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Sample records for larval neuromuscular junction

  1. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

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    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  2. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth.

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    Deidre L Brink

    Full Text Available Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ, we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non-synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ.

  3. Phospho-regulated Drosophila adducin is a determinant of synaptic plasticity in a complex with Dlg and PIP2 at the larval neuromuscular junction

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    Simon Ji Hau Wang

    2014-11-01

    Full Text Available Adducin is a ubiquitously expressed actin- and spectrin-binding protein involved in cytoskeleton organization, and is regulated through phosphorylation of the myristoylated alanine-rich C-terminal kinase (MARCKS-homology domain by protein kinase C (PKC. We have previously shown that the Drosophila adducin, Hu-li tai shao (Hts, plays a role in larval neuromuscular junction (NMJ growth. Here, we find that the predominant isoforms of Hts at the NMJ contain the MARCKS-homology domain, which is important for interactions with Discs large (Dlg and phosphatidylinositol 4,5-bisphosphate (PIP2. Through the use of Proximity Ligation Assay (PLA, we show that the adducin-like Hts isoforms are in complexes with Dlg and PIP2 at the NMJ. We provide evidence that Hts promotes the phosphorylation and delocalization of Dlg at the NMJ through regulation of the transcript distribution of the PAR-1 and CaMKII kinases in the muscle. We also show that Hts interactions with Dlg and PIP2 are impeded through phosphorylation of the MARCKS-homology domain. These results are further evidence that Hts is a signaling-responsive regulator of synaptic plasticity in Drosophila.

  4. MAPK3 at the Autism-Linked Human 16p11.2 Locus Influences Precise Synaptic Target Selection at Drosophila Larval Neuromuscular Junctions.

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    Park, Sang Mee; Park, Hae Ryoun; Lee, Ji Hye

    2017-02-01

    Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures. A mutation of rolled , a Drosophila homolog of human mitogen-activated protein kinase 3 ( MAPK3 ) at the 16p11.2 locus, caused ectopic innervation of axonal branches and their abnormal defasciculation. The specificity of these phenotypes was confirmed by expression of wild-type rolled in the mutant background. Albeit to a lesser extent, we also observed ectopic innervation patterns in mutants defective in Cdk2, Gα q , and Gp93, all of which were expected to interact with Rolled MAPK3. A further genetic analysis in double heterozygous combinations revealed a synergistic interaction between rolled and Gp93 . In addition, results from RT-qPCR analyses indicated consistently reduced rolled mRNA levels in Cdk2 , Gα q , and Gp93 mutants. Taken together, these data suggest a central role of MAPK3 in regulating the precise targeting of presynaptic axons to proper postsynaptic targets, a critical step that may be altered significantly in ASD.

  5. Electrophysiological study in neuromuscular junction disorders

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    Ajith Cherian

    2013-01-01

    Full Text Available This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS, congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS. SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

  6. Motor neuron, nerve, and neuromuscular junction disease.

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    Finsterer, Josef; Papić, Lea; Auer-Grumbach, Michaela

    2011-10-01

    The aim is to review the most relevant findings published during the last year concerning clinical, genetic, pathogenic, and therapeutic advances in motor neuron disease, neuropathies, and neuromuscular junction disorders. Studies on animal and cell models have improved the understanding of how mutated survival motor neuron protein in spinal muscular atrophy governs the pathogenetic processes. New phenotypes of SOD1 mutations have been described. Moreover, animal models enhanced the insight into the pathogenetic background of sporadic and familial amyotrophic lateral sclerosis. Novel treatment options for motor neuron disease have been described in humans and animal models. Considerable progress has been achieved also in elucidating the genetic background of many forms of inherited neuropathies and high clinical and genetic heterogeneity has been demonstrated. Mutations in MuSK and GFTP1 have been shown to cause new types of congenital myasthenic syndromes. A third type of autoantibodies (Lrp4) has been detected to cause myasthenia gravis. Advances in the clinical and genetic characterization of motor neuron diseases, neuropathies, and neuromuscular transmission defects have important implications on the fundamental understanding, diagnosis, and management of these disorders. Identification of crucial steps of the pathogenetic process may provide the basis for the development of novel therapeutic strategies.

  7. Alternative NF-κB Isoforms in the Drosophila Neuromuscular Junction and Brain.

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    Bo Zhou

    Full Text Available The Drosophila NF-κB protein Dorsal is expressed at the larval neuromuscular junction, where its expression appears unrelated to known Dorsal functions in embryonic patterning and innate immunity. Using confocal microscopy with domain-specific antisera, we demonstrate that larval muscle expresses only the B isoform of Dorsal, which arises by intron retention. We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear translocation. We further find that the Dorsal-related immune factor Dif encodes a B isoform, reflecting a conservation of B domains across a range of insect NF-κB proteins. Carrying out mutagenesis of the Dif locus via a site-specific recombineering approach, we demonstrate that Dif B is the major, if not sole, Dif isoform in the mushroom bodies of the larval brain. The Dorsal and Dif B isoforms thus share a specific association with nervous system tissues as well as an alternative protein structure.

  8. Ultrastructural muscle and neuro-muscular junction alterations in polymyositis

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    L. L. Babakova

    2012-01-01

    Full Text Available Ultrastructural analysis of 7 biopsies from m.palmaris longus and m.deltoideus in patients with confirmed polymyositis revealed alterationand degeneration of muscle fibers and anomalies of neuro-muscular junction (NMJ. The NMJ abnormalities and following denervation ofmuscle fibers in polymyositis start with subsynaptic damages. The occurance of regeneration features in muscle fibers at any stage is characteristic for PM.

  9. Silent synapses in neuromuscular junction development.

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    Tomàs, Josep; Santafé, Manel M; Lanuza, Maria A; García, Neus; Besalduch, Nuria; Tomàs, Marta

    2011-01-01

    In the last few years, evidence has been found to suggest that some synaptic contacts become silent but can be functionally recruited before they completely retract during postnatal synapse elimination in muscle. The physiological mechanism of developmental synapse elimination may be better understood by studying this synapse recruitment. This Mini-Review collects previously published data and new results to propose a molecular mechanism for axonal disconnection. The mechanism is based on protein kinase C (PKC)-dependent inhibition of acetylcholine (ACh) release. PKC activity may be stimulated by a methoctramine-sensitive M2-type muscarinic receptor and by calcium inflow though P/Q- and L-type voltage-dependent calcium channels. In addition, tropomyosin-related tyrosine kinase B (trkB) receptor-mediated brain-derived neurotrophic factor (BDNF) activity may oppose the PKC-mediated ACh release depression. Thus, a balance between trkB and muscarinic pathways may contribute to the final functional suppression of some neuromuscular synapses during development. © 2010 Wiley-Liss, Inc.

  10. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

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    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  11. Schwann Cells in Neuromuscular Junction Formation and Maintenance.

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    Barik, Arnab; Li, Lei; Sathyamurthy, Anupama; Xiong, Wen-Cheng; Mei, Lin

    2016-09-21

    The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation. Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences

  12. Active zones of mammalian neuromuscular junctions: formation, density, and aging.

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    Nishimune, Hiroshi

    2012-12-01

    Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2 and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. © 2012 New York Academy of Sciences.

  13. Two Algorithms for High-throughput and Multi-parametric Quantification of Drosophila Neuromuscular Junction Morphology.

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    Castells-Nobau, Anna; Nijhof, Bonnie; Eidhof, Ilse; Wolf, Louis; Scheffer-de Gooyert, Jolanda M; Monedero, Ignacio; Torroja, Laura; van der Laak, Jeroen A W M; Schenck, Annette

    2017-05-03

    Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ. A drawback of qualitative analyses is that many subtle players contributing to NMJ morphology likely remain unnoticed. Whereas quantitative analyses are required to detect the subtler morphological differences, such analyses are not yet commonly performed because they are laborious. This protocol describes in detail two image analysis algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton Morphometrics", available as Fiji-compatible macros, for quantitative, accurate and objective morphometric analysis of the Drosophila NMJ. This methodology is developed to analyze NMJ terminals immunolabeled with the commonly used markers Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp, Csp and Syt is presented in this protocol. The macros are able to assess nine morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ length, NMJ longest branch length, number of islands, number of branches, number of branching points and number of active zones in the NMJ terminal.

  14. Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

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    Kimberly R Hagel

    Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

  15. Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction.

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    Liao, Edward H; Gray, Lindsay; Tsurudome, Kazuya; El-Mounzer, Wassim; Elazzouzi, Fatima; Baim, Christopher; Farzin, Sarah; Calderon, Mario R; Kauwe, Grant; Haghighi, A Pejmun

    2018-01-01

    Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.

  16. Effect of temperature on spontaneous release of transmitter at the mammalian neuromuscular junction

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    Duncan, C J; Statham, H E

    1977-01-01

    Temperature has a multifactorial effect on miniature endplate potential (MEPP) frequency at the mammalian neuromuscular junction, with a negative Q/sub 10/ at 14--28/sup 0/C. The results are explained in terms of the effect of temperature on the various factors that control (Ca/sup 2/+sub i/ at the presynaptic terminals. The temperature-sensitivity of the Ca/sup 2 +/-transport enzyme is believed to be of particular significance and accounts for the observed differences between the amphibian and mammalian neuromuscular junctions.

  17. Protein kinase C isoforms at the neuromuscular junction: localization and specific roles in neurotransmission and development.

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    Lanuza, Maria A; Santafe, Manel M; Garcia, Neus; Besalduch, Núria; Tomàs, Marta; Obis, Teresa; Priego, Mercedes; Nelson, Phillip G; Tomàs, Josep

    2014-01-01

    The protein kinase C family (PKC) regulates a variety of neural functions including neurotransmitter release. The selective activation of a wide range of PKC isoforms in different cells and domains is likely to contribute to the functional diversity of PKC phosphorylating activity. In this review, we describe the isoform localization, phosphorylation function, regulation and signalling of the PKC family at the neuromuscular junction. Data show the involvement of the PKC family in several important functions at the neuromuscular junction and in particular in the maturation of the synapse and the modulation of neurotransmission in the adult. © 2013 Anatomical Society.

  18. Roles of neuro-exocytotic proteins at the neuromuscular junction

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    Sons-Michel, Michèle S.

    2011-01-01

    The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

  19. Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

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    Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

    2012-11-13

    Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

  20. Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.

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    Kazuo Ikeda, K I; Masaki Matsuda, M M; Daisuke Yamauchi, D Y; Katsuro Tomita, K T; Shigenori Tanaka, S T

    2005-07-01

    The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

  1. The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.

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    Obis, Teresa; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Priego, Mercedes; Simon, Anna; Garcia, Neus; Santafe, Manel M; Lanuza, Maria A; Tomàs, Josep

    2015-12-01

    Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.

  2. Acetylcholine-induced inhibition of presynaptic calcium signals and transmitter release in the frog neuromuscular junction

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    Eduard Khaziev

    2016-12-01

    Full Text Available Acetylcholine (ACh, released from axonal terminals of motor neurones in neuromuscular junctions regulates the efficacy of neurotransmission through activation of presynaptic nicotinic and muscarinic autoreceptors. Receptor-mediated presynaptic regulation could reflect either direct action on exocytotic machinery or modulation of Ca2+ entry and resulting intra-terminal Ca2+ dynamics. We have measured free intra-terminal cytosolic Ca2+ ([Ca2+]i using Oregon-Green 488 microfluorimetry, in parallel with voltage-clamp recordings of spontaneous (mEPC and evoked (EPC postsynaptic currents in post-junctional skeletal muscle fibre. Activation of presynaptic muscarinic and nicotinic receptors with exogenous acetylcholine and its non-hydrolized analogue carbachol reduced amplitude of the intra-terminal [Ca2+]i transients and decreased quantal content (calculated by dividing the area under EPC curve by the area under mEPC curve. Pharmacological analysis revealed the role of muscarinic receptors of M2 subtype as well as d-tubocurarine-sensitive nicotinic receptor in presynaptic modulation of [Ca2+]i transients. Modulation of synaptic transmission efficacy by ACh receptors was completely eliminated by pharmacological inhibition of N-type Ca2+ channels. We conclude that ACh receptor-mediated reduction of Ca2+ entry into the nerve terminal through N-type Ca2+ channels represents one of possible mechanism of presynaptic modulation in frog neuromuscular junction.

  3. Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions

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    Shyng, S.L.; Salpeter, M.M.

    1989-01-01

    Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation. No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates

  4. Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase.

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    Campanari, Maria-Letizia; García-Ayllón, María-Salud; Ciura, Sorana; Sáez-Valero, Javier; Kabashi, Edor

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a highly debilitating disease caused by progressive degeneration of motorneurons (MNs). Due to the wide variety of genes and mutations identified in ALS, a highly varied etiology could ultimately converge to produce similar clinical symptoms. A major hypothesis in ALS research is the "distal axonopathy" with pathological changes occurring at the neuromuscular junction (NMJ), at very early stages of the disease, prior to MNs degeneration and onset of clinical symptoms. The NMJ is a highly specialized cholinergic synapse, allowing signaling between muscle and nerve necessary for skeletal muscle function. This nerve-muscle contact is characterized by the clustering of the collagen-tailed form of acetylcholinesterase (ColQ-AChE), together with other components of the extracellular matrix (ECM) and specific key molecules in the NMJ formation. Interestingly, in addition to their cholinergic role AChE is thought to play several "non-classical" roles that do not require catalytic function, most prominent among these is the facilitation of neurite growth, NMJ formation and survival. In all this context, abnormalities of AChE content have been found in plasma of ALS patients, in which AChE changes may reflect the neuromuscular disruption. We review these findings and particularly the evidences of changes of AChE at neuromuscular synapse in the pre-symptomatic stages of ALS.

  5. Adenosine A2B and A3 receptor location at the mouse neuromuscular junction.

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    Garcia, Neus; Priego, Mercedes; Hurtado, Erica; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Lanuza, Maria Angel; Tomàs, Josep

    2014-07-01

    To date, four subtypes of adenosine receptors have been cloned (A(1)R, A(2A)R, A(2B)R, and A(3)R). In a previous study we used confocal immunocytochemistry to identify A(1)R and A(2A)R receptors at mouse neuromuscular junctions (NMJs). The data shows that these receptors are localized differently in the three cells (muscle, nerve and glia) that configure the NMJs. A(1)R localizes in the terminal teloglial Schwann cell and nerve terminal, whereas A(2A)R localizes in the postsynaptic muscle and in the axon and nerve terminal. Here, we use Western blotting to investigate the presence of A(2B)R and A(3)R receptors in striated muscle and immunohistochemistry to localize them in the three cells of the adult neuromuscular synapse. The data show that A(2B)R and A(3)R receptors are present in the nerve terminal and muscle cells at the NMJs. Neither A(2B)R nor A(3)R receptors are localized in the Schwann cells. Thus, the four subtypes of adenosine receptors are present in the motor endings. The presence of these receptors in the neuromuscular synapse allows the receptors to be involved in the modulation of transmitter release. © 2014 Anatomical Society.

  6. Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction.

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    Saveliev, Anatoly; Khuzakhmetova, Venera; Samigullin, Dmitry; Skorinkin, Andrey; Kovyazina, Irina; Nikolsky, Eugeny; Bukharaeva, Ellya

    2015-10-01

    The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions' entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings.

  7. Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction.

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    James, Rebecca E; Hoover, Kendall M; Bulgari, Dinara; McLaughlin, Colleen N; Wilson, Christopher G; Wharton, Kristi A; Levitan, Edwin S; Broihier, Heather T

    2014-12-08

    Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction.

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    Mattei, César; Marquais, Michel; Schlumberger, Sébastien; Molgó, Jordi; Vernoux, Jean-Paul; Lewis, Richard J; Benoit, Evelyne

    2010-10-01

    Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers. Copyright 2009 Elsevier Ltd. All rights reserved.

  9. Nerve terminal contributes to acetylcholine receptor organization at the dystrophic neuromuscular junction of mdx mice.

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    Marques, Maria Julia; Taniguti, Ana Paula Tiemi; Minatel, Elaine; Neto, Humberto Santo

    2007-02-01

    Changes in the distribution of acetylcholine receptors have been reported to occur at the neuromuscular junction of mdx mice and may be a consequence of muscle fiber regeneration rather than the absence of dystrophin. In the present study, we examined whether the nerve terminal determines the fate of acetylcholine receptor distribution in the dystrophic muscle fibers of mdx mice. The left sternomastoid muscle of young (1-month-old) and adult (6-month-old) mdx mice was injected with 60 microl lidocaine hydrochloride to induce muscle degeneration-regeneration. Some mice had their sternomastoid muscle denervated at the time of lidocaine injection. After 10 days of muscle denervation, nerve terminals and acetylcholine receptors were labeled with 4-Di-2-ASP and rhodamine-alpha-bungarotoxin, respectively, for confocal microscopy. In young mdx mice, 75% (n = 137 endplates) of the receptors were distributed in islands. The same was observed in 100% (n = 114 endplates) of the adult junctions. In denervated-regenerated fibers of young mice, the receptors were distributed as branches in 89% of the endplates (n = 90). In denervated-regenerated fibers of adult mice, the receptors were distributed in islands in 100% of the endplates (n = 100). These findings show that nerve-dependent mechanisms are also involved in the changes in receptor distribution in young dystrophic muscles. In older dystrophic muscles, other factors may play a role in receptor distribution.

  10. In vivo imaging of the developing neuromuscular junction in neonatal mice.

    Science.gov (United States)

    Turney, Stephen G; Walsh, Mark K; Lichtman, Jeff W

    2012-11-01

    Although fluorescently labeled structures can be analyzed more easily at high resolution in fixed-tissue preparations than in living animals, some biological questions can only be answered by time-lapse imaging. Changes in nervous system wiring during development cannot be determined reliably by taking tissue from different animals at staggered time points. Rather, the same cells and connections must be viewed repeatedly. To study developmental synapse elimination, we image muscles in transgenic mice that express fluorescent proteins in motor neurons and follow the same neuromuscular junctions (NMJs) over multiple days. This protocol describes the use of confocal microscopy for in vivo imaging of developing NMJs in transgenic neonatal mice expressing cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP). The sternomastoid, a flat, accessible neck muscle with large junctions, is imaged. A principal advantage of confocal microscopy is the ability to acquire multiple fluorescence channels simultaneously. If the channels are acquired sequentially, there is inevitably misalignment because of movement. Moreover, the total imaging time scales linearly with the number of channels. With simultaneous acquisition, only a single scan may be required. With perfect alignment between channels, irrespective of movement that might occur during a scan, color differences can be used to study interactions between axons over time. A limitation of this technique is that axons must be brightly labeled and at the muscle surface. NMJs that are more than one muscle fiber deep may be difficult to scan because of index of refraction changes that cause image blurring.

