximal level. As the force increases further, the twitches overlap and tend towards tetanization, the muscle fibres shorten, the spindles slacken, their excitatory firings decrease, and the net excitation to the homonymous motoneurons decreases. Motoneurons of muscles with greater number of spindles receive a greater decrease in excitation which reduces their firing rates, increases their maximal recruitment threshold, and changes the motoneuron recruitment distribution.

  17. Location of bladder and urethral sphincter motoneurons in the male guinea pig (Cavia porcellus)

    NARCIS (Netherlands)

    Kuipers, R; Izhar, Z; Gerrits, PO; Miner, W; Holstege, G; Gerrits, Peter O.

    2004-01-01

    Although the guinea pig is used widely in experimental medical research, including in studies on micturition control, the spinal origin of preganglionic parasympathetic bladder and somatic external urethral sphincter motoneurons is not known. In the male, guinea pig using wheat germ

  18. Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin

    DEFF Research Database (Denmark)

    Perrier, J F; Mejia-Gervacio, S; Hounsgaard, J

    2000-01-01

    1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or tr...

  19. Spatial integration of local transmitter responses in motoneurones of the turtle spinal cord in vitro

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; Hounsgaard, J

    1994-01-01

    1. Integration of responses to local activation of transmitter receptors in the dendrites of motoneurones was investigated in a slice preparation of the turtle spinal cord. Membrane-active substances were applied from up to three independent iontophoresis electrodes during intracellular recording...

  20. Inhibition of motoneurons during the cutaneous silent period in the spinal cord of the turtle

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jørn Dybkjær; Alaburda, Aidas

    2012-01-01

    motoneurons in the isolated carapace-spinal cord preparation from adult turtles during rhythmic scratch-like reflex. Electrical stimulation of cutaneous nerves induced CSP-like suppression of motor nerve firing during rhythmic network activity. The stimulus that generated the CSP-like suppression of motor...

  1. Shared Components of Rhythm Generation for Locomotion and Scratching Exist Prior to Motoneurons

    Directory of Open Access Journals (Sweden)

    Zhao-Zhe Hao

    2017-08-01

    Full Text Available Does the spinal cord use a single network to generate locomotor and scratching rhythms or two separate networks? Previous research showed that simultaneous swim and scratch stimulation (“dual stimulation” in immobilized, spinal turtles evokes a single rhythm in hindlimb motor nerves with a frequency often greater than during swim stimulation alone or scratch stimulation alone. This suggests that the signals that trigger swimming and scratching converge and are integrated within the spinal cord. However, these results could not determine whether the integration occurs in motoneurons themselves or earlier, in spinal interneurons. Here, we recorded intracellularly from hindlimb motoneurons during dual stimulation. Motoneuron membrane potentials displayed regular oscillations at a higher frequency during dual stimulation than during swim or scratch stimulation alone. In contrast, arithmetic addition of the oscillations during swimming alone and scratching alone with various delays always generated irregular oscillations. Also, the standard deviation of the phase-normalized membrane potential during dual stimulation was similar to those during swimming or scratching alone. In contrast, the standard deviation was greater when pooling cycles of swimming alone and scratching alone for two of the three forms of scratching. This shows that dual stimulation generates a single rhythm prior to motoneurons. Thus, either swimming and scratching largely share a rhythm generator or the two rhythms are integrated into one rhythm by strong interactions among interneurons.

  2. Nucleus retroambiguous projections to lumbosacral motoneuronal cell groups in the male cat

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Holstege, G

    1997-01-01

    Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat, Lumbosacral injections of wheat

  3. Direct projections from the nucleus retroambiguus to cricothyroid motoneurons in the cat

    NARCIS (Netherlands)

    Boers, J.; Klop, E.M.; Hulshoff, A.C.; Weerd, H. de; Holstege, G.

    2002-01-01

    Vocalization can be elicited by stimulation in the periaqueductal gray (PAG). Light-microscopical tracing and physiological studies have revealed that the PAG uses the nucleus retroambiguus (NRA) as a relay to excite the vocalization muscle motoneurons. Direct NRA projections have been demonstrated

  4. Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy

    NARCIS (Netherlands)

    Simic, G.; Mladinov, M.; Seso Simic, D.; Jovanov Milosevic, N.; Islam, A.; Pajtak, A.; Barisic, N.; Sertic, J.; Lucassen, P.J.; Hof, P.R.; Kruslin, B.

    2008-01-01

    The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying

  5. Organization of the motoneurons innervating the pelvic muscles of the male rat

    DEFF Research Database (Denmark)

    Schrøder, H D

    1980-01-01

    The cytoarchitecture of the motoneuron pool of the male rat was studied at the lumbo-sacral transition area, particularly in L6. In the latter segment a dorso-medial (DM), ventral (V), dorso-lateral (DL), and retrodorso-lateral group (RDL) could be defined. The DL group was associated...

  6. EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

    LENUS (Irish Health Repository)

    Burgunder, J-M

    2011-02-01

    These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.

  7. Intrinsic membrane properties causing a bistable behaviour of α-motoneurones

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Jespersen, B.

    1984-01-01

    injected depolarizing current pulse and is terminated by a short train of inhibitory synaptic potentials or a hyperpolarizing current pulse. It is concluded that maintained motor unit firing triggered by a brief train of impulses in Ia afferent reflects an intrinsic bistable behaviour of α-motoneurones....

  8. The nature of corticospinal paths driving human motoneurones during voluntary contractions

    DEFF Research Database (Denmark)

    Butler, Jane E; Larsen, Thomas S; Gandevia, Simon C

    2007-01-01

    The properties of the human motor cortex can be studied non-invasively using transcranial magnetic stimulation (TMS). Stimulation at high intensity excites corticospinal cells with fast conducting axons that make direct connections to motoneurones of human upper limb muscles, while low...

  9. Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtle

    DEFF Research Database (Denmark)

    Perrier, J.F.; Noraberg, J.; Simon, M.

    2000-01-01

    Explant cultures from the spinal cord of adult turtles were established and used to study the sensitivity of the intrinsic response properties of motoneurons to the changes in connectivity and milieu imposed by isolation in culture. Transverse sections 700 microm thick were explanted on cover slips...... the ability to fire repetitively. By the second week in culture, a fraction of motoneurons displayed fast and slow transient outward rectification and low-threshold calcium spikes, features not seen in turtle motoneurons in acute slices. On the other hand, properties mediated by L-type Ca2+ channels...

  10. Physiological consequences of doublet discharges on motoneuronal firing and motor unit force

    Directory of Open Access Journals (Sweden)

    Włodzimierz eMrówczyński

    2015-03-01

    Full Text Available The double discharges are observed at the onset of contractions of mammalian motor units (MUs, especially during their recruitment to strong or fast movements. Doublets lead to MU force increase and improve ability of muscles to maintain high force during prolonged contractions. In this review we discuss an ability to produce doublets by fast and slow motoneurons (MNs, their influence on the course of action potential afterhyperpolarization as well as its role in modulation of the initial stage of the firing pattern of MNs. In conclusion, a generation of doublets is an important strategy of motor control, responsible for fitting the motoneuronal firing rate to the optimal for MUs at the start of their contraction, necessary for increment of muscle force.

  11. Possible functions of transmitter-controlled plateau potentials in α motoneurones

    DEFF Research Database (Denmark)

    Eken, T.; Hultborn, H.; Kiehn, O.

    1989-01-01

    are responsible for this bistable firing property in intact animals. The role of plateau potentials in locomotion is difficult to study. At present there are no clear indications of the utilization of plateau potentials in locomotion in intact animals. However, “clamped frequency” bursts which are observed...... in α motoneurones in reduced preparations is described. Thereafter we present some new data on a bistable behaviour in motor units in unrestrained intact animals during posture. Finally, the possible role of motoneuronal bistability in locomotion and in spasticity is discussed. Recently a bistable...... consequences of a bistable firing behaviour in the intact animal, the firing pattern of individual soleus motor units was studied by means of chronic EMG registration in awake unrestrained rats during quiet standing. Implanted electrodes allowed the delivery of excitatory and inhibitory stimulus trains...

  12. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

  13. Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Jespersen, B.

    1988-01-01

    1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short‐lasting synaptic excitation (‘on’ stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset...... be triggered by short‐lasting excitation and inhibition of the motoneurones is referred to as ‘bistable’ behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection...

  14. Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons.

    Directory of Open Access Journals (Sweden)

    Casie Lindsly

    Full Text Available Synaptic scaling represents a process whereby the distribution of a cell's synaptic strengths are altered by a multiplicative scaling factor. Scaling is thought to be a compensatory response that homeostatically controls spiking activity levels in the cell or network. Previously, we observed GABAergic synaptic scaling in embryonic spinal motoneurons following in vivo blockade of either spiking activity or GABAA receptors (GABAARs. We had determined that activity blockade triggered upward GABAergic scaling through chloride accumulation, thus increasing the driving force for these currents. To determine whether chloride accumulation also underlies GABAergic scaling following GABAAR blockade we have developed a new technique. We expressed a genetically encoded chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides a non-invasive fast measure of intracellular chloride. Using this technique we now show that chloride accumulation underlies GABAergic scaling following blockade of either spiking activity or the GABAAR. The finding that GABAAR blockade and activity blockade trigger scaling via a common mechanism supports our hypothesis that activity blockade reduces GABAAR activation, which triggers synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and widespread nature of GABAergic scaling through chloride accumulation, as it was also observed in spinal interneurons. This suggests that homeostatic scaling via chloride accumulation is a common feature in many neuronal classes within the embryonic spinal cord and opens the possibility that this process may occur throughout the nervous system at early stages of development.

  15. Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.

    Science.gov (United States)

    Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James

    2010-12-01

    To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

  16. Descending Projections From The Nucleus Retroambiguus To The Iliopsoas Motoneuronal Cell Groups In The Female Golden Hamster : Possible role in reproductive behavior

    NARCIS (Netherlands)

    Gerrits, Peter O.; Holstege, Gert

    1999-01-01

    In the cat, the nucleus retroambiguus (NRA) projects to expiratory motoneurons in the brainstem and spinal cord. Recently, it has been demonstrated that the NRA sends fibers to a specific set of motoneurons in the lumbosacral cord, which pathway is thought to play a crucial role in mating behavior.

  17. Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion

    DEFF Research Database (Denmark)

    Ford, T W; Anissimova, Natalia P; Meehan, Claire Francesca

    2016-01-01

    A previous neurophysiological investigation demonstrated an increase in functional projections of expiratory bulbospinal neurons (EBSNs) in the segment above a chronic lateral thoracic spinal cord lesion that severed their axons. We have now investigated how this plasticity might be manifested...... in thoracic motoneurons by measuring their respiratory drive and the connections to them from individual EBSNs. In anesthetized cats, simultaneous recordings were made intracellularly from motoneurons in the segment above a left-side chronic (16 wk) lesion of the spinal cord in the rostral part of T8, T9......, or T10 and extracellularly from EBSNs in the right caudal medulla, antidromically excited from just above the lesion but not from below. Spike-triggered averaging was used to measure the connections between pairs of EBSNs and motoneurons. Connections were found to have a very similar distribution...

  18. Synaptic excitation in spinal motoneurons alternates with synaptic inhibition and is balanced by outward rectification during rhythmic motor network activity

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jorn

    2017-01-01

    channels. Intrinsic outward rectification facilitates spiking by focusing synaptic depolarization near threshold for action potentials. By direct recording of synaptic currents, we also show that motoneurons are activated by out-of-phase peaks in excitation and inhibition during network activity, whereas......Regular firing in spinal motoneurons of red-eared turtles (Trachemys scripta elegans, either sex) evoked by steady depolarization at rest is replaced by irregular firing during functional network activity. The transition caused by increased input conductance and synaptic fluctuations in membrane...... potential was suggested to originate from intense concurrent inhibition and excitation. We show that the conductance increase in motoneurons during functional network activity is mainly caused by intrinsic outward rectification near threshold for action potentials by activation of voltage and Ca2+ gated K...

  19. Activation properties of trigeminal motoneurons in participants with and without bruxism

    Science.gov (United States)

    D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

    2013-01-01

    In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities such as eating, nonnutritive chewing, clenching, and yawning

  20. Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons.

    Science.gov (United States)

    Chesnoy-Marchais, D

    2016-08-25

    In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1μM), both taurine (0.3-1mM) and β-alanine (0.3mM) activated sustained anionic currents, which were partly blocked by TPMPA (100μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration.

    Science.gov (United States)

    Maier, Oliver; Böhm, Julia; Dahm, Michael; Brück, Stefan; Beyer, Cordian; Johann, Sonja

    2013-06-01

    Alpha-motoneurons appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Morphological and physiological degeneration of this neuronal phenotype is typically characterized by a marked decrease of neuronal markers and by alterations of cholinergic metabolism such as reduced choline acetyltransferase (ChAT) expression. The motoneuron-like cell line NSC-34 is a hybrid cell line produced by fusion of neuroblastoma with mouse motoneuron-enriched primary spinal cord cells. In order to further establish this cell line as a valid model system to investigate cholinergic neurodegeneration, NSC-34 cells were differentiated by serum deprivation and additional treatment with all-trans retinoic acid (atRA). Cell maturation was characterized by neurite outgrowth and increased expression of neuronal and cholinergic markers, including MAP2, GAP-43 and ChAT. Subsequently, we used differentiated NSC-34 cells to study early degenerative responses following exposure to various neurotoxins (H2O2, TNF-α, and glutamate). Susceptibility to toxin-induced cell death was determined by means of morphological changes, expression of neuronal marker proteins, and the ratio of pro-(Bax) to anti-(Bcl-2) apoptotic proteins. NSC-34 cells respond to low doses of neurotoxins with increased cell death of remaining undifferentiated cells with no obvious adverse effects on differentiated cells. Thus, the different vulnerability of differentiated and undifferentiated NSC-34 cells to neurotoxins is a key characteristic of NSC-34 cells and has to be considered in neurotoxic studies. Nonetheless, application of atRA induced differentiation of NSC-34 cells and provides a suitable model to investigate molecular events linked to neurodegeneration of differentiated neurons. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections.

    Directory of Open Access Journals (Sweden)

    Yuetong Ding

    Full Text Available Brachial plexus injury (BPI and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST is genetically absent. In adult mice, we tore off right C5-C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs and reduced peak-to-peak amplitudes in electromyogram (EMG, than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.

  3. Comparison of dendritic calcium transients in juvenile wild type and SOD1G93A mouse lumbar motoneurons

    Directory of Open Access Journals (Sweden)

    Katharina Ann Quinlan

    2015-04-01

    Full Text Available Previous studies of spinal motoneurons in the SOD1 mouse model of amyotrophic lateral sclerosis have shown alterations long before disease onset, including increased dendritic branching, increased persistent Na+ and Ca2+ currents, and impaired axonal transport. In this study dendritic Ca2+ entry was investigated using 2 photon excitation fluorescence microscopy and whole-cell patch-clamp of juvenile (P4-11 motoneurons. Neurons were filled with both Ca2+ Green-1 and Texas Red dextrans, and line scans performed throughout. Steps were taken to account for different sources of variability, including 1 dye filling and laser penetration, 2 dendritic anatomy, and 3 the time elapsed from the start of recording. First, Ca2+ Green-1 fluorescence was normalized by Texas Red; next, neurons were reconstructed so anatomy could be evaluated; finally, time was recorded. Customized software detected the largest Ca2+ transients (area under the curve from each line scan and matched it with parameters above. Overall, larger dendritic diameter and shorter path distance from the soma were significant predictors of larger transients, while time was not significant up to 2 hours (data thereafter was dropped. However, Ca2+ transients showed additional variability. Controlling for previous factors, significant variation was found between Ca2+ signals from different processes of the same neuron in 3/7 neurons. This could reflect differential expression of Ca2+ channels, local neuromodulation or other variations. Finally, Ca2+ transients in SOD1G93A motoneurons were significantly smaller than in non-transgenic motoneurons. In conclusion, motoneuron processes show highly variable Ca2+ transients, but these transients are smaller overall SOD1G93A motoneurons.

  4. Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.

    Science.gov (United States)

    Norton, Will H; Mangoli, Maryam; Lele, Zsolt; Pogoda, Hans-Martin; Diamond, Brianne; Mercurio, Sara; Russell, Claire; Teraoka, Hiroki; Stickney, Heather L; Rauch, Gerd-Jörg; Heisenberg, Carl-Philipp; Houart, Corinne; Schilling, Thomas F; Frohnhoefer, Hans-Georg; Rastegar, Sepand; Neumann, Carl J; Gardiner, R Mark; Strähle, Uwe; Geisler, Robert; Rees, Michelle; Talbot, William S; Wilson, Stephen W

    2005-02-01

    In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphenucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.

  5. Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Conway, B.A.; Halliday, D.M.

    2005-01-01

    pairs to antagonistic pools) failed to reveal any short-lasting synchronization. These data demonstrate that short-term synchronization during fictive locomotion is relatively weak and is restricted to close synergists. In addition, coherence analysis failed to identify any specific rhythmic component......The basic locomotor rhythm in the cat is generated by a neuronal network in the spinal cord. The exact organization of this network and its drive to the spinal motoneurones is unknown. The purpose of the present study was to use time (cumulant density) and frequency domain (coherence) analysis...

  6. Changes in corticospinal drive to spinal motoneurones following tablet-based practice of manual dexterity

    DEFF Research Database (Denmark)

    Larsen, Lisbeth Højkjær; Jensen, Thor; Christensen, Mark Schram

    2016-01-01

    ) between EEG-EMG and EMG-EMG activity. Following motor practice performance improved significantly and a significant increase in EEG-EMGAPB and EMGAPB-EMGFDI coherence in the beta band (15-30 Hz) was observed. No changes were observed after the control session. Our results show that tablet-based motor...... practice is associated with changes in the common corticospinal drive to spinal motoneurons involved in manual dexterity. Tablet-based motor practice may be a motivating training tool for stroke patients who struggle with loss of dexterity....

  7. Serotonergic synaptic input to facial motoneurons: localization by electron-microscopic autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Aghajanian, G K; McCall, R B [Yale Univ., New Haven, CT (USA). School of Medicine

    1980-12-01

    Serotonergic nerve terminals in the facial motor nucleus were labelled with (/sup 3/H)5-hydroxytryptamine. When serotonergic nerve terminals were destroyed (by the selective neurotoxin 5,7-dihydroxytryptamine) the labelling was lost. By electron-microscopic autoradiography, labelled serotonergic terminals were found to make axo-dendritic or axo-somatic junctions with facial motor neurons. No axo-axonic junctions were observed. These morphological findings are consistent with physiological studies which indicate that 5-hydroxytryptamine facilitates the excitation of facial motoneurons through a direct postsynaptic action.

  8. Increased activity of pre-motor network does not change the excitability of motoneurons during protracted scratch initiation

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Alaburda, Aidas; Hounsgaard, Jørn Dybkjær

    2013-01-01

    of their intrinsic excitability. Here we employed an experimental paradigm of protracted scratch initiation in the integrated carapace-spinal cord preparation of adult turtles (Chrysemys scripta elegans). The protracted initiation of scratch network activity allows us to investigate the excitability of motoneurons...... and pre-motor network activity in the time interval from the start of sensory stimulation until the onset of scratch activity. Our results suggest that increased activity in the pre-motor network facilitates the onset of scratch episodes but does not change the excitability of motoneurons at the onset...... of scratching....

  9. Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons.

    Science.gov (United States)

    Corsini, Silvia; Tortora, Maria; Nistri, Andrea

    2016-11-15

    Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death. Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 μm nicotine, whereas nAChR antagonists

  10. Secondary Analysis of the NCI-60 Whole Exome Sequencing Data Indicates Significant Presence of Propionibacterium acnes Genomic Material in Leukemia (RPMI-8226 and Central Nervous System (SF-295, SF-539, and SNB-19 Cell Lines.

    Directory of Open Access Journals (Sweden)

    Mark Rojas

    Full Text Available The NCI-60 human tumor cell line panel has been used in a broad range of cancer research over the last two decades. A landmark 2013 whole exome sequencing study of this panel added an exceptional new resource for cancer biologists. The complementary analysis of the sequencing data produced by this study suggests the presence of Propionibacterium acnes genomic sequences in almost half of the datasets, with the highest abundance in the leukemia (RPMI-8226 and central nervous system (SF-295, SF-539, and SNB-19 cell lines. While the origin of these contaminating bacterial sequences remains to be determined, observed results suggest that computational control for the presence of microbial genomic material is a necessary step in the analysis of the high throughput sequencing (HTS data.

  11. The feasibility of using the 25MW super near boiling nuclear reactor (SNB25) to provide thermal and electrical energy for a large Canadian Forces base in the Canadian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, S.; Bonin, H.W.; Baskin, M.; Bowen, K.; Switzer, Z., E-mail: Stephane.Paquette@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2014-07-01

    A feasibility study of a power plant using the Super Near Boiling 25 MWt (SNB25) nuclear reactor as a heat source and capable of supporting the electrical and thermal requirements for a base the size of Canadian Forces Base (CFB) Kingston in the Arctic was carried out. Such a power plant would allow the Canadian Armed Forces (CAF) to have a self-sustaining operational base in the Arctic to conduct Search and Rescue (SAR) and sovereignty missions. The thermal and electrical requirements for a base the size of CFB Kingston are determined to be 31.63 MWt and 7.16 MWe, respectively. Using the Heating Degree Days (HDD) approach to account for temperature differences between Southern Ontario and the Arctic, a base the size of CFB Kingston in the Arctic would require 75.16 MWt to operate. A chemical engineering software program, UniSim, was used to simulate the energy cycle of the base which consisted of a district heating loop to provide hot water and an Organic Rankine Cycle (ORC) using n-pentane as the working fluid to provide the electrical energy. The UniSim simulations determined that the cycle would use six shell and tube heat exchangers, two axial gas turbines coupled to generators, and twelve centrifugal pumps, in addition to a group of five SNB25 reactors that could provide 25.03 MWt and 2.63 MWe to a base in the Arctic with energy requirements about a third of those of CFB Kingston. The design foresees redundancy which is essential to safe operation in the Arctic. (author)

  12. Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior.

    Science.gov (United States)

    Feiguin, Fabian; Godena, Vinay K; Romano, Giulia; D'Ambrogio, Andrea; Klima, Raffaella; Baralle, Francisco E

    2009-05-19

    Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates.

  13. Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes

    Directory of Open Access Journals (Sweden)

    M. Demestre

    2015-09-01

    Full Text Available Striated skeletal muscle cells from humans represent a valuable source for in vitro studies of the motoric system as well as for pathophysiological investigations in the clinical settings. Myoblasts can readily be grown from human muscle tissue. However, if muscle tissue is unavailable, myogenic cells can be generated from human induced pluripotent stem cells (hiPSCs preferably without genetic engineering. Our study aimed to optimize the generation of hiPSCs derived myogenic cells by employing selection of CD34 positive cells and followed by distinct, stepwise culture conditions. Following the expansion of CD34 positive single cells under myogenic cell culture conditions, serum deprived myoblast-like cells finally fused and formed multinucleated striated myotubes that expressed a set of key markers for muscle differentiation. In addition, these myotubes contracted upon electrical stimulation, responded to acetylcholine (Ach and were able to generate action potentials. Finally, we co-cultured motoneurons and myotubes generated from identical hiPSCs cell lines. We could observe the early aggregation of acetylcholine receptors in muscle cells of immature co-cultures. At later stages, we identified and characterised mature neuromuscular junctions (NMJs. In summary, we describe here the successful generation of an iPS cell derived functional cellular system consisting of two distinct communicating cells types. This in vitro co-culture system could therefore contribute to research on diseases in which the motoneurons and the NMJ are predominantly affected, such as in amyotrophic lateral sclerosis or spinal muscular atrophy.

  14. Fast axonal transport of labeled proteins in motoneurons of exercise-trained rats

    International Nuclear Information System (INIS)

    Jasmin, B.J.; Lavoie, P.A.; Gardiner, P.F.

    1988-01-01

    In this study, the fast orthograde axonal transport of radiolabeled proteins was measured to determine the effects of endurance-running training on transport velocity and amounts of transported proteins in rat sciatic motoneurons. Female rats were subjected to a progressive running-training program for 10-12 wk. Twenty-four hours after the last training session, rats underwent right L4-L5 dorsal root ganglionectomy. The next day, 20 microCi of [3H]leucine was injected bilaterally in the vicinity of the motoneuronal cell bodies supplying the sciatic nerve, to study axonal transport parameters. Results showed that peak and average transport velocities of labeled proteins were significantly (P less than 0.05) increased by 22 and 29%, respectively, in the deafferented nerves of the runners as compared with controls. Moreover, the amount of total transported protein-bound radioactivity was increased in both left (40%) and right (37%) sciatic nerves of the runners. An exhaustive exercise session reduced (P less than 0.05) peak displacement (8%) and total transported protein-bound radioactivity (36%) in the sciatic nerves of control rats, whereas no changes were noticed in trained animals. The data suggest that chronic endurance running induces significant adaptations in the fast axonal transport of labeled proteins

  15. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Norifumi; Nagaoka, Shunji; Nojima, Kumie

    2003-01-01

    We investigate effects of localized exposure of heavy ion to the lumbar 4th to 6th segments of the rat spinal cord on the properties of motoneurons and the innervated muscle fibers without surgical treatments. Twenty 7-week-old male Wistar rats were exposed to 5 mm spread-out Bragg peak (SOBP) carbon beam (290 MeV, linear energy transfer (LET)=130 keV/μm): Two doses (15 Gy or 20 Gy) were applied to each group of rats (n=5) in two different depths; one group was exposed only for ventral horn of the spinal cord while other for whole spinal cord. Five rats served as controls. The rats were exposed to carbon irons on October 26, 2002. We will sacrifice the rats soon after they show an abnormal behavior including posture and walking. Cell body size and oxidative enzyme activity of spinal motoneurons of the control and heavy-ion-exposed rats will be analyzed. In addition, cell size, oxidative enzyme activity, and expressions of myosin heavy chain isoforms of the gastrocnemius, soleus, plantaris, extensor digitorum longus, and tibialis anterior muscle fibers will be also determined. This study is performed to test our hypothesis that atrophy and a decrease in cross-sectional area of motoneurons and muscle fibers which they innervate, as well as a decrease in oxidative activity of motoneurons and muscle fibers, will be induced due to exposure to heavy ion. (author)

  16. Estrogen induces axonal outgrowth in the nucleus retroambiguus-lumbosacral motoneuronal pathway in the adult female cat

    NARCIS (Netherlands)

    VanderHorst, VGJM; Holstege, G

    1997-01-01

    In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VG.JM, Holstege G (1995) Caudal medullary pathways to lumbosacral

  17. Retroambiguus projections to the cutaneus trunci motoneurons may form a pathway in the central control of mating

    NARCIS (Netherlands)

    Gerrits, Peter O.; Vodde, Chris; Holstege, Gert

    Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system

  18. Afferent projections to pharynx and soft palate motoneurons : A light and electron microscopical tracing study in the cat

    NARCIS (Netherlands)

    Boers, J; Hulshoff, AC; De Weerd, H; Mouton, LJ; Kuipers, R; Holstege, G; Hulshoff, Antoinette C.

    2005-01-01

    Pharynx and soft palate are muscles for respiration, vocalization, swallowing, and vomiting. In cat, motoneurons innervating pharynx/soft palate are located in the dorsal group of the nucleus ambiguus (dgNA) in the medulla oblongata. In cat, dgNA is the only part of nucleus ambiguus that can be

  19. 5-HT modulation of multiple inward rectifiers in motoneurons in intact preparations of the neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kjaerulff, Ole; Kiehn, Ole

    2001-01-01

    This study introduces novel aspects of inward rectification in neonatal rat spinal motoneurons (MNs) and its modulation by serotonin (5-HT). Whole cell tight-seal recordings were made from MNs in an isolated lumbar spinal cord preparation from rats 1-2 days of age. In voltage clamp, hyperpolarizi...