  11. Generation of functional neuromuscular junctions from human pluripotent stem cell lines

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    Katja ePuttonen

    2015-12-01

    Full Text Available Several neuromuscular diseases involve dysfunction of neuromuscular junctions (NMJs, yet there are no patient-specific human models for electrophysiological characterization of NMJ. We seeded cells of neurally-induced embryoid body-like spheres derived from induced pluripotent stem cell (iPSC or embryonic stem cell (ESC lines as monolayers without basic fibroblast factor (bFGF and observed differentiation of neuronal as well as spontaneously contracting, multinucleated skeletal myotubes. The myotubes showed striation, immunoreactivity for myosin heavy chain, actin bundles typical for myo-oriented cells, and generated spontaneous and evoked action potentials (APs. The myogenic differentiation was associated with expression of MyoD1, myogenin and type I ryanodine receptor. Neurons formed end plate like structures with strong binding of α-bungarotoxin, a marker of nicotinic acetylcholine receptors highly expressed in the postsynaptic membrane of NMJs, and expressed SMI-32, a motoneuron marker, as well as SV2, a marker for synapses. Pharmacological stimulation of cholinergic receptors resulted in strong depolarization of myotube membrane and raised Ca2+ concentration in sarcoplasm, while electrical stimulation evoked Ca2+ transients in myotubes. Stimulation of motoneurons with N-Methyl-D-aspartate resulted in reproducible APs in myotubes and end plates displayed typical MEPs and tonic activity depolarizing myotubes of about 10 mV. We conclude that simultaneous differentiation of neurons and myotubes from patient-specific iPSCs or ESCs results also in the development of functional NMJs. Our human model of NMJ may serve as an important tool to investigate normal development, mechanisms of diseases and novel drug targets involving NMJ dysfunction and degeneration.

  12. Neuromodulation of activity-dependent synaptic enhancement at crayfish neuromuscular junction.

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    Qian, S M; Delaney, K R

    1997-10-17

    Action potential-evoked transmitter release is enhanced for many seconds after moderate-frequency stimulation (e.g. 15 Hz for 30 s) at the excitor motorneuron synapse of the crayfish dactyl opener muscle. Beginning about 1.5 s after a train, activity-dependent synaptic enhancement (ADSE) is dominated by a process termed augmentation (G.D. Bittner, D.A. Baxter, Synaptic plasticity at crayfish neuromuscular junctions: facilitation and augmentation, Synapse 7 (1991) 235-243'[4]; K.L. Magleby, Short-term changes in synaptic efficacy, in: G.M. Edelman, L.E. Gall, C.W. Maxwell (Eds.), Synaptic Function, John Wiley and Sons, New York, 1987, pp. 21-56; K.L. Magleby; J.E. Zengel, Augmentation: a process that acts to increase transmitter release at the frog neuromuscular junction, J. Physiol. (Lond.) 257 (1976) 449-470) which decays approximately exponentially with a time constant of about 10 s at 16 degrees C, reflecting the removal of Ca2+ which accumulates during the train in presynaptic terminals (K.R. Delaney, D.W. Tank, R.S. Zucker, Serotonin-mediated enhancement of transmission at crayfish neuromuscular junction is independent of changes in calcium, J. Neurosci. 11 (1991) 2631-2643). Serotonin (5-HT, 1 microM) increases evoked and spontaneous transmitter release several-fold (D. Dixon, H.L. Atwood, Crayfish motor nerve terminal's response to serotonin examined by intracellular microelectrode, J. Neurobiol. 16 (1985) 409-424; J. Dudel, Modulation of quantal synaptic release by serotonin and forskolin in crayfish motor nerve terminals, in: Modulation of Synaptic Transmission and Plasticity in Nervous Systems, G. Hertting, H.-C. Spatz (Eds.), Springer-Verlag, Berlin, 1988; S. Glusman, E.A. Kravitz. The action of serotonin on excitatory nerve terminals in lobster nerve-muscle preparations, J. Physiol. (Lond.) 325 (1982) 223-241). We found that ADSE persists about 2-3 times longer after moderate-frequency presynaptic stimulation in the presence of 5-HT. This slowing of the

  13. Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism.

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    Stephen G Turney

    Full Text Available During mammalian development, neuromuscular junctions and some other postsynaptic cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons. It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territory in response to sites vacated by other axons. Here we show that soon-to-be-eliminated axons rapidly reverse fate and grow to occupy vacant sites at a neuromuscular junction after laser removal of a stronger input. This reversal supports the idea that axons take over sites that were previously vacated. Indeed, during normal development we observed withdrawal followed by takeover. The stimulus for axon growth is not postsynaptic cell inactivity because axons grow into unoccupied sites even when target cells are functionally innervated. These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity.

  14. Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism.

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    Turney, Stephen G; Lichtman, Jeff W

    2012-01-01

    During mammalian development, neuromuscular junctions and some other postsynaptic cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons. It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territory in response to sites vacated by other axons. Here we show that soon-to-be-eliminated axons rapidly reverse fate and grow to occupy vacant sites at a neuromuscular junction after laser removal of a stronger input. This reversal supports the idea that axons take over sites that were previously vacated. Indeed, during normal development we observed withdrawal followed by takeover. The stimulus for axon growth is not postsynaptic cell inactivity because axons grow into unoccupied sites even when target cells are functionally innervated. These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity.

  15. Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

    Science.gov (United States)

    Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

    2013-12-01

    Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

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    Nijssen, Jik; Frost‐Nylen, Johanna

    2015-01-01

    Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26502195

  17. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

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    Bailey Nichols

    2015-07-01

    Full Text Available Dystrophin-glycoprotein complex (DGC is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin of a muscle fiber to the extracellular matrix (ECM. Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies, and limb-girdle muscular dystrophies (sarcoglycanopathies, are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS, which is localized at the muscle membrane by DGC members (dystrophin and syntrophins, plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.

  18. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

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    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  19. Stem cell-derived neurotrophic support for the neuromuscular junction in spinal muscular atrophy.

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    Wyatt, Tanya J; Keirstead, Hans S

    2010-11-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by specific degeneration of α-motor neurons in the spinal cord. The use of cell transplantation to restore lost function through cell replacement or prevent further degeneration of motor neurons and synapses through neurotrophic support heralds tremendous hope in the SMA field. Much research has been carried out in the last decade on the use of embryonic stem cells in cell replacement strategies for various neurodegenerative diseases. Cell replacement is contingent on the ability of transplanted cells to integrate and form new functional connections with host cells. In the case of SMA, cell replacement is a tall order in that axons of transplanted cells would be required to grow over long distances from the spinal cord through growth-averse terrain to synapse with muscles in the periphery. The efficacy of neurotrophic support is contingent on the ability of transplanted cells to secrete neurotrophins appropriate for degenerating motor neurons in the spinal cord or development/stability of the neuromuscular junction (NMJ) in the periphery. The reader will gain an understanding of the potential of neurotrophins to promote development of the NMJ in a diseased or injured environment. Neurotrophins play a major role in NMJ development and thus may be a key factor in the pathogenesis of NMJs in SMA. Further research into the signaling mechanisms involved in NMJ maturation may identify additional mechanisms by which transplanted cells may be of therapeutic benefit.

  20. Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models

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    James J. Dowling

    2012-11-01

    Myotubular myopathy (MTM is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ transmission is an important and potentially treatable aspect of the disease pathogenesis. We tested this hypothesis in two murine models of MTM. In both models we uncovered evidence of a disorder of NMJ transmission: fatigable weakness, improved strength with neostigmine, and electrodecrement with repetitive nerve stimulation. Histopathological analysis revealed abnormalities in the organization, appearance and size of individual NMJs, abnormalities that correlated with changes in acetylcholine receptor gene expression and subcellular localization. We additionally determined the ability of pyridostigmine, an acetylcholinesterase inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ dysfunction. Pyridostigmine treatment resulted in significant improvement in fatigable weakness and treadmill endurance. In all, these results describe a newly identified pathological abnormality in MTM, and uncover a potential disease-modifying therapy for this devastating disorder.

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

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    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.

  2. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions.

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    Melanie A Samuel

    Full Text Available As synapses form and mature the synaptic partners produce organizing molecules that regulate each other's differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ, these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-α4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.

  3. Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

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    Dupuis, Luc; Gonzalez de Aguilar, Jose-Luis; Echaniz-Laguna, Andoni; Eschbach, Judith; Rene, Frédérique; Oudart, Hugues; Halter, Benoit; Huze, Caroline; Schaeffer, Laurent; Bouillaud, Frédéric; Loeffler, Jean-Philippe

    2009-01-01

    Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases. PMID:19404401

  4. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  5. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

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    Josep Tomàs

    2017-05-01

    Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  6. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

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    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  7. Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction.

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    Gerasimova, E; Lebedeva, J; Yakovlev, A; Zefirov, A; Giniatullin, R; Sitdikova, G

    2015-09-10

    Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. L-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (β-cyano-L-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca(2+)) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to

  8. PKA, PKC, and AKAP localization in and around the neuromuscular junction

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    Newton Alexandra

    2001-10-01

    Full Text Available Abstract Background One mechanism that directs the action of the second messengers, cAMP and diacylglycerol, is the compartmentalization of protein kinase A (PKA and protein kinase C (PKC. A-kinase anchoring proteins (AKAPs can recruit both enzymes to specific subcellular locations via interactions with the various isoforms of each family of kinases. We found previously that a new class of AKAPs, dual-specific AKAPs, denoted D-AKAP1 and D-AKAP2, bind to RIα in addition to the RII subunits. Results Immunohistochemistry and confocal microscopy were used here to determine that D-AKAP1 colocalizes with RIα at the postsynaptic membrane of the vertebrate neuromuscular junction (NMJ and the adjacent muscle, but not in the presynaptic region. The labeling pattern for RIα and D-AKAP1 overlapped with mitochondrial staining in the muscle fibers, consistent with our previous work showing D-AKAP1 association with mitochondria in cultured cells. The immunoreactivity of D-AKAP2 was distinct from that of D-AKAP1. We also report here that even though the PKA type II subunits (RIIα and RIIβ are localized at the NMJ, their patterns are distinctive and differ from the other R and D-AKAP patterns examined. PKCβ appeared to colocalize with the AKAP, gravin, at the postsynaptic membrane. Conclusions The kinases and AKAPs investigated have distinct patterns of colocalization, which suggest a complex arrangement of signaling micro-environments. Because the labeling patterns for RIα and D-AKAP 1 are similar in the muscle fibers and at the postsynaptic membrane, it may be that this AKAP anchors RIα in these regions. Likewise, gravin may be an anchor of PKCβ at the NMJ.

  9. Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction

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    Mate Suzanne E

    2012-09-01

    Full Text Available Abstract Background Recycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ. We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD1 proteinin the Torpedo californica electric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/− NMJs. Methods Localization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/− mouse skeletal muscle. Results Endogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal muscle in vivo. EHD1−/− mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in the T. californica electric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/− mouse skeletal muscle than in wild-type skeletal muscle. Conclusion EHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/− muscle may be due to functional compensation by other EHD paralogs.

  10. A role for tight junction-associated MARVEL proteins in larval sea lamprey (Petromyzon marinus) osmoregulation.

    Science.gov (United States)

    Kolosov, Dennis; Bui, Phuong; Donini, Andrew; Wilkie, Mike P; Kelly, Scott P

    2017-10-15

    This study reports on tight junction-associated MARVEL proteins of larval sea lamprey ( Petromyzon marinus ) and their potential role in ammocoete osmoregulation. Two occludin isoforms (designated Ocln and Ocln-a) and a tricellulin (Tric) were identified. Transcripts encoding ocln , ocln-a and tric were broadly expressed in larval lamprey, with the greatest abundance of ocln in the gut, liver and kidney, ocln-a in the gill and skin, and tric in the kidney. Ocln and Ocln-a resolved as ∼63 kDa and ∼35 kDa MW proteins, respectively, while Tric resolved as a ∼50 kDa protein. Ocln immunolocalized to the gill vasculature and in gill mucous cells while Ocln-a localized to the gill pouch and gill epithelium. Both Ocln and Ocln-a localized in the nephron, the epidermis and the luminal side of the gut. In branchial tissue, Tric exhibited punctate localization, consistent with its presence at regions of tricellular contact. Following ion-poor water (IPW) acclimation of ammocoetes, serum [Na + ] and [Cl - ] decreased, but not [Ca 2+ ], and carcass moisture content increased. In association, Ocln abundance increased in the skin and kidney, but reduced in the gill of IPW-acclimated ammocoetes while Ocln-a abundance reduced in the kidney only. Tric abundance increased in the gill. Region-specific alterations in ocln , ocln-a and tric mRNA abundance were also observed in the gut. Data support a role for Ocln, Ocln-a and Tric in the osmoregulatory strategies of a basal vertebrate. © 2017. Published by The Company of Biologists Ltd.

  11. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

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    Hai-peng Huang

    2016-01-01

    Full Text Available Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10, Zusanli (ST36, Pishu (BL20, and Shenshu (BL23 once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

  12. Abnormally Small Neuromuscular Junctions in the Extraocular Muscles From Subjects With Idiopathic Nystagmus and Nystagmus Associated With Albinism.

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    McLoon, Linda K; Willoughby, Christy L; Anderson, Jill S; Bothun, Erick D; Stager, David; Felius, Joost; Lee, Helena; Gottlob, Irene

    2016-04-01

    Infantile nystagmus syndrome (INS) is often associated with abnormalities of axonal outgrowth and connectivity. To determine if this manifests in extraocular muscle innervation, specimens from children with idiopathic INS or INS and albinism were examined and compared to normal age-matched control extraocular muscles. Extraocular muscles removed during normal surgery on children with idiopathic INS or INS and albinism were immunostained for neuromuscular junctions, myofiber type, the immature form of the acetylcholine receptor, and brain-derived neurotrophic factor (BDNF) and compared to age-matched controls. Muscles from both the idiopathic INS and INS and albinism groups had neuromuscular junctions that were 35% to 71% smaller based on myofiber area and myofiber perimeter than found in age-matched controls, and this was seen on both fast and slow myosin heavy chain isoform-expressing myofibers (all P albinism showed a 7-fold increase in neuromuscular junction numbers on fast myofibers expressing the immature gamma subunit of the acetylcholine receptor. The extraocular muscles from both INS subgroups showed a significant increase in the number and size of slow myofibers compared to age-matched controls. Brain-derived neurotrophic factor was expressed in control muscle but was virtually absent in the INS muscles. These studies suggest that, relative to the final common pathway, INS is not the same between different patient etiologies. It should be possible to modulate these final common pathway abnormalities, via exogenous application of appropriate drugs, with the hope that this type of treatment may reduce the involuntary oscillatory movements in these children.

  13. Effect of purines on calcium-independent acetylcholine release at the mouse neuromuscular junction.

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    Veggetti, M; Muchnik, S; Losavio, A

    2008-07-17

    At the mouse neuromuscular junction, activation of adenosine A(1) and P2Y receptors inhibits acetylcholine release by an effect on voltage dependent calcium channels related to spontaneous and evoked secretion. However, an effect of purines upon the neurotransmitter-releasing machinery downstream of Ca(2+) influx cannot be ruled out. An excellent tool to study neurotransmitter exocytosis in a Ca(2+)-independent step is the hypertonic response. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of the specific adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) and the P2Y(12-13) agonist 2-methylthio-adenosine 5'-diphosphate (2-MeSADP) on the hypertonic response. Both purines significantly decreased such response (peak and area under the curve), and their effect was prevented by specific antagonists of A(1) and P2Y(12-13) receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N-[2-(methylthioethyl)]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with dichloromethylenebiphosphonic acid, tetrasodium salt (AR-C69931MX), respectively. Moreover, incubation of preparations only with the antagonists induced a higher response compared with controls, suggesting that endogenous ATP/ADP and adenosine are able to modulate the hypertonic response by activating their specific receptors. To search for the intracellular pathways involved in this effect, we studied the action of CCPA and 2-MeSADP in hypertonicity in the presence of inhibitors of several pathways. We found that the effect of CPPA was prevented by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) while that of 2-MeSADP was occluded by the protein kinase C antagonist chelerythrine and W-7. On the other hand, the inhibitors of protein kinase A (N-(2[pbromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide, H-89) and phosphoinositide-3 kinase (PI3K) (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran

  14. Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

    Science.gov (United States)

    Dobrowolny, Gabriella; Martini, Martina; Scicchitano, Bianca Maria; Romanello, Vanina; Boncompagni, Simona; Nicoletti, Carmine; Pietrangelo, Laura; De Panfilis, Simone; Catizone, Angela; Bouchè, Marina; Sandri, Marco; Rudolf, Rüdiger; Protasi, Feliciano; Musarò, Antonio

    2018-04-20

    Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

  15. Measuring Neuromuscular Junction Functionality in the SOD1(G93A) Animal Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Rizzuto, Emanuele; Pisu, Simona; Musarò, Antonio; Del Prete, Zaccaria

    2015-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to motor neuron degeneration, alteration in neuromuscular junctions (NMJs), muscle atrophy, and paralysis. To investigate the NMJ functionality in ALS we tested, in vitro, two innervated muscle types excised from SOD1(G93A) transgenic mice at the end-stage of the disease: the Soleus, a postural muscle almost completely paralyzed at that stage, and the diaphragm, which, on the contrary, is functional until death. To this aim we employed an experimental protocol that combined two types of electrical stimulation: the direct stimulation and the stimulation through the nerve. The technique we applied allowed us to determine the relevance of NMJ functionality separately from muscle contractile properties in SOD1(G93A) animal model. Functional measurements revealed that the muscle contractility of transgenic diaphragms is almost unaltered in comparison to control muscles, while transgenic Soleus muscles were severely compromised. In contrast, when stimulated via the nerve, both transgenic muscle types showed a strong decrease of the contraction force, a slowing down of the kinetic parameters, as well as alterations in the neurotransmission failure parameter. All together, these results confirm a severely impaired functionality in the SOD1(G93A) neuromuscular junctions.

  16. Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, Silvana; Veggetti, Mariela; Muchnik, Salomón; Losavio, Adriana

    2004-05-01

    1. At the mouse neuromuscular junction, adenosine (AD) and the A(1) agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) induce presynaptic inhibition of spontaneous acetylcholine (ACh) release by activation of A(1) AD receptors through a mechanism that is still unknown. To evaluate whether the inhibition is mediated by modulation of the voltage-dependent calcium channels (VDCCs) associated with tonic secretion (L- and N-type VDCCs), we measured the miniature end-plate potential (mepp) frequency in mouse diaphragm muscles. 2. Blockade of VDCCs by Cd(2+) prevented the effect of the CCPA. Nitrendipine (an L-type VDCC antagonist) but not omega-conotoxin GVIA (an N-type VDCC antagonist) blocked the action of CCPA, suggesting that the decrease in spontaneous mepp frequency by CCPA is associated with an action on L-type VDCCs only. 3. As A(1) receptors are coupled to a G(i/o) protein, we investigated whether the inhibition of PKA or the activation of PKC is involved in the presynaptic inhibition mechanism. Neither N-(2[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89, a PKA inhibitor), nor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7, a PKC antagonist), nor phorbol 12-myristate 13-acetate (PHA, a PKC activator) modified CCPA-induced presynaptic inhibition, suggesting that these second messenger pathways are not involved. 4. The effect of CCPA was eliminated by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) and by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester epsilon6TDelta-BM, which suggests that the action of CCPA to modulate L-type VDCCs may involve Ca(2+)-calmodulin. 5. To investigate the action of CCPA on diverse degrees of nerve terminal depolarization, we studied its effect at different external K(+) concentrations. The effect of CCPA on ACh secretion evoked by 10 mm K(+) was prevented by the P/Q-type VDCC antagonist omega-agatoxin IVA. 6. CCPA failed to

  17. LL5beta: a regulator of postsynaptic differentiation identified in a screen for synaptically enriched transcripts at the neuromuscular junction.