  20. Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs

    DEFF Research Database (Denmark)

    Ford, Tim W; Meehan, Claire Francesca; Kirkwood, Peter

    2014-01-01

    , 9 being in Group B Dist motoneurones. The complete absence of heteronymous monosynaptic Group I reflex excitation between muscles that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role...... in controlling expiratory movements but, where present, support other motor acts....

  1. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves

    DEFF Research Database (Denmark)

    Wienecke, Jacob; Denton, Manuel Enríquez; Stecina, Katinka

    2015-01-01

    In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves). Seven decerebrate cats, under neuromuscular blockade, were used to stu...

  2. A Simulation Based Analysis of Motor Unit Number Index (MUNIX) Technique Using Motoneuron Pool and Surface Electromyogram Models

    Science.gov (United States)

    Li, Xiaoyan; Rymer, William Zev; Zhou, Ping

    2013-01-01

    Motor unit number index (MUNIX) measurement has recently achieved increasing attention as a tool to evaluate the progression of motoneuron diseases. In our current study, the sensitivity of the MUNIX technique to changes in motoneuron and muscle properties was explored by a simulation approach utilizing variations on published motoneuron pool and surface electromyogram (EMG) models. Our simulation results indicate that, when keeping motoneuron pool and muscle parameters unchanged and varying the input motor unit numbers to the model, then MUNIX estimates can appropriately characterize changes in motor unit numbers. Such MUNIX estimates are not sensitive to different motor unit recruitment and rate coding strategies used in the model. Furthermore, alterations in motor unit control properties do not have a significant effect on the MUNIX estimates. Neither adjustment of the motor unit recruitment range nor reduction of the motor unit firing rates jeopardizes the MUNIX estimates. The MUNIX estimates closely correlate with the maximum M wave amplitude. However, if we reduce the amplitude of each motor unit action potential rather than simply reduce motor unit number, then MUNIX estimates substantially underestimate the motor unit numbers in the muscle. These findings suggest that the current MUNIX definition is most suitable for motoneuron diseases that demonstrate secondary evidence of muscle fiber reinnervation. In this regard, when MUNIX is applied, it is of much importance to examine a parallel measurement of motor unit size index (MUSIX), defined as the ratio of the maximum M wave amplitude to the MUNIX. However, there are potential limitations in the application of the MUNIX methods in atrophied muscle, where it is unclear whether the atrophy is accompanied by loss of motor units or loss of muscle fiber size. PMID:22514208

  3. In vivo intracellular recordings from spinal lumbar motoneurones in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurones

    DEFF Research Database (Denmark)

    Lehnhoff, Janna; Moldovan, Mihai; Hedegaard, Anne

    2014-01-01

    Mice deficient for the peripheral myelin binding protein zero (P0-/-) show a progressive dysmyelinating neuropathy phenotypically resembling severe forms of Charcot-Marie-Tooth (CMT) disease. Traditionally, the progression of the disease was attributed to axonal loss, but the effect of chronic...... dysmyelination remains poorly understood. In this study, in vivo electrophysiological recordings were used to assess the function of both central and axonal components of spinal lumbar motoneurones in adult P0-/- mice.Three month old P0-/- mice (n=7) and wild type (WT) littermate controls (n=5) were...... anaesthetized with Hypnorm (0.315 mg/mL fentanyl-citrate + 10 mg/mL fluanisone), Midazolam (5 mg/mL), and sterile water, mixed in the ratio 1:1:2 (induction: 0.15mL/25g, maintenance: 0.05 mL/20 minutes, S.C.). Anaesthesia during surgery was assessed by the lack of reflexes to a short noxious pinch on the hind...

  4. Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools.

    Science.gov (United States)

    Schoppik, David; Bianco, Isaac H; Prober, David A; Douglass, Adam D; Robson, Drew N; Li, Jennifer M B; Greenwood, Joel S F; Soucy, Edward; Engert, Florian; Schier, Alexander F

    2017-11-22

    Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically relevant stimuli without

  5. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Zanon Renata G

    2010-05-01

    Full Text Available Abstract Background Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO. The present work investigated the importance of inducible nitric oxide synthase (iNOS activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I expression and synaptic plasticity of inputs to lesioned alpha motoneurons. Methods In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/- and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker, Iba-1 (an ionized calcium binding adaptor protein and a microglial marker or synaptophysin (a presynaptic terminal marker. Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data. Results A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J. Conclusion The findings herein indicate that i

  6. APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

    2010-03-16

    Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

  7. The Role of the Heat Shock Protein B8 (HSPB8 in Motoneuron Diseases

    Directory of Open Access Journals (Sweden)

    Paola Rusmini

    2017-06-01

    Full Text Available Amyotrophic lateral sclerosis (ALS and spinal and bulbar muscular atrophy (SBMA are two motoneuron diseases (MNDs characterized by aberrant protein behavior in affected cells. In familial ALS (fALS and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC system. The small heat shock protein B8 (HSPB8 is a chaperone induced by harmful events, like proteasome inhibition. HSPB8 is expressed both in motoneuron and muscle cells, which are both targets of misfolded protein toxicity in MNDs. In ALS mice models, in presence of the mutant proteins, HSPB8 is upregulated both in spinal cord and muscle. HSPB8 interacts with the HSP70 co-chaperone BAG3 and enhances the degradation of misfolded proteins linked to sALS, or causative of fALS and of SBMA. HSPB8 acts by facilitating autophagy, thereby preventing misfolded protein accumulation in affected cells. BAG3 and BAG1 compete for HSP70-bound clients and target them for disposal to the autophagy or proteasome, respectively. Enhancing the selective targeting of misfolded proteins by HSPB8-BAG3-HSP70 to autophagy may also decrease their delivery to the proteasome by the BAG1-HSP70 complex, thereby limiting possible proteasome overwhelming. Thus, approaches aimed at potentiating HSPB8-BAG3 may contribute to the maintenance of proteostasis and may delay MNDs progression.

  8. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons.

    Directory of Open Access Journals (Sweden)

    Olga Gajewska-Woźniak

    Full Text Available The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG. LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models

  9. Targeted Delivery of TrkB Receptor to Phrenic Motoneurons Enhances Functional Recovery of Rhythmic Phrenic Activity after Cervical Spinal Hemisection

    Science.gov (United States)

    Gransee, Heather M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

    2013-01-01

    Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (pphrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery. PMID:23724091

  10. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle...... adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway......-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue...

  11. Developmental plasticity of phrenic motoneuron and diaphragm properties with the inception of inspiratory drive transmission in utero.

    Science.gov (United States)

    Greer, John J; Martin-Caraballo, Miguel

    2017-01-01

    The review outlines data consistent with the hypothesis that inspiratory drive transmission that generates fetal breathing movements (FBMs) is essential for the developmental plasticity of phrenic motoneurons (PMNs) and diaphragm musculature prior to birth. A systematic examination during the perinatal period demonstrated a very marked transformation of PMN and diaphragm properties coinciding with the onset and strengthening of inspiratory drive and FBMs in utero. This included studies of age-dependent changes of: i) morphology, neuronal coupling, passive and electrophysiological properties of PMNs; ii) rhythmic inspiratory activity in vitro; iii) FBMs generated in vivo detected by ultrasonography; iv) contractile and end-plate potential properties of diaphragm musculature. We also propose how the hypothesis can be further evaluated with studies of perinatal hypoglossal motoneuron-tongue musculature and the use of Dbx1 null mice that provide an experimental model lacking descending inspiratory drive transmission in utero. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion

    DEFF Research Database (Denmark)

    Hansen, N.L.; Conway, B.A.; Halliday, D.M.

    2005-01-01

    It is possible to obtain information about the synaptic drive to motoneurons during walking by analyzing motor-unit coupling in the time and frequency domains. The purpose of the present study was to compare motor-unit coupling during walking in healthy subjects and patients with incomplete spina...... as physiological markers of impaired supraspinal control of gait in SCL patients. Such markers could have diagnostic and prognostic value in relation to the recovery of locomotion in patients with central motor lesions....

  13. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

    Science.gov (United States)

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

  14. CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency.

    Science.gov (United States)

    Brockmann, Sarah J; Freischmidt, Axel; Oeckl, Patrick; Müller, Kathrin; Ponna, Srinivas K; Helferich, Anika M; Paone, Christoph; Reinders, Jörg; Kojer, Kerstin; Orth, Michael; Jokela, Manu; Auranen, Mari; Udd, Bjarne; Hermann, Andreas; Danzer, Karin M; Lichtner, Peter; Walther, Paul; Ludolph, Albert C; Andersen, Peter M; Otto, Markus; Kursula, Petri; Just, Steffen; Weishaupt, Jochen H

    2018-02-15

    Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p.R15L and p.G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p.P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p.R15L and p.G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p.R15L, but not of CHCHD10 p.G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p.G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p.P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice.

    Directory of Open Access Journals (Sweden)

    Young-Eun Yoo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT, which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.

  16. Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling.

    Science.gov (United States)

    Madji Hounoum, Blandine; Mavel, Sylvie; Coque, Emmanuelle; Patin, Franck; Vourc'h, Patrick; Marouillat, Sylviane; Nadal-Desbarats, Lydie; Emond, Patrick; Corcia, Philippe; Andres, Christian R; Raoul, Cédric; Blasco, Hélène

    2017-04-01

    The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605. © 2017 Wiley Periodicals, Inc.

  17. Giant multimodal heart motoneurons of Achatina fulica: a new cardioregulatory input in pulmonates.

    Science.gov (United States)

    Zhuravlev, V; Bugaj, V; Kodirov, S; Safonova, T; Staruschenko, A

    2001-08-01

    The regulation of the heartbeat by the two largest neurons, d-VLN and d-RPLN, on the dorsal surface of visceral and right parietal ganglia of Giant African snail, Achatina fulica, was examined. Using the new method of animal preparation, for the first time, discrete biphasic inhibitory-excitatory junction potentials (I-EJPs) in the heart and several muscles of the visceral sac were recorded. The duration of hyperpolarizing phase (H-phase) of biphasic I-EJPs was 269+/-5.6 ms (n=5), which is 2-3 times less than that of the cholinergic inhibitory JPs (682+/-68.5 ms, n=5). The H-phase of I-EJPs was not altered by the application of atropine, picrotoxine, succinylcholinchloride, D-tubocurarine and tetraethylammonium or substitution of Cl(-) ions. Even the low-frequency neuronal discharges (1-2 imp/s) evoked significant facilitation and potentiation of the H-phase. Between the multimodal neurons d-VLN/d-RPLN and mantle or visceral organs there is evidence of direct synaptic connections. These neurons were found to have no axonal branches in the intestinal nerve as once suspected but reach the heart through several other nerves. New giant heart motoneurons do not interact with previously identified cardioregulatory neurons.

  18. EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

    Science.gov (United States)

    Burgunder, J-M; Schöls, L; Baets, J; Andersen, P; Gasser, T; Szolnoki, Z; Fontaine, B; Van Broeckhoven, C; Di Donato, S; De Jonghe, P; Lynch, T; Mariotti, C; Spinazzola, A; Tabrizi, S J; Tallaksen, C; Zeviani, M; Harbo, H F; Finsterer, J

    2011-02-01

    These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

  19. Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

    Science.gov (United States)

    Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

    2014-01-01

    Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

  20. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats. The 2nd report

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Xiao Dong Wang; Nagaoka, Shunji; Nojima, Kumie

    2004-01-01

    We examined the effects of acute exposure of heavy ion on the properties of motoneurons and their innervating muscle fibers. A 40 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in five 8-week-old male rats. Five male rats served as controls. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were analyzed. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no changes in the number of motoneurons between the control and heavy-ion-exposed rats. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in motoneurons of the heavy-ion-exposed rats. There were no changes in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the muscles between the control and heavy-ion-exposed rats. It is concluded that a 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there were no influences on the properties of muscle fibers which they innervate. (author)

  1. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    Science.gov (United States)

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  2. ATF3 expression precedes death of spinal motoneurons in amyotrophic lateral sclerosis-SOD1 transgenic mice and correlates with c-Jun phosphorylation, CHOP expression, somato-dendritic ubiquitination and Golgi fragmentation

    NARCIS (Netherlands)

    Vlug, Angela S; Teuling, Eva; Haasdijk, Elize D; French, Pim; Hoogenraad, Casper C; Jaarsma, Dick

    2005-01-01

    To obtain insight into the morphological and molecular correlates of motoneuron degeneration in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant superoxide dismutase (SOD)1 (G93A mice), we have mapped and characterized 'sick' motoneurons labelled by the 'stress transcription

  3. Influence of active dendritic currents on input-output processing in spinal motoneurons in vivo.

    Science.gov (United States)

    Lee, R H; Kuo, J J; Jiang, M C; Heckman, C J

    2003-01-01

    The extensive dendritic tree of the adult spinal motoneuron generates a powerful persistent inward current (PIC). We investigated how this dendritic PIC influenced conversion of synaptic input to rhythmic firing. A linearly increasing, predominantly excitatory synaptic input was generated in triceps ankle extensor motoneurons by slow stretch (duration: 2-10 s) of the Achilles tendon in the decerebrate cat preparation. The firing pattern evoked by stretch was measured by injecting a steady current to depolarize the cell to threshold for firing. The effective synaptic current (I(N), the net synaptic current reaching the soma of the cell) evoked by stretch was measured during voltage clamp. Hyperpolarized holding potentials were used to minimize the activation of the dendritic PIC and thus estimate stretch-evoked I(N) for a passive dendritic tree (I(N,PASS)). Depolarized holding potentials that approximated the average membrane potential during rhythmic firing allowed strong activation of the dendritic PIC and thus resulted in marked enhancement of the total stretch-evoked I(N) (I(N,TOT)). The net effect of the dendritic PIC on the generation of rhythmic firing was assessed by plotting stretch-evoked firing (strong PIC activation) versus stretch-evoked I(N,PASS) (minimal PIC activation). The gain of this input-output function for the neuron (I-O(N)) was found to be ~2.7 times as high as for the standard injected frequency current (F-I) function in low-input conductance neurons. However, about halfway through the stretch, firing rate tended to become constant, resulting in a sharp saturation in I-O(N) that was not present in F-I. In addition, the gain of I-O(N) decreased sharply with increasing input conductance, resulting in much lower stretch-evoked firing rates in high-input conductance cells. All three of these phenomena (high initial gain, saturation, and differences in low- and high-input conductance cells) were also readily apparent in the differences between

  4. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves.

    Science.gov (United States)

    Wienecke, Jacob; Enríquez Denton, Manuel; Stecina, Katinka; Kirkwood, Peter A; Hultborn, Hans

    2015-01-01

    In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves). Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2) and spontaneously occurring locomotor drive potentials (LDPs) in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves), with a slow rate (periods 9-104 s, mean 39 ± 17 SD). Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

  5. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves

    Directory of Open Access Journals (Sweden)

    Katinka eStecina

    2015-02-01

    Full Text Available In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves. Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2 and spontaneously occurring locomotor drive potentials (LDPs in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves, with a slow rate (periods 9 - 104 s, mean 39 ± 17 SD. Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

  6. Exacerbation of Facial Motoneuron Loss after Facial Nerve Axotomy in CCR3-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-11-01

    Full Text Available We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron survival after facial nerve axotomy that is dependent on CD4+ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4+ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type, a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3–/– mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2 –/– (recombination activating gene-2-deficient mice adoptively transferred CD4+ T-cells isolated from CCR3–/– mice, but not in CCR3–/– mice adoptively transferred CD4+ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4+ T-cell- and CCR3-mediated neuroprotection after FMN injury.

  7. Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans.

    Science.gov (United States)

    Marchand-Pauvert, V; Nicolas, G; Pierrot-Deseilligny, E

    2000-05-15

    Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level. Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents. Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s-1). A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side. It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat

  8. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells due to interferon-gamma exposure

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A.; Krause, James S.; Banik, Naren L.

    2014-01-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. In order to examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis related proteases (caspase-3 and −12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. PMID:24188094

  9. Cross-talk between IGF-1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells because of interferon-gamma exposure.

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Krause, James S; Banik, Naren L

    2014-03-01

    Insulin-like growth factor-1 (IGF-1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. To examine whether IGF-1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 (VSC4.1) motoneuron cells were treated with interferon-gamma (IFN-γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl-2 ratios, and expression of apoptosis-related proteases (caspase-3 and -12) in motoneurons rendered by IFN-γ in a dose-dependent manner. Post-treatment with IGF-1 attenuated these changes. In addition, IGF-1 treatment of motoneurons exposed to IFN-γ decreased expression of inflammatory markers (cyclooxygenase-2 and nuclear factor-kappa B:inhibitor of kappa B ratio). Furthermore, IGF-1 attenuated the loss of expression of IGF-1 receptors (IGF-1Rα and IGF-1Rβ) and estrogen receptors (ERα and ERβ) induced by IFN-γ. To determine whether the protective effects of IGF-1 are associated with ERs, ERs antagonist ICI and selective siRNA targeted against ERα and ERβ were used in VSC4.1 motoneurons. Distinctive morphological changes were observed following siRNA knockdown of ERα and ERβ. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ERα and ERβ-silenced VSC4.1 motoneurons following IFN-γ and IGF-1 exposure. These results suggest that IGF-1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ERα and ERβ. © 2013 International Society for Neurochemistry.

  10. Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical function

    DEFF Research Database (Denmark)

    Petersen, Nicolas Caesar; Butler, Jane E.; Taylor, Janet L.

    2010-01-01

    of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) contribute to drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output...... magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at 'very low' intensities which elicit only short-latency suppression...

  11. Electrophysiological and Morphological Properties of α and γ Motoneurons in the Rat Trigeminal Motor Nucleus

    Directory of Open Access Journals (Sweden)

    Kayo Nishimura

    2018-01-01

    Full Text Available The muscle contraction during voluntary movement is regulated by activities of α- and γ-motoneurons (αMNs and γMNs, respectively. The tension of jaw-closing muscles can be finely tuned over a wide range. This excellent function is likely to be achieved by the specific populations of αMNs innervating jaw-closing muscles. Indeed, we have recently demonstrated that in the rat dorsolateral trigeminal motor nucleus (dl-TMN, the size distribution of αMNs was bimodal and the population of smaller αMNs showed a size distribution similar to that of γMNs, by immunohistochemically identifying αMNs and γMNs based on the expressions of estrogen-related receptor gamma (Err3 and neuronal DNA binding protein NeuN together with ChAT. This finding suggests the presence of αMNs as small as γMNs. However, differences in the electrophysiological membrane properties between αMNs and γMNs remain unknown also in the dl-TMN. Therefore, in the present study, we studied the electrophysiological membrane properties of MNs in the dl-TMN of infant rats at postnatal days 7–12 together with their morphological properties using whole-cell current-clamp recordings followed by immunohistochemical staining with an anti-NeuN and anti-ChAT antibodies. We found that the ChAT-positive and NeuN-positive αMNs were divided into two subclasses: the first one had a larger cell body and displayed a 4-aminopyridine (4-AP-sensitive current while the second one had a smaller cell body and displayed a less prominent 4-AP-sensitive current and a low-threshold spike, suitable for their orderly recruitment. We finally found that γMNs showing ChAT-positive and NeuN-negative immunoreactivities had smaller cell bodies and displayed an afterdepolarization mediated by flufenamate-sensitive cation current. It is suggested that these electrophysiological and morphological features of MNs in the dl-TMN are well correlated with the precise control of occlusion.

  12. Expression of the low affinity neurotrophin receptor p75 in spinal motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Copray, JCVM; Jaarsma, D; Kust, BM; Bruggeman, RWG; Mantingh, [No Value; Brouwer, N; Boddeke, HWGM

    2003-01-01

    Amyotrophic lateral sclerosis is a lethal neurodegenerative disorder involving motoneuron loss in the cortex, brainstem and spinal cord, resulting in progressive paralysis. Aberrant neurotrophin signalling via the low affinity neurotrophin receptor p75 has been suggested to be involved in the

  13. Distribution of serotonin 2A and 2C receptor mRNA expression in the cervical ventral horn and phrenic motoneurons following spinal cord hemisection.

    Science.gov (United States)

    Basura, G J; Zhou, S Y; Walker, P D; Goshgarian, H G

    2001-06-01

    Cervical spinal cord injury leads to a disruption of bulbospinal innervation from medullary respiratory centers to phrenic motoneurons. Animal models utilizing cervical hemisection result in inhibition of ipsilateral phrenic nerve activity, leading to paralysis of the hemidiaphragm. We have previously demonstrated a role for serotonin (5-HT) as one potential modulator of respiratory recovery following cervical hemisection, a mechanism that likely occurs via 5-HT2A and/or 5-HT2C receptors. The present study was designed to specifically examine if 5-HT2A and/or 5-HT2C receptors are colocalized with phrenic motoneurons in both intact and spinal-hemisected rats. Adult female rats (250-350 g; n = 6 per group) received a left cervical (C2) hemisection and were injected with the fluorescent retrograde neuronal tracer Fluorogold into the left hemidiaphragm. Twenty-four hours later, animals were killed and spinal cords processed for in situ hybridization and immunohistochemistry. Using (35)S-labeled cRNA probes, cervical spinal cords were probed for 5-HT2A and 5-HT2C receptor mRNA expression and double-labeled using an antibody to Fluorogold to detect phrenic motoneurons. Expression of both 5-HT2A and 5-HT2C receptor mRNA was detected in motoneurons of the cervical ventral horn. Despite positive expression of both 5-HT2A and 5-HT2C receptor mRNA-hybridization signal over phrenic motoneurons, only 5-HT2A silver grains achieved a signal-to-noise ratio representative of colocalization. 5-HT2A mRNA levels in identified phrenic motoneurons were not significantly altered following cervical hemisection compared to sham-operated controls. Selective colocalization of 5-HT2A receptor mRNA with phrenic motoneurons may have implications for recently observed 5-HT2A receptor-mediated regulation of respiratory activity and/or recovery in both intact and injury-compromised states. Copyright 2001 Academic Press.

  14. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

    Science.gov (United States)

    Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

    2002-01-01

    Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (Ih) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in Ih activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When Ih was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (EK) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of Ih in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of Ih. When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in Ih activation. Thus, halothane and neurotransmitters converge on TASK and Ih channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on Ih. These data suggest that

  15. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Wang, Xiao Dong; Nagaoka, Shunji; Nojima, Kumie

    2005-01-01

    The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

  16. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2015-01-01

    Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

  17. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF.

    Directory of Open Access Journals (Sweden)

    Alexandre eHenriques

    2015-01-01

    Full Text Available ABSTRACTBackgroundAmyotrophic lateral sclerosis (ALS is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. ResultsMotoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age, when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age. Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12.ConclusionsOur data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  18. Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  19. Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

    DEFF Research Database (Denmark)

    Andersen, Birgit; Felding, Ulrik Ascanius; Krarup, Christian

    2012-01-01

    Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased...... probability of repetitive spinal MN activation during exercise even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST (Quadruple stimulation; QuadS and Quintuple stimulation; QuintS) to examine the influence of fatiguing exercise on second and third MN discharges after......, reflecting that a greater proportion of spinal MNs were activated 2 or 3 times by the transcranial stimulus. The size of QuadS responses did not return to pre-contraction levels during 10 min observation time indicating long-lasting increase in excitatory input to spinal MNs. In addition, the post...

  20. Transmitter-controlled properties of α-motoneurones causing long-lasting motor discharge to brief excitatory inputs

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Hultborn, H.; Kiehn, O.

    1986-01-01

    Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced ...... flipflops, which are set at one of two levels by short excitatory or inhibitory inputs. However, when the whole motoneuronal pool is considered, many different levels can be maintained by recruitment of new units.......Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced...

  1. The expression of a motoneuron-specific serine protease, motopsin (PRSS12), after facial nerve axotomy in mice.

    Science.gov (United States)

    Numajiri, Toshiaki; Mitsui, Shinichi; Hisa, Yasuo; Ishida, Toshihiro; Nishino, Kenichi; Yamaguchi, Nozomi

    2006-01-01

    Motopsin (PRSS12) is a mosaic serine protease that is preferentially expressed in motor neurons. To study the relationship between motopsin and motoneuron function, we investigated the expression of motopsin mRNA in facial nerve nuclei after facial nerve axotomy at the anterior margin of the parotid gland in mice. Neuronal function was monitored by assessing vibrissal motion in 3 months. Vibrissal behaviour on the injured side disappeared until the day 14 post-operation, and then recovered between the day 21 and 35. Motopsin expression decreased at the day 14, but markedly recovered by the day 21. In contrast, expression of growth-associated protein-43 (GAP-43) was induced at the day 3. These results suggest that the recovery of motopsin expression is correlated with the recovery of the facial motor neuronal function.

  2. Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

    Science.gov (United States)

    Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

    2009-08-25

    The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

  3. Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle.

    Science.gov (United States)

    Dideriksen, Jakob L; Holobar, Ales; Falla, Deborah

    2016-08-01

    Pain is associated with changes in the neural drive to muscles. For the upper trapezius muscle, surface electromyography (EMG) recordings have indicated that acute noxious stimulation in either the cranial or the caudal region of the muscle leads to a relative decrease in muscle activity in the cranial region. It is, however, not known if this adaption reflects different recruitment thresholds of the upper trapezius motor units in the cranial and caudal region or a nonuniform nociceptive input to the motor units of both regions. This study investigated these potential mechanisms by direct motor unit identification. Motor unit activity was investigated with high-density surface EMG signals recorded from the upper trapezius muscle of 12 healthy volunteers during baseline, control (intramuscular injection of isotonic saline), and painful (hypertonic saline) conditions. The EMG was decomposed into individual motor unit spike trains. Motor unit discharge rates decreased significantly from control to pain conditions by 4.0 ± 3.6 pulses/s (pps) in the cranial region but not in the caudal region (1.4 ± 2.8 pps; not significant). These changes were compatible with variations in the synaptic input to the motoneurons of the two regions. These adjustments were observed, irrespective of the location of noxious stimulation. These results strongly indicate that the nociceptive synaptic input is distributed in a nonuniform way across regions of the upper trapezius muscle. Copyright © 2016 the American Physiological Society.

  4. Effects of tripolar TENS on slow and fast motoneurons: a preliminary study using H-reflex recovery curve method.

    Science.gov (United States)

    Simorgh, L; Torkaman, G; Firoozabadi, S M

    2008-01-01

    This study aimed at examining the effect of tripolar TENS of vertebral column on the activity of slow and fast motoneurons on 10 healthy non-athlete women aged 22.7 +/- 2.21 yrs. H-reflex recovery curve of soleus (slow) and gastrocnemius (fast) muscles were recorded before and after applying tripolar TENS. For recording of this curve, rectangular paired stimuli were applied on tibial nerve (with 40-520 ISI, frequency of 0.2 Hz and pulse width of 600 micros). Our findings showed that maximum H-reflex recovery in gastrocnemius muscle appeared in the shorter ISI, while in soleus muscle, it appeared in the longer ISI and its amplitude slightly decreased after applying tripolar TENS. It is suggested that tripolar TENS excites not only the skin but also Ia and Ib afferents in the dorsal column. A Synaptic interaction of these afferents in spinal cord causes the inhibition of type I MNs and facilitation of type II MNs. This effect can be used in muscle tone modulation.

  5. Effects of calcium (Ca(2+)) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: insight from a mathematical model.

    Science.gov (United States)

    Horn, Kyle G; Solomon, Irene C

    2014-01-01

    Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca(2+), which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca(2+) and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca(2+) handling processes. For the current study, a series of HM models that include Ca(2+) pumps, Na(+)/Ca(2+) exchangers, and a generic exponential decay of excess Ca(2+) were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca(2+)-related mechanisms: BK channels, Ca(2+) buffering, and diffusion of [Ca(2+)]i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca(2+) seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca(2+) appears to be necessary for capturing longer term frequency changes. © 2014 Elsevier B.V. All rights reserved.

  6. Neuromodulation of reciprocal glutamatergic inhibition between antagonistic motoneurons by 5-hydroxytryptamine (5-HT) in crayfish walking system.

    Science.gov (United States)

    Pearlstein, E; Clarac, F; Cattaert, D

    1998-01-23

    In an in vitro preparation of the crayfish thoracic locomotor system, paired intracellular recordings were performed from antagonistic depressor (Dep) and levator (Lev) motoneurons (MNs) that control the second joint of walking legs. Connections between these two groups of MNs consist mainly of inhibitory connections and weak electrotonic synapses. Injection of depolarizing current into a Lev MN results in a hyperpolarization in a Dep MN, and vice versa. This reciprocal glutamatergic inhibition, is not changed in the presence of the sodium channel blocker tetrodotoxin (TTX) and therefore is likely supported by a direct connection between MNs. By contrast, reciprocal inhibition is largely reduced in the presence of 5-hydroxytryptamine (5-HT; 10 microM). Direct micro-application of glutamate pressure-ejected close to an intracellularly recorded MN, evoked an inhibitory response in that MN, accompanied by a decrease of input resistance. These two effects were dramatically reduced in the presence of 5-HT. Thus 5-HT could be involved in mechanisms of dynamic reconfigurations of the neural network controlling leg movements in crayfish.

  7. Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females.

    Science.gov (United States)

    Garner, Sarah Rose C; Castellanos, Monica C; Baillie, Katherine E; Lian, Tianshun; Allan, Douglas W

    2018-01-08

    Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex-determination gene fruitless ( fru ) into the Fru MC isoform. However, in females, fru alleles that only generate Fru M isoforms failed to kill FS-Ilp7 motoneurons. This blockade of Fru M -dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer ( tra ), a gene encoding the RNA splicing activator that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the Fru M isoform is expressed. In addition, we found that Fru MC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, Fru MC -dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons. © 2018. Published by The Company of Biologists Ltd.

  8. Adult mouse motor units develop almost all of their force in the subprimary range: a new all-or-none strategy for force recruitment?

    Science.gov (United States)

    Manuel, Marin; Heckman, C J

    2011-10-19

    Classical studies of the mammalian neuromuscular system have shown an impressive adaptation match between the intrinsic properties of motoneurons and the contractile properties of their motor units. In these studies, the rate at which motoneurons start to fire repetitively corresponds to the rate at which individual twitches start to sum, and the firing rate increases linearly with the amount of excitation ("primary range") up to the point where the motor unit develops its maximal force. This allows for the gradation of the force produced by a motor unit by rate modulation. In adult mouse motoneurons, however, we recently described a regime of firing ("subprimary range") that appears at lower excitation than what is required for the primary range, a finding that might challenge the classical conception. To investigate the force production of mouse motor units, we simultaneously recorded, for the first time, the motoneuron discharge elicited by intracellular ramps of current and the force developed by its motor unit. We showed that the motor unit developed nearly its maximal force during the subprimary range. This was found to be the case regardless of the input resistance of the motoneuron, the contraction speed, or the tetanic force of the motor unit. Our work suggests that force modulation in small mammals mainly relies on the number of motor units that are recruited rather than on rate modulation of individual motor units.

  9. SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.

    Science.gov (United States)

    Romeo-Guitart, David; Leiva-Rodríguez, Tatiana; Espinosa-Alcantud, María; Sima, Núria; Vaquero, Alejandro; Domínguez-Martín, Helena; Ruano, Diego; Casas, Caty

    2018-05-10

    Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.

  10. Spatiotemporal organization of alpha-motoneuron activity in the human spinal cord during different gaits and gait transitions.

    Science.gov (United States)

    Ivanenko, Y P; Cappellini, G; Poppele, R E; Lacquaniti, F

    2008-06-01

    Here we studied the spatiotemporal organization of motoneuron (MN) activity during different human gaits. We recorded the electromyographic (EMG) activity patterns in 32 ipsilateral limb and trunk muscles from normal subjects while running and walking on a treadmill (3-12 km/h). In addition, we recorded backward walking and skipping, a distinct human gait that comprises the features of both walking and running. We mapped the recorded EMG activity patterns onto the spinal cord in approximate rostrocaudal locations of the MN pools. The activation of MNs tends to occur in bursts and be segregated by spinal segment in a gait-specific manner. In particular, sacral and cervical activation timings were clearly gait-dependent. Swing-related activity constituted an appreciable fraction (> 30%) of the total MN activity of leg muscles. Locomoting at non-preferred speeds (running and walking at 5 and 9 km/h, respectively) showed clear differences relative to preferred speeds. Running at low speeds was characterized by wider sacral activation. Walking at high non-preferred speeds was accompanied by an 'atypical' locus of activation in the upper lumbar spinal cord during late stance and by a drastically increased activation of lumbosacral segments. The latter findings suggest that the optimal speed of gait transitions may be related to an optimal intensity of the total MN activity, in addition to other factors previously described. The results overall support the idea of flexibility and adaptability of spatiotemporal activity in the spinal circuitry with constraints on the temporal functional connectivity of hypothetical pulsatile burst generators.

  11. Reduced phrenic motoneuron recruitment during sustained inspiratory threshold loading compared to single-breath loading: a twitch interpolation study

    Directory of Open Access Journals (Sweden)

    Mathieu Raux

    2016-11-01

    reflecting motoneuron recruitment, this study supports motor reorganisation compatible with diaphragm sparing when an inspiratory threshold load becomes sustained

  12. The motor system plays the violin: a musical metaphor inferred from the oscillatory activity of the α-motoneuron pools during locomotion.

    Science.gov (United States)

    Chiovetto, Enrico

    2011-04-01

    Despite substantial advances in the field, particularly resulting from physiological studies in animals, the neural mechanisms underlying the generation of many motor behaviors in humans remain unclear. A recent study (Cappellini G et al. J Neurophysiol 104: 3064-3073, 2010) sheds more light on this topic. Like the string of a violin, the α-motoneuron pools in the spinal cord during locomotion show continuous and oscillatory patterns of activation. In this report, the implications and relevance of this finding are discussed in a general framework that includes neurophysiology, optimal control theory, and robotics.

  13. cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae.

    Science.gov (United States)

    Krill, Jennifer L; Dawson-Scully, Ken

    2016-01-01

    While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia.

  14. Reduction of common motoneuronal drive on the affected side during walking in hemiplegic stroke patients

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Brittain, John-Stuart; Halliday, David M.

    2008-01-01

    walking in eight subjects with unilateral stroke. RESULTS: On the unaffected side, short-term synchronization was evident from the presence of a narrow central peak in cumulant densities and from the presence of significant coherence between these signals in the 10-25 Hz band. Such indicators of short...... on the affected side in hemiplegic patients during walking. SIGNIFICANCE: This is of importance for understanding the mechanisms responsible for reduced gait ability and development of new strategies for gait restoration....

  15. Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice

    DEFF Research Database (Denmark)

    Hedegaard, Anne; Lehnhoff, Janna; Moldovan, Mihai

    2015-01-01

    Post Activation Depression (PActD) of Ia afferent EPSPs in spinal motoneurons results in a long lasting depression of the stretch reflex. PActD is of clinical interest as it has been shown to be reduced in a number of spastic disorders. Using in vivo intracellular recordings of Ia EPSPs in adult...... mice, we demonstrate that PActD in adult (100-220 days) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both magnitude (approximately 20% depression of EPSPs at 0.5 ms after a stimuli train) and time course (returning...... Sclerosis (ALS). Using the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both pre-symptomatic (16% depression) and symptomatic (17.3% depression) time points compared to aged-matched controls (22...

  16. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    Science.gov (United States)

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  17. Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

    Science.gov (United States)

    Rukhadze, I; Kamani, H; Kubin, L

    2011-12-01

    In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

  18. The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

    Science.gov (United States)

    Okamoto, Keiko; Emura, Norihito; Sato, Hajime; Fukatsu, Yuki; Saito, Mitsuru; Tanaka, Chie; Morita, Yukako; Nishimura, Kayo; Kuramoto, Eriko; Xu Yin, Dong; Furutani, Kazuharu; Okazawa, Makoto; Kurachi, Yoshihisa; Kaneko, Takeshi; Maeda, Yoshinobu; Yamashiro, Takashi; Takada, Kenji; Toyoda, Hiroki; Kang, Youngnam

    2016-01-01

    Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN.

  19. Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

    Science.gov (United States)

    Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A; Mezzarane, Rinaldo A; Komiyama, Tomoyoshi; Ohki, Yukari

    2017-01-01

    Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and

  20. Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii

    Science.gov (United States)

    Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A.; Mezzarane, Rinaldo A.; Komiyama, Tomoyoshi; Ohki, Yukari

    2017-01-01

    Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and

  1. Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

    Directory of Open Access Journals (Sweden)

    Simone Mosole

    2016-11-01

    more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977.

  2. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

    Science.gov (United States)

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-01-01

    , i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. Trial Registration: ClinicalTrials.gov: NCT01679977 PMID:28078066

  3. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

    Science.gov (United States)

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-09-15

    , i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging. ClinicalTrials.gov: NCT01679977.

  4. Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease

    Directory of Open Access Journals (Sweden)

    Zippelius Annette

    2009-06-01

    in individual cells an established cellular model of ALS. The primary goals of this paper are (1 method development, and (2 screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca2+-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS.

  5. A systematic approach for development of a PWR cladding corrosion model

    International Nuclear Information System (INIS)

    Quecedo, M.; Serna, J.J.; Weiner, R.A.; Kersting, P.J.

    2001-01-01

    A new model for the in-reactor corrosion of Improved (low-tin) Zircaloy-4 cladding irradiated in commercial pressurized water reactors (PWRs) is described. The model is based on an extensive database of PWR fuel cladding corrosion data from fuel irradiated in commercial reactors, with a range of fuel duty and coolant chemistry control strategies which bracket current PWR fuel management practices. The fuel thermal duty with these current fuel management practices is characterized by a significant amount of sub-cooled nucleate boiling (SNB) during the fuel's residence in-core, and the cladding corrosion model is very sensitive to the coolant heat transfer models used to calculate the coolant temperature at the oxide surface. The systematic approach to developing the new corrosion model therefore began with a review and evaluation of several alternative models for the forced convection and SNB coolant heat transfer. The heat transfer literature is not sufficient to determine which of these heat transfer models is most appropriate for PWR fuel rod operating conditions, and the selection of the coolant heat transfer model used in the new cladding corrosion model has been coupled with a statistical analysis of the in-reactor corrosion enhancement factors and their impact on obtaining the best fit to the cladding corrosion data. The in-reactor corrosion enhancement factors considered in this statistical analysis are based on a review of the current literature for PWR cladding corrosion phenomenology and models. Fuel operating condition factors which this literature review indicated could have a significant effect on the cladding corrosion performance were also evaluated in detail in developing the corrosion model. An iterative least squares fitting procedure was used to obtain the model coefficients and select the coolant heat transfer models and in-reactor corrosion enhancement factors. This statistical procedure was completed with an exhaustive analysis of the model

  6. Development and aminergic neuromodulation of a spinal locomotor network controlling swimming in Xenopus larvae.

    Science.gov (United States)

    Sillar, K T; Reith, C A; McDearmid, J R

    1998-11-16

    In this article we review our research on the development and intrinsic neuromodulation of a spinal network controlling locomotion in a simple vertebrate. Swimming in hatchling Xenopus embryos is generated by a restricted network of well-characterized spinal neurons. This network produces a stereotyped motor pattern which, like real swimming, involves rhythmic activity that alternates across the body and progresses rostrocaudally with a brief delay between muscle segments. The stereotypy results from motoneurons discharging a single impulse in each cycle; because all motoneurons appear to behave similarly there is little scope for altering the output to the myotomes from one cycle to the next. Just one day later, however, Xenopus larvae generate a more complex and flexible motor pattern in which motoneurons can discharge a variable number of impulses which contribute to ventral root bursts in each cycle. This maturation of swimming is due, in part, to the influence of serotonin released from brain-stem raphespinal interneurons whose axonal projections innervate the cord early in larval life. Larval swimming is differentially modulated by both serotonin and by noradrenaline: serotonin leads to relatively fast, intense swimming whereas noradrenaline favors slower, weaker activity. Thus, these two biogenic amines select opposite extremes from the spectrum of possible output patterns that the swimming network can produce. Our studies on the cellular and synaptic effects of the amines indicate that they can control the strength of reciprocal glycinergic inhibition in the spinal cord. Serotonin and noradrenaline act presynaptically on the terminals of glycinergic commissural interneurons to weaken and strengthen, respectively, crossed glycinergic inhibition during swimming. As a result, serotonin reduces and noradrenaline increases interburst intervals. The membrane properties of spinal neurons are also affected by the amines. In particular, serotonin can induce

  7. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

    2001-01-01

    neurogenesis seemed initially normal. A degeneration of motoneurons and sensory neurons occurred later in development. The mechanism that leads to the dramatic effects on the neural crest derived cell lineages in the dorsal root ganglia (DRG), however, has not been examined up to now. Here, we provide...... a detailed analysis of proliferation and apoptosis in the DRG during the time of their generation and lineage segregation (between E 9.5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism....

  8. Perinatal Development of the Motor Systems Involved in Postural Control

    Directory of Open Access Journals (Sweden)

    Laurent Vinay

    2005-01-01

    Full Text Available Motor behaviors of some species, such as the rat and the human baby, are quite immature at birth. Here we review recent data on some of the mechanisms underlying the postnatal maturation of posture in the rat, in particular the development of pathways descending from the brain stem and projecting onto the lumbar enlargement of the spinal cord. A short-lasting depletion in serotonin affects both posture and the excitability of motoneurons. Here we try to extrapolate to human development and suggest that the abnormalities in motor control observed in childhood—e.g, deficits in motor coordination—might have their roots in the prenatal period, in particular serotonin depletion due to exposure to several environmental and toxicological factors during pregnancy.

  9. Motoneuron firing in amyotrophic lateral sclerosis (ALS

    Directory of Open Access Journals (Sweden)

    Mamede eDe Carvalho

    2014-09-01

    Full Text Available Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials.

  10. A neurochemical map of the developing amphioxus nervous system

    Directory of Open Access Journals (Sweden)

    Candiani Simona

    2012-06-01

    Full Text Available Abstract Background Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates, the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. Results By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC, the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. Conclusions In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons.

  11. Development.

    Science.gov (United States)

    Boydell, Tom

    1982-01-01

    Explores the theories and models of self-actualization and human development. Twelve tables illustrate developmental stages, ways of knowing, moral and ethical development, management style, goals of learning, organizational development, and other dimensions. Availability: M.E.A.D. Subscriptions, C.S.M.L., University of Lancaster, Lancaster LA1…

  12. Developer

    OpenAIRE

    Lakew, Lakachew

    2016-01-01

    As companies grow managing the work becomes harder and harder, thus the ad-vantages of technology come into hand for increasing communication and facili-tating work. This thesis documents the design and development of a web and mobile applica-tion for a service company. The web and mobile applications are built using Laravel and Android Studio respectively. These two applications are designed to communicate with one another so that similar data can be used across these two platforms. ...

  13. Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process

    DEFF Research Database (Denmark)

    Jahn, Patrick; Berg, Rune W; Hounsgaard, Jørn

    2011-01-01

    models can only be applied over short time windows. However, experimental data show varying time constants, state dependent noise, a graded firing threshold and time-inhomogeneous input. In the present study we build a jump diffusion model that incorporates these features, and introduce a firing...

  14. Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization.

    Science.gov (United States)

    Bou-Flores, C; Berger, A J

    2001-04-01

    Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal communication via gap junctions and inhibitory synaptic transmission.

  15. Intense synaptic activity enhances temporal resolution in spinal motoneurons

    DEFF Research Database (Denmark)

    Berg, Rune W; Ditlevsen, Susanne; Hounsgaard, Jørn Dybkjær

    2008-01-01

    In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems...... of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory...

  16. Parasympathetic preganglionic cardiac motoneurons labeled after voluntary diving

    Directory of Open Access Journals (Sweden)

    W Michael ePanneton

    2014-01-01

    Full Text Available A dramatic bradycardia is induced by underwater submersion in vertebrates. The location of parasympathetic preganglionic cardiac motor neurons driving this aspect of the diving response was investigated using cFos immunohistochemistry combined with retrograde transport of cholera toxin subunit B (CTB to double-label neurons. After pericardial injections of CTB, trained rats voluntarily dove underwater, and their heart rates dropped immediately to 95±2bpm, an 80% reduction. After immunohistochemical processing, the vast majority of CTB labeled neurons were located in the reticular formation from the rostral cervical spinal cord to the facial motor nucleus, confirming previous studies. Labeled neurons caudal to the rostral ventrolateral medulla were usually spindle-shaped aligned along an oblique line running from the dorsal vagal nucleus to the ventrolateral reticular formation, while those more rostrally were multipolar with extended dendrites. Nine percent of retrogradely-labeled neurons were positive for both cFos and CTB after diving and 74% of these were found rostral to the obex. CTB also was transported transganglionically in primary afferent fibers, resulting in large granular deposits in dorsolateral, ventrolateral, and commissural subnuclei of the nucleus tractus solitarii and finer deposits in lamina I and IV-V of the trigeminocervical complex. The overlap of parasympathetic preganglionic cardiac motor neurons activated by diving with those activated by baro- and chemoreceptors in the rostral ventrolateral medulla is discussed. Thus the profound bradycardia seen with underwater submersion reinforces the notion that the mammalian diving response is the most powerful autonomic reflex known.

  17. Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury

    Science.gov (United States)

    Lee, Kun-Ze; Dougherty, Brendan J.; Sandhu, Milapjit S.; Lane, Michael A.; Reier, Paul J.; Fuller, David D.

    2013-01-01

    Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8 wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths*min−1) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. PMID:23954215

  18. Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury.

    Science.gov (United States)

    Lee, Kun-Ze; Dougherty, Brendan J; Sandhu, Milapjit S; Lane, Michael A; Reier, Paul J; Fuller, David D

    2013-11-01

    Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths∗min(-1)) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. © 2013.

  19. Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models

    Directory of Open Access Journals (Sweden)

    Lucky eMehra

    2016-03-01

    Full Text Available Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB, caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum. The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early

  20. Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models.

    Science.gov (United States)

    Mehra, Lucky K; Cowger, Christina; Gross, Kevin; Ojiambo, Peter S

    2016-01-01

    Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB), caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum). The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR) and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF), in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors) collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early assessment of

  1. Calsyntenins Are Expressed in a Dynamic and Partially Overlapping Manner during Neural Development

    Directory of Open Access Journals (Sweden)

    Gemma de Ramon Francàs

    2017-08-01

    Full Text Available Calsyntenins form a family of linker proteins between distinct populations of vesicles and kinesin motors for axonal transport. They were implicated in synapse formation and synaptic plasticity by findings in worms, mice and humans. These findings were in accordance with the postsynaptic localization of the Calsyntenins in the adult brain. However, they also affect the formation of neural circuits, as loss of Calsyntenin-1 (Clstn1 was shown to interfere with axonal branching and axon guidance. Despite the fact that Calsyntenins were discovered originally in embryonic chicken motoneurons, their distribution in the developing nervous system has not been analyzed in detail so far. Here, we summarize our analysis of the temporal and spatial expression patterns of the cargo-docking proteins Clstn1, Clstn2 and Clstn3 during neural development by comparing the dynamic distribution of their mRNAs by in situ hybridization in the spinal cord, the cerebellum, the retina and the tectum, as well as in the dorsal root ganglia (DRG.

  2. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    International Nuclear Information System (INIS)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques

    2015-01-01

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester

  3. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Duc; Moses, Gregory [University of Wisconsin—Madison, 1500 Engineering Drive, Madison, Wisconsin 53706 (United States); Delettrez, Jacques [Laboratory for Laser Energetics of the University of Rochester, 250 East River Road, Rochester, New York 14623 (United States)

    2015-08-15

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester.

  4. Improved non-local electron thermal transport model for two-dimensional radiation hydrodynamics simulations

    Science.gov (United States)

    Cao, Duc; Moses, Gregory; Delettrez, Jacques

    2015-08-01

    An implicit, non-local thermal conduction algorithm based on the algorithm developed by Schurtz, Nicolai, and Busquet (SNB) [Schurtz et al., Phys. Plasmas 7, 4238 (2000)] for non-local electron transport is presented and has been implemented in the radiation-hydrodynamics code DRACO. To study the model's effect on DRACO's predictive capability, simulations of shot 60 303 from OMEGA are completed using the iSNB model, and the computed shock speed vs. time is compared to experiment. Temperature outputs from the iSNB model are compared with the non-local transport model of Goncharov et al. [Phys. Plasmas 13, 012702 (2006)]. Effects on adiabat are also examined in a polar drive surrogate simulation. Results show that the iSNB model is not only capable of flux-limitation but also preheat prediction while remaining numerically robust and sacrificing little computational speed. Additionally, the results provide strong incentive to further modify key parameters within the SNB theory, namely, the newly introduced non-local mean free path. This research was supported by the Laboratory for Laser Energetics of the University of Rochester.

  5. Ultrastructure and synaptic organization of the spinal accessory nucleus of the rat.

    Science.gov (United States)

    Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

    2002-06-01

    The accessory nucleus is composed of neurons in the medial column that innervate the sternocleidomastoid muscle, and neurons in the lateral column that innervate the trapezius muscle. We retrogradely labeled these neurons by injection of cholera toxin conjugated horseradish peroxidase into the sternomastoid (SM) or the clavotrapezius (CT) muscles, and investigated fine structure and synaptology of these neurons. Almost all SM and CT motoneurons had the appearance of alpha-motoneurons, i.e., large, oval or polygonal cells containing well-developed organelles, Nissl bodies, and a prominent spherical nucleus. More than 60% of the somatic membrane was covered with terminals. The SM motoneurons (34.4 x 52.2 microm, 1,363.1 microm(2) in a section) were slightly larger than the CT motoneurons (32.8 x 54.2 microm, 1,180.8 microm(2)). The average number of axosomatic terminals in a section was 52.2 for the SM, and 54.2 for the CT motoneurons. More than half of them (58.0%) contained pleomorphic vesicles and made symmetric synaptic contacts (Gray's type II) with the SM motoneurons, while 57.9% of them contained round vesicles and made asymmetric synaptic contacts (Gray's type I) with the CT motoneurons. A few C-terminals were present on the SM (3.5) and the CT (3.7) motoneurons. About 60% of the axodendritic terminals were Gray's type I in both the SM and the CT motoneurons. A few labeled small motoneurons were also found among the SM and the CT motoneurons. They were small (19.2 x 26.2 microm, 367.0 microm(2)), round cells containing poorly developed organelles with a few axosomatic terminals (9.3). Only 20% of the somatic membrane was covered with the terminals. Thus, these neurons were presumed to be gamma-motoneurons. These results indicate that the motoneurons in the medial and the lateral column of the accessory nucleus have different ultrastructural characteristics.

  6. Two novel COLVI long chains in zebrafish that are essential for muscle development.

    Science.gov (United States)

    Ramanoudjame, Laetitia; Rocancourt, Claire; Lainé, Jeanne; Klein, Arnaud; Joassard, Lucette; Gartioux, Corine; Fleury, Marjory; Lyphout, Laura; Kabashi, Edor; Ciura, Sorana; Cousin, Xavier; Allamand, Valérie

    2015-12-01

    Collagen VI (COLVI), a protein ubiquitously expressed in connective tissues, is crucial for structural integrity, cellular adhesion, migration and survival. Six different genes are recognized in mammalians, encoding six COLVI-chains that assemble as two 'short' (α1, α2) and one 'long' chain (theoretically any one of α3-6). In humans, defects in the most widely expressed heterotrimer (α123), due to mutations in the COL6A1-3 genes, cause a heterogeneous group of neuromuscular disorders, collectively termed COLVI-related muscle disorders. Little is known about the function(s) of the recently described α4-6 chains and no mutations have been detected yet. In this study, we characterized two novel COLVI long chains in zebrafish that are most homologous to the mammalian α4 chain; therefore, we named the corresponding genes col6a4a and col6a4b. These orthologues represent ancestors of the mammalian Col6a4-6 genes. By in situ hybridization and RT-qPCR, we unveiled a distinctive expression kinetics for col6a4b, compared with the other col6a genes. Using morpholino antisense oligonucleotides targeting col6a4a, col6a4b and col6a2, we modelled partial and complete COLVI deficiency, respectively. All morphant embryos presented altered muscle structure and impaired motility. While apoptosis was not drastically increased, autophagy induction was defective in all morphants. Furthermore, motoneuron axon growth was abnormal in these morphants. Importantly, some phenotypical differences emerged between col6a4a and col6a4b morphants, suggesting only partial functional redundancy. Overall, our results further confirm the importance of COLVI in zebrafish muscle development and may provide important clues for potential human phenotypes associated with deficiency of the recently described COLVI-chains. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Role of brain-derived neurotrophic factor in the excitatory-inhibitory imbalance during the critical period of postnatal respiratory development in the rat.

    Science.gov (United States)

    Gao, Xiu-Ping; Zhang, Hanmeng; Wong-Riley, Margaret

    2015-11-01

    The critical period of respiratory development in rats is a narrow window toward the end of the second postnatal week (P12-13), when abrupt neurochemical, electrophysiological, and ventilatory changes occur, when inhibition dominates over excitation, and when the animals' response to hypoxia is the weakest. The goal of this study was to further test our hypothesis that a major mechanism underlying the synaptic imbalance during the critical period is a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors. Our aims were to determine (1) that the inhibitory dominance observed in hypoglossal motoneurons during the critical period was also demonstrable in a key respiratory chemosensor, NTSVL; (2) if in vivo application of a TrkB agonist, 7,8-DHF, would prevent, but a TrkB antagonist, ANA-12, would accentuate the synaptic imbalance; and (3) if hypoxia would also heighten the imbalance. Our results indicate that (1) the synaptic imbalance was evident in the NTSVL during the critical period; (2) intraperitoneal injections of 7,8-DHF prevented the synaptic imbalance during the critical period, whereas ANA-12 in vivo accentuated such an imbalance; and (3) acute hypoxia induced the weakest response in both the amplitude and frequency of sEPSCs during the critical period, but it increased the frequency of sIPSCs during the critical period. Thus, our findings are consistent with and strengthen our hypothesis that BDNF and TrkB play a significant role in inducing a synaptic imbalance during the critical period of respiratory development in the rat. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. Motoneurons have different membrane resistance during fictive scratching and weight support

    DEFF Research Database (Denmark)

    Perreault, Marie-Claude

    2002-01-01

    locomotion; central pattern generator; spinal cord; synaptic integration; membrane conductance; glycine; postsynaptic inhibition; chloride......locomotion; central pattern generator; spinal cord; synaptic integration; membrane conductance; glycine; postsynaptic inhibition; chloride...

  9. Hypothyroidism in the rat results in decreased soleus motoneurone soma size

    NARCIS (Netherlands)

    Bakels, R; Nijenhuis, Albertine; Mast, L; Kernell, D

    1998-01-01

    Adult female rats were thyroidectomized. After an average of 17 weeks, horseradish peroxidase (HRP) was injected into the right side soleus muscle. Two days later, left side soleus muscle properties were recorded and muscles and spinal cord were removed for further histological measurements. Soleus

  10. Changes in corticospinal drive to spinal motoneurones following visuo-motor skill learning in humans

    DEFF Research Database (Denmark)

    Perez, Monica A.; Jensen, Jesper Lundbye; Nielsen, Jens Bo

    2006-01-01

    learning. Here we investigated the effect of visuo-motor skill training involving the ankle muscles on the coupling between electroencephalographic (EEG) activity recorded from the motor cortex (Cz) and electromyographic (EMG) activity recorded from the left tibialis anterior (TA) muscle in 11 volunteers...... between cortex and muscle as part of the motor learning process....