    Science.gov (United States)

    Kishi, Masashi; Kummer, Terrance T; Eglen, Stephen J; Sanes, Joshua R

    2005-04-25

    In both neurons and muscle fibers, specific mRNAs are concentrated beneath and locally translated at synaptic sites. At the skeletal neuromuscular junction, all synaptic RNAs identified to date encode synaptic components. Using microarrays, we compared RNAs in synapse-rich and -free regions of muscles, thereby identifying transcripts that are enriched near synapses and that encode soluble membrane and nuclear proteins. One gene product, LL5beta, binds to both phosphoinositides and a cytoskeletal protein, filamin, one form of which is concentrated at synaptic sites. LL5beta is itself associated with the cytoplasmic face of the postsynaptic membrane; its highest levels border regions of highest acetylcholine receptor (AChR) density, which suggests a role in "corraling" AChRs. Consistent with this idea, perturbing LL5beta expression in myotubes inhibits AChR aggregation. Thus, a strategy designed to identify novel synaptic components led to identification of a protein required for assembly of the postsynaptic apparatus.

  18. The effects of neurotoxins and radiation on the neuromuscular junction of the mouse: a physiological and morphological study

    International Nuclear Information System (INIS)

    Gomez, S.

    Some of the factors controlling axonal growth are studied by observing the effects of botulinum toxin, black widow spider venom and X-irradiation on teh neuromuscular junction in mice. Irradiation alone caused no changes since radiation is believed to affect only the Schwann cells. Irradiation prior to the administration of botulinum delayed the recovery of transmission and led to the failure of maturation and myelination of newly formed axons; this illustrates the importance of the Schwann cell for continued growth, functional maturation and myelination of axons. The effect of black widow spider venom on the end-plates was degeneration of the nerve terminals within a few hours but after a few days there was regeneration and restoration of normal transmission. The effects of black widow spider venom on muscles paralysed by botulinum were also studied; the recovery from the action of botulinum was greatly accelerated by the venom and axonal sprouting was either abolished or greatly reduced. (U.K.)

  19. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

    Science.gov (United States)

    2012-01-01

    Backgound Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz), and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different. PMID:22443542

  20. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

    Directory of Open Access Journals (Sweden)

    Xia Ruohan

    2012-03-01

    Full Text Available Abstract Backgound Amyotrophic lateral sclerosis (ALS is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus. However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz, and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS or adding a nuclear export signal (NES blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different.

  1. INTERACTION OF VERAPAMIL AND LITHIUM AT THE NEUROMUSCULAR JUNCTION ON RAT ISOLATED MUSCLE-HEMIDIAPHRAGM

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    H. R. Sadeghipour

    1998-08-01

    Full Text Available It has been reported that cither lithium or verapamil can potentiate the neuromuscular blocking activity of certain neuromuscular blockers. In the present investigation, possible interaction of verapamil with lithium has been described. The dose ■ response effects of verapamil and lithium on diaphragmatic contractility were assessed in vitro. Mechanical responses of the muscle to indirect (nerve and direct (muscle electrical stimulation were recorded. Verapamil depressed rat diaphragm twitch tensions induced by nerve stimulation in a dose - dependent manner with the 50 percent depression of the original twitch tensions (ICSQ by 5.6 xlO^mmol/l."nThe IC50 of verapamil for direct stimulation of the muscle was LI x W'5 mmol II. Partial replacement of sodium chloride by lithium chloride (0.5, 1.5 and 5 mmol /1 in the medium did not change the depressant effect of verapamil on muscle twitches induced by direct (muscle or indirect (nerve electrical stimulation.

  2. Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

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    Stefan Hettwer

    Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

  3. Adenosine A₁ and A₂A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction.

    Science.gov (United States)

    Garcia, Neus; Priego, Mercedes; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Besalduch, Nuria; Lanuza, M Angel; Tomàs, Josep

    2013-07-01

    Immunocytochemistry shows that purinergic receptors (P1Rs) type A1 and A2A (A1 R and A2 A R, respectively) are present in the nerve endings at the P6 and P30 Levator auris longus (LAL) mouse neuromuscular junctions (NMJs). As described elsewhere, 25 μm adenosine reduces (50%) acetylcholine release in high Mg(2+) or d-tubocurarine paralysed muscle. We hypothesize that in more preserved neurotransmission machinery conditions (blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB) the physiological role of the P1Rs in the NMJ must be better observed. We found that the presence of a non-selective P1R agonist (adenosine) or antagonist (8-SPT) or selective modulators of A1 R or A2 A R subtypes (CCPA and DPCPX, or CGS-21680 and SCH-58261, respectively) does not result in any changes in the evoked release. However, P1Rs seem to be involved in spontaneous release (miniature endplate potentials MEPPs) because MEPP frequency is increased by non-selective block but decreased by non-selective stimulation, with A1 Rs playing the main role. We assayed the role of P1Rs in presynaptic short-term plasticity during imposed synaptic activity (40 Hz for 2 min of supramaximal stimuli). Depression is reduced by micromolar adenosine but increased by blocking P1Rs with 8-SPT. Synaptic depression is not affected by the presence of selective A1 R and A2 A R modulators, which suggests that both receptors need to collaborate. Thus, A1 R and A2 A R might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of acetylcholine and may protect synaptic function by reducing the magnitude of depression during repetitive activity. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Glucuronylated core 1 glycans are required for precise localization of neuromuscular junctions and normal formation of basement membranes on Drosophila muscles.

    Science.gov (United States)

    Itoh, Kazuyoshi; Akimoto, Yoshihiro; Kondo, Shu; Ichimiya, Tomomi; Aoki, Kazuhiro; Tiemeyer, Michael; Nishihara, Shoko

    2018-04-15

    T antigen (Galβ1-3GalNAcα1-Ser/Thr) is an evolutionary-conserved mucin-type core 1 glycan structure in animals synthesized by core 1 β1,3-galactosyltransferase 1 (C1GalT1). Previous studies showed that T antigen produced by Drosophila C1GalT1 (dC1GalT1) was expressed in various tissues and dC1GalT1 loss in larvae led to various defects, including decreased number of circulating hemocytes, hyper-differentiation of hematopoietic stem cells in lymph glands, malformation of the central nervous system, mislocalization of neuromuscular junction (NMJ) boutons, and ultrastructural abnormalities in NMJs and muscle cells. Although glucuronylated T antigen (GlcAβ1-3Galβ1-3GalNAcα1-Ser/Thr) has been identified in Drosophila, the physiological function of this structure has not yet been clarified. In this study, for the first time, we unraveled biological roles of glucuronylated T antigen. Our data show that in Drosophila, glucuronylation of T antigen is predominantly carried out by Drosophila β1,3-glucuronyltransferase-P (dGlcAT-P). We created dGlcAT-P null mutants and found that mutant larvae showed lower expression of glucuronylated T antigen on the muscles and at NMJs. Furthermore, mislocalization of NMJ boutons and a partial loss of the basement membrane components collagen IV (Col IV) and nidogen (Ndg) at the muscle 6/7 boundary were observed. Those two phenotypes were correlated and identical to previously described phenotypes in dC1GalT1 mutant larvae. In addition, dGlcAT-P null mutants exhibited fewer NMJ branches on muscles 6/7. Moreover, ultrastructural analysis revealed that basement membranes that lacked Col IV and Ndg were significantly deformed. We also found that the loss of dGlcAT-P expression caused ultrastructural defects in NMJ boutons. Finally, we showed a genetic interaction between dGlcAT-P and dC1GalT1. Therefore, these results demonstrate that glucuronylated core 1 glycans synthesized by dGlcAT-P are key modulators of NMJ bouton localization

  5. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes.

    Science.gov (United States)

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2014-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers-which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal-has hitherto been technically impossible. With the aim of quantifying both Ca(2+) currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 pA and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 μM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  6. 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.

  7. 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.

  8. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  9. ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions.

    Science.gov (United States)

    Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Potluri, Srilatha; Fu, Xiu-Qing; Luo, Zhen-Ge; Nagappan, Guhan; Chan, Jia Pei; Hempstead, Barbara; Son, Young-Jin; Lu, Bai

    2013-06-12

    During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo.

  10. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó-Ollé, Anna; Cilleros-Mañé, Víctor; Just-Borràs, Laia

    2018-01-01

    In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR) in the mammalian neuromuscular junction (NMJ). Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally). These observations underlie the relevance of AR in the NMJ function.

  11. The interaction between tropomyosin-related kinase B receptors and serine kinases modulates acetylcholine release in adult neuromuscular junctions.

    Science.gov (United States)

    Santafé, Manel M; Garcia, Neus; Tomàs, Marta; Obis, Teresa; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

    2014-02-21

    We conducted an electrophysiological study of the functional link between the tropomyosin-related kinase B (trkB) receptor signaling mechanism and serine-threonine kinases, both protein kinase C (PKC) and protein kinase A (PKA). We describe their coordinated role in transmitter release at the neuromuscular junction (NMJ) of the Levator auris longus muscle of the adult mouse. The trkB receptor normally seems to be coupled to stimulate ACh release because inhibiting the trkB receptor with K-252a results in a significant reduction in the size of EPPs. We found that the intracellular PKC pathway can operate as in basal conditions (to potentiate ACh release) without the involvement of the trkB receptor function, although the trkB pathway needs an operative PKC pathway if it is to couple to the release mechanism and potentiate it. To actively stimulate PKA (which also results in ACh release potentiation), the operativity of trkB is a necessary condition, and one effect of trkB may be PKA stimulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2018-04-01

    Full Text Available In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR in the mammalian neuromuscular junction (NMJ. Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally. These observations underlie the relevance of AR in the NMJ function.

  13. Functional neuromuscular junctions formed by embryonic stem cell-derived motor neurons.

    Directory of Open Access Journals (Sweden)

    Joy A Umbach

    Full Text Available A key objective of stem cell biology is to create physiologically relevant cells suitable for modeling disease pathologies in vitro. Much progress towards this goal has been made in the area of motor neuron (MN disease through the development of methods to direct spinal MN formation from both embryonic and induced pluripotent stem cells. Previous studies have characterized these neurons with respect to their molecular and intrinsic functional properties. However, the synaptic activity of stem cell-derived MNs remains less well defined. In this study, we report the development of low-density co-culture conditions that encourage the formation of active neuromuscular synapses between stem cell-derived MNs and muscle cells in vitro. Fluorescence microscopy reveals the expression of numerous synaptic proteins at these contacts, while dual patch clamp recording detects both spontaneous and multi-quantal evoked synaptic responses similar to those observed in vivo. Together, these findings demonstrate that stem cell-derived MNs innervate muscle cells in a functionally relevant manner. This dual recording approach further offers a sensitive and quantitative assay platform to probe disorders of synaptic dysfunction associated with MN disease.

  14. Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

    International Nuclear Information System (INIS)

    Rotzler, S.; Brenner, H.R.

    1990-01-01

    The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125 I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed

  15. Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, S; Veggetti, M; Muchnik, S; Losavio, A

    2006-09-29

    At the neuromuscular junction, ATP is co-released with the neurotransmitter acetylcholine (ACh) and once in the synaptic space, it is degraded to the presynaptically active metabolite adenosine. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of extracellular ATP (100 muM) and the slowly hydrolysable ATP analog 5'-adenylylimidodiphosphate lithium (betagamma-imido ATP) (30 muM) on miniature end-plate potential (MEPP) frequency. We found that application of ATP and betagamma-imido ATP decreased spontaneous secretion by 45.3% and 55.9% respectively. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) adenosine receptor antagonist and alpha,beta-methylene ADP sodium salt (alphabeta-MeADP), which is an inhibitor of ecto-5'-nucleotidase, did not prevent the inhibitory effect of ATP, demonstrating that the nucleotide is able to modulate spontaneous ACh release through a mechanism independent of the action of adenosine. Blockade of Ca(2+) channels by both, Cd(2+) or the combined application of nitrendipine and omega-conotoxin GVIA (omega-CgTx) (L-type and N-type Ca(2+) channel antagonists, respectively) prevented the effect of betagamma-imido ATP, indicating that the nucleotide modulates Ca(2+) influx through the voltage-dependent Ca(2+) channels related to spontaneous secretion. betagamma-Imido ATP-induced modulation was antagonized by the non-specific P2 receptor antagonist suramin and the P2Y receptor antagonist 1-amino-4-[[4-[[4-chloro-6-[[3(or4)-sulfophenyl] amino]-1,3,5-triazin-2-yl]amino]-3-sulfophenyl] amino]-9,10-dihydro-9,10-dioxo-2-anthracenesulfonic acid (reactive blue-2), but not by pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS), which has a preferential antagonist effect on P2X receptors. Pertussis toxin and N-ethylmaleimide (NEM), which are blockers of G(i/o) proteins, prevented the action of the nucleotide, suggesting that the effect is mediated by P2Y receptors

  16. Validation of simple and inexpensive algometry using sphygmomanometer cuff and neuromuscular junction monitor with standardized laboratory algometer

    Science.gov (United States)

    Durga, Padmaja; Wudaru, Sreedhar Reddy; Khambam, Sunil Kumar Reddy; Chandra, Shobha Jagadish; Ramachandran, Gopinath

    2016-01-01

    Background and Aims: The availability, ergonomics and economics prohibit the routine use of algometers in clinical practice and research by the anesthesiologists. A simple bedside technique of quantitative pain measurement would enable the routine use of algometry. We proposed to validate simple pain provocation using sphygmomanometer cuff and the electric stimulation of neuromuscular junction monitor (TOF-guard, Organon Teknika) to measure pain against a standardized laboratory pressure algometer. Material and Methods: Pain detection threshold (Pdt) and pain tolerance threshold (Ptt) were measured in forty healthy volunteers of both genders, using the above three techniques. All measurements were repeated three times. The co-efficient of inter-rater reliability (or consistency) between three independent measurements obtained from each of the techniques was determined by Cronbach's co-efficient alpha (α C). The correlation between the mean Pdt and Ptt values recorded by standardized algometer and the sphygmomanometer technique and nerve stimulator technique was performed using Pearson Correlation. An r >0.5 and a two-tailed significance of algometer and the tested techniques. Results: There was a good inter-rater reliability (α C > 0.7) for the three techniques. There was a good correlation with r >0.65 (P algometer and the two techniques being tested as alternatives for algometer to measure pain. Conclusion: The sphygmomanometer cuff technique and electrical stimulation with the peripheral nerve stimulator to measure pain threshold and tolerance provide a simple, efficient, repeatable measure of pain intensity and can be used as suitable alternatives to standard algometers. PMID:27006546

  17. Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria Angel; Cilleros, Victor; Tomàs, Josep Maria

    2016-01-01

    The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A2A, M1, M4, and A1 receptors (in this order of ability) delayed axonal elimination at P7. M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway, which suggests that they cooperate. M2 receptors may modulate (by allowing a permissive action) the other receptors, mainly M4 and A1. The continued action of these receptors (now including M2 but not M4) finally promotes axonal loss at P9. All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary. The M4 receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M1, A1, and A2A receptors, which show an additive effect, whereas the potent M2 effect is largely independent of the other receptors (though can be modulated by M4). At P9, there is a full mutual dependence between the A1 and A2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes.

  18. Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies

    NARCIS (Netherlands)

    Slater, CR; Young, C; Wood, SJ; Bewick, GS; Anderson, LVB; Baxter, P; Fawcett, PRW; Roberts, M; Jacobson, L; Kuks, J; Vincent, A; NewsomDavis, J

    Congenital myasthenic syndromes are a heterogenous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the

  19. The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction.

    Science.gov (United States)

    Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Besalduch, Nuria; Priego, Merche; Tomàs, Josep

    2010-08-16

    We use immunocytochemistry to show that the trophic molecule glial cell line-derived neurotrophic factor (GDNF) and its receptor GDNF family receptor alpha-1 (GFRalpha-1) are present in both neonatal (P6) and adult (P45) rodent neuromuscular junctions (NMJ) colocalized with several synaptic markers. However, incubation with exogenous GDNF (10-200ng/ml, 1-3h), does not affect spontaneous ACh release. Moreover, GDNF does not change the size of the evoked ACh release from the weak and the strong axonal inputs on dually innervated postnatal endplates nor in the most developed singly-innervated synapses at P6 and P45. Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction.

    Science.gov (United States)

    Hurtado, Erica; Cilleros, Víctor; Just, Laia; Simó, Anna; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

    2017-01-01

    Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB) in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min). Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1) protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release.

  1. Repouso da junção neuromuscular no tratamento de crises miastênicas e colinérgicas Management of the myasthenic and cholinergic crisis by neuromuscular junction rest

    Directory of Open Access Journals (Sweden)

    J. Lamartine de Assis

    1968-06-01

    Full Text Available Os autores trataram 18 crises miastênicas e colinérgicas desenvolvidas em 12 pacientes com forma generalizada e severa de miastenia grave, mediante o "repouso" da junção neuromuscular. Êste foi conseguido, em um grupo de 6 enfermos, pela suspensão das drogas anticolinesterásicas, emprego da respiração artificial e alimentação por sonda nasogástrica — "repouso relativo". Outro grupo de 6 pacientes foi submetido ao "repouso absoluto" da junção neuromuscular, mediante o uso da respiração artificial, alimentação por sonda nasogástrica e curarização prolongada pela galamina. Em mais de 50% das crises observaram-se melhoras imediatas e acentuadas com o método de tratamento pelo "repouso" da junção neuromuscular, ao lado de redução significativa da taxa de mortalidade nas crises. A evolução mostrou que os pacientes que responderam melhor durante e logo após o tratamento da crise, tiveram, também, melhor evolução ulterior. Dos 12 enfermos somente um era portador de timoma e, mesmo nesse paciente, a evolução foi satisfatória. A sensibilidade inicial ao curare foi muito grande em todos os doentes submetidos à curarização prolongada, mas, em prazo relativamente curto (alguns dias, esta hipersensibilidade diminuiu sensivelmente. Apesar de todos os cuidados, as infecções respiratórias foram a regra, exigindo tratamento enérgico e bem orientado.The neuromuscular junction rest method was employed in the treatment of 18 myasthenic and cholinergic crisis occurring in 12 patients with severe forms of myasthenia gravis. Six of these patients received a "relative rest" and other six patients received an "absolute rest" treatment. In the first group of patients the method consisted essentially in withdrawal of anticholinesterase therapy and mechanical respiratory support with early performance of traqueostomy and use of the intermitente positive pressure breathing (I.P.P.B. with cuffed traqueostomy tube. The patients of

  2. Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Erica Hurtado

    2017-08-01

    Full Text Available Conventional protein kinase C βI (cPKCβI is a conventional protein kinase C (PKC isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ. It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1. Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min. Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1 protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release.

  3. Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.

    Science.gov (United States)

    Yano, Michiko; Minegishi, Yoshihiko; Sugita, Satoshi; Ota, Noriyasu

    2017-10-15

    Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Localization of brain-derived neurotrophic factor, neurotrophin-4, tropomyosin-related kinase b receptor, and p75 NTR receptor by high-resolution immunohistochemistry on the adult mouse neuromuscular junction.

    Science.gov (United States)

    Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, M Angel; Besalduch, Nuria; Tomàs, Josep

    2010-03-01

    Neurotrophins and their receptors, the trk receptor tyrosine kinases (trks) and p75(NTR), are differentially expressed among the cell types that make up synapses. It is important to determine the precise location of these molecules involved in neurotransmission. Here we use immunostaining and Western blotting to study the localization and expression of neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase b (trkB) and p75(NTR) at the adult neuromuscular junction. Our confocal immunofluorescence results on the whole mounts of the mouse Levator auris longus muscle and on semithin cross-sections showed that BDNF, NT-4, trkB, and p75(NTR) were localized on the three cells in the neuromuscular synapse (motor axons, post-synaptic muscle and Schwann cells).