  11. Calcium and the role of motoneuronal doublets in skeletal muscle control

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2009-01-01

    + resources and the dynamics of calcium transport is proposed. The model correctly accounts for catch-like effects in slow and fast-twitch fibers during long-train stimulations and force-frequency relations in different muscle types. Results obtained from the model compare favorably to experiments showing...... in the central nervous system. This is a potentially very useful property directly mediated by the catch-like process modeled here. One further prediction of the model is that the slope of the frequency-tension profile of a given muscle is highly sensitive to changes in the efficiency and temporal...

  12. Spatial facilitation of reciprocal inhibition and crossed inhibitory responses to soleus motoneurons during walking

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Geertsen, Svend Sparre; Nielsen, Jens Bo

    2016-01-01

    In humans, short-latency crossed spinal inhibitory reflexes are elicited in the contralateral soleus (cSOL) muscle following stimulation of the ipsilateral posterior tibial nerve (iPTN). To date, the spinal interneurons mediating the cSOL inhibition are unknown. This study investigated whether...

  13. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

    Directory of Open Access Journals (Sweden)

    Christelle Anaclet

    2010-01-01

    Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle phasic activity during REMS.

  14. Maintained changes in motoneuronal excitability by short‐lasting synaptic inputs in the decerebrate cat

    DEFF Research Database (Denmark)

    Crone, C.; Hultborn, H.; Kiehn, O.

    1988-01-01

    1. During investigation of the tonic stretch reflex in the unanaesthetized decerebrate cat we observed that a short train of impulses in Ia afferents from the soleus muscle (or its synergists) may cause a prolonged activity in the soleus muscle as judged by EMG and tension recordings. This excita......1. During investigation of the tonic stretch reflex in the unanaesthetized decerebrate cat we observed that a short train of impulses in Ia afferents from the soleus muscle (or its synergists) may cause a prolonged activity in the soleus muscle as judged by EMG and tension recordings...

  15. Calcium dynamics and buffering in motoneurones of the mouse spinal cord

    Czech Academy of Sciences Publication Activity Database

    Paleček, Jiří; Lips, M. B.; Keller, B. U.

    1999-01-01

    Roč. 520, č. 2 (1999), s. 485-502 ISSN 0928-4257 R&D Projects: GA ČR(CZ) GA305/96/0680 Institutional research plan: CEZ:AV0Z5011922 Keywords : spinal cord * motor neuron toxicity * amyotrophic lateral sclerosis Subject RIV: FH - Neurology Impact factor: 1.130, year: 1999

  16. Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro

    DEFF Research Database (Denmark)

    Mosfeldt Laursen, A; Rekling, J C

    1989-01-01

    nucleus prepositus hypoglossi. In both nuclei the two types were mixed. Antidromic spikes elicited from hypoglossal root fibres had initial segment and somatodendritic components. Electrical stimulation of the reticular matter dorsolateral to the hypoglossal nucleus elicited excitatory postsynaptic...

  17. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    Science.gov (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  18. Validation and head-to-head comparison of three nomograms predicting probability of lymph node invasion of prostate cancer in patients undergoing extended and/or sentinel lymph node dissection

    Energy Technology Data Exchange (ETDEWEB)

    Grivas, Nikolaos; Wit, Esther; Tillier, Corinne; Muilekom, Erik van; Poel, Henk van der [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Urology, Amsterdam (Netherlands); Pos, Floris [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Radiation Oncology, Amsterdam (Netherlands); Winter, Alexander [School of Medicine and Health Sciences, Carl von Ossietzky University, University Hospital for Urology, Klinikum Oldenburg, Oldenburg (Germany)

    2017-12-15

    The updated Winter nomogram is the only nomogram predicting lymph node invasion (LNI) in prostate cancer (PCa) patients based on sentinel node (SN) dissection (sLND). The aim of the study was to externally validate the Winter nomogram and examine its performance in patients undergoing extended pelvic lymph node dissection (ePLND), ePLND combined with SN biopsy (SNB) and sLND only. The results were compared with the Memorial Sloan Kettering Cancer Center (MSKCC) and updated Briganti nomograms. This retrospective study included 1183 patients with localized PCa undergoing robot-assisted laparoscopic radical prostatectomy (RARP) combined with pelvic lymphadenectomy and 224 patients treated with sLND and external beam radiotherapy (EBRT), aiming to offer pelvic radiotherapy only in case of histologically positive SNs. In the RARP population, ePLND was applied in 956 (80.8%) patients,while 227 (19.2%) patients were offered ePLND combined with additional SNB. The median numbers of removed nodes were 10 (interquartile range, IQR = 6-14), 15 (IQR = 10-20) and 7 (IQR = 4-10) in the ePLND, ePLND + SNB, and sLND groups, respectively. Corresponding LNI rates were 16.6%, 25.5% and 42%. Based on the AUC, the performance of the Briganti nomogram (0.756) in the ePLND group was superior to both the MSKCC (0.744) and Winter nomogram (0.746). The Winter nomogram, however, was the best predictor of LNI in both the ePLND + SNB (0.735) and sLND (0.709) populations. In the calibration analysis, all nomograms showed better accuracy in the low/intermediate risk patients, while in the high-risk population, an overestimation of the risk for LNI was observed. The SN-based updated nomogram showed better prediction in the SN population. The results were also comparable, relative to predictive tools developed with (e)PLND, suggesting a difference in sampling accuracy between SNB and non-SNB. Patients who benefit most from the nomogram would be those with a low/intermediate risk of LN metastasis

  19. Brain Development

    Science.gov (United States)

    ... Become a Member Home Early Development & Well-Being Brain Development A child’s brain undergoes an amazing period of development from birth ... neural connections each second. The development of the brain is influenced by many factors, including a child’s ...

  20. Employees development

    OpenAIRE

    Kilijánová, Radka

    2010-01-01

    Employees development is one of the main activities of human resources management. It is connected with other activites, such as training of employees, career development and performance management. In the recent days there is an increased importance put on employees development, although the current economic crisis still has some consequences, such as reduced development budget of many organizations. The thesis mentiones employees development in the first place in the context of management o...

  1. Multimobile Development

    CERN Document Server

    Baxter-Reynolds, Matthew

    2010-01-01

    You've developed a killer app for one mobile device - now it's time to maximize your intellectual investment and develop for the full spectrum of mobile platforms and devices. With Multimobile Development, you'll learn how to quickly retool between the iPhone and Android platforms and broaden the interest and audience of your app, without working with burdensome and error-prone compatibility layers and toolkits. Multimobile Development takes you, the developer, through the same mobile software development project on both platforms, learning the differences between and the relative strengths an

  2. Major trends of work of VNIIKRneft in the area of creating and perfecting drilling solutions on a nonaqaueous base

    Energy Technology Data Exchange (ETDEWEB)

    Kasperskii, B V

    1981-01-01

    Solution on a nonaqueous base (SNB) have good lubricating properties, are resistant to the effect of high temperatures, salt and hydrogen sulfide corrosion. The aqueous component is not filtered out of them into the bed. Carried out at VNIIKRneft were the perfection of recipes and the technology of application of the calcareous-bituminous solutions (CBS) developed at MINKhiGP im. Gubkina and the development of SNB of new types. To stabilize the CBS during drilling of clay rocks we recommend the mineralization of the aqueous component of the CBS by calcium chloride. Developed and incorporated into production is the technology of preliminary processing of a barite weighting compound of surfactants which increase its wetting ability by oil. Great attention is given to the development of methods of regulating structural-rheological properties of SNB by small additives of reagents. This permits a decrease in the formation of excesses of solutions. For CBS such regulators can be products of the interaction of organic acids and amines, particularly the commercially produced emulsifiers emul'tal and ukramine. The most effective agents which decrease viscosity of both nonaqueous and emulsion CBS are products of the low-temperature condensation reaction of polyethylene polyamines and organic acids. As a source of organic acids for synthesis of these products we can use SZhK of the C /sub 17/ fraction and higher, oxidized petrolatum, tall oil, asphalt tars of plant fats. Test results are presented for such additives in drilling boreholes at a depth of 5145 and 5432 m with the use of CBS. A recipe has been developed for a weighting compound of emulsion SNB.

  3. Representing Development

    DEFF Research Database (Denmark)

    Representing Development presents the different social representations that have formed the idea of development in Western thinking over the past three centuries. Offering an acute perspective on the current state of developmental science and providing constructive insights into future pathways, ...

  4. Economic Development

    Science.gov (United States)

    Recruitment Events Community Commitment Giving Campaigns, Drives Economic Development Employee Funded : Environmental Documents, Reports LANL Home Calendar Search Contacts Community » Economic Development LANL 75th logo Economic Development Los Alamos National Laboratory is committed to investing and partnering in

  5. Modularizing development

    DEFF Research Database (Denmark)

    Müller, Anders Riel; Doucette, Jamie

    a deeper and wider understanding of Korea’s development experience with the hope that Korea’s past can offer lessons for developing countries in search of sustainable and broad‐based development" (KSP 2011). To do so, the KSP provides users with a modularized set of policy narratives that represent Korea...

  6. Developing Collaborative Product Development Capabilities

    DEFF Research Database (Denmark)

    Mahnke, Volker; Tran, Yen

    2012-01-01

    innovation strategies’. Our analyses suggest that developing such collaboration capabilities benefits from the search for complementary practices, the combination of learning styles, and the development of weak and strong ties. Results also underscore the crucial importance of co-evolution of multi......Collaborative product development capabilities support a company’s product innovation activities. In the context of the fast fashion sector, this paper examines the development of the product development capabilities (PDC) that align product development capabilities in a dual innovation context......, one, slow paced, where the firm is well established and the other, fast paced, which represents a new competitive arena in which the company competes. To understand the process associated with collaborative capability development, we studied three Scandinavian fashion companies pursuing ‘dual...

  7. Numerical Development

    Science.gov (United States)

    Siegler, Robert S.; Braithwaite, David W.

    2016-01-01

    In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

  8. Child Development

    Science.gov (United States)

    ... developmental conditions. More Child Development Basics Early Brain Development Developmental Screening Screening for Professionals Positive Parenting Tips Infants (0-1 year) Toddlers (1-2 years) Toddlers (2-3 years) Preschoolers (3-5 years) Middle Childhood (6-8 years) Middle Childhood (9-11 years) ...

  9. Stamen development

    NARCIS (Netherlands)

    Keijzer, C.J.

    1986-01-01

    In this thesis the development of the stamen is investigated, using structural and histochemical observations, micromanipulation and in-vitro culture.

    Formation and exposure of pollen are the two main goals of the developing stamen. The main processes of the pollen formation were

  10. Africa Development

    African Journals Online (AJOL)

    Africa Development is the quarterly bilingual journal of CODESRIA. It is a social science journal whose major focus is on issues which are central to the development of society. Its principal objective is to provide a forum for the exchange of ideas among African scholars from a variety of intellectual persuasions and various ...

  11. Photocathode development

    International Nuclear Information System (INIS)

    Hinrichs, C.K.; Estrella, R.M.

    1979-01-01

    A research program for the development of photocathodes for use in streak image tubes is described. This is one task in the development of a high-resolution, high-speed x-ray streak camera system whose primary application is for diagnostics in underground nuclear testing. There are three objectives in the photocathode development program: (1) the development of new x-ray photocathodes compatible with the requirements of streak tubes; (2) the development of the capability to process high-quality visible light photocathodes as well as x-ray photocathodes; and (3) the design and construction of a transfer photocathode system. Design and construction of all the major components of the transfer photocathode system were completed. Assembly should be completed in early FY 80

  12. Developing markets?

    DEFF Research Database (Denmark)

    Figueiredo, Bernardo; Chelekis, Jessica; DeBerry-Spence, Benet

    2015-01-01

    acknowledging complex, systemic interdependencies between markets, marketing, and society. Based on a critical review of the meaning of development and an interrogation of various developmental discourses, the authors develop a conceptual framework that brings together issues of development, wellbeing......, and social inequalities. We suggest that these issues are better understooda nd addressed when examined via grounded investigations of the role of markets in shaping the management of resources, consumer agency, power inequalities and ethics. The use of markets as units of analysis may lead to further cross...

  13. Developing Friendships:

    DEFF Research Database (Denmark)

    Hansen, Annette Skovsted

    2005-01-01

    reparations and - to a lesser degree - ODA as repentance for war crimes. Officials and other invlved parties often coded their interventions of development projects in language of friendship, whereby they expressed a Japanese desire to change the image of Japan from enemy to friend. In the wake of WWII...... of these programs in development assistance initiatives reflected Japanese attempts to redefine themselves as friends rather than enemies in the minds of Asian neighbors. Other donors also used friendship vocabulary in relation to their development assistance and I will apply a comparative perspective in order...

  14. Organisational development.

    Science.gov (United States)

    2017-03-30

    The aim of the NHS Improvement national leadership and improvement strategy is to encourage leaders at all levels to develop leadership skills in their staff and themselves. It focuses on fostering compassionate, collaborative and inclusive leadership.

  15. Personality Development

    Directory of Open Access Journals (Sweden)

    Osman Ozdemir

    2012-12-01

    Full Text Available Personality is the integration of characteristics acquired or brought by birth which separate the individual from others. Personality involves aspects of the individual's mental, emotional, social, and physical features in continuum. Several theories were suggested to explain developmental processes of personality. Each theory concentrates on one feature of human development as the focal point, then integrates with other areas of development in general. Most theories assume that childhood, especially up to 5-6 years, has essential influence on development of personality. The interaction between genetic and environmental factors reveals a unique personality along growth and developmental process. It could be said that individual who does not have any conflict between his/her basic needs and society's, has well-developed and psychologically healthy personality.

  16. Toddler Development

    Science.gov (United States)

    ... is exciting to watch your toddler learn new skills. The normal development of children aged 1-3 includes several areas: Gross motor - walking, running, climbing Fine motor - feeding themselves, drawing Sensory - seeing, hearing, tasting, ...

  17. Untenable development

    International Nuclear Information System (INIS)

    Coimbra, Guilhermina Lavoz

    1995-01-01

    The author analyses the energy - the role of law and environmental rights for sustainable development - from a critical point of view that is in accordance with internationally accepted jurisprudence. (author). 12 refs

  18. Toddler development

    Science.gov (United States)

    ... a secure place. Keep toddlers away from the kitchen with a safety gate. Place them in a ... development. In: Marcdante KJ, Kliegman RM, eds. Nelson Essentials of Pediatrics . 7th ed. Elsevier Saunders; 2015:chap ...

  19. Site development

    International Nuclear Information System (INIS)

    Noack, J.

    1975-01-01

    The subject of this paper is a general view over all necessary considerations to develop the site after it has been chosen and before starting with the construction of a nuclear power plant. (orig./RW) [de

  20. Professional development

    International Nuclear Information System (INIS)

    McAndrew-Benavidas, E.

    2007-01-01

    This presentation outlines the functions of the North American Young Generation in Nuclear. Activities of the organization include professional development, recruiting, retention, public outreach, leadership, networking, workforce issues, mentoring and communications

  1. Adolescent development

    Science.gov (United States)

    ... to: Understand abstract ideas. These include grasping higher math concepts, and developing moral philosophies, including rights and ... of safe play and how to approach more advanced activities. Young people need to be very aware ...

  2. Toddler development.

    Science.gov (United States)

    Colson, E R; Dworkin, P H

    1997-08-01

    The toddler years are ones of exciting and challenging changes in cognitive, affective, and physical growth. Physical growth is particularly remarkable for the child's increasing skills and ability to navigate the environment. Affective development is marked by the push for autonomy and independence and the highly visible nature of the child's temperament or behavioral style. The toddler also enters the wonderful years of imagination and pretend play. Perhaps most noteworthy is the child's dramatic increase in ability to communicate with others through speech and language, as evidence of the progression to symbolic thinking. The dynamic changes in children's development during the toddler years have important implications for child health supervision. Familiarity with toddler development will enable the pediatrician to monitor children's development effectively and to address common, stage-related behaviors with families during anticipatory guidance.

  3. Recent Developments

    CERN Multimedia

    Lankford, A J

    Progress has proceeded rapidly on many parallel developments throughout the Trigger, Data Acquisition, and Detector Controls Project. As design has proceeded on the component TDAQ/DCS systems and subsystems, significant integration tests have been performed. Late last year and early this year, high level trigger and data acquisition developments were brought together in what we called the Phase 1 integrated prototype. During the same period, work was started on integrating the Detector Control System (DCS) with the Online Software that will be used to control, configure, and monitor ATLAS. In addition, integration tests between components of the Level 1 Trigger (LVL1) and Dataflow systems have been performed. The Phase 1 integrated prototype involved integrating the prototype level 2 trigger system (LVL2) developed by the LVL2 Pilot Project with the prototype data acquisition system and one of the Event Filter prototypes developed by the DAQ/EF -1 Prototype project. The integrated prototype included a VME Re...

  4. Process development

    Energy Technology Data Exchange (ETDEWEB)

    Schuegerl, K

    1984-01-01

    The item 'process development' comprises the production of acetonic/butonal with C. acetobylicum and the yeasting of potato waste. The target is to increase productivity by taking the following measures - optimation of media, on-line process analysis, analysis of reaction, mathematic modelling and identification of parameters, process simulation, development of a state estimator with the help of the on-line process analysis and the model, optimization and adaptive control.

  5. Instrumentation development

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Areas being investigated for instrumentation improvement during low-level pollution monitoring include laser opto-acoustic spectroscopy, x-ray fluorescence spectroscopy, optical fluorescence spectroscopy, liquid crystal gas detectors, advanced forms of atomic absorption spectroscopy, electro-analytical chemistry, and mass spectroscopy. Emphasis is also directed toward development of physical methods, as opposed to conventional chemical analysis techniques for monitoring these trace amounts of pollution related to energy development and utilization

  6. Future development

    International Nuclear Information System (INIS)

    Zavitz, J.; Hetherington, C.

    1997-01-01

    Issues regarding future development by oil and gas companies in Canada's Arctic and the Beaufort Sea were discussed. It was suggested in the Berger report that Northern development should be under the control of the people whose lives and economy are being changed. Aboriginal people are now much more sophisticated politically, and have a better understanding of what is involved. Most of them would like the financial benefits from development, but the development would have to be on their terms. Most people involved with Arctic oil exploration feel that there is enough oil in the Arctic to warrant production. (Reserves in the Beaufort Sea are estimated at two billion barrels of good quality oil). If development were to continue, there exist two methods of transportation to move the oil to market. Gulf, Imperial Oil and Panarctic favour the use of pipelines, whereas Dome Petroleum Ltd. favours the use of ice-breaking tankers. In each case the favored option seems to depend upon the location of the company's leases, the capital and operating costs, and the potential environmental impacts. Undoubtedly, any future development will be guided by the scientific information and technical expertise of oil industry pioneers of the 1960s and the 1970s, and the wisdom gained from the experiences of the many participants whose views and insights are recorded in this book

  7. Testing nonlocal models of electron thermal conduction for magnetic and inertial confinement fusion applications

    Science.gov (United States)

    Brodrick, J. P.; Kingham, R. J.; Marinak, M. M.; Patel, M. V.; Chankin, A. V.; Omotani, J. T.; Umansky, M. V.; Del Sorbo, D.; Dudson, B.; Parker, J. T.; Kerbel, G. D.; Sherlock, M.; Ridgers, C. P.

    2017-09-01

    Three models for nonlocal electron thermal transport are here compared against Vlasov-Fokker-Planck (VFP) codes to assess their accuracy in situations relevant to both inertial fusion hohlraums and tokamak scrape-off layers. The models tested are (i) a moment-based approach using an eigenvector integral closure (EIC) originally developed by Ji, Held, and Sovinec [Phys. Plasmas 16, 022312 (2009)]; (ii) the non-Fourier Landau-fluid (NFLF) model of Dimits, Joseph, and Umansky [Phys. Plasmas 21, 055907 (2014)]; and (iii) Schurtz, Nicolaï, and Busquet's [Phys. Plasmas 7, 4238 (2000)] multigroup diffusion model (SNB). We find that while the EIC and NFLF models accurately predict the damping rate of a small-amplitude temperature perturbation (within 10% at moderate collisionalities), they overestimate the peak heat flow by as much as 35% and do not predict preheat in the more relevant case where there is a large temperature difference. The SNB model, however, agrees better with VFP results for the latter problem if care is taken with the definition of the mean free path. Additionally, we present for the first time a comparison of the SNB model against a VFP code for a hohlraum-relevant problem with inhomogeneous ionisation and show that the model overestimates the heat flow in the helium gas-fill by a factor of ˜2 despite predicting the peak heat flux to within 16%.

  8. Site development

    International Nuclear Information System (INIS)

    Gaynor, R.K.

    1989-01-01

    Development of a low-level radioactive waste land disposal facility is little different than any industrial development of similar scope. Consideration must be made for normal business and operations management, security, facility maintenance, traffic control and necessary amenities for personnel. The item specific to the low-level waste site is the handling of radioactive waste materials and the regulatory and environmental protection procedures that must be planned for and accomodated in the site design and development. Each of these elements and the facility as a whole must be designed to be compatible with local land use plans, available transportation and support services, and the social and economic goals of the local community. Plans should also be made for quality control and orderly construction. This chapter deals with those aspects of the facility, its design and construction which are integral parts to the overall performance of the site

  9. Divine development

    DEFF Research Database (Denmark)

    Agarwala, Rina

    2015-01-01

    position in the world system and support poverty alleviation efforts within a neoliberal development framework. Indian-American Muslims draw from their poor status in India to overturn economic inequities within India by shifting India's development rhetoric from identity to class. Collective religious......This article examines how Indian Americans’ religious organizations send not only financial remittances to India, but also social remittances that shape development ideologies. Comparing Indian-American Hindu and Muslim organizations, I find both groups draw from their socioeconomic experiences...... in India and use their position as elite immigrants in the United States to identify and empower their respective religious constituencies in India and overturn different social relations (not just religious practices). Hindu Americans draw from their majority status in India to overturn India's lower...

  10. Diagnostic development

    International Nuclear Information System (INIS)

    Barnett, C.F.; Brisson, D.A.; Greco, S.E.

    1978-01-01

    During the past year the far-infrared or submillimeter diagnostic research program resulted in three major developments: (1) an optically pumped 0.385-μm D 2 O-laser oscillator-amplifier system was operated at a power level of 1 MW with a line width of less than 50 MHz; (2) a conical Pyrex submillimeter laser beam dump with a retention efficiency greater than 10 4 was developed for the ion temperature Thompson scattering experiment; and (3) a new diagnostic technique was developed that makes use of the Faraday rotation of a modulated submillimeter laser beam to determine plasma current profile. Measurements of the asymmetric distortion of the H/sub α/ (6563 A) spectral line profile show that the effective toroidal drift velocity, dv/sub two vertical bars i/dT/sub i/, may be used as an indicator of plasma quality and as a complement to other ion temperature diagnostics

  11. Development economics

    International Nuclear Information System (INIS)

    Roebuck, F.

    1992-01-01

    This paper discusses term development economics which refers to the economic evaluation of investment opportunities that occur after the discovery well is drilled and completed. with specific regard to the techniques used and the economic yardsticks available for investment decisions. Three potential situations are considered in this paper: the incorporation of development wells into the outcomes of the original exploration project, mutually exclusive or alternative investment opportunities, and the installation of improved or enhanced recovery projects during or at the end of the primary producing life of a property

  12. Diverting Developments

    DEFF Research Database (Denmark)

    Taudal Poulsen, René

    2013-01-01

    developments in the two industries have diverted after 1970. All the large and medium-sized Danish shipyards have ceased, whereas several equipment suppliers have endured and some have built up strong positions within their respective fields. Focusing on corporate strategies in shipbuilding and marine...... equipment manufacturing, this article examines the diverting developments of the two industries and asks what has caused this divergence?......Over the last couple of decades, the shipbuilding and marine equipment industries in Denmark and elsewhere in Europe have been exposed to strong competition from new and rapidly expanding maritime nations in Asia. In the 1970s, Denmark had a stronghold in both industries, which have been closely...

  13. The surgical importance of an axillary arch in sentinel node biopsy.

    LENUS (Irish Health Repository)

    Ridgway, P F

    2011-03-01

    When Carl Langer described the aberrant axillary arch in 1846 its relevance in sentinel node biopsy (SNB) surgery could not have been contemplated. The authors define an incidence and elucidate relevance of the arch in SNB of the axilla.

  14. Interorganizational Development.

    Science.gov (United States)

    Schermerhorn, John R., Jr.

    1979-01-01

    Interorganizational development is the application of social science knowledge to the creation of planned, systematic and mutually beneficial cooperative relationships between otherwise autonomous organizations. This paper introduces the concept as a means of focusing attention on key action and research issues associated with interorganizational…

  15. Leadership Development

    OpenAIRE

    Oana Simona Hudea

    2014-01-01

    This paper aims at rendering the main characteristics distinguishing leaders from common individuals, as well as from managers, while identifying the progressive steps and the key elements needed for leader development. Learning how to lead oneself is a prerequisite for leading others, but without continuous training, coaching or mentoring, and above all, without effective experience, individuals will never get to become real leaders.

  16. New Developments

    Science.gov (United States)

    Lohmander, Maelis Karlson; Vandenbroeck, Michel; Pirard, Florence; Peeters, Jan; Alvestad, Marit

    2009-01-01

    New developments and challenges regarding early childhood education (ECE) policy and practice in Norway and in the Flemish and French communities in Belgium are presented in this issue. There are clear differences between the countries when comparing systems they have chosen for ECE. In Belgium, supervision and responsibilities for education,…

  17. Developing Globalization

    DEFF Research Database (Denmark)

    Hansen, Annette Skovsted

    2017-01-01

    This chapter is the first qualitative micro case study of one aspect of globalization: personal networks as a concrete outcome of development assistance spending. The empirical findings related in this paper present circumstantial evidence that Japanese foreign aid has contributed to globalization...

  18. Infrastructure Development

    DEFF Research Database (Denmark)

    Williams, Idongesit

    2012-01-01

    access and service of telecommunications/ICTs have been stalled. This paper throws light on a possible Public Private Partnership framework as a development path that will enable affordable network technologies to be deployed in rural areas at a cost that will translate to what the rural dweller...

  19. Process development

    International Nuclear Information System (INIS)

    Zapata G, G.

    1989-01-01

    Process development: The paper describes the organization and laboratory facilities of the group working on radioactive ore processing studies. Contains a review of the carried research and the plans for the next future. A list of the published reports is also presented

  20. Contraceptive Development.

    Science.gov (United States)

    Troen, Philip; And Others

    This report provides an overview of research activities and needs in the area of contraceptive development. In a review of the present state, discussions are offered on the effectiveness and drawbacks of oral contraceptives, intrauterine devices, barrier methods, natural family planning, and sterilization. Methods of contraception that are in the…

  1. Dairy development

    NARCIS (Netherlands)

    Leegwater, P.; Hoorweg, J.C.

    2000-01-01

    The growth of the dairy sector as it has occurred in Kilifi and Malindi Districts is one of the few examples of successful agricultural development in the coastal region in the past decades. Between 1985 and 1997 dairy cattle have more than doubled in number. Three livestock systems are described:

  2. Instrumentation development

    International Nuclear Information System (INIS)

    Ubbes, W.F.; Yow, J.L. Jr.

    1988-01-01

    Instrumentation is developed for the Civilian Radioactive Waste Management Program to meet several different (and sometimes conflicting) objectives. This paper addresses instrumentation development for data needs that are related either directly or indirectly to a repository site, but does not touch on instrumentation for work with waste forms or other materials. Consequently, this implies a relatively large scale for the measurements, and an in situ setting for instrument performance. In this context, instruments are needed for site characterization to define phenomena, develop models, and obtain parameter values, and for later design and performance confirmation testing in the constructed repository. The former set of applications is more immediate, and is driven by the needs of program design and performance assessment activities. A host of general technical and nontechnical issues have arisen to challenge instrumentation development. Instruments can be classed into geomechanical, geohydrologic, or other specialty categories, but these issues cut across artificial classifications. These issues are outlined. Despite this imposing list of issues, several case histories are cited to evaluate progress in the area

  3. Leadership Development

    Science.gov (United States)

    Mallon, Melissa

    2017-01-01

    This issue's column focuses on online tools and resources available for leadership development of academic, public services staff. The resources are not targeted solely to professional librarians, but rather to all levels of library staff engaged with the public. In addition to inspirational and coaching videos, reviewers recommend resource guides…

  4. Sustainable development

    International Nuclear Information System (INIS)

    Boiteux, M.

    2004-01-01

    Marcel Boiteux evokes the results of the work on the sustainable development by the Academie des Sciences Morales et Politiques. This is a vast political programme with the goal of allowing all humanity to live well in growing unity while protecting the environment and favouring economic growth. (author)

  5. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Ethiopia is selected as a case study in light of its pace in economic growth ... Interrogating the Economy-First Paradigm in 'Sustainable Development' … 65 .... agreement, since such effective global cooperation on climate change ultimately ..... and foster innovation; reduce inequality within and among countries; make cities.

  6. Engendering Development

    OpenAIRE

    Monsod, Solita C.

    1994-01-01

    This article discusses the productive and reproductive roles Filipino women perform and assesses their contributions to human development. It also examines the reality of their marginalization from the country’s social, economic and political life. It then suggests on measures by which women can be empowered to achieve the goals of gender equality and equity.

  7. Polarization developments

    International Nuclear Information System (INIS)

    Prescott, C.Y.

    1993-07-01

    Recent developments in laser-driven photoemission sources of polarized electrons have made prospects for highly polarized electron beams in a future linear collider very promising. This talk discusses the experiences with the SLC polarized electron source, the recent progress with research into gallium arsenide and strained gallium arsenide as a photocathode material, and the suitability of these cathode materials for a future linear collider based on the parameters of the several linear collider designs that exist

  8. EOS developments

    Science.gov (United States)

    Sindrilaru, Elvin A.; Peters, Andreas J.; Adde, Geoffray M.; Duellmann, Dirk

    2017-10-01

    CERN has been developing and operating EOS as a disk storage solution successfully for over 6 years. The CERN deployment provides 135 PB and stores 1.2 billion replicas distributed over two computer centres. Deployment includes four LHC instances, a shared instance for smaller experiments and since last year an instance for individual user data as well. The user instance represents the backbone of the CERNBOX service for file sharing. New use cases like synchronisation and sharing, the planned migration to reduce AFS usage at CERN and the continuous growth has brought EOS to new challenges. Recent developments include the integration and evaluation of various technologies to do the transition from a single active in-memory namespace to a scale-out implementation distributed over many meta-data servers. The new architecture aims to separate the data from the application logic and user interface code, thus providing flexibility and scalability to the namespace component. Another important goal is to provide EOS as a CERN-wide mounted filesystem with strong authentication making it a single storage repository accessible via various services and front- ends (/eos initiative). This required new developments in the security infrastructure of the EOS FUSE implementation. Furthermore, there were a series of improvements targeting the end-user experience like tighter consistency and latency optimisations. In collaboration with Seagate as Openlab partner, EOS has a complete integration of OpenKinetic object drive cluster as a high-throughput, high-availability, low-cost storage solution. This contribution will discuss these three main development projects and present new performance metrics.

  9. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram.......01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% (P

  10. Leadership Development

    Directory of Open Access Journals (Sweden)

    Oana Simona Hudea

    2014-12-01

    Full Text Available This paper aims at rendering the main characteristics distinguishing leaders from common individuals, as well as from managers, while identifying the progressive steps and the key elements needed for leader development. Learning how to lead oneself is a prerequisite for leading others, but without continuous training, coaching or mentoring, and above all, without effective experience, individuals will never get to become real leaders.

  11. Professional development

    Science.gov (United States)

    Yoon, Jin Hee; Hartline, Beverly Karplus; Milner-Bolotin, Marina

    2013-03-01

    The three sessions of the professional development workshop series were each designed for a different audience. The purpose of the first session was to help mid-career physicists aspire for and achieve leadership roles. The second session brought together students, postdoctoral fellows, and early-career physicists to help them plan their career goals and navigate the steps important to launching a successful career. The final session sought to increase awareness of the results of physics education research, and how to use them to help students-especially women-learn physics better. The presentations and discussions were valuable for both female and male physicists.

  12. Energy development

    Science.gov (United States)

    Lovich, Jeffrey E.; Jones, L.L.C.; Lovich, R. L.; Halama, K.J.

    2016-01-01

    Large areas of the desert southwest are currently developed or being evaluated for construction of utility-scale renewable energy projects. These projects include numerous solar and wind energy facilities some of which will be massive. Unfortunately, peer-reviewed scientific publications are not yet available to evaluate the potential effects of solar-based utility-scale renewable energy development (USRED) on any species of wildlife, including amphibians and reptiles (herpetofauna). Scientific publications on the effects of wind-based USRED and operation (USREDO) are focused almost exclusively on flying wildlife including birds and bats. To the best of our knowledge the only publications on the effects of wind-based USREDO on herpetofauna are three publications on desert tortoise ecology at a wind energy facility near Palm Springs, California. Those studies suggested that not all effects of USREDO were detrimental in the short-term. However, additional research is required to determine if wind energy operation is compatible with conservation of this long-lived species over longer periods of time.

  13. Accelerator development

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    Because the use of accelerated heavy ions would provide many opportunities for new and important studies in nuclear physics and nuclear chemistry, as well as other disciplines, both the Chemistry and Physics Divisions are supporting the development of a heavy-ion accelerator. The design of greatest current interest includes a tandem accelerator with a terminal voltage of approximately 25 MV injecting into a linear accelerator with rf superconducting resonators. This combined accelerator facility would be capable of accelerating ions of masses ranging over the entire periodic table to an energy corresponding to approximately 10 MeV/nucleon. This approach, as compared to other concepts, has the advantages of lower construction costs, lower operating power, 100 percent duty factor, and high beam quality (good energy resolution, good timing resolution, small beam size, and small beam divergence). The included sections describe the concept of the proposed heavy-ion accelerator, and the development program aiming at: (1) investigation of the individual questions concerning the superconducting accelerating resonators; (2) construction and testing of prototype accelerator systems; and (3) search for economical solutions to engineering problems. (U.S.)

  14. Biofilm Development

    DEFF Research Database (Denmark)

    Tolker-Nielsen, Tim

    2015-01-01

    During the past decade we have gained much knowledge about the molecular mechanisms that are involved in initiation and termination of biofilm formation. In many bacteria, these processes appear to occur in response to specific environmental cues and result in, respectively, induction or terminat......During the past decade we have gained much knowledge about the molecular mechanisms that are involved in initiation and termination of biofilm formation. In many bacteria, these processes appear to occur in response to specific environmental cues and result in, respectively, induction...... or termination of biofilm matrix production via the second messenger molecule c-di-GMP. In between initiation and termination of biofilm formation we have defined specific biofilm stages, but the currently available evidence suggests that these transitions are mainly governed by adaptive responses......, and not by specific genetic programs. It appears that biofilm formation can occur through multiple pathways and that the spatial structure of the biofilms is species dependent as well as dependent on environmental conditions. Bacterial subpopulations, e.g., motile and nonmotile subpopulations, can develop...

  15. The Neuronal Network Orchestration behind Motor Behaviors

    DEFF Research Database (Denmark)

    Petersen, Peter Christian

    to motoneurons during rhythmic motor behaviors, and specifically the hypothesis that motoneurons receive concurrent excitatory and inhibitory (E/I) inputs. Berg et al. (2007) presented the concurrent hypothesis, which goes against the classical feed forward reciprocal model for spinal motor networks that has...... gained widespread acceptance. We developed an adult turtle preparation where the spinal motor network was intact, which also allowed us to perform intracellular recordings from motoneurons during rhythmic motor activity. We estimated the synaptic excitatory and inhibitory conductances by two individual...... (Buzsáki and Mizuseki, 2014). Roxin et al. (2011) detailed the firing rate distribution in networks in the balanced regime, and found it to be similar to a lognormal distribution and describing the data from the population studies very well. Our experimental observations and analysis are in agreement...

  16. Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

    Science.gov (United States)

    2014-04-01

    conducted experiments using intraspinal injections of AAV10-NG2Ab combined with AAV10 vector expressing neurotrophin 3 (AAV10-NT3-gfp) in adult rat...mediated delivery of NG2-Ab and neurotrophin NT3 expressing units significantly improved locomotor function following SCI. These behavioral improvements...mediated delivery of NG2-Ab combined with neurotrophin NT3 in rats that received either hemisection or contusion SCI. We found that rats that

  17. Stiff person syndrome associated anti-amphiphysin antibodies reduce GABA associated [Ca(2+)]i rise in embryonic motoneurons.

    Science.gov (United States)

    Geis, C; Beck, M; Jablonka, S; Weishaupt, A; Toyka, K V; Sendtner, M; Sommer, C

    2009-10-01

    Autoantibodies to the synaptic protein amphiphysin play a crucial pathogenic role in paraneoplastic stiff-person syndrome. Impairment of GABAergic inhibition is the presumed pathophysiological mechanism by which these autoantibodies become pathogenic. Here we used calcium imaging on rat embryonic motor neurons to investigate whether antibodies to amphiphysin directly hinder GABAergic signaling. We found that the immunoglobulin G fraction from a patient with stiff-person syndrome, containing high titer antibodies to amphiphysin and inducing stiffness in rats upon passive transfer, reduced GABA-induced calcium influx in embryonic motor neurons. Depletion of the anti-amphiphysin fraction from the patient's IgG by selective affinity chromatography abolished this effect, showing its specificity for amphiphysin. Quantification of the surface expression of the Na(+)/K(+)/2Cl(2-) cotransporter revealed a reduction after incubation with anti-amphiphysin IgG, which is concordant with a lower intracellular chloride concentration and thus impairment of GABA mediated calcium influx. Thus, anti-amphiphysin antibodies exert a direct effect on GABA signaling, which is likely to contribute to the pathogenesis of SPS.

  18. Immature spinal locomotor output in children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Germana Cappellini

    2016-10-01

    Full Text Available Detailed descriptions of gait impairments have been reported in cerebral palsy (CP, but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analysed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years and 33 typically developing (TD children (1-12 years. TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children. Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behaviour.

  19. Introduction: translocal development, development corridors and development chains.

    NARCIS (Netherlands)

    Zoomers, E.B.; Westen, A.C.M. van

    2011-01-01

    This paper offers an introduction to this Special Issue of International Development Planning Review. It uses the concepts of translocal development, development corridors and development chains to secure a better grasp of what development means in the context of globalisation and how ‘local

  20. Leading and Managing Continuing Professional Development: Developing People, Developing Schools

    Science.gov (United States)

    Earley, Peter; Bubb, Sara

    2004-01-01

    This book has been written for those who lead and manage continuing professional development (CPD). Continuing professional development co-coordinators hold a key role and one that needs to be developed further in many schools. This book is intended to help people think more deeply about the professional development and training of staff--all…

  1. Rural Community Development: Bedrock for National Development ...

    African Journals Online (AJOL)

    This paper advocates that community development is the bedrock for national development. For any meaningful development to take place, whether national or global development must have its building blocks or firm-root in rural development. However, the rural communities are characterized by isolation from ideas and ...

  2. Sustainable Development: The Challenge for Community Development.

    Science.gov (United States)

    Gamble, Dorothy N.; Weil, Marie O.

    1997-01-01

    Five areas of inquiry shape the sustainable development movement: environmental movement, women's movement, overpopulation concerns, critique of development models, and new indicators of social progress. Community development workers are challenged to prepare local development projects within a sustainable development framework. (SK)

  3. Sustainable development in a developing economy: Challenges ...

    African Journals Online (AJOL)

    USER

    2013-08-21

    Aug 21, 2013 ... towards environmental management in Nigeria which is a fast developing economy. The basic ... almost every developing country in which it is grown ..... perspective of Development in Formal and Integrated Management of.

  4. Developed-developing country partnerships: Benefits to developed countries?

    Directory of Open Access Journals (Sweden)

    Syed Shamsuzzoha B

    2012-06-01

    Full Text Available Abstract Developing countries can generate effective solutions for today’s global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed—this is perhaps the single most immediate need in planning for, and realizing, the full potential of international

  5. Developed-developing country partnerships: benefits to developed countries?

    Science.gov (United States)

    Syed, Shamsuzzoha B; Dadwal, Viva; Rutter, Paul; Storr, Julie; Hightower, Joyce D; Gooden, Rachel; Carlet, Jean; Bagheri Nejad, Sepideh; Kelley, Edward T; Donaldson, Liam; Pittet, Didier

    2012-06-18

    Developing countries can generate effective solutions for today's global health challenges. This paper reviews relevant literature to construct the case for international cooperation, and in particular, developed-developing country partnerships. Standard database and web-based searches were conducted for publications in English between 1990 and 2010. Studies containing full or partial data relating to international cooperation between developed and developing countries were retained for further analysis. Of 227 articles retained through initial screening, 65 were included in the final analysis. The results were two-fold: some articles pointed to intangible benefits accrued by developed country partners, but the majority of information pointed to developing country innovations that can potentially inform health systems in developed countries. This information spanned all six WHO health system components. Ten key health areas where developed countries have the most to learn from the developing world were identified and include, rural health service delivery; skills substitution; decentralisation of management; creative problem-solving; education in communicable disease control; innovation in mobile phone use; low technology simulation training; local product manufacture; health financing; and social entrepreneurship. While there are no guarantees that innovations from developing country experiences can effectively transfer to developed countries, combined developed-developing country learning processes can potentially generate effective solutions for global health systems. However, the global pool of knowledge in this area is virgin and further work needs to be undertaken to advance understanding of health innovation diffusion. Even more urgently, a standardized method for reporting partnership benefits is needed--this is perhaps the single most immediate need in planning for, and realizing, the full potential of international cooperation between developed and

  6. App Development Paradigms for Instructional Developers

    Science.gov (United States)

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

  7. Entrepreneurial Intentions in Developing and Developed Countries

    Science.gov (United States)

    Iakovleva, Tatiana; Kolvereid, Lars; Stephan, Ute

    2011-01-01

    Purpose: This study proposes to use the Theory of Planned Behaviour to predict entrepreneurial intentions among students in five developing and nine developed countries. The purpose is to investigate whether entrepreneurial intention and its antecedents differ between developing and developed countries, and to test the theory in the two groups of…

  8. Open Data for Development | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Open Data for Development (OD4D) program brings together a network of ... other open data initiatives to ensure they benefit people in developing countries. ... that benefits everyone, empowering women and achieving gender equality, ...

  9. Drug discovery and developments in developing countries ...

    African Journals Online (AJOL)

    the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.

  10. Development | Page 25 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Theoretical Perspectives on Gender and Development demystifies the theory of gender ... and development theory, introduces competing theoretical frameworks, and ... Unfortunately, however, the research environment in the Middle East and ...

  11. Preceptor development. Use a staff development specialist.

    Science.gov (United States)

    Schneller, S; Hoeppner, M

    1994-01-01

    Preceptor orientation is a well identified need. Less often identified is the critical role the staff development specialist plays in the ongoing support and development of preceptors. In this article, the authors explain activities of coaching, facilitating, mentoring, and consulting. These role components are essential in the ongoing development of preceptors. This support also may help retain preceptors.

  12. Clean development mechanism: Perspectives from developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Sari, Agus P.; Meyers, Stephen

    1999-06-01

    This paper addresses the political acceptability and workability of CDM by and in developing countries. At COP-3 in Kyoto in 1997, the general position among developing countries changed from strong rejection of joint implementation to acceptance of CDM. The outgrowth of CDM from a proposal from Brazil to establish a Clean Development Fund gave developing countries a sense of ownership of the idea. More importantly, establishing support for sustainable development as a main goal for CDM overcame the resistance of many developing countries to accept a carbon trading mechanism. The official acceptance of CDM is not a guarantee of continued acceptance, however. Many developing countries expect CDM to facilitate a substantial transfer of technology and other resources to support economic growth. There is concern that Annex I countries may shift official development assistance into CDM in order to gain carbon credits, and that development priorities could suffer as a result. Some fear that private investments could be skewed toward projects that yield carbon credits. Developing country governments are wary regarding the strong role of the private sector envisioned for CDM. Increasing the awareness and capacity of the private sector in developing countries to initiate and implement CDM projects needs to be a high priority. While private sector partnerships will be the main vehicle for resource transfer in CDM, developing country governments want to play a strong role in overseeing and guiding the process so that it best serves their development goals. Most countries feel that establishment of criteria for sustainable development should be left to individual countries. A key issue is how CDM can best support the strengthening of local capacity to sustain and replicate projects that serve both climate change mitigation and sustainable development objectives.There is support among developing countries for commencing CDM as soon as possible. Since official commencement must

  13. Development Application - Terra Nova Development - Development Application Summary

    International Nuclear Information System (INIS)

    1996-01-01

    This summary is part of the application for approval of the development of the Terra Nova Field off the coast of Newfoundland, prepared and submitted by Petro-Canada, on behalf of, and with the cooperation of its co-proponents. The full application consists of five parts, comprising the development plan itself, the Canada-Newfoundland benefits plan detailing commitments with regards to contracts and employment, the environmental impact statement concerning the impact of development on the physical and biological environment, and a statement of socio-economic impacts, characterizing existing and projected impacts of the development on the fisheries, industry, employment, demography, social and public infrastructures and facilities, and socio-cultural issues

  14. Measurement and analysis of bubble behavior in subcooled nucleate boiling flow field with high fidelity imaging system

    International Nuclear Information System (INIS)

    Wu, W.; Jones, B.G.; Newell, T.A.

    2004-01-01

    Axial offset anomaly (AOA) is an unexpected deviation in the core axial power distribution from the predicted curve. AOA is a current major consideration for reactors operating at increased power levels and is becoming immediate threat to nuclear power's competitiveness in the market. Despite much effort focusing on this topic, a comprehensive understanding is far from being developed. However, previous research indicates first, that a close connection exists between subcooled nucleate boiling occurring in core region and the formation of crud, which directly results in AOA phenomena, secondly, that deposition is greater, and sometimes much greater, on heated than on unheated surfaces. A number of researchers have suggested that boiling promotes deposition, and several observed increased deposition in the subcooled boiling region. Limited detailed information is available on the interaction between heat and mass transfer in subcooled nucleate boiling (SNB) flow. Bubbles formed in SNB region play an important role in helping the formation of crud. This research examines bubble behavior under SNB condition from the dynamic point of view, using a high fidelity digital imaging apparatus. Freon R-134a is chosen as a simulant fluid due to its merit of having smaller surface tension and lower boiling temperature. The apparatus is operated at reduced pressure. Series of images at frame rates up to 4000 frames/s were obtained, showing different characteristics of bubble behavior with varying experimental parameters e.g. flow velocity, fluid subcooled level, etc. Analyses that combine the experimental results with analytical result on flow field in velocity boundary layer are considered. A tentative suggestion is that a rolling movement of a bubble accompanies its sliding along the heating surface in the flow channel. Numerical computations using FLUENT v5.5 have been performed to support this conclusion

  15. Wordpress web application development

    CERN Document Server

    Ratnayake, Rakhitha Nimesh

    2015-01-01

    This book is intended for WordPress developers and designers who want to develop quality web applications within a limited time frame and for maximum profit. Prior knowledge of basic web development and design is assumed.

  16. Practical web development

    CERN Document Server

    Wellens, Paul

    2015-01-01

    This book is perfect for beginners who want to get started and learn the web development basics, but also offers experienced developers a web development roadmap that will help them to extend their capabilities.

  17. International Development Research Centre

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... development. Learn moreArtificial intelligence and human development ... New initiative will match climate knowledge to developing country needs. Aminata Camara ... Shadow Libraries: Access to Knowledge in Global Higher Education.

  18. SUSTAINABLE DEVELOPMENT THROUGH ECO-ECONOMIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Vergina CHIRITESCU

    2013-12-01

    Full Text Available The issue of the relationship between humankind and the environment became scientific and economic concerns of the international community since the first UN Conference on the Human Environment (Stockholm, 1972 and resulted in the work of the World Commission on Environment and Development, established in 1985. Report of the Commission presented in 1987 by GH Brundtland, entitled "Our Common Future" provided the first universally accepted definition of sustainable development as "development that meets the needs of the present generation without compromising the opportunities of future generations to meet their own needs". Brundtland Report, 1987, was reaffirmed by the United Nations Conference on Environment and Development / Earth Summit held in Rio de Janeiro - Brazil, 1992 which established the principles of Agenda 21, which was intended to be a guide implementation of sustainable development for the 21st century, a development that was required to be applied at national, regional and local level. [1] In the context of developing new eco-economic system adopted a number of international conventions that establish detailed obligations of the States and strict implementation deadlines climate change, biodiversity conservation, protection of forests and wetlands, limiting the use of certain chemicals, access information on the state of the environment and other international legal space outlining the practical application of the principles of sustainable economic development in ecological conditions.

  19. Development | Page 24 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Two years ago, the International Development Research Centre created CIME, a development communication program that reflects the interrelations between Communication at the grassroots level, the exchange of Information, two-way Media, and nonformal Education. This book presents the conceptual framework that led ...

  20. Sustainable development in a developing economy: Challenges ...

    African Journals Online (AJOL)

    Sustainable development implies development which ensures maximization of human well being for today's generation which does not lead to declines in future well being. Attaining this path requires eliminating those negative externalities that are responsible for natural resource depletion and environmental degradation.

  1. Sustainable development goals and inclusive development

    NARCIS (Netherlands)

    Gupta, J.; Vegelin, C.

    Achieving sustainable development has been hampered by trade-offs in favour of economic growth over social well-being and ecological viability, which may also affect the sustainable development goals (SDGs) adopted by the member states of the United Nations. In contrast, the concept of inclusive

  2. Dialogue on leadership development

    OpenAIRE

    Reddy, C Manohar; Srinivasan, Vasanthi

    2015-01-01

    Sharing our considerable experience as teachers who have designed and conducted leadership development programmes, we discuss the challenges in the field of leadership development. We distinguish between leader development and leadership development; differentiate leadership theories from leadership development theories; discuss the goals of leadership development programmes and their implications for the design of such programmes – the knowing, being and doing gap and how the goal, cognitive...

  3. Open development networked innovations in international development

    CERN Document Server

    Reilly, Katherine M A

    2014-01-01

    The emergence of open networked models made possible by digital technology has the potential to transform international development. Open network structures allow people to come together to share information, organize, and collaborate. Open development harnesses this power, to create new organizational forms and improve people's lives; it is not only an agenda for research and practice but also a statement about how to approach international development. In this volume, experts explore a variety of applications of openness, addressing challenges as well as opportunities. Open development requires new theoretical tools that focus on real world problems, consider a variety of solutions, and recognize the complexity of local contexts. After exploring the new theoretical terrain, the book describes a range of cases in which open models address such specific development issues as biotechnology research, improving education, and access to scholarly publications. Contributors then examine tensions between open model...

  4. Vehicle Development Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems.DESCRIPTION: The Vehicle Development Laboratory is...

  5. CDBG Economic Development Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to economic development, including commercial or industrial rehab, commercial or industrial land acquisition, commercial or industrial...

  6. Dialogue on leadership development

    Directory of Open Access Journals (Sweden)

    C. Manohar Reddy

    2015-03-01

    Full Text Available Sharing our considerable experience as teachers who have designed and conducted leadership development programmes, we discuss the challenges in the field of leadership development. We distinguish between leader development and leadership development; differentiate leadership theories from leadership development theories; discuss the goals of leadership development programmes and their implications for the design of such programmes – the knowing, being and doing gap and how the goal, cognitive understanding vs. deeper internalization vs. transformation would impact the design; the need to synthesize Western and Indian approaches to leadership development; and the importance of designing coherent leadership development programmes which combine multiple methods and approaches.

  7. Sencha Architect app development

    CERN Document Server

    Groner, Loiane

    2013-01-01

    A standard tutorial-based approach for using Sencha Architect to develop applications in Ext JS and Sencha Touch.Sencha Architect App Development is for Ext JS and Sencha Touch developers that are looking to improve their productivity by using Sencha Architect for app development. Basic knowledge of Ext JS and Sencha Touch is required.

  8. Agile Software Development

    Science.gov (United States)

    Biju, Soly Mathew

    2008-01-01

    Many software development firms are now adopting the agile software development method. This method involves the customer at every level of software development, thus reducing the impact of change in the requirement at a later stage. In this article, the principles of the agile method for software development are explored and there is a focus on…

  9. Regional Economic Development

    Science.gov (United States)

    ; Sponsored Work Regional Economic Development Technology Opportunities User Facilities About Us Metrics In the News Publications Policies Feynman Center » Deploying Innovation » Regional Economic Development Regional Economic Development Supporting companies in every stage of development through access to

  10. Information and Rural Development.

    Science.gov (United States)

    Storm, Bonnie L.

    1982-01-01

    Outlines approaches taken to development in lesser developed countries in the past, discusses the importance of appropriate technology and human development, and summarizes the information needs of the rural poor in developing nations. Information dissemination programs using video- and audiotape technology in Bangladesh, Guatemala, and Peru are…

  11. Web Developer | IDRC - International Development Research Centre

    International Development Research Centre (IDRC) Digital Library (Canada)

    Primary Duties or Responsibilities Web Development Leads all technical web ... design, and maintain the corporate website and any other internet properties IDRC ... and testing site for use by members of the website and social media team.

  12. Innovation in Product Development

    DEFF Research Database (Denmark)

    McAloone, Tim C.; Restrepo-Giraldo, John Dairo

    2005-01-01

    The course on Innovation in Product Development attempts to identify and understand the nature of innovation and product development and their important factors. The course takes both a theoretical and a practical approach and employs a mix of lectures, project work and group discussion. Format...... insight. Course content The following aspects of innovation in product development are considered: - Humans and products - Needs and products - Product life - Teams creating products - Products creating business - Product development models - Organising product development - Product development tools...... - The future of product development....

  13. Rural development policy and food industry development

    DEFF Research Database (Denmark)

    Baker, Derek; Abildtrup, Jens; Hedetoft, Anders

    2007-01-01

    Food industry firms in remote areas face a set of constraints, which have motivated the form and function of assistance instruments under various regional and rural development programmes. Recent food industry developments present new challenges to these firms, for which available assistance may...... be less appropriate. This paper employs telephone interviews and workshop discussions with firms in isolated locations to investigate their satisfaction with assistance programmes, their ability to innovate (through product introductions) and respond to challenges in the food industry (the emergence...

  14. Project development symposium

    Energy Technology Data Exchange (ETDEWEB)

    1983-01-01

    Papers were presented on the following: project evaluation; case studies - minerals; finance; applied finance; legal; manpower/industrial relations; and new technologies. Those papers on the coal industry were: mine planning for coal project development; the planning and management of a lignite exploration contract in Thailand; development of the West Cliff extended project; Ulan: a resource development; Saxonvale mine development a case study in project planning and project management; the role of marketing in the development of a new coal project; technical support for coal marketing; infrastructure development for the Ulan project; underground mine project developments; the bucketwheel excavator at Goonyella - a case study; tax aspects of mining development projects; cost of capital mining development projects; and trends in development project finance. 16 papers were abstracted separately.