  5. Excitatory effect of the A2A adenosine receptor agonist CGS-21680 on spontaneous and K+-evoked acetylcholine release at the mouse neuromuscular junction.

    Science.gov (United States)

    Palma, A G; Muchnik, S; Losavio, A S

    2011-01-13

    The mechanism of action of the A2A adenosine receptor agonist 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) in the facilitation of spontaneous (isotonic and hypertonic condition) and K+-evoked acetylcholine (ACh) release was investigated in the mouse diaphragm muscles. At isotonic condition, the CGS-21680-induced excitatory effect on miniature end-plate potential (MEPP) frequency was not modified in the presence of CdCl2 and in a medium free of Ca2+ (0Ca2+-EGTA), but it was abolished after buffering the rise of intracellular Ca2+ with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxy-methyl) (BAPTA-AM) and when the Ca2+-ATPase inhibitor thapsigargin was used to deplete intracellular Ca2+ stores. CGS-21680 did not have a direct effect on the Ca2+-independent neurotransmitter-releasing machinery, since the modulatory effect on the hypertonic response was also occluded by BAPTA-AM and thapsigargin. CGS-21680 facilitation on K+-evoked ACh release was not altered by the P/Q-type voltage-dependent calcium channel (VDCC) blocker ω-Agatoxin IVA, but it was completely prevented by both, the L-type VDCC blocker nitrendipine (which is known to immobilize their gating charges), or thapsigargin, suggesting that the effects of CGS-21680 on L-type VDCC and thapsigargin-sensitive internal stores are associated. We found that the VDCC pore blocker Cd2+ (2 mM Ca2+ or 0Ca2+-EGTA) failed to affect the CGS-21680 effect in high K+ whereas nitrendipine in 0Ca2+-EGTA+Cd2+ occluded its action. The blockade of Ca2+ release from endoplasmic reticulum with ryanodine antagonized the facilitating effect of CGS-21680 in control and high K+ concentration. It is concluded that, at the mouse neuromuscular junction, activation of A2A receptors facilitates spontaneous and K+-evoked ACh release by an external Ca2+-independent mechanism but that involves mobilization of Ca2+ from internal stores: during spontaneous ACh release

  6. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction.

    Science.gov (United States)

    Tomàs, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomàs, Marta; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M 1 , M 2 and M 4 ), adenosine receptors (AR; A 1 and A 2A ) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A 1 , M 1 and TrkB operate mainly by stimulating PKC whereas A 2A , M 2 and M 4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and

  7. Membrane Receptor-Induced Changes of the Protein Kinases A and C Activity May Play a Leading Role in Promoting Developmental Synapse Elimination at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Josep M. Tomàs

    2017-08-01

    Full Text Available Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh receptors (subtypes mAChR; M1, M2 and M4, adenosine receptors (AR; A1 and A2A and the tropomyosin-related kinase B receptor (TrkB, among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC, to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ. This hypothesis is supported by: (i the tonic effect (shown by using selective inhibitors of several membrane receptors that accelerates axon loss between postnatal days P5–P9; (ii the synergistic, antagonic and modulatory effects (shown by paired inhibition of the receptors on axonal loss; (iii the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various

  8. Neuromuscular Disorders

    Science.gov (United States)

    ... lead to twitching, cramps, aches and pains, and joint and movement problems. Sometimes it also affects heart function and your ability to breathe. Examples of neuromuscular disorders include Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia ...

  9. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  10. Doenças neuromusculares Neuromuscular disorders

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    Umbertina C. Reed

    2002-08-01

    differential diagnosis among the main neuromuscular disorders in children, that include the diseases affecting the motor unity, i.e. spinal motor neurons, peripheral nerves, neuromuscular junction and muscular fibers. Sources: the review of the clinical aspects that should be considered for a prompt differential diagnosis among several neuromuscular disorders as well as between those and the main causes of secondary muscular hypotonia due to central nervous system or systemic disturbances is based on the clinical experience acquired along the last 12 years in following-up children with Neuromuscular Disorders attended at the outpatient Service of Neuromuscular Disorders at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. In addition, it is based on Medline and on the review of the most recent numbers of Neuromuscular Disorders, the official journal of the World Muscle Society. Summary of the findings: most of neuromuscular disorders are genetic conditions in children and the most common of them are X-linked Progressive Muscular Dystrophy of Duchenne, Spinal Muscular Atrophy, Congenital Muscular Dystrophy, Myotonic Dystrophy and Congenital Myopathies. Conclusions: due to the phenomenal development in human molecular genetics the pathogenesis of several neuromuscular disorders in children has been clarified over the last decade. Nowadays many new diagnostic methods, including techniques of fetal diagnosis, and a more objective genotype-phenotype correlation as well as classification are available.

  11. [Characteristics of neuromuscular scoliosis].

    Science.gov (United States)

    Putzier, M; Groß, C; Zahn, R K; Pumberger, M; Strube, P

    2016-06-01

    Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research.

  12. BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction

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    Anna Simó

    2018-06-01

    Full Text Available Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1 synaptic activity at the neuromuscular junction, (2 nPKCε and cPKCβI isoforms activity, (3 muscle contraction per se, and (4 the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min with or without contraction (abolished by μ-conotoxin GIIIB. Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB. Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity–induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity–induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling.

  13. BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction.

    Science.gov (United States)

    Simó, Anna; Just-Borràs, Laia; Cilleros-Mañé, Víctor; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

    2018-01-01

    Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at the neuromuscular junction, (2) nPKCε and cPKCβI isoforms activity, (3) muscle contraction per se , and (4) the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity-induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity-induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling.

  14. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep

    2016-06-23

    The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors

  15. Analysis of synaptic growth and function in Drosophila with an extended larval stage.

    Science.gov (United States)

    Miller, Daniel L; Ballard, Shannon L; Ganetzky, Barry

    2012-10-03

    The Drosophila larval neuromuscular junction (NMJ) is a powerful system for the genetic and molecular analysis of neuronal excitability, synaptic transmission, and synaptic development. However, its use for studying age-dependent processes, such as maintenance of neuronal viability and synaptic stability, are temporally limited by the onset of pupariation and metamorphosis. Here we characterize larval NMJ growth, growth regulation, structure, and function in a developmental variant with an extended third instar (ETI). RNAi-knockdown of the prothoracicotropic hormone receptor, torso, in the ring gland of developing larvae leaves the timing of first and second instar molts largely unchanged, but triples duration of the third instar from 3 to 9.5 d (McBrayer et al., 2007; Rewitz et al., 2009). During this ETI period, NMJs undergo additional growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGFβ/BMP pathway. NMJ growth during the ETI period occurs via addition of new branches, satellite boutons, and interstitial boutons, and continues even after muscle growth levels off. Throughout the ETI, organization of synapses and active zones remains normal, and synaptic transmission is unchanged. These results establish the ETI larval system as a viable model for studying motor neuron diseases and for investigating time-dependent effects of perturbations that impair mechanisms of neuroprotection, synaptic maintenance, and response to neural injury.

  16. Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular Influencia de la procainamida sobre el bloqueo neuromuscular producido por el rocuronio e investigación sobre el mecanismo de acción de la procainamida en la junción neuromuscular Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Thalita Duque Martins

    2007-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada: procainamida - 20 µg.mL-1 (Grupo I; rocurônio - 4 µg.mL-1 (Grupo II e rocurônio - 4 µg.mL-1 e procainamida - 20 µg.mL-1 (Grupo III. Avaliaram-se: 1 a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2 os potenciais de placa terminal em miniatura (PPTM; 3 a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5 e diafragma de rato desnervado (n = 5, observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067 em relação ao Grupo II (10,4% ± 4,5%, revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida.JUSTIFICATIVA Y OBJETIVOS: La potenciación de la procainamida sobre

  17. A perisynaptic ménage à trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions.

    Science.gov (United States)

    Bachmann, André; Kobler, Oliver; Kittel, Robert J; Wichmann, Carolin; Sierralta, Jimena; Sigrist, Stephan J; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

    2010-04-28

    Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. At Drosophila larval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7. In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.

  18. Neuromuscular blockade in children Bloqueadores neuromusculares em crianças

    Directory of Open Access Journals (Sweden)

    João Fernando Lourenço de Almeida

    2000-06-01

    Full Text Available Neuromuscular blocking agents (NMBAs have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000 and active search of articles were the mechanisms used in this review.Os bloqueadores neuromusculares têm sido amplamente utilizados para controlar pacientes que necessitem imobilidade para algum tipo de intervenção médica, desde a realização de procedimentos invasivos até a obtenção de sincronismo com a ventilação mecânica. O objetivo básico desta monografia é revisar a farmacologia dos principais bloqueadores neuromusculares, analisar as diferenças existentes na junção neuromuscular de neonatos, lactentes, pré-escolares e adultos, além de discutir suas indicações em pacientes criticamente enfermos internados em unidade de terapia intensiva pediátrica. Revisão computadorizada da literatura (Medline 1990-2000 associado a busca ativa de artigos compuseram o mecanismo de busca dos dados desta revisão.

  19. Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

    Science.gov (United States)

    Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

    2016-01-01

    The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

  20. Objective neuromuscular monitoring of neuromuscular blockade in Denmark

    DEFF Research Database (Denmark)

    Söderström, C M; Eskildsen, K Z; Gätke, M R

    2017-01-01

    BACKGROUND: Neuromuscular blocking agents are commonly used during general anaesthesia but can lead to postoperative residual neuromuscular blockade and associated morbidity. With appropriate objective neuromuscular monitoring (objNMM) residual blockade can be avoided. In this survey, we investig...

  1. TEACHING NEUROMUSCULAR RELAXATION.

    Science.gov (United States)

    NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

    THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

  2. BIOLOGY OF SOME NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Gerta Vrbova

    2004-12-01

    unit is slower. The rate of maturation is critical for the survival of both motoneurone and muscle and that events that interfere with the time course of maturation cause both motoneurone and muscle fibre death. The proposal that the SMN gene/protein is involved in the process to developmental changes in cells and therefore crucial for their survival is put forward. The understanding of the developmental changes and their influence on motoneurone and muscle survival may help to devise therapeutic interventions. These may include a protection of the motoneurone cell body during a critical period of its development by reducing its excitability or enhancing its defences by upregulating heat shock proteins, b stabilizing neuromuscular junctions to enhance and prolong the retrograde influences from the muscle that affect motoneurone survival, c protecting muscle fibres from apoptosis, as well as stimulating their maturation by activity appropriate to their younger age that results from their delayed development.These approaches should be considered in addition to or in conjunction with possible interference with the gene and its product.In order to understand and possibly interfere/treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. In this presentation I would illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1 Duchenne muscular dystrophy, and 2 Spinal muscular atrophy.

  3. Neuromuscular complications of thyrotoxicosis.

    Science.gov (United States)

    Kung, Annie W C

    2007-11-01

    Thyroid hormones exert multiple effects on the neuromuscular system and the brain, with the most important being their role in stimulating the development and differentiation of the neuromuscular system and brain in foetal and neonatal life. In the presence of hyperthyroidism, muscular and neurological symptoms may be the presenting clinical features of the disease. The frequency and severity of neuromuscular complications vary considerably and are probably related to the degree of hyperthyroidism, although in some patients the neuromuscular dysfunction is caused by associated disorders rather than by hyperthyroidism per se. This update focuses on the most common neurological and muscular disorders that occur in patients with thyrotoxicosis. It is beyond the scope of this paper to discuss thyroid eye disease and cardiac complications, in themselves separate complications of specific myocytes.

  4. FUNCTIONS OF A NEUROMUSCULAR CENTRE

    Directory of Open Access Journals (Sweden)

    Janez Zidar

    2004-12-01

    Full Text Available Main functions of a neuromuscular (NM centre are making diagnosis, treatment and counselling. Some other functions, e. g. forming a register and epidemiological endeavours, could be added. All these activities are expected to be achieved by multidisciplinary approach with the idea that members use the same guidelines and share the same knowledge.NM diseases affect lower levels of the nervous system that is motor units (motor cells in the brainstem and spinal cord, nerve roots, cranial and peripheral nerves, neuromuscular junction, and muscles. There are many such diseases; a few are more common others are rare.Rational approach in making a diagnosis can be divided into several steps. The process begins with a person with clinical symptoms and signs which raise the suspicion of NM disease. The first step is the description of the predominant pattern of muscular wasting and weakness (e. g. limb-girdle, distal, ocular, facio-scapulo-humeral. Each of these syndromes require a differential diagnosis within the motor unit territory what is achieved by means of EMG and muscle biopsy. The latter is even more important to define the nature of the abnormality. Disease nature can also be determined biochemically and, as NM disorders are commonly genetically determined, at the molecular genetic level. Treatment modalities include drugs (causative and symptomatic and other measures such as promoting and maintaining good general health, preventing skeletal deformities, physiotherapy, orthoses, surgery, and prevention of respiratory and cardiac functions. Counselling is mainly by social workers that focus on the practical aspects of coping with illness and disability and by genetic counsellors who gave advise on family planning.

  5. Neuromuscular diseases: Diagnosis and management.

    Science.gov (United States)

    Mary, P; Servais, L; Vialle, R

    2018-02-01

    Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the

  6. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  7. Partial neuromuscular blockade in humans enhances muscle blood flow during exercise independently of muscle oxygen uptake and acetylcholine receptor blockade

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Krustrup, Peter; Iaia, F Marcello

    2009-01-01

    This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one-legged k......This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one...... conductance during exercise, events that are not associated with either acetylcholine or an increased oxygen demand. The results do not support an essential role for acetylcholine, released form the neuromuscular junction, in exercise hyperaemia or for the enhanced blood flow during neuromuscular blockade....... The enhanced exercise hyperemia during partial neuromuscular blockade may be related to a greater recruitment of fast-twitch muscle fibres. Key words: blood flow, neuromuscular blockade, exercise, skeletal muscle....

  8. MRI in neuromuscular disorders

    International Nuclear Information System (INIS)

    Fischmann, Arne

    2014-01-01

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  9. Gap Junctions

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

  10. The Action of Botulinum Toxin at the Neuromuscular Junction

    Science.gov (United States)

    1980-12-22

    fast - twitch " (gastrocnemius) and " slow - twitch " (soleus) muscles ... muscle fibers -"_re not significantly affected by the toxin. It is interesting to note that, although fast - twitch and slow - twitch mucles were...Duchen LW: An electron microscopic study of the changes induced by borulinum o::in in the motor end-plates of slow and fast skeletal muscle fibres of

  11. Some effects of lead at mammalian neuromuscular junction

    Energy Technology Data Exchange (ETDEWEB)

    Pickett, J.B.; Bornstein, J.C.

    1984-03-01

    The effect of lead on transmitter release was investigated in a rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode techniques. Lead reduced the number of quanta released by a nerve stimulus (m) in a dose-dependent fashion. As extracellular Ca/sup 2 +/ concentration ((Ca/sup 2 +/)/sub 0/) was varied in the absence of lead, a linear relationship between ln(m) and ln((Ca/sup 2 +/)/sub 0/) was obtained. Lead shifted the relationship between ln(m) and ln((Ca/sup 2 +/)/sub 0/) to the right without altering the slope. This suggested lead competed with Ca/sup 2 +/, which was confirmed by using a modified Lineweaver-Burk plot. Lead inhibits Ca/sup 2 +/ entry into frog sympathetic preganglionic nerve terminals, and a similar mechanism may underlie this present finding; such a mechanism, however, could not explain all the observed actions of lead. Lead increased the frequency of spontaneous quantal release in a dose-dependent manner, and 10/sup -4/ M lead doubled the magnitude of facilitation of evoked release seen with five stimuli at 60 Hz. It is suggested that these effects result from inhibition of some, or all, of the nerve terminal's Ca/sup 2 +/ sequestration mechanisms.

  12. Effect of calcium on excitatory neuromuscular transmission in the crayfish

    Science.gov (United States)

    Bracho, H.; Orkand, R. K.

    1970-01-01

    1. The effects of varying the external Ca concentration from 1·8 to 30 mM/l. (⅛-2 times normal) have been studied at the in vitro crayfish excitatory neuromuscular junction. Electrophysiological techniques were used to record transmembrane junctional potentials from muscle fibres and extracellular junctional currents from the vicinity of nerve terminals. 2. The excitatory junctional potential amplitude was proportional to [Ca]0n, where n varied between 0·68 and 0·94 (mean 0·82) when [Ca]0 was varied from 1·8 to 15 mM/l. 3. The increase in junctional potential amplitude on raising [Ca]0 resulted primarily from an increase in the average number of quanta of excitatory transmitter released from the presynaptic nerve terminal by the nerve impulse. 4. The size of the quanta, synaptic delay, presynaptic potential and electrical properties of the muscle membrane were little affected by changes in calcium concentration in the range studied. PMID:5498460

  13. Neuromuscular disease classification system

    Science.gov (United States)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  14. Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

    Science.gov (United States)

    Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

    2018-01-15

    Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Neuromuscular control and ankle instability.

    Science.gov (United States)

    Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

    2009-04-01

    Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

  16. Neuromuscular ultrasound of cranial nerves.

    Science.gov (United States)

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  17. Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

    2017-11-16

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

  18. Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

    Science.gov (United States)

    Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

    2011-04-01

    We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

  19. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab0)2 and whole IgG antivenoms

    OpenAIRE

    Herrera Vega, María; de Cássia de O. Collaço, Rita; Villalta, Mauren; Segura Ruiz, Álvaro; Vargas Arroyo, Mariángela; Wright, Christine E.; Paiva, Owen K.; Matainaho, Teatulohi; Jensen, Simon D.; León Montero, Guillermo; Williams, David J.; Rodrigues Simioni, Lea; Gutiérrez, José María

    2016-01-01

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21 °C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent add...

  20. Neutralization Of The Neuromuscular Inhibition Of Venom And Taipoxin From The Taipan (oxyuranus Scutellatus) By F(ab ') 2 And Whole Igg Antivenoms

    OpenAIRE

    Herrera; Maria; de O Collaco; Rita de Cassia; Villalta; Mauren; Segura; Alvaro; Vargas; Mariangela; Wright; Christine E.; Paiva; Owen K.; Matainaho; Teatulohi; Jensen; Simon D.; Leon; Guillermo; Williams; David J.; Rodrigues-Simioni; Lea; Maria Gutierrez; Jose

    2016-01-01

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21 degrees C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independ...

  1. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F.; Wevers, C. W.; Wintzen, A. R.; Busch, H. F.; Höweler, C. J.; de Jager, A. E.; Padberg, G. W.; de Visser, M.; Wokke, J. H.

    1997-01-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  2. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F; Wevers, CWJ; Wintzen, AR; Busch, HFM; Howeler, CJ; deJager, AEJ; Padberg, GW; deVisser, M; Wokke, JHJ

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  3. Palliative care in neuromuscular diseases

    NARCIS (Netherlands)

    de Visser, Marianne; Oliver, David J.

    2017-01-01

    Purpose of review Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness. Neuromuscular disorders (NMDs) are characterized by progressive muscle weakness, leading to pronounced and incapacitating

  4. Effectiveness of Neuromuscular Training Based on the Neuromuscular Risk Profile.

    Science.gov (United States)

    Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

    2017-07-01

    The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Controlled laboratory study. Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

  5. Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

    Science.gov (United States)

    Fauroux, Brigitte; Khirani, Sonia

    2014-08-01

    Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

  6. [Respiratory treatments in neuromuscular disease].