  15. Perawatan Maloklusi Angle Klas II Divisi 1 Menggunakan Bionator Myofungsional

    Directory of Open Access Journals (Sweden)

    Ragil Irawan

    2014-06-01

    Full Text Available Maloklusi Angle klas II divisi 1 mempunyai ciri tonjol mesiobukal molar pertama atas beroklusi dengan interdental premolar kedua  dan molar pertama bawah, jarak gigit yang besar, lengkung gigi sempit dan profil cembung. Bionator pertama kali diperkenalkan oleh Balter dan merupakan alat ortodontik myofungsional yang digunakan untuk merawat diskrepansi rahang. Tujuan pemaparan kasus adalah menyajikan kemajuan kasus maloklusi Angle Klas II divisi 1 disertai diskrepansi rahang menggunakan alat myofunctional bionator. Seorang perempuan berusia 13 tahun mengeluhkan gigi depan atas maju. Diagnosis pasien maloklusi Angle klas II divisi 1, hubungan skeletal klas II dengan protrusif maksila dan retrusif mandibula, protrusif insisivus atas disertai palatal bite, cross bite posterior, jarak gigit 11 mm, tumpang gigit 5,25 mm, SNA 84°, SNB 76°. Pasien dirawat menggunakan alat myofungsional bionator. Hasil perawatan setelah satu tahun overjet menjadi 6,25 mm dan SNB 78°. Kesimpulannya adalah alat myofungsional bionator efektif untuk merawat maloklusi Angle Klas II divisi 1 yang disertai diskrepansi rahang. Class II division 1 Angle Malocclussion Treatment  Using  Myofunctional  Bionator. Malocclusion Angle Class II division I is characterized by the upper mesio-buccal cups first permanent molars occludes in interdental second bicuspid and lower first molar permanent, increased overjet, narrow arch form, and convex profile. Bionator originally developed by Balter and used to treat jaw discrepancy. The goal of this case is to present the progress of myofunctional bionator appliance in treating malocclusion Class II division 1 with jaw discrepancies. A Female 13 years old complained protrusive anterior teeth. Diagnosis is malocclusion Angle Class II division I, class II skeletal relationship with maxilla protrusive, mandible retrusive, protrusive upper incisor, palatal bite, posterior cross bite, overjet 11 mm, overbite 5,25 mm SNA 84°, SNB 76

  16. Cuban energy development perspectives

    International Nuclear Information System (INIS)

    Berdellans Escobar, Ilse; Perez Martin, David; Lopez Lopez, Ileana; Ricardo Mora, Henry; Gomez De la Torre, Yoandys

    2005-01-01

    In this paper from energy demand scenario calculated for the country until 2025, energy supply options were assessed. Three energy development scenarios considering economic and social development projections and different energy options were evaluated: a reference scenario which includes the nowadays energy development projections; a second scenario basing the development on intensive use of domestic fossil fuels; and a third scenario, where the development is based on the maximum use of domestic renewable energy potential. The results are analyzed and recommendations are formulated

  17. Education for sustainable development

    DEFF Research Database (Denmark)

    Breiting, Søren

    2009-01-01

     An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related ...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....... An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...

  18. Hanford Site Development Plan

    Energy Technology Data Exchange (ETDEWEB)

    Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J. (Westinghouse Hanford Co., Richland, WA (USA)); Yancey, E.F. (Pacific Northwest Lab., Richland, WA (USA))

    1990-01-01

    The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs.

  19. Hanford Site Development Plan

    International Nuclear Information System (INIS)

    Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J.; Yancey, E.F.

    1990-01-01

    The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs

  20. Teacher Professional Development

    Directory of Open Access Journals (Sweden)

    Nareerat Rakwichitkul

    2017-06-01

    Full Text Available Teacher professional development are the teachers’ learning process throughout their career stages to ensure that teachers have knowledge, skills and needed competencies for teaching among rapid changes in social, economic and technology which have the impact on learning and teaching. This article deals with the topics of the framework for teaching, teacher career stages and teacher professional development. The research findings related to teacher professional development, teacher professional development activities, suggestions for planning the professional development. Those research findings can be applied and implemented by the school principals, educational supervisors and other professional developers.

  1. Hanford Site Development Plan

    International Nuclear Information System (INIS)

    Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

    1993-05-01

    The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans

  2. Economic Development and Development of Human Resources

    Directory of Open Access Journals (Sweden)

    Metod Černetič

    1998-12-01

    Full Text Available Černetič deals with certain dilemmas and problems related to employee training within companies, and discusses the complexity of the relationship between technological development and education, developmental gap between the developed and underdevdoped economies, and the goals of social development in Slovenia. Cernetič stresses that training programmes should above all provide flexibility of employment; the competitive edge of an entire state actually depends on effective use of human resources. Slovenia cannot exert any substantial influence on the global economy, it can only follow the main market trends. Knowledge is therefore of great importance, as the wealth of smaller nations is primarily based on the education level of their inhabitants.

  3. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    Energy Technology Data Exchange (ETDEWEB)

    Kathryn Baskin

    2005-04-30

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  4. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    Energy Technology Data Exchange (ETDEWEB)

    Kathryn Baskin

    2004-10-31

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts. In addition to analysis of domestic policies and programs, this project will include the development of a U.S.-Brazil Biodiesel Pilot Project. The purpose of this effort is to promote and facilitate the commercialization of biodiesel and bioenergy production and demand in Brazil.

  5. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    International Nuclear Information System (INIS)

    Kathryn Baskin

    2001-01-01

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts

  6. DEVELOPING STATE POLICIES SUPPORTIVE OF BIOENERGY DEVELOPMENT

    International Nuclear Information System (INIS)

    Kathryn Baskin

    2002-01-01

    Working within the context of the Southern States Biobased Alliance (SSBA) and with officials in each state, the Southern States Energy Board (SSEB) is identifying bioenergy-related policies and programs within each state to determine their impact on the development, deployment or use of bioenergy. In addition, SSEB will determine which policies have impacted industry's efforts to develop, deploy or use biobased technologies or products. As a result, SSEB will work with the Southern States Biobased Alliance to determine how policy changes might address any negative impacts or enhance positive impacts

  7. FPG Child Development Institute

    Science.gov (United States)

    ... shows how implicit racial biases are adversely affecting African American students--especially boys... read more Emphasis Areas ... Development, Teaching, and Learning The Frank Porter Graham Child Development Institute will partner with Zero to Three ...

  8. Odoo development essentials

    CERN Document Server

    Reis, Daniel

    2015-01-01

    This book is intended for developers who need to quickly become productive with Odoo. You are expected to have experience developing business applications, as well as an understanding of MVC application design and knowledge of the Python programming language.

  9. Game development tool essentials

    CERN Document Server

    Berinstein, Paula; Ardolino, Alessandro; Franco, Simon; Herubel, Adrien; McCutchan, John; Nedelcu, Nicusor; Nitschke, Benjamin; Olmstead, Don; Robinet, Fabrice; Ronchi, Christian; Turkowski, Rita; Walter, Robert; Samour, Gustavo

    2014-01-01

    Offers game developers new techniques for streamlining the critical game tools pipeline. Inspires game developers to share their secrets and improve the productivity of the entire industry. Helps game industry practitioners compete in a hyper-competitive environment.

  10. Next Generation Software Development

    National Research Council Canada - National Science Library

    Manna, Zohar

    2005-01-01

    Under this grant we have studied the development of a scientifically sound basis for software development that builds on widely used pragmatic methods but is firmly grounded in well-established formal...

  11. REGIONAL DEVELOPMENT IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Remus Gherman

    2015-10-01

    Full Text Available Regional development policy is a policy of investment for economic development by supporting competitiveness, increasing the standards of living, improving the quality of life, creating new jobs. Regions and regional development policy occupies in recent decades an increasingly important position in the list of the economic and social factors being found on the agendas of governments, both central and local authorities, of political groups and civil society. Regional development and regional development policy in Romania are present both in the economic reform and in social one. Development Regions from Romania are set up in 1998 by Law number 151 and supported by their own institutional framework. The applicability of regional development in Romania must take into account the fundamental elements of the possibilities of Regional Development, meaning the major indicators of reference for measuring the level of disparities, GDP per capita and unemployment.

  12. Your Child's Development: Newborn

    Science.gov (United States)

    ... Your Child's Development: Newborn Print en español El desarrollo de su hijo: recién nacido From the moment ... when touched on the sole of the foot Social and Emotional Development soothed by a parent's voice ...

  13. Mobile systems development

    DEFF Research Database (Denmark)

    Pedersen, Ole; Kristiansen, Martin Lund; Kammersgaard, Marc N.

    2007-01-01

    in XP. In general, we find XP well-suited for mobile systems development projects. However, based on our experiences and an analytical comparison we propose the following modifications to XP: Make an essential design to avoid the worst time waste during refactoring. For faster development, reuse code......Development of mobile software is Surrounded by much uncertainty. Immature software platforms on mobile clients, a highly competitive market calling for innovation, efficiency and effectiveness in the development life cycle, and lacking end-user adoption are just some of the realities facing...... development teams in the mobile software industry. By taking a process view on development of mobile systems we seek to explore the strengths and limitations of eXtreme Programming (XP) in the context of mobile software development. Following an experimental approach a mobile systems development project...

  14. Localisation for industrial development

    CSIR Research Space (South Africa)

    Bhugwandin, Ashley

    2017-10-01

    Full Text Available This presentation focuses on localisation for industrial development, and is presented by Ashley Bhugwandin at The 6th CSIR Conference: Ideas that work for industrial development, 5-6 October 2017, CSIR International Convention Centre, Pretoria...

  15. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

  16. Gammasphere software development

    International Nuclear Information System (INIS)

    Piercey, R.B.

    1993-01-01

    Activities of the nuclear physics group are described. Progress was made in organizing the Gammasphere Software Working Group, establishing a nuclear computing facility, participating in software development at Lawrence Berkeley, developing a common data file format, and adapting the ORNL UPAK software to run at Gammasphere. A universal histogram object was developed that defines a file format and provides for an objective-oriented programming model. An automated liquid nitrogen fill system was developed for Gammasphere (110 Ge detectors comprise the sphere)

  17. Coalbed gas development

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This book includes: Overview of coalbed gas development; Coalbed gas development in the West Coalbed gas development on Indian lands; Multi-mineral development conflicts; Statutory solutions to ownership disputes; State and local regulation; Environmental regulations; Status of the section 29 tax credit extension; Using the section 29 credit; Leasing coalbed gas prospects; Coalbed gas joint operating agreements and Purchase and sale agreements for coalbed gas properties

  18. Development | Page 28 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Dnipro River is Europe's second longest river and flows through the heartland of Russia, Belarus, and Ukraine. For many centuries, it has played a vital role in the historical, cultural, religious and economic development of this vast region. Indeed, it is true to say that nobody can understand this vast region of the world ...

  19. Development | Page 15 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Land is an important source of security against poverty across the developing world, but, in many places, unequal rights to land put women at a disadvantage, ... Upgrading is a key concept for value chain analysis and refers to the acquisition of technological capabilities and market linkages that enable firms to improve their ...

  20. Development | Page 32 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This book describes and analyzes the 3-year-long “L-20” project, whose objective ... in the environment for research and development (R&D) around the world. ... the “capability approach” of economist and Nobel Prize laureate Amartya Sen.

  1. Dental Curriculum Development in Developing Countries.

    Science.gov (United States)

    Phantumvanit, Prathip

    1996-01-01

    Since establishment of formal dental education in Southeast Asia, changes stemming from research and technology have led to dental curriculum changes. Development of the dental curriculum can be divided into three phases: disease oriented; health oriented; and community oriented. Evolution of these phases is traced in the dental curricula of Laos,…

  2. The China Development Bank and Sustainable Development

    Directory of Open Access Journals (Sweden)

    Valentina Levanchuk

    2016-11-01

    Full Text Available In this article, the author presents an empirical study of sustainable banking in China and examines the flagship China DevelopmentBank (CDB. The CDB is directly supervised by the State Council of the People’s Republic of China and is one ofthe largest state-owned financial institutions in the country. Its overseas lending is growing rapidly; it increasingly acts as aglobal player, influenced by a variety of international actors. Using the mercantilist framework, the author investigates how the CDB’s social policies diverge from those set by the Chinese authorities. The analysis discusses CDB’s policy variations that are not in line with government interests or prescribed directly by governmental bodies. It concludes that the bank has been active in developing and establishing its own corporate strategy for implementing the concept of sustainable development to promote a balanced development of the economy, society and the environment. That strategy contains the norms and rules set by Chinese regulatory agencies with regard to social and environmental areas, as well as important elements ofthe international practice of corporate responsibility and sustainable funding. The CDB is most likely driven by its desire tobe considered internationally a good corporate citizen and often acts independently from governmental guidance, which insome sense undermines mercantilist perceptions.

  3. Sentinel node biopsy in head and neck cancer

    DEFF Research Database (Denmark)

    Ross, Gary L; Soutar, David S; Gordon MacDonald, D

    2004-01-01

    BACKGROUND: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique. METHODS: Between June 1998 and June 2002, 227 SNB procedu...... cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool....

  4. Interest Rate Dynamics and Monetary Policy Implementation in Switzerland

    OpenAIRE

    Puriya Abbassi; Dieter Nautz; Christian Offermanns

    2010-01-01

    The maturity of the operational target of monetary policy is a distinguishing feature of the SNB's operational framework of monetary policy. While most central banks use targets for the overnight rate to signal the policy-intended interest rate level, the SNB announces a target range for the three-month Libor. This paper investigates the working and the consequences of the SNB's unique operational framework for the behavior of Swiss money market rates before and during the financial crisis.

  5. Fusion development and technology

    International Nuclear Information System (INIS)

    Montgomery, D.B.

    1991-01-01

    This report discusses the following topics: superconducting magnet technology high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies -- Aries; ITER physics; ITER superconducting PF scenario and magnet analysis; and safety, environmental and economic factors in fusion development

  6. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  7. Moral Development in Adolescence

    Science.gov (United States)

    Hart, Daniel; Carlo, Gustavo

    2005-01-01

    Themes in the papers in this special issue of the "JRA" on moral development are identified. We discuss the intersection of moral development research with policy concerns, the distinctive qualities of moral life in adolescence that warrant investigation, the multiple connotations of "moral", the methods typical of moral development research, and…

  8. World Development Report 1984.

    Science.gov (United States)

    World Bank, Washington, DC.

    This report, seventh in a series of annual publications, examines the relationship between population change and development, showing why continuing rapid population growth in developing countries is likely to mean a lower quality of life for millions of people. The first part of the report concludes that the economies of developing countries can…

  9. The sustainable development

    International Nuclear Information System (INIS)

    2004-01-01

    In the framework of the sustainable development week (june 2003), Actu Environnement published a complete document on the sustainable development to inform the public, recall the main steps of this notion (Rio conference and the following conferences) and the possible employments. It presents also the main organizations acting in the sustainable development domain. (A.L.B.)

  10. Participatory Development Communication

    International Development Research Centre (IDRC) Digital Library (Canada)

    Training Needs in Participatory Development Communication .... to the development of society (communications in the service of development), ... There are also some definitions that give a more restrictive meaning to the way ...... Although proponents of participation appreciate that there is more good than bad in the ...

  11. Mechanisms in Plant Development

    Energy Technology Data Exchange (ETDEWEB)

    Hake, Sarah [USDA ARS Plant Gene Expression Center

    2013-08-21

    This meeting has been held every other year for the past twenty-two years and is the only regularly held meeting focused specifically on plant development. Topics covered included: patterning in developing tissues; short and long distance signaling; differentiation of cell types; the role of epigenetics in development; evolution; growth.

  12. Curriculum Development in Geomorphology.

    Science.gov (United States)

    Gregory, Kenneth J.

    1988-01-01

    Examines the context of present curriculum development in geomorphology and the way in which it has developed in recent years. Discusses the content of the geomorphology curriculum in higher education and the consequences of curriculum development together with a consideration of future trends and their implications. (GEA)

  13. Interpreting sustainable development

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    Over the past decade, the term" sustainable development"has emerged as the principal concept in the development field. The concept emerged in the 1970s and was first promoted in the international environmental and development communities with the publication of the " world conservation strategy"(1980). It was popularized by the Brundtland report, " Our common future"(1987). The Brundtland Commission defined sustainable development as " development which meets the needs of the present, without compromising the sustainability of future generation to meet their own needs". The Earth Summit(1992) established "sustainable development" as the most important policy of the 21st century. Since then, the relationship between development and environment has been widely discussed and sustainabale development is now an important part of the vocabulary of environmental policy research and analysis. In this paper, we begin by tracing the evolution of the concept of sustainable development. Definitions of sustainable development in ecology, economics and sociology are then explored and discussed. This paper also examine the contribution that a broadly-based concept of sustainable development can make: as a goal, an attitude and as a guiding principle for integrating economic development and environmental protection.

  14. Professional Development. Issue Brief

    Science.gov (United States)

    Keleher, Julia

    2017-01-01

    In this professional development research brief, the author sets forth the overarching considerations that should be kept in mind when conceptualizing professional development for educators working with neglected or delinquent youth (N or D). The brief begins by defining professional development and demonstrating why it is a critical support for…

  15. Institutionalizing Staff Development.

    Science.gov (United States)

    Shawl, William F.

    Three years ago, Golden West College (GWC) decided to make a major commitment to staff development as a means of revitalizing the college. This commitment was evidenced through the creation of the position of Dean of Educational Development, who is responsible solely for serving faculty needs; the Educational Development Center, which houses the…

  16. Domestic biogas development in developing countries

    International Nuclear Information System (INIS)

    Rakotojaona, Loic

    2013-07-01

    Communities that rely mostly on agriculture and livestock farming in developing countries can face strong pressure related to: - Energy access: for instance, in Africa, it is estimated that 68% of the population live without clean cooking facilities [1]. Energy access plays a key role in poverty alleviation. - Resources depletion: if a household uses firewood for cooking purposes, forests depletion in some areas makes firewood collection tougher. - Climate change mitigation: agriculture (i.e. the production of crop and livestock products) accounts for 13.5%2 of the global GHG emissions, and extensive systems are sometimes blamed for being less efficient than intensive ones when it comes to climate change mitigation (given that the later involve lower direct emissions per kg of product). In this context, access to clean and sustainable energy through domestic biogas production can help rural communities alleviate current pressures on the environment. In an urban context, domestic biogas in developing countries is also considered as a means for improving hygiene conditions (especially when it comes to public washrooms issues). This report only focuses on domestic biogas development within the frame of small scale agriculture and livestock production (i.e. in rural areas). The main objective of this document is to provide domestic biogas project developers with relevant information on the key issues to have in mind regarding national integration of such projects. This document gives a general presentation of domestic biogas and its main environmental, social and economic benefits. It also browses the main aspects one should have in mind (checklist) in order to assess local risks and opportunities for domestic biogas development

  17. Competence development in UAS

    DEFF Research Database (Denmark)

    Thorslund, Jørgen; Brodersen, Anne Mygind

    As a University of Applied Science (UAS) University College Lillebaelt in Denmark is addressing education, knowledge production and professional development in perspective of life-long and life-wide learning. It is our basic assumption that that internal competence development ? individually...... and organizationally - among UAS educators should be based on same learning concepts as used in professional development to avoid parallelism. Do for yourself, what you preach for others. Second, competence development of faculty is a central element in transformation of our institutions from schools of higher...... education to universities of applied science (UAS). Competence development strategies should thus include objectives for the institutions ability to contribute to knowledge production....

  18. Environmental Control Subsystem Development

    Science.gov (United States)

    Laidlaw, Jacob; Zelik, Jonathan

    2017-01-01

    Kennedy Space Center's Launch Pad 39B, part of Launch Complex 39, is currently undergoing construction to prepare it for NASA's Space Launch System missions. The Environmental Control Subsystem, which provides the vehicle with an air or nitrogen gas environment, required development of its local and remote display screens. The remote displays, developed by NASA contractors and previous interns, were developed without complete functionality; the remote displays were revised, adding functionality to over 90 displays. For the local displays, multiple test procedures were developed to assess the functionality of the screens, as well as verify requirements. One local display screen was also developed.

  19. COMPETITIVENESS IN REGIONAL DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    ELENA MĂDĂLINA OPRIȚESCU

    2012-12-01

    Full Text Available The development and diversification of the economic activities, the stimulation of investments both in the public sector, but mainly in the private one, the reduction of unemployment, the improvement of living standards are just some of the concepts aimed at by the regional development. The main method which can lead to a balanced development of the regions is financing them differentially so that the underdeveloped regions would obtain proportionally more funds that the developed ones. At a region level, the main objective is represented by the more accelerated growth of the less developed regions, in an effort to diminish the inter-regional and intra-regional development disparities. A key role is played by the sustainable economic growth concept, while also analyzing the competitiveness at a regional level, as well as the main development factors.

  20. World Development Report 2008: Agriculture for development

    OpenAIRE

    The World Bank

    2007-01-01

    The world's demand for food is expected to double within the next 50 years, while the natural resources that sustain agriculture will become increasingly scarce, degraded, and vulnerable to the effects of climate change. In many poor countries, agriculture accounts for at least 40 percent of GDP and 80 percent of employment. At the same time, about 70 percent of the world's poor live in rural areas and most depend on agriculture for their livelihoods. World Development Report 2008 seeks t...

  1. Doing physics with scientific notebook a problem solving approach

    CERN Document Server

    Gallant, Joseph

    2012-01-01

    The goal of this book is to teach undergraduate students how to use Scientific Notebook (SNB) to solve physics problems. SNB software combines word processing and mathematics in standard notation with the power of symbolic computation. As its name implies, SNB can be used as a notebook in which students set up a math or science problem, write and solve equations, and analyze and discuss their results. Written by a physics teacher with over 20 years experience, this text includes topics that have educational value, fit within the typical physics curriculum, and show the benefits of using SNB.

  2. ACCELERATING CONSTRUCTION INDUSTRY DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Mohan M. Kumaraswamy

    2006-06-01

    Full Text Available The needs for construction industry development are initially viewed from the broader perspectives of imperatives for infrastructure development and national development. All these are clearly more critical in developing countries. A non-exhaustive set of potential drivers and common barriers to construction industry development is identified from previous research. These suggest the usefulness of consolidating a cluster of recent proposals and exercises aiming at (a construction organization development in terms of an over-arching management support system model, as well as improved information and knowledge management; and (b project team development in the context of relationally integrated teams and supply chains, joint risk management and ‘technology and knowledge exchange’ in joint ventures, as well as longer term public private partnerships. These apparently disparate research thrusts are threaded together into a pattern that may inspire, if not feed, specific research and development (R & D agendas for construction industry development in different countries according to their own priorities, constraints and stages of infrastructure and national development.

  3. Cooperative method development

    DEFF Research Database (Denmark)

    Dittrich, Yvonne; Rönkkö, Kari; Eriksson, Jeanette

    2008-01-01

    The development of methods tools and process improvements is best to be based on the understanding of the development practice to be supported. Qualitative research has been proposed as a method for understanding the social and cooperative aspects of software development. However, qualitative...... research is not easily combined with the improvement orientation of an engineering discipline. During the last 6 years, we have applied an approach we call `cooperative method development', which combines qualitative social science fieldwork, with problem-oriented method, technique and process improvement....... The action research based approach focusing on shop floor software development practices allows an understanding of how contextual contingencies influence the deployment and applicability of methods, processes and techniques. This article summarizes the experiences and discusses the further development...

  4. Hanford Site Development Plan

    International Nuclear Information System (INIS)

    Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

    1992-05-01

    The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides a land use plan for the Hanford Site and presents a picture of what is currently known and anticipated in accordance with DOE Order 4320.1B. Site Development Planning. The HSDP wig be updated annually as future decisions further shape the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans

  5. Energy and Sustainable Development

    International Nuclear Information System (INIS)

    2013-01-01

    None of the eight Millennium Development Goals (MDGs) adopted by the United Nations in 2000 directly addressed energy, although for nearly all of them - from eradicating poverty and hunger to improving education and health - progress has depended on greater access to modern energy. Thirteen years later, energy is being given more attention. The target date for the MDGs is 2015, and in 2012 the UN began deliberations to develop sustainable development goals to guide support for sustainable development beyond 2015. The Future We Want, the outcome document of the 2012 United Nations Conference on Sustainable Development (also known as Rio+20) gives energy a central role: ''We recognize the critical role that energy plays in the development process, as access to sustainable modern energy services contributes to poverty eradication, saves lives, improves health and helps provide for basic human needs''

  6. Energy and development

    Energy Technology Data Exchange (ETDEWEB)

    Gururaja, J.

    1980-03-15

    The developing countries will require higher per capita energy for improving the quality of life. This paper examines the goals and strategies for development vis-a-vis those of the developed countries. Crucial issues in India are listed. The role of technology in the utilization of energy is discussed. Difficulties in choosing the technology are pointed out. The problem of integrating several alternative energy sources in villages is mentioned. Environmental issues are considered. (DLC)

  7. Centrifuge design and development

    International Nuclear Information System (INIS)

    Edwards, T.T.; Holmes, M.D.

    1987-01-01

    BNFL has been enriching uranium on an industrial scale using the centrifuge process for over a decade. Together with its Urenco partners, a joint development programme has been and is being vigorously pursued to reduce specific costs, increase output and maintain competitiveness throughout the 1990s. The paper summarises the development of the centrifuge from its earliest concepts through to the centrifuges of today which are jointly designed by the Urenco partners. The potential for further development is also examined. (author)

  8. Fusion development and technology

    International Nuclear Information System (INIS)

    Montgomery, D.B.

    1992-01-01

    This report discusses the following: superconducting magnet technology; high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies--aries; ITER physics: alpha physics and alcator R ampersand D for ITER; lower hybrid current drive and heating in the ITER device; ITER superconducting PF scenario and magnet analysis; ITER systems studies; and safety, environmental and economic factors in fusion development

  9. CANDU project development

    Energy Technology Data Exchange (ETDEWEB)

    Hedges, K R [Atomic Energy of Canada Ltd., Mississauga, ON (Canada)

    1996-12-31

    Advanced CANDU reactor design strategy follows an evolutionary approach, taking manageable steps in the development of power plants from today`s available designs, and in parallel carrying out longer-term studies to develop future-generation reactor concepts. The major emphasis is on safety, on on reducing cost and schedule. New features are developed and thoroughly proof-tested before introduction into designs, in order to maximize owner confidence. (author). 4 figs.

  10. Renewable energy project development

    Energy Technology Data Exchange (ETDEWEB)

    Ohi, J.

    1996-12-31

    The author presents this paper with three main thrusts. The first is to discuss the implementation of renewable energy options in China, the second is to identify the key project development steps necessary to implement such programs, and finally is to develop recommendations in the form of key issues which must be addressed in developing such a program, and key technical assistance needs which must be addressed to make such a program practical.

  11. Finance and Economic Development

    OpenAIRE

    Panizza, Ugo

    2012-01-01

    Published by Palgrave Macmillan This chapter reviews the literature on finance and economic development. It starts with a description of the roles of finance, a definition of financial efficiency, and a discussion of whether countries may have financial sectors that are ‘too large’ compared to the size of the domestic economy. Next, the author describes several indicators of financial development and reviews the literature on the relationship between financial development and economic growth....

  12. CANDU project development

    International Nuclear Information System (INIS)

    Hedges, K.R.

    1995-01-01

    Advanced CANDU reactor design strategy follows an evolutionary approach, taking manageable steps in the development of power plants from today's available designs, and in parallel carrying out longer-term studies to develop future-generation reactor concepts. The major emphasis is on safety, on on reducing cost and schedule. New features are developed and thoroughly proof-tested before introduction into designs, in order to maximize owner confidence. (author). 4 figs

  13. Tax havens and development

    OpenAIRE

    Norwegian Government Commission on Capital Flight from Poor Countries

    2009-01-01

    Tax havens harm both industrialised and developing countries, but the damaging impacts are largest in developing countries. This is partly because these countries are poor and thereby have more need to protect their national tax base, and partly because they generally have weaker institutions and thereby fewer opportunities for enforcing the laws and regulations they adopt. Tax treaties between tax havens and developing countries often contribute to a significant reduction in the tax base of...

  14. Patterns of strategy development

    OpenAIRE

    Bailey, Andy; Johnson, Gerry

    1996-01-01

    This paper builds on a multidimensional framework of strategy development to more clearly understand the processes by which strategy develops within organisations. It reports on a survey based research project which employs senior executives’ perceptions of the strategy development process in their organisations to examine how context specific configurations of dimensions explaining such processes can advance our understanding of strategic management. Six configurations are ide...

  15. Strategy Development in Organisations

    DEFF Research Database (Denmark)

    Sørensen, Lene

    1999-01-01

    There exist certain ambiguities with the converging fields of information technology and organisational strategy development. The term "IT strategy" has evolved and reflects in some respects this confusion. This paper discusses some of the ambiguities and difficulties of the term "IT strategy......" as used in practice and literature. Emphasis is put on how the term is related to the problem, the organisation, the strategy process and the practical way of methodologically developing the strategy. Finally, alternative strategy developing perspectives are presented....

  16. Environment and development

    International Nuclear Information System (INIS)

    1992-01-01

    As part of its contribution to the United Nations Conference on Environment and Development, held in Rio de Janeiro in June 1992, the IAEA produced a booklet entitled ''Nuclear Power, Nuclear Techniques and Sustainable Development''. The second half of this dealt with the relevance of the IAEA's work to ''Agenda 21'', an agenda of environmental conservation and sustainable development for the twenty-first century. This article briefly summarizes the text

  17. Node web development

    CERN Document Server

    Herron, David

    2013-01-01

    Presented in a simple, step-by-step format, this book is an introduction to web development with Node.This book is for anybody looking for an alternative to the ""P"" languages (Perl, PHP, Python), or anyone looking for a new paradigm of server-side application development.The reader should have at least a rudimentary understanding of JavaScript and web application development.

  18. Agile software development

    CERN Document Server

    Dingsoyr, Torgeir; Moe, Nils Brede

    2010-01-01

    Agile software development has become an umbrella term for a number of changes in how software developers plan and coordinate their work, how they communicate with customers and external stakeholders, and how software development is organized in small, medium, and large companies, from the telecom and healthcare sectors to games and interactive media. Still, after a decade of research, agile software development is the source of continued debate due to its multifaceted nature and insufficient synthesis of research results. Dingsoyr, Dyba, and Moe now present a comprehensive snapshot of the kno

  19. Pro Access 2010 Development

    CERN Document Server

    Collins, Mark

    2011-01-01

    Pro Access 2010 Development is a fundamental resource for developing business applications that take advantage of the features of Access 2010 and the many sources of data available to your business. In this book, you'll learn how to build database applications, create Web-based databases, develop macros and Visual Basic for Applications (VBA) tools for Access applications, integrate Access with SharePoint and other business systems, and much more. Using a practical, hands-on approach, this book will take you through all the facets of developing Access-based solutions, such as data modeling, co

  20. Nuclear standardization development study

    International Nuclear Information System (INIS)

    Pan Jianjun

    2010-01-01

    Nuclear industry is the important part of national security and national economic development is key area of national new energy supported by government. nuclear standardization is the important force for nuclear industry development, is the fundamental guarantee of nuclear safe production, is the valuable means of China's nuclear industry technology to the world market. Now nuclear standardization faces to the new development opportunity, nuclear standardization should implement strategy in standard system building, foreign standard research, company standard building, and talented people building to meet the requirement of nuclear industry development. (author)

  1. Hydroelectricity and sustainable development

    International Nuclear Information System (INIS)

    Dubeau, D.

    1995-01-01

    From 1975 to 1992, hydroelectricity helped reduce greenhouse gas emissions in Quebec by 20%. For Hydro-Quebec, energy conservation and hydroelectric development are basic complementary tools for sustainable development. Recent studies show that developing only 50% of economically exploitable hydroelectric potential (30% of the gross theoretical potential) of different regions worldwide would considerably reduce greenhouse gas and SO 2 emissions. However, hydroelectric systems produce environmental and social impacts locally that require mitigative measures. To fulfill its mandate in a sustainable development context, Hydro-Quebec has adopted methods such as integrated resource planning, the assessment of externalities, multi criteria decision tools and public participations

  2. Shopify application development

    CERN Document Server

    Larkin, Michael

    2014-01-01

    This is an easy-to follow manual that will guide you through the entire process of application development with Shopify, beginning with the installation and configuration of your local development environment for your app to the deployment of the app to Heroku. If you are a web developer or a designer who wants to extend Shopify stores by building apps, then this book is for you. A basic understanding of programming concepts and some familiarity with Shopify is all that is required to get started with Shopify app development.

  3. Small Business Development Center

    Data.gov (United States)

    Small Business Administration — Small Business Development Centers (SBDCs) provide assistance to small businesses and aspiring entrepreneurs throughout the United States and its territories. SBDCs...

  4. Creativity and Strategy Development

    DEFF Research Database (Denmark)

    Sørensen, Lene Tolstrup; Vidal, Rene Victor Valqui

    This paper focus on how creative thinking, processes and methods can support the strategy development and planning process in organisations. First, several fundamental concepts related to both strategy development and planning are stipulated. In addition, the concept of living organisation...... will be discussed as well as the interaction between strategy and creativity. Then, methodological ideas to support the strategy making process are presented enhancing the use of creative methods and tools. Finally, a case study related to the development of a strategy for organisational development using...... creativity tools is discussed....

  5. Visualforce development cookbook

    CERN Document Server

    Bowden, Keir

    2013-01-01

    Visualforce Development Cookbook is written in such a way that even complex concepts are explained in an easy-to-understand manner. Following a Cookbook structure, the book covers some essential technical scenarios and includes over 75 recipes focusing on real-world development problems. This book is packed with illustrations and also contains lots of code samples for the better understanding of the reader.""Visualforce Development Cookbook"" is aimed at developers who have already grasped the basics of Visualforce. Awareness of the standard component library and the purpose of controllers is

  6. Physics and sustainable development

    International Nuclear Information System (INIS)

    Emre, B.

    2005-01-01

    Is there a relationship with between physics and sustainable development? The answer of this question is yes since in the past to the health and welfare of people and nations physics has made tremendous contributions. Think of the contributions that physics has made to the world economy in areas such as electronics, materials, and computer technology, also to health x-rays, magnetic resonance imaging and nuclear medicine. However, many of these contributions have benefited people in the developed world more than those in the developing world. Moreover current physics curricula do not have vision of to offer the student a full perspective of sustainable development

  7. REGIONAL DEVELOPMENT STRATEGY

    Directory of Open Access Journals (Sweden)

    Vaduva Maria

    2011-01-01

    Full Text Available Regional development policies in the EU Member States have included tools whoseimportance varied from one country to another. Can be identified by negative incentives forregional development policy towards location in crowded areas or control over the location,the reallocation of economic activities in national territory, creation of adequateinfrastructure, measures to enhance development, financial incentives granted toenterprises. Sustainable business development, rehabilitation of social infrastructure,including social housing and improved social services. Improved regional and localtransportation are key areas of intervention rehabilitation and upgrading of county roads,city streets, including road construction and rehabilitation of belt.

  8. Environment, employment and development

    International Nuclear Information System (INIS)

    Bhalla, A.S.

    1992-01-01

    It is generally recognised that the question of sustainable development is a global problem, emphasizing the increasingly interdependent nature of relationships among nations. Solutions to the problem are as much political as they are economic and technological. Notwithstanding the deepening and widening of the debate on sustainable development, its implications for employment - a major concern of the ILO under its World Employment Programme - have remained largely unexplored. This volume, therefore, has a very modest objective, namely to place the employment question on the policy agenda in the context of the current debate on environment and development. The design of environmental policies should allow for the differences that exist between countries with a high level of development and technological dynamism and those with a low level of development and low technological capability. One must also recognize the costs imposed by adjustment and the consequent distributional impact. In the long term, technology choice plays a crucial role in promoting sustainable development in both industrialized and developing countries. It is not only environment-friendly technologies that need to be developed and diffused; in the case of the least developed countries, technological transformation needs to be accelerated in order to minimise their dependence on natural resources for economic growth. Refs, figs and tabs

  9. Energy, technology, development

    Energy Technology Data Exchange (ETDEWEB)

    Goldemberg, J [Ministerio da Educacao, Brasilia (Brazil)

    1992-02-01

    Energy and technology are essential ingredients of development, it is only through their use that it became possible to sustain a population of almost 5 billion on Earth. The challenges to eradicate poverty and underdevelopment in developing countries in the face of strong population increases can only be successfully met with the use of advanced technology, leapfrogging the path followed in the past by today's industrialized countries. It is shown in the paper that energy consumption can be decoupled from economic development. Such possibility will contribute significantly in achieving sustainable development. 10 refs., 4 figs., 3 tabs.

  10. Xcode 5 developer reference

    CERN Document Server

    Wentk, Richard

    2014-01-01

    Design, code, and build amazing apps with Xcode 5 Thanks to Apple's awesome Xcode development environment, you can create the next big app for Macs, iPhones, iPads, or iPod touches. Xcode 5 contains gigabytes of great stuff to help you develop for both OS X and iOS devices - things like sample code, utilities, companion applications, documentation, and more. And with Xcode 5 Developer Reference, you now have the ultimate step-by-step guide to it all. Immerse yourself in the heady and lucrative world of Apple app development, see how to tame the latest features and functions, and find loads of

  11. Six Sigma software development

    CERN Document Server

    Tayntor, Christine B

    2002-01-01

    Since Six Sigma has had marked success in improving quality in other settings, and since the quality of software remains poor, it seems a natural evolution to apply the concepts and tools of Six Sigma to system development and the IT department. Until now however, there were no books available that applied these concepts to the system development process. Six Sigma Software Development fills this void and illustrates how Six Sigma concepts can be applied to all aspects of the evolving system development process. It includes the traditional waterfall model and in the support of legacy systems,

  12. Telemedicine for Developing Countries

    Science.gov (United States)

    Combi, Carlo; Pozzani, Gabriele

    2016-01-01

    Summary Background Developing countries need telemedicine applications that help in many situations, when physicians are a small number with respect to the population, when specialized physicians are not available, when patients and physicians in rural villages need assistance in the delivery of health care. Moreover, the requirements of telemedicine applications for developing countries are somewhat more demanding than for developed countries. Indeed, further social, organizational, and technical aspects need to be considered for successful telemedicine applications in developing countries. Objective We consider all the major projects in telemedicine, devoted to developing countries, as described by the proper scientific literature. On the basis of such literature, we want to define a specific taxonomy that allows a proper classification and a fast overview of telemedicine projects in developing countries. Moreover, by considering both the literature and some recent direct experiences, we want to complete such overview by discussing some design issues to be taken into consideration when developing telemedicine software systems. Methods We considered and reviewed the major conferences and journals in depth, and looked for reports on the telemedicine projects. Results We provide the reader with a survey of the main projects and systems, from which we derived a taxonomy of features of telemedicine systems for developing countries. We also propose and discuss some classification criteria for design issues, based on the lessons learned in this research area. Conclusions We highlight some challenges and recommendations to be considered when designing a telemedicine system for developing countries. PMID:27803948

  13. Emigration for Development?

    DEFF Research Database (Denmark)

    Careja, Romana

    2013-01-01

    is necessary if resources from emigration are to become seeds for development. By analysing the case of Romania, one of the largest labour sending countries in Eastern Europe, it argues that its laissez-faire approach is likely not enough to capitalize on emigrants' resources for development. International......This article explores the proposition that the developmental potential of emigration depends on the context of the sending countries. It builds on the insights from the institutional approach to development and adapts them to the migration-development nexus. It argues that government involvement...... Migration...

  14. Continuous Platform Development

    DEFF Research Database (Denmark)

    Nielsen, Ole Fiil

    low risks and investments but also with relatively fuzzy results. When looking for new platform projects, it is important to make sure that the company and market is ready for the introduction of platforms, and to make sure that people from marketing and sales, product development, and downstream......, but continuous product family evolution challenges this strategy. The concept of continuous platform development is based on the fact that platform development should not be a one-time experience but rather an ongoing process of developing new platforms and updating existing ones, so that product family...

  15. Population, environment and development.

    Science.gov (United States)

    Karkal, M

    1994-06-01

    Western development models label subsistence economies, which do not participate in the market economy on a grand scale and do not consume commodities produced for and distributed through the market, to be poor. Yet, subsistence does not always indicate a low quality of life. The Western development process has destroyed wholesome and sustainable lifestyles. In India, the Green Revolution caused many small farmers to lose their land. In comparison to traditional economies, industrial economies have longer technological chains dependent on higher energy and resource inputs and exclude large numbers of people without power to buy goods. Further, they generate new and artificial needs, necessitating increased production of industrial goods and services. They erode resource bases for survival. This erosion is marginalizing people who were traditionally in nature's economy. Developed countries did not deliver 0.15% of their GNP to development projects in developing countries as promised. The US made population growth in these countries its cause. The UN and other multinational agencies during 1962-1972, at the US's request, began to support population and family planning programs in developing countries. These countries opposed the 1st draft at the 1974 Bucharest Population Conference, but by the conference in Mexico City, most supported the need for family planning. Yet, the US politicized this conference and had a greater say in the recommendations than did developing countries. Structural adjustments and external debt repayments required of developing countries in the 1980s set them back. In fact, the number of developing countries increased from 31 to 42. The UN recognizes the right to development, but social inequalities are barriers to this right. If environmental degradation continues, poverty will only increase. Women's groups are playing a great role in preparations for the International Conference on Population and Development in Cairo in September 1994.

  16. EMI Registry Development Plan

    CERN Document Server

    Memon, S.; Szigeti, G.; Field, L.

    2012-01-01

    This documents describes the overall development plan of the EMI Registry product, the plan focuses on the realisation of the EMI Registry specification as defined in the document. It is understood that during the course of the development phase the specification will likely evolve and the changes will be fed into the specification document.

  17. Promoting teachers' professional development

    NARCIS (Netherlands)

    Runhaar, Pietsje Roelofje

    2008-01-01

    Because teacher quality has a great influence on pupil attainment, teachers’ professional development receives a lot of attention in educational policy. This dissertation contains five studies on how teachers’ professional development, in terms of learning at the workplace, can be explained and

  18. Counter radicalization development assistance

    OpenAIRE

    van Hippel, Karin

    2006-01-01

    The paper reviews current research and practice and recommends strategies for development agencies working in the Arab and Muslim world. It builds on the basic assumption that the realization of the Millennium Development Goals will be vital to reduce support for terrorism in the long term. Within this overall framework, emphasis is placed on particular programs that could be specifically applied to counter radicalization.

  19. Develop your presentation skills

    CERN Document Server

    Theobald, Theo

    2016-01-01

    Going beyond handling nerves and presenting PowerPoint slides, the third edition of "Develop Your Presentation Skills "offers practical advice on developing a captivating presentation, constructing compelling content, and boosting self-confidence. The book includes three new chapters on delivering a "stripped down"presentation, using new media to engage with the audience, and handling being asked to present on short notice."

  20. Trends in organization development

    NARCIS (Netherlands)

    Allegro, J.T.; Steensma, H.O.; Allegro, J.T.; Steensma, H.O.

    1985-01-01

    Organisation Development (OD) is an extraordinarly complex phenomenon of human society in which in the last few years there have been some interesting developments. Without making any claim to completeness the following topics would seem to have been a focus of interest in recent research on the

  1. Development of geothermal resources

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    This paper describes the geothermal development promotion survey project. NEDO is taking the lead in investigation and development to reduce risks for private business entities and promote their development. The program is being moved forward by dividing the surveys into three ranks of A, B and C from prospects of geothermal resource availability and the state of data accumulation. The survey A lacks number of data, but covers areas as wide as 100 to 300 km{sup 2}, and studies possible existence of high-temperature geothermal energy. The survey B covers areas of 50 to 70 km{sup 2}, investigates availability of geothermal resources, and assesses environmental impacts. The survey C covers areas of 5 to 10 km{sup 2}, and includes production well drilling and long-term discharge tests, other than those carried out by the surveys A and B. Results derived in each fiscal year are evaluated and judged to establish development plans for the subsequent fiscal year. This paper summarizes development results on 38 areas from among 45 areas surveyed since fiscal 1980. Development promotion surveys were carried out over seven areas in fiscal 1994. Development is in progress not only on utilization of high-temperature steam, but also on binary cycle geothermal power generation utilizing hot waters of 80 to 150{degree}C. Fiscal 1994 has carried out discussions for spread and practical use of the systems (particularly on economic effects), and development of small-to-medium scale binary systems. 2 figs., 1 tab.

  2. Improvisation for Leadership Development.

    Science.gov (United States)

    Trepanier, Sylvain; Nordgren, Mollie

    2017-04-01

    Leaders are required to demonstrate agility, creativity, and innovation. Professional development educators can help leaders to develop the skills to listen carefully, be present in the moment, and contribute to any conversation by using improvisation. J Contin Educ Nurs. 2017;48(4):151-153. Copyright 2017, SLACK Incorporated.

  3. Strategic port development

    DEFF Research Database (Denmark)

    Olesen, Peter Bjerg; Dukovska-Popovska, Iskra; Steger-Jensen, Kenn

    2012-01-01

    This paper proposes a framework for strategic development of a port’s collaboration with its hinterland. The framework is based on literature relevant to port development and undertakes market perspective by considering import/export data relevant for the region of interest. The series of steps...

  4. Thermodynamics and sustainable development

    NARCIS (Netherlands)

    Cornelissen, Rene

    1997-01-01

    It is the objective of this thesis to demonstrate exergy analysis as a powerful instrument to obtain sustainable development. An important aspect of sustainable development is the minimisation of irreversibilities caused by the use of non-renewables. In order to limit the scope of this thesis

  5. concrete5 for developers

    CERN Document Server

    Uzayr, Sufyan bin

    2014-01-01

    Whether you have had some previous experience with concrete5 or are entirely new to it, this book will help you understand all that you need to know in order to get started with concrete5 development. A background in PHP is required; some knowledge of HTML/CSS is needed in order to fully grasp the concepts underlying concrete5 theme development.

  6. Developing Successful Global Leaders

    Science.gov (United States)

    Training, 2011

    2011-01-01

    Everyone seems to agree the world desperately needs strong leaders who can manage a global workforce and all the inherent challenges that go with it. That's a big part of the raison d'etre for global leadership development programs. But are today's organizations fully utilizing these programs to develop global leaders, and, if so, are they…

  7. Character Development in Adolescents.

    Science.gov (United States)

    Kessler, Glenn R.; And Others

    1986-01-01

    Explored the effects of a program consisting of communication and counseling skills, assertiveness training and moral dilemmas on the character development of high school students. The results demonstrated that the character development of the students in the experimental treatment group was affected significantly over time by the program.…

  8. International thermal reactor development

    International Nuclear Information System (INIS)

    Zebroski, E.L.

    1977-01-01

    The worldwide development of nuclear power plants is reviewed. Charts are presented which show the commitment to light-water reactor capacity construction with breakdown by region and country. Additional charts show the major nuclear research centers which have substantial scope in light water reactor development and extensive international activities

  9. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development welcomes the results of original research, field surveys, advances in field and laboratory techniques, book reviews, and informal status reports from research, conservation, development and management programs and in-field projects in Madagascar. In addition, notes on changes ...

  10. Hydropower development in India

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, Praveen [Govt. of India, New Delhi (India). Ministry of New and Renewable Energy], E-mail: psaxena_98@yahoo.com; Kumar, Arun [Indian Institute of Technology Roorkee, Uttarakhand (India). Alternate Hydro Energy Centre], E-mail: aheciitr@gmail.com

    2011-04-15

    India is posed for large deployment of hydropower in present conducive policy and investment environment. Growing energy demand and concern for carbon emission is making hydropower development more favorable. The Government of India is ensuring a good performance of the new SHP stations by linking the incentives to the SHP developers with the performance of the station. (author)

  11. Accelerated product development

    NARCIS (Netherlands)

    Langerak, F.; Seth, J.N.; Malhotra, N.K.

    2011-01-01

    Accelerated product development is a competitive strategy that seeks to reduce the development cycle time of new products. However, there has been little theoretical advancement and empirical model testing in the identification of the conditions under which cycle time reduction is appropriate, the

  12. Global product development

    DEFF Research Database (Denmark)

    Taylor, Thomas Paul; Ahmed-Kristensen, Saeema

    2016-01-01

    Selecting key performance indicators in conventional product development is a challenging task for project management and is compound by global product development. Informed from the findings of two in depth case studies conducted with large Danish manufacturing companies, in this paper we develo...

  13. Evaluating professional development

    CERN Document Server

    Guskey, Thomas R

    2000-01-01

    This is a practical guide to evaluating professional development programs at five increasing levels of sophistication: participants' reaction to professional development; how much participants learned; evaluating organizational support and change; how participants use their new knowledge and skills; and improvements in student learning.

  14. Beijing Development Zones

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Beijing Badaling Development Area The Development Area is planned to cover an area of 6.56 km2.Currently,more than 300 enterprises have located in the area.Their investments add up to about RMB 1 billion.Major business trades include machine building,mineral ore processing,medicine,electronic parts,foodstuff processing,and warehousing transportation.

  15. Improving Software Developer's Competence

    DEFF Research Database (Denmark)

    Abrahamsson, Pekka; Kautz, Karlheinz; Sieppi, Heikki

    2002-01-01

    Emerging agile software development methods are people oriented development approaches to be used by the software industry. The personal software process (PSP) is an accepted method for improving the capabilities of a single software engineer. Five original hypotheses regarding the impact...

  16. Youth Development: Maori Styles

    Science.gov (United States)

    Ware, Felicity; Walsh-Tapiata, Wheturangi

    2010-01-01

    Despite the innovative approach of the Youth Development Strategy Aotearoa and the applicability of its Rangatahi Development Package, the diverse realities and experiences of Maori youth are still presenting unique challenges to national policy in Aotearoa New Zealand. A Maori youth research approach that utilised a combination of action research…

  17. Fashions in Instructional Development.

    Science.gov (United States)

    Knapper, Christopher K.

    This paper on instructional development notes the trend toward teaching improvement efforts, classifies instructional development centers in terms of their differing philosophies of operation, and identifies some general problems that have been encountered in institutional efforts to improve teaching and learning. Centers in North America, Europe,…

  18. Medical device development.

    Science.gov (United States)

    Panescu, Dorin

    2009-01-01

    The development of a successful medical product requires not only engineering design efforts, but also clinical, regulatory, marketing and business expertise. This paper reviews items related to the process of designing medical devices. It discusses the steps required to take a medical product idea from concept, through development, verification and validation, regulatory approvals and market release.

  19. Financing Sustainable Development

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe; Funder, Mikkel; Engberg-Pedersen, Lars

    . But what are in fact the interests and modes of operation of such actors in the context of development financing, and to what extent do they align with the aims of the SDGs? And how do national governments of developing countries themselves perceive and approach these new sources of financing?...

  20. Culture and Development

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2006-01-01

    textabstractDiscourses on culture and development vary according to their conceptions of culture and of development and according to their standpoint. The ‘culture and development’ problematic has typically: (1) arisen from a conception of ‘culture’ as a relatively fixed, homogeneous set of mental

  1. Strategic port development

    DEFF Research Database (Denmark)

    Olesen, Peter Bjerg; Dukovska-Popovska, Iskra; Hvolby, Hans-Henrik

    2014-01-01

    While large global ports are recognised as playing a central role in many supply chains as logistic gateways, smaller regional ports have been more stagnant and have not reached the same level of development as the larger ports. The research literature in relation to port development is also...

  2. Data Centric Development Methodology

    Science.gov (United States)

    Khoury, Fadi E.

    2012-01-01

    Data centric applications, an important effort of software development in large organizations, have been mostly adopting a software methodology, such as a waterfall or Rational Unified Process, as the framework for its development. These methodologies could work on structural, procedural, or object oriented based applications, but fails to capture…

  3. New Services Development

    Directory of Open Access Journals (Sweden)

    Peter Ciganek

    2004-01-01

    Full Text Available Dynamic changes in traditional technologies and rising of new technologies call for development of new services. If service providers want to stay on information technologies market, they must keep track with this trend and adjust their services to customer requirements or develop new services. New applications will mainly depend on communication bandwidth and end users ability to handle it. If network providers will be able to ensure necessary bandwidth, there will be nothing that can stop service providers and developers in new service development. People know about growing necessity of new service and ask for them, but they hardly understand that the most important thing for service providers is merchantability and economic return of resources they gave to the developmentand implementation. By the lack of flexible development environment that is able to develop, test and provide final service for operation, new service development is not easy. There are different new service design procedures for various technological and user areas. This is the reason why this paper provides brief description of new service development procedure from technological and administrative point of view.

  4. Standards and Professional Development

    Science.gov (United States)

    Zengler, Cynthia J.

    2017-01-01

    The purpose of this paper is to describe the professional development that has taken place in conjunction with Ohio adopting the College and Career Readiness (CCR) Standards. The professional development (PD) has changed over time to include not only training on the new standards and lesson plans but training on the concepts defined in the…

  5. Law, Democracy & Development

    African Journals Online (AJOL)

    The evolution and implementation of democracy, good governance practices, human rights and socio-economic development are critical issues facing South Africa and Africa as a whole. Law interacts with this process in ways that may promote or inhibit it. Law, Democracy & Development addresses this interaction. Our aim ...

  6. Media and child development

    NARCIS (Netherlands)

    Piotrowski, J.T.; Vossen, H.G.M.; Valkenburg, P.M.; Wright, J.D.

    2015-01-01

    Decades of research have shown that the relationship between media and childhood is not unidirectional but reciprocal. In this article, both directions of the media-child development relationship are presented. We discuss how child development predisposes children's media use and preferences by

  7. Globalization, consumption, development

    NARCIS (Netherlands)

    Binsbergen, van W.M.J.; Fardon, R.; Binsbergen, van W.M.J.; Dijk, van R.A.

    1999-01-01

    The papers collected in this volume were first presented at a conference on 'Globalization, development and the making of consumers: what are collective identities for?' which was held in The Hague, The Netherlands, on 13-16 March 1997. The papers are concerned with the challenge to the development

  8. Microsoft Azure development cookbook

    CERN Document Server

    Freato, Roberto

    2014-01-01

    If you are an architect, this book will help you make the correct decisions about which Azure building blocks to use. If you are a developer, this book will help you understand how to use them appropriately, and if you are a .NET developer, this book is a pure delight.

  9. Centrifugal analyzer development

    International Nuclear Information System (INIS)

    Burtis, C.A.; Bauer, M.L.; Bostick, W.D.

    1976-01-01

    The development of the centrifuge fast analyzer (CFA) is reviewed. The development of a miniature CFA with computer data analysis is reported and applications for automated diagnostic chemical and hematological assays are discussed. A portable CFA system with microprocessor was adapted for field assays of air and water samples for environmental pollutants, including ammonia, nitrates, nitrites, phosphates, sulfates, and silica. 83 references

  10. ENTERPRISES DEVELOPMENT: MANAGEMENT MODEL

    Directory of Open Access Journals (Sweden)

    Lina Shenderivska

    2018-01-01

    Full Text Available The paper’s purpose is to provide recommendations for the effective managing the companies’ development taking into account the sectoral key elements’ transformation. Methodology. The enterprise profits’ econometric simulation is conducted to determine the most significant factors influencing their development. According to the model testing result, their multicollinearity was revealed. To get rid of the multicollinearity phenomenon from the profit models, isolated regressors are excluded, namely, return on assets, material returns, return on equity. To obtain qualitative models with a small error of model parameters estimation and, accordingly, high reliability of the conclusion about the interrelation between the factors of the model and the resulting feature, factors in the income model that are not closely interconnected, that is, not multicollinear, are included. Determination coefficients R2 and F-criterion were calculated for model quality checking. The modern printing enterprises of Ukraine key elements, connected with integration into the global information space, are analysed. Results. The interrelation between a company’s development and earning capacity is identified in the study. The profit importance as the main source for enterprise financing is substantiated. Factors that have the greatest impact on the enterprises’ development are labour productivity, financial autonomy, working capital turnover, and the character of their influence is most adequately reflected by the power model. Peculiarities of the enterprises’ activity include increased competition at the inter-branch level, poorly developed industrial relations, and the own sources of financing activities shortage. Practical implications. Based on information on the most significant developmental impact factors, directions for perspective enterprises development for their competitiveness increase are proposed: diversification based on the activity expansion

  11. Finance and Economic Development

    Directory of Open Access Journals (Sweden)

    Ugo Panizza

    2012-03-01

    Full Text Available Published by Palgrave MacmillanThis chapter reviews the literature on finance and economic development. It starts with a description of the roles of finance, a definition of financial efficiency, and a discussion of whether countries may have financial sectors that are ‘too large’ compared to the size of the domestic economy. Next, the author describes several indicators of financial development and reviews the literature on the relationship between financial development and economic growth. In the literature review, he discusses in detail some recent evidence indicating that the marginal contribution of financial development to gross domestic product (GDP growth becomes negative when credit to the private sector reaches 110 per cent of GDP. The chapter concludes with some policy conclusions targeted to developing countries.