    Science.gov (United States)

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  7. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  8. Identification and Simulation as Tools for Measurement of Neuromuscular Properties

    National Research Council Canada - National Science Library

    Kearney, R

    2001-01-01

    Quantitative, objective methods for the evaluation of neuromuscular properties are required for the diagnosis of neuromuscular disorders and the evaluation of the effectiveness of treatment and rehabilitation...

  9. Neuromuscular Control and Coordination during Cycling

    Science.gov (United States)

    Li, Li

    2004-01-01

    The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

  10. Kinship and interaction in neuromuscular pharmacology

    NARCIS (Netherlands)

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  11. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  12. A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

    Science.gov (United States)

    Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

    2016-04-01

    Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

  13. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark

    2012-01-01

    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative, and f...

  14. Larval helminths in intermediate hosts

    DEFF Research Database (Denmark)

    Fredensborg, Brian Lund; Poulin, R

    2005-01-01

    Density-dependent effects on parasite fitness have been documented from adult helminths in their definitive hosts. There have, however, been no studies on the cost of sharing an intermediate host with other parasites in terms of reduced adult parasite fecundity. Even if larval parasites suffer a ...

  15. Larval outbreaks in West Greenland

    DEFF Research Database (Denmark)

    Lund, Magnus; Raundrup, Katrine; Westergaard-Nielsen, Andreas

    2017-01-01

    effects of a larval outbreak in 2011 on vegetation productivity and CO2 exchange. We estimate a decreased carbon (C) sink strength in the order of 118–143 g C m−2, corresponding to 1210–1470 tonnes C at the Kobbefjord catchment scale. The decreased C sink was, however, counteracted the following years...

  16. Kauri seeds and larval somersaults

    DEFF Research Database (Denmark)

    Dupont, Steen Thorleif

    2012-01-01

    The trunk morphology of the larvae of the kauri pine (Agathis) seed infesting moth Agathiphaga is described using conventional, polarization, and scanning electron microscopy. The pine seed chamber formed by the larva is also described and commented on. The simple larval chaetotaxy includes more ...

  17. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

  18. Junction and circuit fabrication

    International Nuclear Information System (INIS)

    Jackel, L.D.

    1980-01-01

    Great strides have been made in Josephson junction fabrication in the four years since the first IC SQUID meeting. Advances in lithography have allowed the production of devices with planar dimensions as small as a few hundred angstroms. Improved technology has provided ultra-high sensitivity SQUIDS, high-efficiency low-noise mixers, and complex integrated circuits. This review highlights some of the new fabrication procedures. The review consists of three parts. Part 1 is a short summary of the requirements on junctions for various applications. Part 2 reviews intergrated circuit fabrication, including tunnel junction logic circuits made at IBM and Bell Labs, and microbridge radiation sources made at SUNY at Stony Brook. Part 3 describes new junction fabrication techniques, the major emphasis of this review. This part includes a discussion of small oxide-barrier tunnel junctions, semiconductor barrier junctions, and microbridge junctions. Part 3 concludes by considering very fine lithography and limitations to miniaturization. (orig.)

  19. Neuromuscular complications of immune checkpoint inhibitor therapy.

    Science.gov (United States)

    Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

    2018-01-17

    Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  20. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

    DEFF Research Database (Denmark)

    Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

    2017-01-01

    INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys...

  1. Neuromuscular control of prey capture in frogs.

    OpenAIRE

    Nishikawa, K C

    1999-01-01

    While retaining a feeding apparatus that is surprisingly conservative morphologically, frogs as a group exhibit great variability in the biomechanics of tongue protraction during prey capture, which in turn is related to differences in neuromuscular control. In this paper, I address the following three questions. (1) How do frog tongues differ biomechanically? (2) What anatomical and physiological differences are responsible? (3) How is biomechanics related to mechanisms of neuromuscular cont...

  2. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    Science.gov (United States)

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

  3. Neuromuscular blockade in the elderly patient

    Directory of Open Access Journals (Sweden)

    Lee LA

    2016-06-01

    Full Text Available Luis A Lee, Vassilis Athanassoglou, Jaideep J Pandit Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Abstract: Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids. Other drugs (atracurium, cisatracurium have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. Keywords: anesthesia, elderly, drugs, pharmacokinetics, pharmacodynamics 

  4. First feeding of larval herring

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Munk, Peter; Støttrup, Josianne

    1985-01-01

    The transition period from endogenous to exogenous feeding by larval herring was investigated in the laboratory for four herring stocks in order to evaluate the chances of survival at the time of fiest feeding. Observations on larval activity, feeding and growth were related to amount of yolk......, visual experience with potential prey organisms prior to first feeding and prey density. Herring larvae did not initiate exogenous feeding until around the time of yolk resorption. The timing of first feeding was not influenced by prior exposure to potential prey organisms during the yolk sac stage....... In the light of these observations, the ecological significance of the yolk sac stage is discussed. Initiation of exogenous feeding was delayed by 1-4 days at a low (7.5 nauplii .cntdot. l-1) compared to a high (120 nauplii .cntdot. l-1) prey density, but even at prey densities corresponding to the lower end...

  5. 'Peer pressure' in larval Drosophila?

    Science.gov (United States)

    Niewalda, Thomas; Jeske, Ines; Michels, Birgit; Gerber, Bertram

    2014-06-06

    Understanding social behaviour requires a study case that is simple enough to be tractable, yet complex enough to remain interesting. Do larval Drosophila meet these requirements? In a broad sense, this question can refer to effects of the mere presence of other larvae on the behaviour of a target individual. Here we focused in a more strict sense on 'peer pressure', that is on the question of whether the behaviour of a target individual larva is affected by what a surrounding group of larvae is doing. We found that innate olfactory preference of a target individual was neither affected (i) by the level of innate olfactory preference in the surrounding group nor (ii) by the expression of learned olfactory preference in the group. Likewise, learned olfactory preference of a target individual was neither affected (iii) by the level of innate olfactory preference of the surrounding group nor (iv) by the learned olfactory preference the group was expressing. We conclude that larval Drosophila thus do not take note of specifically what surrounding larvae are doing. This implies that in a strict sense, and to the extent tested, there is no social interaction between larvae. These results validate widely used en mass approaches to the behaviour of larval Drosophila. © 2014. Published by The Company of Biologists Ltd.

  6. Josephson junction arrays

    International Nuclear Information System (INIS)

    Bindslev Hansen, J.; Lindelof, P.E.

    1985-01-01

    In this review we intend to cover recent work involving arrays of Josephson junctions. The work on such arrays falls naturally into three main areas of interest: 1. Technical applications of Josephson junction arrays for high-frequency devices. 2. Experimental studies of 2-D model systems (Kosterlitz-Thouless phase transition, commensurate-incommensurate transition in frustrated (flux) lattices). 3. Investigations of phenomena associated with non-equilibrium superconductivity in and around Josephson junctions (with high current density). (orig./BUD)

  7. Equivalent Josephson junctions

    International Nuclear Information System (INIS)

    Boyadzhiev, T.L.; ); Semerdzhieva, E.G.; Shukrinov, Yu.M.; Fiziko-Tekhnicheskij Inst., Dushanbe

    2008-01-01

    The magnetic field dependences of critical current are numerically constructed for a long Josephson junction with a shunt- or resistor-type microscopic inhomogeneities and compared to the critical curve of a junction with exponentially varying width. The numerical results show that it is possible to replace the distributed inhomogeneity of a long Josephson junction by an inhomogeneity localized at one of its ends, which has certain technological advantages. It is also shown that the critical curves of junctions with exponentially varying width and inhomogeneities localized at the ends are unaffected by the mixed fluxon-antifluxon distributions of the magnetic flux [ru

  8. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Intrauterine neuromuscular blockade in fetus.

    Science.gov (United States)

    Fan, S Z; Huang, F Y; Lin, S Y; Wang, Y P; Hsieh, F J

    1990-03-01

    Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/- 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method.

  10. Protein defects in neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Vainzof M.

    2003-01-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

  11. Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

    Science.gov (United States)

    Sloan, Paul A; Rasul, Mazhar

    2002-01-01

    We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

  12. Supramolecular tunneling junctions

    NARCIS (Netherlands)

    Wimbush, K.S.

    2012-01-01

    In this study a variety of supramolecular tunneling junctions were created. The basis of these junctions was a self-assembled monolayer of heptathioether functionalized ß-cyclodextrin (ßCD) formed on an ultra-flat Au surface, i.e., the bottom electrode. This gave a well-defined hexagonally packed

  13. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.Cachexia, ageing and disuse and their effects on the human and animals neuromuscular system are reviewed. Disuse induces reduction of muscle fibers (mainly II diameter with peripheral myofibrils lost; there is no core-targetoid or even reduction on myophosphorilase activity, both typical of denervation; the acetylcholine spontaneous release and trophic factors on myoneural junction are maintained; muscle fibers could change to angular shape. Ageing affects nerve and muscle by a continuous and progressive process of denervation and reinner

  14. Computed tomography (CT) in neuromuscular disorders

    International Nuclear Information System (INIS)

    Novak, M.; Ambler, Z.

    1997-01-01

    For 24 patients with confirmed neuromuscular disorders, the clinical picture of the disease was complemented with CT examination. It is concluded, in accordance with the literature, that CT has a supplementary value as regards the extent and degree of disorder of the affected muscle groups. The basic pathological picture includes muscular atrophies, dystrophies, hypertrophies, and their combinations. The CT images are non-specific for the individual neuromuscular disorders and are of minor importance in the diagnostic process. 1 tab., 7 figs., 6 refs

  15. Research highlights of partial neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Cheng ZHANG

    2014-05-01

    Full Text Available In order to understand the latest progression on neuromuscular disorders for clinicians, this review screened and systemized the papers on neuromuscular disorders which were collected by PubMed from January 2013 to February 2014. This review also introduced the clinical diagnosis and treatment hightlights on glycogen storage disease type Ⅱ (GSD Ⅱ, Duchenne muscular dystrophy (DMD, amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA. The important references will be useful for clinicians. doi: 10.3969/j.issn.1672-6731.2014.05.004

  16. Models of prey capture in larval fish

    NARCIS (Netherlands)

    Drost, M.R.

    1986-01-01

    The food uptake of larval carp and pike is described from high speed movies with synchronous lateral and ventral views.

    During prey intake by larval fishes the velocities of the created suction flow are high relative to their own size: 0.3 m/s for carp larvae of 6

  17. [Canine peritoneal larval cestodosis caused by Mesocestoides spp. larval stages].

    Science.gov (United States)

    Häußler, T C; Peppler, C; Schmitz, S; Bauer, C; Hirzmann, J; Kramer, M

    2016-01-01

    In a female dog with unspecific clinical symptoms, sonography detected a hyperechoic mass in the middle abdomen and blood analysis a middle grade systemic inflammatory reaction. Laparotomy revealed a peritoneal larval cestodosis (PLC). The diagnosis of an infection with tetrathyridia of Mesocestoides spp. was confirmed by parasitological examination and molecularbiological analysis. Reduction of the intra-abdominal parasitic load as well as a high dose administration of fenbendazole over 3 months led to a successful treatment which could be documented sonographically and by decreased concentrations of C-reactive protein (CRP). Seven months after discontinuation of fenbendazole administration, PLC recurred, pre-empted by an elevation of serum CRP values. According to the literature a life-long fenbendazole treatment was initiated. In cases of unclear chronic granulomatous inflammations in the abdominal cavity in dogs, PLC should be considered. CRP concentration and sonographic examinations are suitable to control for treatment success and a possibly occurring relapse.

  18. Sugammadex Improves Neuromuscular Function in Patients ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... aminoglycosides), history of allergy to neuromuscular blocking agents, opioids or other drugs, and alcohol and drug dependence. Patients were divided into two ... titration microcalorimetry investigated the likelihood of the formation of complexes between sugammadex and other steroidal and nonsteroidal ...

  19. Neuromuscular transmission: new concepts and agents.

    NARCIS (Netherlands)

    Boer, H.D. de

    2009-01-01

    Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

  20. Primary Tunnel Junction Thermometry

    International Nuclear Information System (INIS)

    Pekola, Jukka P.; Holmqvist, Tommy; Meschke, Matthias

    2008-01-01

    We describe the concept and experimental demonstration of primary thermometry based on a four-probe measurement of a single tunnel junction embedded within four arrays of junctions. We show that in this configuration random sample specific and environment-related errors can be avoided. This method relates temperature directly to Boltzmann constant, which will form the basis of the definition of temperature and realization of official temperature scales in the future

  1. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang

    2012-09-12

    Colloidal quantum dot solids combine convenient solution-processing with quantum size effect tuning, offering avenues to high-efficiency multijunction cells based on a single materials synthesis and processing platform. The highest-performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising the benefits of facile quantum tuning. Here we report rectifying junctions constructed entirely using inherently band-aligned quantum-tuned materials. Realizing these quantum junction diodes relied upon the creation of an n-type quantum dot solid having a clean bandgap. We combine stable, chemically compatible, high-performance n-type and p-type materials to create the first quantum junction solar cells. We present a family of photovoltaic devices having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum-to-bulk devices fail to perform. Devices having optimal single-junction bandgaps exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over doping in quantum solids, and the successful integration of these materials to form stable quantum junctions, offers a powerful new degree of freedom to colloidal quantum dot optoelectronics. © 2012 American Chemical Society.

  2. Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Drachman, R J; Stanley, E F

    1992-05-29

    The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.

  3. Soundscapes and Larval Settlement: Larval Bivalve Responses to Habitat-Associated Underwater Sounds.

    Science.gov (United States)

    Eggleston, David B; Lillis, Ashlee; Bohnenstiehl, DelWayne R

    2016-01-01

    We quantified the effects of habitat-associated sounds on the settlement response of two species of bivalves with contrasting habitat preferences: (1) Crassostrea virginicia (oyster), which prefers to settle on other oysters, and (2) Mercenaria mercenaria (clam), which settles on unstructured habitats. Oyster larval settlement in the laboratory was significantly higher when exposed to oyster reef sound compared with either off-reef or no-sound treatments. Clam larval settlement did not vary according to sound treatments. Similar to laboratory results, field experiments showed that oyster larval settlement in "larval housings" suspended above oyster reefs was significantly higher compared with off-reef sites.

  4. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

    Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

    2015-01-01

    PURPOSE: To evaluate the effects of a 12-week, home-based, physiotherapist-guided neuromuscular exercise program on the knee adduction moment (an indicator of mediolateral knee load distribution) in people with a medial arthroscopic partial meniscectomy within the past 3-12 months. METHODS......: An assessor-blinded, randomised controlled trial including people aged 30-50 years with no to mild pain following medial arthroscopic partial meniscectomy was conducted. Participants were randomly allocated to either a 12-week neuromuscular exercise program that targeted neutral lower limb alignment...... or a control group with no exercise. The exercise program included eight individual sessions with one of seven physiotherapists in private clinics, together with home exercises. Primary outcomes were the peak external knee adduction moment during normal pace walking and during a one-leg sit-to-stand. Secondary...

  5. Four-junction superconducting circuit

    Science.gov (United States)

    Qiu, Yueyin; Xiong, Wei; He, Xiao-Ling; Li, Tie-Fu; You, J. Q.

    2016-01-01

    We develop a theory for the quantum circuit consisting of a superconducting loop interrupted by four Josephson junctions and pierced by a magnetic flux (either static or time-dependent). In addition to the similarity with the typical three-junction flux qubit in the double-well regime, we demonstrate the difference of the four-junction circuit from its three-junction analogue, including its advantages over the latter. Moreover, the four-junction circuit in the single-well regime is also investigated. Our theory provides a tool to explore the physical properties of this four-junction superconducting circuit. PMID:27356619

  6. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia...... and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel...... practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit...

  7. Tunable Nitride Josephson Junctions.

    Energy Technology Data Exchange (ETDEWEB)

    Missert, Nancy A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Henry, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lewis, Rupert M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Howell, Stephen W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfley, Steven L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Brunke, Lyle Brent [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolak, Matthaeus [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    We have developed an ambient temperature, SiO2/Si wafer - scale process for Josephson junctions based on Nb electrodes and Ta x N barriers with tunable electronic properties. The films are fabricated by magnetron sputtering. The electronic properties of the TaxN barriers are controlled by adjusting the nitrogen flow during sputtering. This technology offers a scalable alternative to the more traditional junctions based on AlOx barriers for low - power, high - performance computing.

  8. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an......-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x)....

  9. Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block

  10. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang; Liu, Huan; Zhitomirsky, David; Hoogland, Sjoerd; Wang, Xihua; Furukawa, Melissa; Levina, Larissa; Sargent, Edward H.

    2012-01-01

    -performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising

  11. Involvement of neurotrophin-3 (NT-3) in the functional elimination of synaptic contacts during neuromuscular development.

    Science.gov (United States)

    Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

    2010-04-05

    Confocal immunohistochemistry shows that neurotrophin-3 (NT-3) and its receptor tropomyosin-related tyrosin kinase C (trkC) are present in both neonatal (P6) and adult (P45) mouse motor nerve terminals in neuromuscular junctions (NMJ) colocalized with several synaptic proteins. NT-3 incubation (1-3h, in the range 10-200ng/ml) does not change the size of the evoked and spontaneous endplate potentials at P45. However, NT-3 (1h, 100ng/ml) strongly potentiates evoked ACh release from the weak (70%) and the strong (50%) axonal inputs on dually innervated postnatal endplates (P6) but not in the most developed postnatal singly innervated synapses at P6. The present results indicate that NT-3 has a role in the developmental mechanism that eliminates redundant synapses though it cannot modulate synaptic transmission locally as the NMJ matures.

  12. Neurotrophin-4 couples to locally modulated ACh release at the end of neuromuscular synapse maturation.

    Science.gov (United States)

    Garcia, N; Santafe, M M; Tomas, M; Lanuza, M A; Besalduch, N; Tomas, J

    2010-01-01

    We use immunocytochemistry to show that neurotrophin-4 (NT-4) and its receptor proteins (p75(NTR) and tropomyosin-related tyrosine kinase B) are present in neonatal neuromuscular junctions (NMJ) colocalized with several synaptic markers. NT-4 incubation (1h, in the range 2-12 nM) does not change the size of the endplate potential between P6 and P45. However, extended exposure (3h) to a relatively low dose of NT-4 (2 nM) potentiates ACh release (approx. 70%) in adult but not in neonatal muscles. The present results suggest that the developmental mechanism of axonal competition and neonatal elimination of redundant synapses cannot be modulated by added NT-4. However, this neurotrophin was able to modulate synaptic transmission locally in the adult NMJ.

  13. Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse.

    Science.gov (United States)

    Besalduch, Núria; Tomàs, Marta; Santafé, Manel M; Garcia, Neus; Tomàs, Josep; Lanuza, Maria Angel

    2010-01-10

    Protein kinase C (PKC) is essential for signal transduction in a variety of cells, including neurons and myocytes, and is involved in both acetylcholine release and muscle fiber contraction. Here, we demonstrate that the increases in synaptic activity by nerve stimulation couple PKC to transmitter release in the rat neuromuscular junction and increase the level of alpha, betaI, and betaII isoforms in the membrane when muscle contraction follows the stimulation. The phosphorylation activity of these classical PKCs also increases. It seems that the muscle has to contract in order to maintain or increase classical PKCs in the membrane. We use immunohistochemistry to show that PKCalpha and PKCbetaI were located in the nerve terminals, whereas PKCalpha and PKCbetaII were located in the postsynaptic and the Schwann cells. Stimulation and contraction do not change these cellular distributions, but our results show that the localization of classical PKC isoforms in the membrane is affected by synaptic activity.