  12. Development concept plan

    International Nuclear Information System (INIS)

    1992-06-01

    The following management objectives for New River Gorge National River relate to the Kaymoor site to: Preserve coal mining, railroad, and other historic resources that best illustrate park significance; Develop a system of land- and water-based recreation opportunities that allow visitors to experience the park's resources to the extent that natural, cultural, and scenic values are not imparied; and Work with the community to the extent possible to help it maximize economic benefits related to park development without impairing key resources. The Development Concept Plant outlining a plan of development for Kaymoor is a part of a larger emphasis by the National Park Service to identify and develop significant coal-related historic and cultural resources in southern West Virginia in cooperation with the West Virginia State Historic Preservation Office

  13. Urban Quality Development & Management

    DEFF Research Database (Denmark)

    Lehmann, Martin; Fryd, Ole

    2008-01-01

    Purpose: The purpose of this article is to describe and discuss the development and the structure of a new international master on the subject of Urban Quality Development & Management, and explore the potential of the process and the outcome in serving as models adoptable by faculty at other......: Urban quality development and management is dependent on human resource development, institutionalised networks and confident exchange of knowledge, and must identify and incorporate multiple environmental, social, economic and cultural aspects. The authors find that at the core of innovative societies......, an interlinkage exists between practice (business, civil society, governance) and theory (research, education). The case illustrates how a new curriculum takes time to develop and implement and how it relies on confidence and trust between partners, in this case cities and universities, before being able to plant...

  14. Environment: Development plan 1993

    International Nuclear Information System (INIS)

    1992-01-01

    The concept of sustainable development is gradually being incorporated into the activities of Hydro-Quebec as part of that utility's environmental policy. In its proposed development plan, Hydro-Quebec's principal strategic environmental orientations comprise making environmental concerns an integral part of the planning process, managing impacts associated with the construction of generating and transmission facilities, and evaluating the utility's environmental performance. The approaches used, tools to be developed, and information required in each of these orientations are described. Issues considered include the strategic choices available for meeting electricity requirements, including renewable energy sources; the evaluation of environmental externalities; the use of environmental impact assessment studies and environmental monitoring; relationships with native peoples and mitigation of the social impacts of northern hydroelectric development; protection and management of natural and human habitats; the utility's contribution to regional development; management of wastes and rights-of-way; and environmental auditing. 1 tab

  15. Global product development

    DEFF Research Database (Denmark)

    Hansen, Zaza Nadja Lee; Ahmed-Kristensen, Saeema

    2011-01-01

    Globalisation has enabled companies to globalise their product development process. Today, everything from manufacturing to R&D can be globally distributed. This has led to a more complex and disintegrated product development process. This paper investigates the impacts companies have experienced...... operational solutions to counteract the negative impacts with varying degrees of success. This paper presents a unique look into global product development through an investigation of its impact on the organisation, the product development process, and the product. Furthermore, it shows the solutions...... as a result of this, and how they have been addressed. Data was collected through case studies of five Danish multinational corporations. The findings showed that the companies experienced several challenges when they globalised their product development process. They consequently implemented various...

  16. The development of colliders

    International Nuclear Information System (INIS)

    Sessler, A.M.

    1993-02-01

    Don Kerst, Gersh Budker, and Bruno Touschek were the individuals, and the motivating force, which brought about the development of colliders, while the laboratories at which it happened were Stanford, MURA, the Cambridge Electron Accelerator, Orsay, Frascati, CERN, and Novosibirsk. These laboratories supported, during many years, this rather speculative activity. Of course, many hundreds of physicists contributed to the development of colliders but the men who started it, set it in the right direction, and forcefully made it happen, were Don, Gersh, and Bruno. Don was instrumental in the development of proton-proton colliders, while Bruno and Gersh spearheaded the development of electron-positron colliders. In this brief review of the history, I will sketch the development of the concepts, the experiments, and the technological developments which made possible the development of colliders. It may look as if the emphasis is on theoretical concepts, but that is really not the case, for in this field -- the physics of beams -- the theory and experiment go hand in hand; theoretical understanding and advances are almost always motivated by the need to explain experimental results or the desire to construct better experimental devices

  17. A new development agenda.

    Science.gov (United States)

    Sadik, N

    1992-01-01

    The successful report of the UN Commission on Environment and Development and the Earth Summit demonstrate the strong potential of making future concerted strides toward sustainable development. The process pointed out how social injustice prevents economic and political development and emphasize the need to eradicate extreme poverty, poor health, illiteracy, unwanted high fertility, and the oppression of women. The middle classes must also be aided and the burden on the environment reduced in the attempt to achieve sustainable development. Human-centered development is the basis of sustainable development and is capable of reducing poverty and population pressures. Agenda 21 details links between population, environment, development, and international responsibility. While honoring the rights of individuals to freely choose among reproductive options, international policymakers should agree to keep overall population growth within or slightly below the medium projection of 6.2 billion by the end of the century, 10 billion by mid-century, and eventually 11 billion. By the end of the century, it is also hoped that the number of couples using family planning will increase by 50%, marriage age will increase, teen pregnancy and maternal and infant mortality will be reduced, and resources devoted to population programs will double.

  18. Pipeline for Contraceptive Development

    Science.gov (United States)

    Blithe, Diana L.

    2016-01-01

    The high rates of unplanned pregnancy reflect unmet need for effective contraceptive methods for women, especially for individuals with health risks such as obesity, diabetes, hypertension, and other conditions that may contraindicate use of an estrogen-containing product. Improvements in safety, user convenience, acceptability and availability of products remain important goals of the contraceptive development program. Another important goal is to minimize the impact of the products on the environment. Development of new methods for male contraception has the potential to address many of these issues with regard to safety for women who have contraindications to effective contraceptive methods but want to protect against pregnancy. It also will address a huge unmet need for men who want to control their fertility. Products under development for men would not introduce eco-toxic hormones in the waste water. Investment in contraceptive research to identify new products for women has been limited in the pharmaceutical industry relative to investment in drug development for other indications. Pharmaceutical R&D for male contraception was active in the 1990’s but was abandoned over a decade ago. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969. Through a variety of programs including research grants and contracts, NICHD has developed a pipeline of new targets/products for male and female contraception. A number of lead candidates are under evaluation in the NICHD Contraceptive Clinical Trials Network (CCTN) (1–3). PMID:27523300

  19. Transdisciplinary product development

    Directory of Open Access Journals (Sweden)

    Tomaž Savšek

    2015-12-01

    Full Text Available Research Question (RQ: How can transdisciplinary approach increase the product development process in future industry? Purpose: The aim of the research is to develop a model of an effective product development in the automotive industry based on the transdisciplinary approach. Method: We used a qualitative research approach in order to develop a theoretical framework of transdisciplinarity. The framework comprises the concurrent engineering and experts from different disciplines. The framework was represented by a mathematical model which based on stochastic dynamic programming. Results: We developed a theoretical frameworkand a practical case of transdisciplinary product development in the automotive industry. We presented a mathematical model and information environment which supports such a model. Organization: The findings of the research will provide higher productivity, lower operating costs, change in personnel structure, higher added value, lower sales costs, lower administration costs, reduction in growth of expenses, and lower costs of work equipment. Society: The research impact on higher customer’s satisfaction, increased flexibility of operations, better quality of information, improved control of sources, less waste materials and less pollution, improved planning process, more favourable consideration of employees , improved portfolio management, and better corporate presentation of company. Originality: Transdisciplinary framework combines methods of concurrent engineering and interdisciplinary approach in a process of product development. The development of such a framework is a complete novelty and represents an original approach to product development, which will be particularly suitable for the smart factories of the future. Transdisciplinary framework was transformed in to a mathematical model based on stochastic dynamic programming. Model is supported by the existing information warehouse and represents a potential for

  20. Agile software development

    CERN Document Server

    Stober, Thomas

    2009-01-01

    Software Development is moving towards a more agile and more flexible approach. It turns out that the traditional 'waterfall' model is not supportive in an environment where technical, financial and strategic constraints are changing almost every day. But what is agility? What are today's major approaches? And especially: What is the impact of agile development principles on the development teams, on project management and on software architects? How can large enterprises become more agile and improve their business processes, which have been existing since many, many years? What are the limit

  1. Piezoelectric Accelerometers Development

    DEFF Research Database (Denmark)

    Liu, Bin; Bang, Lisbet Fogh

    1999-01-01

    The paper describes the development of piezoelectric accelerometers using Finite Element (FE) approach. Brüel & Kjær Accelerometer Type 8325 is chosen as an example to illustrate the advanced accelerometer development procedure. The deviation between simulated results and measured results of Type...... 8325 are below 6%. It is proved that the specifications of the accelerometer can be effectively predicted using the FE method, especially when modifications of the accelerometer are required. The development process of piezoelectric accelerometers in Brüel & Kjær is becoming more efficient...

  2. Piezoelectric accelerometeres development

    DEFF Research Database (Denmark)

    Liu, Bin

    1999-01-01

    The paper describes the development of piezoelectric accelerometers using Finite Element (FE) approach. Brüel & Kjær Accelerometer Type 8325 is chosen as an example to illustrate the advanced accelerometer development procedure. The deviation between simulated results and measured results of Type...... 8325 are below 6%. It is proved that the specifications of the accelerometer can be effectively predicted using the FE method, especially when modifications of the accelerometer are required. The development process of piezoelectric accelerometers in Brüel & Kjær is becoming more efficient....

  3. Community development planning

    International Nuclear Information System (INIS)

    Gray, S.I.

    1983-01-01

    The focus of this paper will be methods of local community involvement in the community development planning efforts which will be required at the recommended sites. Community development planning will include capital improvement plans, housing plans, zoning changes, business development plans and other community service and fiscal plans required to meet the projected needs of new residents as a result of the repository construction and operation. This paper will present, (1) the need for community planning, (2) methods of responding to community planning needs, (3) current community planning issues to be addressed. 2 references, 1 figure

  4. The sustainable development

    International Nuclear Information System (INIS)

    Robreau, Y.; Porcher, P.

    2002-11-01

    This document aims to define the sustainable development concept with a special attention for France and Israel position. The first part recalls the history of the sustainable development from the ''Man and Biosphere'' program of the UNESCO to Rio protocol. Then are described the principles of the sustainable development, the France plans and the France position at Johannesburg conference. The last part is devoted to the Israel position and a short presentation of the consequences of the greenhouse gases on the human health and the environment. (A.L.B.)

  5. Beginning Nokia Apps Development

    CERN Document Server

    Rischpater, Ray

    2010-01-01

    While media buzz regularly circulates around iPhone and Android, Nokia still leads the pack in terms of world market share. Symbian, for instance, remains the most widely used mobile operating system. With Nokia's open development platform, the opportunities available for mobile developers to target this vastly popular operating system are abundant and clear. * Use Qt to target both platforms: Symbian, the most widely used mobile operating system in the world, as well as MeeGo, the Intel/Nokia platform for mobile devices. * Develop HTML5 applications for both Symbian and MeeGo platforms that w

  6. Materials development for TESOL

    CERN Document Server

    Mishan, Freda

    2015-01-01

    Materials development has become much more important in the field of TESOL in the last twenty years: modules on materials development are now commonplace on MA TESOL courses around the world. The overall aim of the book is to introduce readers to a wide range of theoretical and practical issues in materials development to enable them to make informed and principled choices in the selection, evaluation, adaptation and production of materials. The book aims to show how these choices need to be informed by an awareness of culture, context and purpose.

  7. Textile technology development

    Science.gov (United States)

    Shah, Bharat M.

    1995-01-01

    The objectives of this report were to evaluate and select resin systems for Resin Transfer Molding (RTM) and Powder Towpreg Material, to develop and evaluate advanced textile processes by comparing 2-D and 3-D braiding for fuselage frame applications and develop window belt and side panel structural design concepts, to evaluate textile material properties, and to develop low cost manufacturing and tooling processes for the automated manufacturing of fuselage primary structures. This research was in support of the NASA and Langley Research Center (LaRc) Advanced Composite Structural Concepts and Materials Technologies for Primary Aircraft Structures program.

  8. Developing students’ entrepreneurial spirit

    Directory of Open Access Journals (Sweden)

    Grădinaru, E.

    2012-01-01

    Full Text Available This paper contains a research study about the necessity to develop the entrepreneurial spirit in universities and how students could be involved in such initiatives. A qualitative research based on three focus groups was conducted, having as main objective to identify students’ opinions regarding the initiative to develop an on-line magazine for students and young people. The results reveal that students prefer the online media to the traditional ones and the pilot numbers of the magazine received good appreciations. A business plan for the future development of the magazine is also presented.

  9. Tracking Your Development

    CERN Document Server

    Hennum, Kelly M

    2011-01-01

    This book provides you with the means to set development goals and to track your progress on achieving them. It can help you efficiently gather and make sense of information about your progress and avoid common pitfalls that can block your development. Tracking your development can be captures in a few steps: articulating your goal, creating an action plan, gathering information about your behavior, indentifying barriers and support, and revising your action plan. Taking these steps will greatly increase the likelihood of achieving your goals.

  10. Development without a metropolis

    DEFF Research Database (Denmark)

    Monsson, Christian Kjær

    2014-01-01

    to the universal advice replete in some types of place-based development guidelines and literature. The paper consequently formulates propositions about beneficial practices for the development of non-metropolitan territories. The essence of these is that non-metropolitan regions can benefit from initiatives...... focusing on the management capabilities of a broad set of regional companies rather than pursuing industry-specific ‘smart’ specialisation strategies. These initiatives can include alternative models for learning and knowledge development based on shared challenges rather than industrial relatedness...

  11. Leap Motion development essentials

    CERN Document Server

    Spiegelmock, Mischa

    2013-01-01

    This book is a fast-paced guide with practical examples that aims to help you understand and master the Leap Motion SDK.This book is for developers who are either involved in game development or who are looking to utilize Leap Motion technology in order to create brand new user interaction experiences to distinguish their products from the mass market. You should be comfortable with high-level languages and object-oriented development concepts in order to get the most out of this book.

  12. Laser Cutting, Development Trends

    DEFF Research Database (Denmark)

    Olsen, Flemming Ove

    1999-01-01

    In this paper a short review of the development trends in laser cutting will be given.The technology, which is the fastest expanding industrial production technology will develop in both its core market segment: Flat bed cutting of sheet metal, as it will expand in heavy industry and in cutting...... of 3-dimensional shapes.The CO2-laser will also in the near future be the dominating laser source in the market, although the new developments in ND-YAG-lasers opens for new possibilities for this laser type....

  13. Neutral beam development plan

    International Nuclear Information System (INIS)

    Staten, H.S.

    1980-08-01

    The national plan is presented for developing advanced injection systems for use on upgrades of existing experiments, and use on future facilities such as ETF, to be built in the late 1980's or early 90's where power production from magnetic fusion will move closer to a reality. Not only must higher power and longer pulse length systems be developed , but they must operate reliably; they must be a tool for the experimenter, not the experiment itself. Neutral beam systems handle large amounts of energy and as such, they often are as complicated as the plasma physics experiment itself. This presents a significant challenge to the neutral beam developer

  14. Developing Bigraphical Languages

    DEFF Research Database (Denmark)

    Damgaard, Troels Christoffer

    In this dissertation, we study bigraphical languages—languages based on the theory for bigraphs and bigraphical reactive systems developed by Milner and coworkers. We begin by examining algebraic theory for binding bigraphs. We give a term language for binding bigraphs and develop a complete......, a prototype tool for experimenting with bigraphical reactive systems. In a second line of work, we study bigraphical reactive systems as a vehicle for developing a language to model biochemical reactions at the level of cells and proteins. We discuss and isolate B,R-calculi, a family of bigraphical reactive...

  15. Industrialized Information Systems Development

    DEFF Research Database (Denmark)

    Havn, Erling; Bansler, Jørgen P.

    1996-01-01

    The production of application software is rapidly being industrialized. Computer manufacturers and software houses produce a rapidly growing number of generic software applications and systems, and more and more user companies choose to build their computer-based information systems...... with such generic products, instead of custom made software. We discuss how the move away from traditional in-house development and the increasing use of generic software is likely to transform IS development in the near future. We conclude that these developments will make new demands on the information systems...

  16. Inequality, poverty and development.

    Science.gov (United States)

    Ahluwalia, M S

    1976-12-01

    Dicussion explores the nature of the relationship between the distribution of income and the process of development on the basis of cross country data on income inequality. The results presented are based on a sample of 60 countries, including 40 developing countries, 14 developed countries, and 6 socialist countries. The approach adopted is essentially exploratory. Multivariate regression analysis was used to estimate cross country relationships between the income shares of different percentile groups and selected variables reflecting aspects of the development process which are likely to influence income inequality. The estimated equations are then used as a basis for broad generalizations about the relationship between income distribution and development. There was strong support for the proposition that relative inequaltiy increases substantially in the early stages of development, with a reversal of this tendency in the later stages. The propositions held whether the sample was restricted to developing countries or expanded to include developed and socialist countries. The process was most prolonged for the poorest group. There were a number of processes occurring "pari passu" with development which were correlated with income inequality and which can plausibly be interpreted as causal. These were intersectoral shifts in the structure of production, expansion in education attainment and skill level of the labor force; and reduction in the growth of population. The operation of these processes appeared to explain some of the improvement in income distribution observed in the later stages of development, but they did not serve to explain the marked deterioration observed in the earlier stages. The cross section results failed to support the stronger hypothesis that the deterioration in relative inequality reflected a prolonged absolute impoverishment of large sections of the population in the course of development. The cross country pattern showed average

  17. JBoss AS 7 development

    CERN Document Server

    Marchioni, Francesco

    2013-01-01

    This book will kick-start your productivity and help you to master JBoss AS development. The author's experience with JBoss enables him to share insights on JBoss AS development in a clear and friendly way. By the end of the book, you will have the confidence to apply all the newest programming techniques to your JBoss applications.If you are a Java architect or developer who wants to get the most out of the latest release of the JBoss application server, then this book is for you. You are not expected to have accumulated experience on the application server though you must know the basic conc

  18. Professional mobile application development

    CERN Document Server

    McWherter, Jeff

    2012-01-01

    Create applications for all major smartphone platforms Creating applications for the myriad versions and varieties of mobile phone platforms on the market can be daunting to even the most seasoned developer. This authoritative guide is written in such as way that it takes your existing skills and experience and uses that background as a solid foundation for developing applications that cross over between platforms, thereby freeing you from having to learn a new platform from scratch each time. Concise explanations walk you through the tools and patterns for developing for all the mobile platfo

  19. Developing Effective Performance Measures

    Science.gov (United States)

    2014-10-14

    University When Performance Measurement Goes Bad Laziness Vanity Narcissism Too Many Pettiness Inanity 52 Developing Effective...Kasunic, October 14, 2014 © 2014 Carnegie Mellon University Narcissism Measuring performance from the organization’s point of view, rather than from

  20. Peace, Conflict and Development

    International Development Research Centre (IDRC) Digital Library (Canada)

    elaferriere

    in Palestinian communities has a dual strategy: it contains both a ... It will consolidate the theory ... and equitable and sustainable development; to build domestic ownership of peace processes; to open spaces for discussion and dialogue;.

  1. Logistic Fuel Processor Development

    National Research Council Canada - National Science Library

    Salavani, Reza

    2004-01-01

    ... to light gases then steam reform the light gases into hydrogen rich stream. This report documents the efforts in developing a fuel processor capable of providing hydrogen to a 3kW fuel cell stack...

  2. Food and Development

    African Journals Online (AJOL)

    issue, but also food is perhaps the most important development issue, if not global issue, of our time, ... Other boxes include the pet food market, genetically modified (GM) crops, land grabs, the financialisation of food,. African bean sauces ...

  3. Catalyzing RE Project Development

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Kate; Elgqvist, Emma; Walker, Andy; Cutler, Dylan; Olis, Dan; DiOrio, Nick; Simpkins, Travis

    2016-09-01

    This poster details how screenings done with REopt - NREL's software modeling platform for energy systems integration and optimization - are helping to catalyze the development of hundreds of megawatts of renewable energy.

  4. User interface development

    Science.gov (United States)

    Aggrawal, Bharat

    1994-01-01

    This viewgraph presentation describes the development of user interfaces for OS/2 versions of computer codes for the analysis of seals. Current status, new features, work in progress, and future plans are discussed.

  5. Splunk developer's guide

    CERN Document Server

    Smith, Kyle

    2015-01-01

    If you are a Splunk user and want to enter the wonderful world of Splunk application development, then this book is for you. Some experience with Splunk, writing searches, and designing basic dashboards is expected.

  6. Partnerships for Development

    DEFF Research Database (Denmark)

    Christensen, David; Drysdale, David; Hansen, Kenneth

    2014-01-01

    Municipal solid waste (MSW) management systems of many developing countries are commonly constrained by factors such as limited financial resources and poor governance, making it a difficult proposition to break with complex, entrenched and unsustainable technologies and systems. This paper...

  7. Learning Spring application development

    CERN Document Server

    Soni, Ravi Kant

    2015-01-01

    This book is intended for those who are interested in learning the core features of the Spring Framework. Prior knowledge of Java programming and web development concepts with basic XML knowledge is expected.

  8. Logistics innovation development

    DEFF Research Database (Denmark)

    Pedrosa, Alex; Blazevic, Vera; Jasmand, Claudia

    2014-01-01

    to investigate the role of boundary-spanning employees in deepening and broadening customer knowledge while developing logistics service innovations. Findings The results show that boundary-spanning employees’ engage sequentially in deepening and broadening customer knowledge throughout the logistics innovation...... development process. In particular it shows that deepening customer knowledge tends to occur in one-to-one interactions. When boundary-spanning employees engage in broadening customer knowledge, they develop a rich understanding of current customer. Research limitations/implications (if applicable) In general......Purpose This paper aims to investigate the microfoundations—boundary-spanning employees activities and behaviors—of deepening and broadening customer knowledge during logistics innovation development. Design/methodology/approach A multiple case study approach (six case studies) was adopted...

  9. Game development with Swift

    CERN Document Server

    Haney, Stephen

    2015-01-01

    If you wish to create and publish fun iOS games using Swift, then this book is for you. You should be familiar with basic programming concepts. However, no prior game development or Apple ecosystem experience is required.

  10. Advanced Hydrogen Turbine Development

    Energy Technology Data Exchange (ETDEWEB)

    Marra, John [Siemens Energy, Inc., Orlando, FL (United States)

    2015-09-30

    Under the sponsorship of the U.S. Department of Energy (DOE) National Energy Technology Laboratories, Siemens has completed the Advanced Hydrogen Turbine Development Program to develop an advanced gas turbine for incorporation into future coal-based Integrated Gasification Combined Cycle (IGCC) plants. All the scheduled DOE Milestones were completed and significant technical progress was made in the development of new technologies and concepts. Advanced computer simulations and modeling, as well as subscale, full scale laboratory, rig and engine testing were utilized to evaluate and select concepts for further development. Program Requirements of: A 3 to 5 percentage point improvement in overall plant combined cycle efficiency when compared to the reference baseline plant; 20 to 30 percent reduction in overall plant capital cost when compared to the reference baseline plant; and NOx emissions of 2 PPM out of the stack. were all met. The program was completed on schedule and within the allotted budget

  11. Fiber Optics Instrumentation Development

    Science.gov (United States)

    Chan, Patrick Hon Man; Parker, Allen R., Jr.; Richards, W. Lance

    2010-01-01

    This is a general presentation of fiber optics instrumentation development work being conducted at NASA Dryden for the past 10 years and recent achievements in the field of fiber optics strain sensors.

  12. Development of ADRA

    International Nuclear Information System (INIS)

    Brtis, J.S.

    1987-01-01

    All nuclear power plant modifications must be designed in a way that keeps the radiation dose to radiation workers and the public As Low As is Reasonably Achievable (ALARA). This is not only a good design practice, it is required by the NRC in accord with Title 10 of the Code of Federal Regulations). As a result, millions of dollars are spent each year developing, analyzing, and justifying the ALARA design of plant modifications. Providing the necessary design reviews is a major challenge to the industry. In response, Sargent and Lundy has developed ADRA (the ALARA Design Review Assistant), a microcomputer-based system that aids in developing, reviewing, and documenting good ALARA designs. ADRA is now in an early operational stage, undergoing testing at Sargent and Lundy. This paper reviews the findings and results of the ADRA development effort

  13. Doing Systems Development

    DEFF Research Database (Denmark)

    Koch, Christian; Mathiasen, John Bang

    2014-01-01

    Systems development of wind turbine control is competitive with respect to innovation, time and cost. So how can learning possibly occur under such circumstances? Dewey’s pragmatist approach to learning is adopted, emphasising reciprocity between the systems developer’s individual experience...... and the sociotechnical practice. The framework involves the concepts of sociotechnical practice, anchoring of indeterminate situation, and strip of doings towards determinate situation. An ethnographic study was made of four cases of systems development and learning do occur in the cases, enabled by converging anchoring...... of the indeterminate situation and the systems developers different experience. However, an extreme case reveals initiated learning processes and that the interchanges between materiality of the artefacts and systems developers block the learning processes due to a customer with imprecise demands and unclear system...

  14. Ocean Technology Development Tank

    Data.gov (United States)

    Federal Laboratory Consortium — The new SWFSC laboratory in La Jolla incorporates a large sea- and fresh-water Ocean Technology Development Tank. This world-class facility expands NOAA's ability to...

  15. Sustainable development. First part

    International Nuclear Information System (INIS)

    Colombo, U.; Lanzavecchia, G.; Berrini, M; Zambrini, M.; Bologna, G.; Carraro, C.; Hinterberger, F.; Mastino, G.; Federico, A.; Gaudioso, D.; Luise, A.; Mauro, F.; Padovani, L.; Federico, A.

    1998-01-01

    This paper summarizes a collective effort and represents the second edition of: Environment, energy, economy: a sustainable future. In this work are reported various interventions on sustainable development problem [it

  16. Investment in Developing Countries

    Science.gov (United States)

    Motooka, Takeshi

    1973-01-01

    The fundamental problems of investment in rural education in the present developing countries are analyzed. Needs of rural education are outlined and financial considerations related to investment in the improvement of rural educational programs are discussed. (SM)

  17. (ICTs) for Social Development

    African Journals Online (AJOL)

    Nekky Umera

    mention here. ICT has exponentially increased the speed of business for commercial interactions and is primarily responsible for rendering global ..... witnessing in today's business environment but the rapid developments in. ICT have given ...

  18. Personal professional development

    CSIR Research Space (South Africa)

    Rao, S

    2008-10-01

    Full Text Available Three workshop sessions on personal professional development were held during the Third IUPAP Women in Physics Conference. These were designed to teach participants about planning for career success, "survival skills," negotiation, and ways...

  19. Developing Friendship and Intimacy.

    Science.gov (United States)

    Maslow, Abraham H.

    1991-01-01

    Presents previously unpublished paper written by Abraham Maslow in April 1968 in which Maslow speculates on the issue that society had become pathologically individualistic and needed to develop better means of facilitating close relationships among people. (Author/ABL)

  20. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2014) >. Log in or Register to get access to full text downloads.