  14. Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Pilar eMartinez-Martinez

    2013-09-01

    Full Text Available Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the CNS, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand–activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.

  15. Classification of neuromuscular blocking agents in a new neuromuscular preparation of the chick in vitro

    NARCIS (Netherlands)

    Riezen, H. van

    1968-01-01

    A neuromuscular preparation of the chick is described: 1. 1. The sciatic nerve-tibilis anterior muscle preparation of the 2–10 days old chick fulfils all criteria of an assay preparation and differentiates between curare-like and decamethonium-like agents. 2. 2. The preparation responds to

  16. Anopheline larval habitats seasonality and species distribution: a prerequisite for effective targeted larval habitats control programmes.

    Directory of Open Access Journals (Sweden)

    Eliningaya J Kweka

    Full Text Available Larval control is of paramount importance in the reduction of malaria vector abundance and subsequent disease transmission reduction. Understanding larval habitat succession and its ecology in different land use managements and cropping systems can give an insight for effective larval source management practices. This study investigated larval habitat succession and ecological parameters which influence larval abundance in malaria epidemic prone areas of western Kenya.A total of 51 aquatic habitats positive for anopheline larvae were surveyed and visited once a week for a period of 85 weeks in succession. Habitats were selected and identified. Mosquito larval species, physico-chemical parameters, habitat size, grass cover, crop cycle and distance to nearest house were recorded. Polymerase chain reaction revealed that An. gambiae s.l was the most dominant vector species comprised of An.gambiae s.s (77.60% and An.arabiensis (18.34%, the remaining 4.06% had no amplification by polymerase chain reaction. Physico-chemical parameters and habitat size significantly influenced abundance of An. gambiae s.s (P = 0.024 and An. arabiensis (P = 0.002 larvae. Further, larval species abundance was influenced by crop cycle (P≤0.001, grass cover (P≤0.001, while distance to nearest houses significantly influenced the abundance of mosquito species larvae (r = 0.920;P≤0.001. The number of predator species influenced mosquito larval abundance in different habitat types. Crop weeding significantly influenced with the abundance of An.gambiae s.l (P≤0.001 when preceded with fertilizer application. Significantly higher anopheline larval abundance was recorded in habitats in pasture compared to farmland (P = 0.002. When habitat stability and habitat types were considered, hoof print were the most productive followed by disused goldmines.These findings suggest that implementation of effective larval control programme should be targeted with larval

  17. Neuromuscular adaptations induced by adjacent joint training.

    Science.gov (United States)

    Ema, R; Saito, I; Akagi, R

    2018-03-01

    Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training. © 2017 The Authors. Scandinavian Journal of Medicine & Science In Sports Published by John Wiley & Sons Ltd.

  18. Neuromuscular Manifestations of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    A. Arturo eLeis

    2012-03-01

    Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

  19. Acute neuromuscular weakness associated with dengue infection

    Directory of Open Access Journals (Sweden)

    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  20. Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

    2015-07-01

    Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Medical back belt with integrated neuromuscular electrical stimulation

    NARCIS (Netherlands)

    Bottenberg, E. (Eliza); Brinks, G.J. (Ger); Hesse, J. (Jenny)

    2014-01-01

    The medical back belt with integrated neuromuscular electrical stimulation is anorthopedic device, which has two main functions. The first function is to stimulate the backmuscles by using a neuromuscular electrical stimulation device that releases regular,electrical impulses. The second function of

  2. Neuromuscular function during a forward lunge in meniscectomized patients

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Damgaard, Jacob; Roos, Ewa M.

    2012-01-01

    This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients....... Such differences may represent early changes in neuromuscular function potentially contributing to the development of knee osteoarthritis....

  3. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  4. Rehydration of forensically important larval Diptera specimens.

    Science.gov (United States)

    Sanford, Michelle R; Pechal, Jennifer L; Tomberlin, Jeffery K

    2011-01-01

    Established procedures for collecting and preserving evidence are essential for all forensic disciplines to be accepted in court and by the forensic community at large. Entomological evidence, such as Diptera larvae, are primarily preserved in ethanol, which can evaporate over time, resulting in the dehydration of specimens. In this study, methods used for rehydrating specimens were compared. The changes in larval specimens with respect to larval length and weight for three forensically important blow fly (Diptera: Calliphoridae) species in North America were quantified. Phormia regina (Meigen), Cochliomyia macellaria (F.), and Chrysomya rufifacies (Macquart) third-instar larvae were collected from various decomposing animals and preserved with three preservation methods (80% ethanol, 70% isopropyl alcohol, and hot-water kill then 80% ethanol). Preservative solutions were allowed to evaporate. Rehydration was attempted with either of the following: 80% ethanol, commercial trisodium phosphate substitute solution, or 0.5% trisodium phosphate solution. All three methods partially restored weight and length of specimens recorded before preservation. Analysis of variance results indicated that effects of preservation, rehydration treatment, and collection animal were different in each species. The interaction between preservative method and rehydration treatment had a significant effect on both P. regina and C. macellaria larval length and weight. In addition, there was a significant interaction effect of collection animal on larval C. macellaria measurements. No significant effect was observed in C. rufifacies larval length or weight among the preservatives or treatments. These methods could be used to establish a standard operating procedure for dealing with dehydrated larval specimens in forensic investigations.

  5. RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

    Directory of Open Access Journals (Sweden)

    Sandeep Raut

    2017-07-01

    Full Text Available Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.

  6. Development of the mouse neuromuscular junction in the absence of regulated secretion

    NARCIS (Netherlands)

    Heeroma, J.H.; Plomp, J.J.; Roubos, E.W.; Verhage, M.

    2003-01-01

    To investigate the role of neurotransmitter secretion in the development and stabilization of synapses, the innervation of the diaphragm and intercostal muscles was studied in munc18-1 null mutant mice, which lack regulated secretion. We found that this mutant is completely devoid of both

  7. Cholinergic regulation of the evoked quantal release at frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Nikolsky, E. E.; Vyskočil, František; Bukharaeva, E. A.; Samigullin, D.; Magazanik, L. G.

    2004-01-01

    Roč. 560, č. 1 (2004), s. 77-88 ISSN 0022-3751 R&D Projects: GA AV ČR IAA5011411; GA ČR GA305/02/1333 Institutional research plan: CEZ:AV0Z5011922 Keywords : acetylcholine * quantal * synapse Subject RIV: ED - Physiology Impact factor: 4.346, year: 2004

  8. Temperature effect on carbachol-induced depression of spontaneous quantal transmitter release in frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Strunsky, E. G.; Borisover, M. D.; Nikolsky, E. E.; Vyskočil, František

    2001-01-01

    Roč. 26, 8-9 (2001), s. 891-897 ISSN 0364-3190 R&D Projects: GA AV ČR IAA7011902; GA MŠk OK 267 Grant - others:RFBR(RU) 99-04-48286; EU(XX) Nesting Institutional research plan: CEZ:AV0Z5011922 Keywords : carbachol * temperature * acetylcholine release Subject RIV: ED - Physiology Impact factor: 1.638, year: 2001

  9. Calcium dependence of uni-quantal release latencies and quantal content at mouse neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Samigullin, D.; Bukharaeva, E. A.; Vyskočil, František; Nikolsky, E. E.

    2005-01-01

    Roč. 54, č. 1 (2005), s. 129-132 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA5011411; GA ČR(CZ) GA305/02/1333 Grant - others:RFBR(RU) 05-04-49723; Russian Science Support Foundation(RU) 1063.2003.4; GA-(RU) MK-2153.2003.04 Institutional research plan: CEZ:AV0Z50110509 Keywords : quantal release * synaptic latency * calcium Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  10. Possible mechanisms of action of Gymnodinium breve toxin at the mammalian neuromuscular junction.

    Science.gov (United States)

    Shinnick-Gallagher, P.

    1980-01-01

    1 The mechanism of action of a crude fraction of Gymnodinium breve toxin (GBTX) was investigated by intracellular recording techniques in the rat phrenic nerve diaphragm preparation. 2 GBTX (2 micrograms/ml) decreased the input resistance of the muscle membrane concomitantly with a depolarization of the resting membrane potential. 3 A low sodium solution reversed or prevented a GBTX-induced membrane depolarization. 4 Tetrodotoxin (TTX) antagonized a GBTX-induced increase in miniature endplate potential (m.e.p.p.) frequency and repolarized a GBTX-depolarized membrane. Pretreatment with TTX prevented GBTX effects. 5 GBTX reversibly reduced depolarizations produced by bath applied acetylcholine (ACh). The membrane depolarization was not responsible for the depression of ACh responses. 6 These findings suggest that GBTX increases m.e.p.p. frequency and depolarizes the resting membrane potential by increasing sodium permeability. The reduction of ACh-induced depolarizations suggests that GBTX may be acting at some site on the ACh receptor. PMID:7190452

  11. Interaction of glutamate- and adenosine-induced decrease of acetylcholine quantal release at frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Adámek, S.; Shakirzyanova, V.; Malomouzh, A. I.; Naumenko, N. V.; Vyskočil, František

    2010-01-01

    Roč. 59, č. 5 (2010), s. 803-810 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905; GA ČR GA202/09/0806 Institutional research plan: CEZ:AV0Z50110509 Keywords : Endplate potentials * Guanylyl cyclase Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  12. Glutamate regulation of non-quantal release of acetylcholine in the rat neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Malomouzh, A. I.; Mukhtarov, M. R.; Nikolsky, E. E.; Vyskočil, František; Lieberman, E. M.; Urazaev, A. K.

    2003-01-01

    Roč. 85, č. 1 (2003), s. 206-213 ISSN 0022-3042 R&D Projects: GA AV ČR IAA7011902; GA ČR GA305/02/1333; GA ČR GA202/02/1213 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100003 Keywords : muscle endplate * nitric oxide * N-methyl-D-aspartate receptor Subject RIV: CG - Electrochemistry Impact factor: 4.825, year: 2003

  13. The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat.

    Science.gov (United States)

    Amir, I; Harris, J B; Zar, M A

    1997-06-01

    Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (< 10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types-clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.

  14. Josephson junctions array resonators

    Energy Technology Data Exchange (ETDEWEB)

    Gargiulo, Oscar; Muppalla, Phani; Mirzaei, Iman; Kirchmair, Gerhard [Institute for Quantum Optics and Quantum Information, Innsbruck (Austria)

    2016-07-01

    We present an experimental analysis of the self- and cross-Kerr effect of extended plasma resonances in Josephson junction chains. The chain consists of 1600 individual junctions and we can measure quality factors in excess of 10000. The Kerr effect manifests itself as a frequency shift that depends linearly on the number of photons in a resonant mode. By changing the input power we are able to measure this frequency shift on a single mode (self-kerr). By changing the input power on another mode while measuring the same one, we are able to evaluate the cross-kerr effect. We can measure the cross-Kerr effect by probing the resonance frequency of one mode while exciting another mode of the array with a microwave drive.

  15. Curved Josephson junction

    International Nuclear Information System (INIS)

    Dobrowolski, Tomasz

    2012-01-01

    The constant curvature one and quasi-one dimensional Josephson junction is considered. On the base of Maxwell equations, the sine–Gordon equation that describes an influence of curvature on the kink motion was obtained. It is showed that the method of geometrical reduction of the sine–Gordon model from three to lower dimensional manifold leads to an identical form of the sine–Gordon equation. - Highlights: ► The research on dynamics of the phase in a curved Josephson junction is performed. ► The geometrical reduction is applied to the sine–Gordon model. ► The results of geometrical reduction and the fundamental research are compared.

  16. Soundscapes and Larval Settlement: Characterizing the Stimulus from a Larval Perspective.

    Science.gov (United States)

    Lillis, Ashlee; Eggleston, David B; Bohnenstiehl, DelWayne R

    2016-01-01

    There is growing evidence that underwater sounds serve as a cue for the larvae of marine organisms to locate suitable settlement habitats; however, the relevant spatiotemporal scales of variability in habitat-related sounds and how this variation scales with larval settlement processes remain largely uncharacterized, particularly in estuarine habitats. Here, we provide an overview of the approaches we have developed to characterize an estuarine soundscape as it relates to larval processes, and a conceptual framework is provided for how habitat-related sounds may influence larval settlement, using oyster reef soundscapes as an example.

  17. Genetic diversity, classification and comparative study on the larval ...

    African Journals Online (AJOL)

    Genetic diversity, classification and comparative study on the larval phenotypic ... B. mori showed different performance based on larval phenotypic data. The analysis of variance regarding the studied traits showed that different strains have ...

  18. Biophysical models of larval dispersal in the Benguela Current ...

    African Journals Online (AJOL)

    We synthesise and update results from the suite of biophysical, larval-dispersal models developed in the Benguela Current ecosystem. Biophysical models of larval dispersal use outputs of physical hydrodynamic models as inputs to individual-based models in which biological processes acting during the larval life are ...

  19. Neuromuscular blockade in cardiac surgery: An update for clinicians

    Directory of Open Access Journals (Sweden)

    Hemmerling Thomas

    2008-01-01

    Full Text Available There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

  20. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never...... been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render 3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus...

  1. Tight junctions and human diseases.

    Science.gov (United States)

    Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

    2003-09-01

    Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

  2. Gap junctions and motor behavior

    DEFF Research Database (Denmark)

    Kiehn, Ole; Tresch, Matthew C.

    2002-01-01

    The production of any motor behavior requires coordinated activity in motor neurons and premotor networks. In vertebrates, this coordination is often assumed to take place through chemical synapses. Here we review recent data suggesting that electrical gap-junction coupling plays an important role...... in coordinating and generating motor outputs in embryonic and early postnatal life. Considering the recent demonstration of a prevalent expression of gap-junction proteins and gap-junction structures in the adult mammalian spinal cord, we suggest that neuronal gap-junction coupling might also contribute...... to the production of motor behavior in adult mammals....

  3. [The hip joint in neuromuscular disorders].

    Science.gov (United States)

    Strobl, W M

    2009-07-01

    Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

  4. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  5. The role of proprioception and neuromuscular stability in carpal instabilities.

    Science.gov (United States)

    Hagert, E; Lluch, A; Rein, S

    2016-01-01

    Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

  6. Effects of napping on neuromuscular fatigue in myasthenia gravis.

    Science.gov (United States)

    Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

    2013-11-01

    The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

  7. Junction detection and pathway selection

    Science.gov (United States)

    Peck, Alex N.; Lim, Willie Y.; Breul, Harry T.

    1992-02-01

    The ability to detect junctions and make choices among the possible pathways is important for autonomous navigation. In our script-based navigation approach where a journey is specified as a script of high-level instructions, actions are frequently referenced to junctions, e.g., `turn left at the intersection.' In order for the robot to carry out these kind of instructions, it must be able (1) to detect an intersection (i.e., an intersection of pathways), (2) know that there are several possible pathways it can take, and (3) pick the pathway consistent with the high level instruction. In this paper we describe our implementation of the ability to detect junctions in an indoor environment, such as corners, T-junctions and intersections, using sonar. Our approach uses a combination of partial scan of the local environment and recognition of sonar signatures of certain features of the junctions. In the case where the environment is known, we use additional sensor information (such as compass bearings) to help recognize the specific junction. In general, once a junction is detected and its type known, the number of possible pathways can be deduced and the correct pathway selected. Then the appropriate behavior for negotiating the junction is activated.

  8. Mixing in T-junctions

    NARCIS (Netherlands)

    Kok, Jacobus B.W.; van der Wal, S.

    1996-01-01

    The transport processes that are involved in the mixing of two gases in a T-junction mixer are investigated. The turbulent flow field is calculated for the T-junction with the k- turbulence model by FLOW3D. In the mathematical model the transport of species is described with a mixture fraction

  9. Dynamics of Josephson junction arrays

    International Nuclear Information System (INIS)

    Hadley, P.

    1989-01-01

    The dynamics of Josephson junction arrays is a topic that lies at the intersection of the fields of nonlinear dynamics and Josephson junction technology. The series arrays considered here consist of several rapidly oscillating Josephson junctions where each junction is coupled equally to every other junction. The purpose of this study is to understand phaselocking and other cooperative dynamics of this system. Previously, little was known about high dimensional nonlinear systems of this sort. Numerical simulations are used to study the dynamics of these arrays. Three distinct types of periodic solutions to the array equations were observed as well as period doubled and chaotic solutions. One of the periodic solutions is the symmetric, in-phase solution where all of the junctions oscillate identically. The other two periodic solutions are symmetry-broken solutions where all of the junction do not oscillate identically. The symmetry-broken solutions are highly degenerate. As many as (N - 1) stable solutions can coexist for an array of N junctions. Understanding the stability of these several solutions and the transitions among them is vital to the design of useful devices

  10. Neuromuscular fatigue and recovery profiles in individuals with intellectual disability

    OpenAIRE

    Borji , Rihab; Zghal , Firas; Zarrouk , Nidhal; Martin , Vincent; Sahli , Sonia; Rebai , Haithem

    2017-01-01

    International audience; Purpose: This study aimed to explore neuromuscular fatigue and recovery profiles in individuals with intellectual disability (ID) after exhausting submaximal contraction.Methods: Ten men with ID were compared to 10 men without ID. The evaluation of neuromuscular function consisted in brief (3 s) isometric maximal voluntary contraction (IMVC) of the knee extension superimposed with electrical nerve stimulation before, immediately after, and during 33 min after an exhaus...

  11. Effect of massing on larval growth rate.

    Science.gov (United States)

    Johnson, Aidan P; Wallman, James F

    2014-08-01

    Estimation of minimum postmortem interval commonly relies on predicting the age of blowfly larvae based on their size and an estimate of the temperatures to which they have been exposed throughout their development. The majority of larval growth rate data have been developed using small larval masses in order to avoid excess heat generation. The current study collected growth rate data for larvae at different mass volumes, and assessed the temperature production of these masses, for two forensically important blow fly species, Chrysomya rufifacies and Calliphora vicina. The growth rate of larvae in a small mass, exposed to the higher temperatures equivalent to those experienced by large masses, was also assessed to determine if observed differences were due to the known temperature effects of maggot masses. The results showed that temperature production increased with increasing mass volume, with temperature increases of 11 °C observed in the large Ch. rufifacies masses and increases of 5 °C in the large C. vicina masses. Similarly, the growth rate of the larvae was affected by mass size. The larvae from small masses grown at the higher temperatures experienced by large masses displayed an initial delay in growth, but then grew at a similar rate to those larvae at a constant 23 °C. Since these larvae from masses of equivalent sizes displayed similar patterns of growth rate, despite differing temperatures, and these growth rates differed from larger masses exposed to the same temperatures, it can be concluded that larval growth rate within a mass may be affected by additional factors other than temperature. Overall, this study highlights the importance of understanding the role of massing in larval development and provides initial developmental data for mass sizes of two forensically important blowfly species commonly encountered in Australian forensic casework. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.

    Science.gov (United States)

    Tenforde, Adam S; Shull, Pete B; Fredericson, Michael

    2012-05-01

    Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Granulomatous responses in larval taeniid infections.

    Science.gov (United States)

    Díaz, Á; Sagasti, C; Casaravilla, C

    2018-05-01

    Granulomas are responses to persistent nonliving bodies or pathogens, centrally featuring specialized macrophage forms called epithelioid and multinucleated giant cells. The larval stages of the cestode parasites of the Taeniidae family (Taenia, Echinococcus) develop for years in fixed tissue sites in mammals. In consequence, they are targets of granulomatous responses. The information on tissue responses to larval taeniids is fragmented among host and parasite species and scattered over many decades. We attempt to draw an integrated picture of these responses in solid tissues. The intensity of inflammation around live parasites spans a spectrum from minimal to high, parasite vitality correlating with low inflammation. The low end of the inflammatory spectrum features collagen capsules proximal to the parasites and moderate distal infiltration. The middle of the spectrum is dominated by classical granulomatous responses, whereas the high end features massive eosinophil invasions. Across the range of parasite species, much observational evidence suggests that eosinophils are highly effective at killing larval taeniids in solid tissues, before and during chronic granulomatous responses. The evidence available also suggests that these parasites are adapted to inhibit host granulomatous responses, in part through the exacerbation of host regulatory mechanisms including regulatory T cells and TGF-β. © 2018 John Wiley & Sons Ltd.

  14. The neuromuscular differential diagnosis of joint hypermobility.

    Science.gov (United States)

    Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

    2015-03-01

    Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. © 2015 Wiley Periodicals, Inc.

  15. Assessment of Motor Units in Neuromuscular Disease.

    Science.gov (United States)

    Henderson, Robert D; McCombe, Pamela A

    2017-01-01

    The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an effective biomarker for assessing disease progression and for use in clinical trials in amyotrophic lateral sclerosis has stimulated the study of methods to measure the number of motor units. Since 1970 a number of different methods, including the incremental, F-wave, multipoint, and statistical methods, have been developed but none has achieved widespread applicability. Two methods (MUNIX and the multipoint incremental method) are in current use across multiple centres and are discussed in detail in this review, together with other recently published methods. Imaging with magnetic resonance and ultrasound is increasingly being applied to this area. Motor unit number estimates have also been applied to other neuromuscular diseases such as spinal muscular atrophy, compression neuropathies, and prior poliomyelitis. The need for an objective measure for the assessment of motor units remains tantalizingly close but unfulfilled in 2016.

  16. Neuromuscular dentistry: Occlusal diseases and posture.

    Science.gov (United States)

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture.

  17. Neuromuscular Fatigue During 200 M Breaststroke

    Directory of Open Access Journals (Sweden)

    Ana Conceição

    2014-03-01

    Full Text Available The aims of this study were: i to analyze activation patterns of four upper limb muscles (duration of the active and non-active phase in each lap of 200m breaststroke, ii quantify neuromuscular fatigue, with kinematics and physiologic assessment. Surface electromyogram was collected for the biceps brachii, deltoid anterior, pectoralis major and triceps brachii of nine male swimmers performing a maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the 1st to the 3rd lap. SR increased on the 4th lap (35.91 ± 2.99 stroke·min-1. Peak blood lactate was 13.02 ± 1.72 mmol·l-1 three minutes after the maximal trial. The EMG average rectified value (ARV increased at the end of the race for all selected muscles, but the deltoid anterior and pectoralis major in the 1st lap and for biceps brachii, deltoid anterior and triceps brachii in the 4th lap. The mean frequency of the power spectral density (MNF decreased at the 4th lap for all muscles. These findings suggest the occurrence of fatigue at the beginning of the 2nd lap in the 200m breaststroke trial, characterized by changes in kinematic parameters and selective changes in upper limb muscle action. There was a trend towards a non-linear fatigue state.

  18. Stem cell route to neuromuscular therapies.

    Science.gov (United States)

    Partridge, Terence A

    2003-02-01

    As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body-wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology.

  19. Fish larval transport in the coastal waters through ecological modelling

    Digital Repository Service at National Institute of Oceanography (India)

    George, G.

    are as follows: (i) to find out the influence of environmental parameters on the biology of the given ecosystem (ii) to track larval transport and biological abundance in relation to environmental vari- ables (iii) to compare biological abundance and fish larval... include the following investigations: (i) analysis of satellite chlorophyll data along the southwest coastal waters of India to derive a biological calender for sardine (ii) tracking the larval survival and establish a link between food and sardine inter...

  20. Evaluating sampling strategies for larval cisco (Coregonus artedi)

    Science.gov (United States)

    Myers, J.T.; Stockwell, J.D.; Yule, D.L.; Black, J.A.

    2008-01-01

    To improve our ability to assess larval cisco (Coregonus artedi) populations in Lake Superior, we conducted a study to compare several sampling strategies. First, we compared density estimates of larval cisco concurrently captured in surface waters with a 2 x 1-m paired neuston net and a 0.5-m (diameter) conical net. Density estimates obtained from the two gear types were not significantly different, suggesting that the conical net is a reasonable alternative to the more cumbersome and costly neuston net. Next, we assessed the effect of tow pattern (sinusoidal versus straight tows) to examine if propeller wash affected larval density. We found no effect of propeller wash on the catchability of larval cisco. Given the availability of global positioning systems, we recommend sampling larval cisco using straight tows to simplify protocols and facilitate straightforward measurements of volume filtered. Finally, we investigated potential trends in larval cisco density estimates by sampling four time periods during the light period of a day at individual sites. Our results indicate no significant trends in larval density estimates during the day. We conclude estimates of larval cisco density across space are not confounded by time at a daily timescale. Well-designed, cost effective surveys of larval cisco abundance will help to further our understanding of this important Great Lakes forage species.

  1. Turbulence-enhanced prey encounter rates in larval fish : Effects of spatial scale, larval behaviour and size

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; MacKenzie, Brian

    1995-01-01

    Turbulent water motion has several effects on the feeding ecology of larval fish and other planktivorous predators. In this paper, we consider the appropriate spatial scales for estimating relative velocities between larval fish predators and their prey, and the effect that different choices of s...... in the range in which turbulent intensity has an overall positive effect on larval fish ingestion rate probability. However, experimental data to test the model predictions are lacking. We suggest that the model inputs require further empirical study....

  2. Adaptive locomotor behavior in larval zebrafish.

    Science.gov (United States)

    Portugues, Ruben; Engert, Florian

    2011-01-01

    In this study we report that larval zebrafish display adaptive locomotor output that can be driven by unexpected visual feedback. We develop a new assay that addresses visuomotor integration in restrained larval zebrafish. The assay involves a closed-loop environment in which the visual feedback a larva receives depends on its own motor output in a way that resembles freely swimming conditions. The experimenter can control the gain of this closed feedback loop, so that following a given motor output the larva experiences more or less visual feedback depending on whether the gain is high or low. We show that increases and decreases in this gain setting result in adaptive changes in behavior that lead to a generalized decrease or increase of motor output, respectively. Our behavioral analysis shows that both the duration and tail beat frequency of individual swim bouts can be modified, as well as the frequency with which bouts are elicited. These changes can be implemented rapidly, following an exposure to a new gain of just 175 ms. In addition, modifications in some behavioral parameters accumulate over tens of seconds and effects last for at least 30 s from trial to trial. These results suggest that larvae establish an internal representation of the visual feedback expected from a given motor output and that the behavioral modifications are driven by an error signal that arises from the discrepancy between this expectation and the actual visual feedback. The assay we develop presents a unique possibility for studying visuomotor integration using imaging techniques available in the larval zebrafish.

  3. Instabilities in thin tunnel junctions

    International Nuclear Information System (INIS)

    Konkin, M.K.; Adler, J.G.

    1978-01-01

    Tunnel junctions prepared for inelastic electron tunneling spectroscopy are often plagued by instabilities in the 0-500-meV range. This paper relates the bias at which the instability occurs to the barrier thickness

  4. The Control of Junction Flows

    National Research Council Canada - National Science Library

    Smith, Charles

    1997-01-01

    An experimental study of the effects of spatially-limited (i.e. localized) surface suction on unsteady laminar and turbulent junction flows was performed using hydrogen bubble flow visualization and Particle Image Velocimetry (PIV...

  5. Microhabitat influence on larval fish assemblages within ...

    Science.gov (United States)

    We examined larval and juvenile fish assemblage structure in relation to microhabitat variables within the St. Louis River estuary, a drowned river mouth of Lake Superior. Fish were sampled in vegetated beds throughout the estuary, across a gradient of vegetation types and densities (including disturbed, preserved and post-restoration sites). Canonical correspondence analysis, relating species abundances to environmental variables revealed that plant species richness, turbidity and aquatic plant cover were most influential in structuring assemblages. Results from this microhabitat analysis at this crucial life stage has potential to inform wetland restoration efforts within the St. Louis River and other Great Lake coastal wetlands. not applicable

  6. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    Science.gov (United States)

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Josephson junctions with ferromagnetic interlayer

    International Nuclear Information System (INIS)

    Wild, Georg Hermann

    2012-01-01

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO x /Pd 0.82 Ni 0.18 /Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to π-coupling is observed for a thickness d F =6 nm of the ferromagnetic Pd 0.82 Ni 0.18 interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd 0.82 Ni 0.18 has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  8. Josephson junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Georg Hermann

    2012-03-04

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO{sub x}/Pd{sub 0.82}Ni{sub 0.18}/Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to {pi}-coupling is observed for a thickness d{sub F}=6 nm of the ferromagnetic Pd{sub 0.82}Ni{sub 0.18} interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd{sub 0.82}Ni{sub 0.18} has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  9. Electronic thermometry in tunable tunnel junction

    Science.gov (United States)

    Maksymovych, Petro

    2016-03-15

    A tunable tunnel junction thermometry circuit includes a variable width tunnel junction between a test object and a probe. The junction width is varied and a change in thermovoltage across the junction with respect to the change in distance across the junction is determined. Also, a change in biased current with respect to a change in distance across the junction is determined. A temperature gradient across the junction is determined based on a mathematical relationship between the temperature gradient, the change in thermovoltage with respect to distance and the change in biased current with respect to distance. Thermovoltage may be measured by nullifying a thermoelectric tunneling current with an applied voltage supply level. A piezoelectric actuator may modulate the probe, and thus the junction width, to vary thermovoltage and biased current across the junction. Lock-in amplifiers measure the derivatives of the thermovoltage and biased current modulated by varying junction width.

  10. Peltier cooling in molecular junctions

    Science.gov (United States)

    Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

    2018-02-01

    The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

  11. Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

    DEFF Research Database (Denmark)

    Viby-Mogensen, J.; Østergaard, D.; Donati, F.

    2000-01-01

    Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

  12. Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

  13. Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

    Directory of Open Access Journals (Sweden)

    Andreas Totzeck

    2016-09-01

    Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

  14. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade

    DEFF Research Database (Denmark)

    Brueckmann, B; Sasaki, N; Grobara, P

    2015-01-01

    BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed...... by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual...... measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch® SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P

  15. Total hip arthroplasty in patients with neuromuscular imbalance.

    Science.gov (United States)

    Konan, S; Duncan, C P

    2018-01-01

    Patients with neuromuscular imbalance who require total hip arthroplasty (THA) present particular technical problems due to altered anatomy, abnormal bone stock, muscular imbalance and problems of rehabilitation. In this systematic review, we studied articles dealing with THA in patients with neuromuscular imbalance, published before April 2017. We recorded the demographics of the patients and the type of neuromuscular pathology, the indication for surgery, surgical approach, concomitant soft-tissue releases, the type of implant and bearing, pain and functional outcome as well as complications and survival. Recent advances in THA technology allow for successful outcomes in these patients. Our review suggests excellent benefits for pain relief and good functional outcome might be expected with a modest risk of complication. Cite this article: Bone Joint J 2018;100-B(1 Supple A):17-21. ©2018 The British Editorial Society of Bone & Joint Surgery.

  16. Surgical Space Conditions During Low-Pressure Laparoscopic Cholecystectomy with Deep Versus Moderate Neuromuscular Blockade

    DEFF Research Database (Denmark)

    Staehr-Rye, Anne K; Rasmussen, Lars S.; Rosenberg, Jacob

    2014-01-01

    : In this assessor-blinded study, 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade (rocuronium bolus plus infusion maintaining a posttetanic count 0-1) or moderate neuromuscular blockade...... (rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function). Patients received anesthesia with propofol, remifentanil, and rocuronium. The primary outcome was the proportion of procedures with optimal surgical space conditions (assessed by the surgeon...

  17. Reduced larval feeding rate is a strong evolutionary correlate of ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 85; Issue 3. Reduced larval feeding rate is a strong evolutionary correlate of rapid development in Drosophila melanogaster. M. Rajamani N. Raghavendra ... Keywords. life-history evolution; development time; larval feeding rate; competition; tradeoffs; Drosophila melanogaster.

  18. The larval development of the red mangrove crab Sesarma meinerti ...

    African Journals Online (AJOL)

    The larval stages of the red mangrove crab Sesarma meinerti de Man were reared in the laboratory. Larval development consists of five zoeal stages and one megalopa. Zoeal development lasts an average of 25 days at 25°C. The external morphology of larvae is described in detail and their relationship with larvae of.

  19. Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

    Science.gov (United States)

    Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

    2008-11-15

    We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

  20. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John

    2016-01-01

    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...

  1. New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

    Institute of Scientific and Technical Information of China (English)

    Charles H Knowles; Joanne E Martin

    2009-01-01

    Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

  2. Neuromuscular exercise as treatment of degenerative knee disease

    DEFF Research Database (Denmark)

    Ageberg, Eva; Roos, Ewa M.

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional...... instability associated with the degenerative knee disease than traditionally used training methods.SUMMARY FOR TABLE OF CONTENTS PAGECurrent data suggests that the effect from neuromuscular exercise on pain and function is comparable to the effects seen from other forms of exercise....

  3. Neuromuscular Activity and Knee Kinematics in Adolescents with Patellofemoral Pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Samani, Afshin; Olesen, Jens L

    2013-01-01

    This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS).......This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)....

  4. Relative Roles of Gap Junction Channels and Cytoplasm in Cell-to-Cell Diffusion of Fluorescent Tracers

    Science.gov (United States)

    Safranyos, Richard G. A.; Caveney, Stanley; Miller, James G.; Petersen, Nils O.

    1987-04-01

    Intercellular (tissue) diffusion of molecules requires cytoplasmic diffusion and diffusion through gap junctional (or cell-to-cell) channels. The rates of tissue and cytoplasmic diffusion of fluorescent tracers, expressed as an effective diffusion coefficient, De, and a cytoplasmic diffusion coefficient, Dcyt, have been measured among the developing epidermal cells of a larval beetle, Tenebrio molitor L., to determine the contribution of the junctional channels to intercellular diffusion. Tracer diffusion was measured by injecting fluorescent tracers into cells and quantitating the rate of subsequent spread into adjacent cells. Cytoplasmic diffusion was determined by fluorescence photobleaching. These experiments show that gap junctional channels constitute approximately 70-80% of the total cell-to-cell resistance to the diffusion of organic tracers at high concentrations in this tissue. At low concentrations, however, the binding of tracer to cytoplasm slows down the cytoplasmic diffusion, which may limit intercellular diffusion.

  5. Blocking p75 (NTR) receptors alters polyinnervationz of neuromuscular synapses during development.

    Science.gov (United States)

    Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

    2011-09-01

    High-resolution immunohistochemistry shows that the receptor protein p75(NTR) is present in the nerve terminal, muscle cell, and glial Schwann cell at the neuromuscular junction (NMJ) of postnatal rats (P4-P6) during the synapse elimination period. Blocking the receptor with the antibody anti-p75-192-IgG (1-5 μg/ml, 1 hr) results in reduced endplate potentials (EPPs) in mono- and polyinnervated synapses ex vivo, but the mean number of functional inputs per NMJ does not change for as long as 3 hr. Incubation with exogenous brain-derived neurotrophic factor (BDNF) for 1 hr (50 nM) resulted in a significant increase in the size of the EPPs in all nerve terminals, and preincubation with anti-p75-192-IgG prevented this potentiation. Long exposure (24 hr) in vivo of the NMJs to the antibody anti-p75-192-IgG (1-2 μg/ml) results in a delay of postnatal synapse elimination and even some regrowth of previously withdrawn axons, but also in some acceleration of the morphologic maturation of the postsynaptic nicotinic acetylcholine receptor (nAChR) clusters. The results indicate that p75(NTR) is involved in both ACh release and axonal retraction during postnatal axonal competition and synapse elimination. Copyright © 2011 Wiley-Liss, Inc.

  6. The effect of ventilatory muscle training on respiratory function and capacity in ambulatory and bed-ridden patients with neuromuscular disease.

    Science.gov (United States)

    Gross, D; Meiner, Z

    1993-08-01

    Most patients with neuromuscular disease develop muscle weakness, including the ventilatory muscles leading to respiratory difficulty and, at times, respiratory insufficiency. We studied the effect of ventilatory muscle training on the ventilatory function and capacity of patients with various types of neuromuscular disease. The ambulatory patients were divided into three major groups. Group I (n = 6) patients with motor neuron disease (MND), such as amyotrophic latera sclerosis; Group II (n = 11) patients with myoneural junction disease (MNJ), such as myasthenia gravis and: Group III (n = 7) patients with muscle diseases such as progressive muscular disease. Patients were evaluated for their neuromuscular diagnosis and status of the disease. A complete physical examination and the various neuromuscular tests were performed. A complete respiratory evaluation was applied: pulmonary function tests (PFT), maximum inspiratory pressure (MIP). Patients then started ventilatory muscle training by resistive breathing, as a prophylactic treatment, for 10 min, three times daily, with a resistance which would induce fatigue. All tests were repeated every six weeks, and the results were as follow: forced vital capacity (FVC) changed from 38.8 +/- 12.3 to 53.2 +/- 9.6% (NS) of predicted value in group I, from 49.8 +/- 8.7 to 66.1 +/- 7.5% (p < 0.002) in group II, and from 47.0 +/- 7.5 to 53.3 +/- 7.6% (p < 0.04) in group III. Forced expiratory volume in one second (FEV1) was 34.8 +/- 11.0, 46.3 +/- 5, and 45.1 +/- 9% for the three groups, respectively, and did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

    Science.gov (United States)

    Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

    1999-01-01

    Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

  8. Transport properties of molecular junctions

    CERN Document Server

    Zimbovskaya, Natalya A

    2013-01-01

    A comprehensive overview of the physical mechanisms that control electron transport and the characteristics of metal-molecule-metal (MMM) junctions is presented. As far as possible, methods and formalisms presented elsewhere to analyze electron transport through molecules are avoided. This title introduces basic concepts—a description of the electron transport through molecular junctions—and briefly describes relevant experimental methods. Theoretical methods commonly used to analyze the electron transport through molecules are presented. Various effects that manifest in the electron transport through MMMs, as well as the basics of density-functional theory and its applications to electronic structure calculations in molecules are presented. Nanoelectronic applications of molecular junctions and similar systems are discussed as well. Molecular electronics is a diverse and rapidly growing field. Transport Properties of Molecular Junctions presents an up-to-date survey of the field suitable for researchers ...

  9. NbN tunnel junctions

    International Nuclear Information System (INIS)

    Villegier, J.C.; Vieux-Rochaz, L.; Goniche, M.; Renard, P.; Vabre, M.

    1984-09-01

    All-niobium nitride Josephon junctions have been prepared successfully using a new processing called SNOP: Selective Niobium (nitride) Overlap Process. Such a process involves the ''trilayer'' deposition on the whole wafer before selective patterning of the electrodes by optically controlled dry reactive ion etching. Only two photomask levels are need to define an ''overlap'' or a ''cross-type'' junction with a good accuracy. The properties of the niobium nitride films deposited by DC-magnetron sputtering and the surface oxide growth are analysed. The most critical point to obtain high quality and high gap value junctions resides in the early stage of the NbN counterelectrode growth. Some possibilities to overcome such a handicap exist even if the fabrication needs substrate temperatures below 250 0 C

  10. GROWTH AND BEHAVIOR OF LARVAL ZEBRAFISH Danio ...

    Science.gov (United States)

    Because Zebrafish (Danio rerio) have become a popular and important model for scientific research, the capability to rear larval zebrafish to adulthood is of great importance. Recently research examining the effects of diet (live versus processed) have been published. In the current study we examined whether the larvae can be reared on a processed diet alone, live food alone, or the combination while maintaining normal locomotor behavior, and acceptable survival, length and weight at 14 dpf in a static system. A 14 day feeding trial was conducted in glass crystallizing dishes containing 500 ml of 4 ppt Instant Ocean. On day 0 pdf 450 embryos were selected as potential study subjects and placed in a 26○C incubator on a 14:10 (light:dark) light cycle. At 4 dpf 120 normally developing embryos were selected per treatment and divided into 3 bowls of 40 embryos (for an n=3 per treatment; 9 bowls total). Treatment groups were: G (Gemma Micro 75 only), R (L-type marine rotifers (Brachionus plicatilis) only) or B (Gemma and rotifers). Growth (length), survival, water quality and rotifer density were monitored on days 5-14. On day 14, weight of larva in each bowl was measured and 8 larva per bowl were selected for use in locomotor testing. This behavior paradigm tests individual larval zebrafish under both light and dark conditions in a 24-well plate.After 14 dpf, survival among the groups was not different (92-98%). By days 7 -14 R and B larvae were ~2X longer

  11. Mosquito larval source management for controlling malaria

    Science.gov (United States)

    Tusting, Lucy S; Thwing, Julie; Sinclair, David; Fillinger, Ulrike; Gimnig, John; Bonner, Kimberly E; Bottomley, Christian; Lindsay, Steven W

    2015-01-01

    Background Malaria is an important cause of illness and death in people living in many parts of the world, especially sub-Saharan Africa. Long-lasting insecticide treated bed nets (LLINs) and indoor residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding). Objectives To evaluate the effectiveness of mosquito LSM for preventing malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS Abstracts; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles. Selection criteria We included cluster randomized controlled trials (cluster-RCTs), controlled before-and-after trials with at least one year of baseline data, and randomized cross-over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish. Data collection and analysis At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software

  12. Diagnostic value of CT scanning in neuromuscular diseases

    International Nuclear Information System (INIS)

    Bulcke, J.A.L.; Leuven Univ.; Herpels, V.

    1983-01-01

    The diagnosis of myopathies has become easier since the CT technique is available. In this article the possibilities of CT for diagnostic procedures of neuromuscular diseases are pointed out. Density measurements increase differentiation of atrophy or hypertrophy of muscles as well as other pathological changes. (orig.)

  13. Volume of the effect compartment in simulations of neuromuscular block

    NARCIS (Netherlands)

    Nigrovic, Vladimir; Proost, Johannes H.; Amann, Anton; Bhatt, Shashi B.

    2005-01-01

    Background: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. Methods: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent

  14. Neuromuscular stimulation after stroke: from technology to clinical deployment

    NARCIS (Netherlands)

    IJzerman, Maarten Joost; Renzenbrink, Gerbert J.; Geurts, Alexander C.H.

    2009-01-01

    Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades

  15. Elbow joint position sense after neuromuscular training with handheld vibration.

    Science.gov (United States)

    Tripp, Brady L; Faust, Donald; Jacobs, Patrick

    2009-01-01

    Clinicians use neuromuscular control exercises to enhance joint position sense (JPS); however, because standardizing such exercises is difficult, validations of their use are limited. To evaluate the acute effects of a neuromuscular training exercise with a handheld vibrating dumbbell on elbow JPS acuity. Crossover study. University athletic training research laboratory. Thirty-one healthy, college-aged volunteers (16 men, 15 women, age = 23 + or - 3 years, height = 173 + or - 8 cm, mass = 76 + or - 14 kg). We measured and trained elbow JPS using an electromagnetic tracking device that provided auditory and visual biofeedback. For JPS testing, participants held a dumbbell and actively identified the target elbow flexion angle (90 degrees ) using the software-generated biofeedback, followed by 3 repositioning trials without feedback. Each neuromuscular training protocol included 3 exercises during which participants held a 2.55-kg dumbbell vibrating at 15, 5, or 0 Hz and used software-generated biofeedback to locate and maintain the target elbow flexion angle for 15 seconds. We calculated absolute (accuracy) and variable (variability) errors using the differences between target and reproduced angles. Training protocols using 15-Hz vibration enhanced accuracy and decreased variability of elbow JPS (P or = .200). Our results suggest these neuromuscular control exercises, which included low-magnitude, low-frequency handheld vibration, may enhance elbow JPS. Future researchers should examine vibration of various durations and frequencies, should include injured participants and functional multijoint and multiplanar measures, and should examine long-term effects of training protocols on JPS and injury.

  16. Imaging of respiratory muscles in neuromuscular disease: A review.

    Science.gov (United States)

    Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

    2018-03-01

    Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

  17. Neuromuscular blockade for improvement of surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Scheppan, Susanne; Kissmeyer, Peter

    2015-01-01

    neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS...

  18. Neuromuscular Bandage: Neurophysiological Effects and the Role of Fascias

    Directory of Open Access Journals (Sweden)

    Ximena María Villota Chicaíza

    2014-05-01

    Full Text Available During the last years, neuromuscular bandage, a therapeutic application created in 1979 by doctor Kenzo Kase has been introduced in the management of many disorders of the musculo-skeletal system and even more so in the treatment of neurological disorders; This therapeutic tool which consists of a self adhesive elastic bandage allows recovery of the injured party without diminishing its bodily function. According to the existing literature on the physiological effects of this therapeutic application in the body, you could say that there is consensus. However in this article the author wants to highlight the significant although little highlighted role played by the fas¬cias on the therapeutic effects of neuromuscular bandage, analyzing from a reflective perspective the analgesic, neuromechanical and circulatory effects, as fundamental effects of neuromuscular bandage and fascias in the same function, trying to bring a global understanding on the way they relate to all connective tissues, aspects that are of great importance for the proper evaluation of alterations and prescription of neuromuscular bandage

  19. Alterations in neuromuscular function in girls with generalized joint hypermobility

    DEFF Research Database (Denmark)

    Jensen, Bente Rona; Melcher, Jesper Sandfeld; Melcher, Pia Grethe Sandfeld

    2016-01-01

    BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions...

  20. Influence of intense neuromuscular blockade on surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Donatsky, Anders Meller; Jensen, Bente Rona

    2015-01-01

    endotracheally intubated, mechanically ventilated, anesthetized with propofol and fentanyl, and randomized into two groups in a cross-over assessor-blinded design. Neuromuscular block was established with rocuronium. Artificial laparotomy for ileus was performed. We investigated the influence of intense...

  1. Neuromuscular function during stair descent in meniscectomized patients and controls

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Roos, Ewa M; Aagaard, Per

    2011-01-01

    The aim of this study was to identify differences in knee range of motion (ROM), movement speed, ground reaction forces (GRF) profile, neuromuscular activity, and muscle coactivation during the transition between stair descent and level walking in meniscectomized patients at high risk of knee...

  2. Comparison of the Effect of Neuromuscular Electrical Stimulation ...

    African Journals Online (AJOL)

    Children with cerebral palsy (CP) often demonstrate poor hand function due to spasticity. Thus spasticity in the wrist and finger flexors poses a great deal of functional limitations. This study was therefore designed to compare the effectiveness of Cryotherapy and Neuromuscular Electrical Stimulation (NMES) on spasticity ...

  3. Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

    Science.gov (United States)

    Ohlendieck, Kay

    2002-01-01

    This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

  4. Gravitation at the Josephson Junction

    Directory of Open Access Journals (Sweden)

    Victor Atanasov

    2018-01-01

    Full Text Available A geometric potential from the kinetic term of a constrained to a curved hyperplane of space-time quantum superconducting condensate is derived. An energy conservation relation involving the geometric field at every material point in the superconductor is demonstrated. At a Josephson junction the energy conservation relation implies the possibility of transforming electric energy into geometric field energy, that is, curvature of space-time. Experimental procedures to verify that the Josephson junction can act as a voltage-to-curvature converter are discussed.

  5. Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

    Science.gov (United States)

    de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

    1993-01-01

    To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

  6. Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

    Directory of Open Access Journals (Sweden)

    Alejandro Carbajal-Saucedo

    2014-01-01

    Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

  7. Stunted PFC activity during neuromuscular control under stress with obesity.

    Science.gov (United States)

    Mehta, Ranjana K

    2016-02-01

    Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

  8. Electronic noise of superconducting tunnel junction detectors

    International Nuclear Information System (INIS)

    Jochum, J.; Kraus, H.; Gutsche, M.; Kemmather, B.; Feilitzsch, F. v.; Moessbauer, R.L.

    1994-01-01

    The optimal signal to noise ratio for detectors based on superconducting tunnel junctions is calculated and compared for the cases of a detector consisting of one single tunnel junction, as well as of series and of parallel connections of such tunnel junctions. The influence of 1 / f noise and its dependence on the dynamical resistance of tunnel junctions is discussed quantitatively. A single tunnel junction yields the minimum equivalent noise charge. Such a tunnel junction exhibits the best signal to noise ratio if the signal charge is independent of detector size. In case, signal charge increases with detector size, a parallel or a series connection of tunnel junctions would provide the optimum signal to noise ratio. The equivalent noise charge and the respective signal to noise ratio are deduced as functions of tunnel junction parameters such as tunneling time, quasiparticle lifetime, etc. (orig.)

  9. Current noise in tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Frey, Moritz; Grabert, Hermann [Physikalisches Institut, Universitaet Freiburg, Hermann-Herder-Strasse 3, 79104, Freiburg (Germany)

    2017-06-15

    We study current fluctuations in tunnel junctions driven by a voltage source. The voltage is applied to the tunneling element via an impedance providing an electromagnetic environment of the junction. We use circuit theory to relate the fluctuations of the current flowing in the leads of the junction with the voltage fluctuations generated by the environmental impedance and the fluctuations of the tunneling current. The spectrum of current fluctuations is found to consist of three parts: a term arising from the environmental Johnson-Nyquist noise, a term due to the shot noise of the tunneling current and a third term describing the cross-correlation between these two noise sources. Our phenomenological theory reproduces previous results based on the Hamiltonian model for the dynamical Coulomb blockade and provides a simple understanding of the current fluctuation spectrum in terms of circuit theory and properties of the average current. Specific results are given for a tunnel junction driven through a resonator. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Effect of Hyperglycemia on Purinergic and Nitrergic Inhibitory Neuromuscular Transmission in the Antrum of the Stomach: Implications for Fast Gastric Emptying

    Directory of Open Access Journals (Sweden)

    Xue-Dao He

    2018-01-01

    Full Text Available BackgroundHyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO, at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. However, hyperglycemia has also been reported to cause fast gastric emptying that may be due to suppression of the inhibitory motor neurons.AimsThe purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia.MethodsInhibitory electrical junction potentials were recorded from gastric antral muscle strips, using intracellular electrodes under non-adrenergic, non-cholinergic conditions. Studies were performed in non-hyperglycemic NOD (NH-NOD, NOD mice as they develop hyperglycemia (H-NOD and their age-matched controls. The purinergic inhibitory junction potential (pIJP and nitrergic IJP (nIJP were isolated pharmacologically.ResultsThe control pIJP was large, around −18 mV and nIJP was small, around −9 mV. In NH-NOD the IJPs were not affected, but in H-NOD pIJP was nearly abolished and nIJP was significantly reduced. In H-NOD mice, membrane hyperpolarization caused by exogenous α,β-MeATP or diethylenetriamine NO adduct was similar to that in wild-type controls (P > 0.05. H-NOD smooth muscles were significantly depolarized as compared to NH-NOD smooth muscles.ConclusionThese observations show that hyperglycemia causes suppression of purinergic and nitrergic transmission by acting on the motor neurons that form the last neuron in the vagovagal circuit. Moreover, the loss the neurotransmission is due to a defect in neurotransmitter release rather than a defect in signal transduction. Hyperglycemia also causes depolarization of smooth muscles that may increase their excitability.

  11. Stability of large-area molecular junctions

    NARCIS (Netherlands)

    Akkerman, Hylke B.; Kronemeijer, Auke J.; Harkema, Jan; van Hal, Paul A.; Smits, Edsger C. P.; de Leeuw, Dago M.; Blom, Paul W. M.

    The stability of molecular junctions is crucial for any application of molecular electronics. Degradation of molecular junctions when exposed to ambient conditions is regularly observed. In this report the stability of large-area molecular junctions under ambient conditions for more than two years

  12. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current depe...

  13. Measurements and Counts for Larval and Juvenile Beryx Specimens

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Larval alfonsin (Beryx species) were collected in the vicinity of the Southeast Hancock Seamount. A three-net Tucker trawl (I m2 effective mouth opening and 0.333 mm...

  14. Larval diet affects mosquito development and permissiveness to Plasmodium infection

    OpenAIRE

    Gendrin, MEM; Christophides; Linenberg, Inbar

    2016-01-01

    The larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. Richness in the nutrient supply to larvae influences the development and metabolism of larvae and adults. Here, we investigated the effects of larval diet on the development, microbiota content and permissiveness to Plasmodium of Anopheles coluzzii . We tested three fish diets often used to rear mosquitoes in the laboratory, including two pelleted diets, Dr. Clar...

  15. Contributions for larval development optimization of Homarus gammarus

    Directory of Open Access Journals (Sweden)

    Pedro Tiago Fonseca Sá

    2014-06-01

    The seawater rising temperature resulted in a decrease of intermoult period in all larval development stages and at all tested temperatures, ranging from 4.77 (Z1 to 16.5 days (Z3 at 16°C, whereas at 23°C, ranged from 3:02 (Z1 and 9.75 days (Z3. The results obtained are an extremely useful guide for future optimization of protocols on larval development of H. gammarus.

  16. The role of patient advocacy organisations in neuromuscular disease R&D - The case of the Dutch neuromuscular disease association VSN

    NARCIS (Netherlands)

    Boon, W.P.C.; Broekgaarden, R.

    2010-01-01

    This article investigates to what extent patient advocacy organisations play a role in influencing R&D and policymaking for rare neuromuscular diseases. The Dutch neuromuscular disease organisation VSN is studied in depth. A brief history of the VSN is sketched along with the international

  17. Ferromagnetic Josephson Junctions for Cryogenic Memory

    Science.gov (United States)

    Niedzielski, Bethany M.; Gingrich, Eric C.; Khasawneh, Mazin A.; Loloee, Reza; Pratt, William P., Jr.; Birge, Norman O.

    2015-03-01

    Josephson junctions containing ferromagnetic materials are of interest for both scientific and technological purposes. In principle, either the amplitude of the critical current or superconducting phase shift across the junction can be controlled by the relative magnetization directions of the ferromagnetic layers in the junction. Our approach concentrates on phase control utilizing two junctions in a SQUID geometry. We will report on efforts to control the phase of junctions carrying either spin-singlet or spin-triplet supercurrent for cryogenic memory applications. Supported by Northorp Grumman Corporation and by IARPA under SPAWAR Contract N66001-12-C-2017.

  18. Method of manufacturing Josephson junction integrated circuits

    International Nuclear Information System (INIS)

    Jillie, D.W. Jr.; Smith, L.N.

    1985-01-01

    Josephson junction integrated circuits of the current injection type and magnetically controlled type utilize a superconductive layer that forms both Josephson junction electrode for the Josephson junction devices on the integrated circuit as well as a ground plane for the integrated circuit. Large area Josephson junctions are utilized for effecting contact to lower superconductive layers and islands are formed in superconductive layers to provide isolation between the groudplane function and the Josephson junction electrode function as well as to effect crossovers. A superconductor-barrier-superconductor trilayer patterned by local anodization is also utilized with additional layers formed thereover. Methods of manufacturing the embodiments of the invention are disclosed

  19. Helminths parasitizing larval fish from Pantanal, Brazil.

    Science.gov (United States)

    Lacerda, A C F; Santin, M; Takemoto, R M; Pavanelli, G C; Bialetzki, A; Tavernari, F C

    2009-03-01

    Fish larvae of 'corvinas' (Pachyurus bonariensis and Plagioscion ternetzi) from Sinhá Mariana Lagoon, Mato Grosso State, were collected from March 2000 to March 2004, in order to determine the parasitic fauna of fishes. Larvae from the two species were parasitized by the same endoparasites: Contracaecum sp. Type 2 (larvae) (Nematoda: Anisakidae) in the mesentery and Neoechinorhynchus (Neoechinorhynchus) paraguayensis (Acanthocephala: Neoechinorhynchidae) in the stomach and the terminal portion of the intestine. Statistical analysis showed that there was a significant positive correlation between the standard length of hosts and the abundance of acanthocephalans and nematodes, and that the prevalence of nematodes presented a significant positive correlation with the standard length of the two species of hosts, indicating the presence of a cumulative process of infection. The present study constitutes the first record of nematodes and acanthocephalans parasitizing larval fish, as well as the first record of endoparasites in fish larvae in Brazil. In addition, it lists a new locality and two species of hosts for Contracaecum sp. Type 2 (larva) and N. (N.) paraguayensis.

  20. Arrested larval development in cattle nematodes.

    Science.gov (United States)

    Armour, J; Duncan, M

    1987-06-01

    Most economically important cattle nematodes are able to arrest their larval development within the host - entering a period of dormancy or hypobiosis. Arrested larvae have a low death rate, and large numbers can accumulate in infected cattle during the grazing season. Because of this, outbreaks of disease caused by such nematodes can occur at times when recent infection with the parasites could not have occurred, for example during winter in temperature northern climates when cattle are normally housed. The capacity to arrest is a heritable trait. It is seen as an adaptation by the parasite to avoid further development to its free-living stages during times when the climate is unsuitable for free-living survival. But levels of arrestment can vary markedly in different regions, in different cattle, and under different management regimes. Climatic factors, previous conditioning, host immune status, and farm management all seem to affect arrestment levels. In this article, James Armour and Mary Duncan review the biological basis of the phenomenon, and discuss the apparently conflicting views on how it is controlled.

  1. Assessment of sampling mortality of larval fishes

    International Nuclear Information System (INIS)

    Cada, G.F.; Hergenrader, G.L.

    1978-01-01

    A study was initiated to assess the mortality of larval fishes that were entrained in the condenser cooling systems of two nuclear power plants on the Missouri River in Nebraska. High mortalities were observed not only in the discharge collections but also in control samples taken upriver from the plants where no entrainment effects were possible. As a result, entrainment mortality generally could not be demonstrated. A technique was developed which indicated that (1) a significant portion of the observed mortality above the power plants was the result of net-induced sampling mortality, and (2) a direct relationship existed between observed mortality and water velocity in the nets when sampling at the control sites, which was described by linear regression equations. When these equations were subsequently used to remove the effects of wide differences in sampling velocities between control and discharge collections, significant entrainment mortality was noted in all cases. The equations were also used to derive estimates of the natural mortality of ichthyoplankton in this portion of the Missouri River

  2. Molecular series-tunneling junctions.

    Science.gov (United States)

    Liao, Kung-Ching; Hsu, Liang-Yan; Bowers, Carleen M; Rabitz, Herschel; Whitesides, George M

    2015-05-13

    Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS) is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(-β1d1 - β2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.

  3. Sandeel ( Ammodytes marinus ) larval transport patterns in the North Sea from an individual-based hydrodynamic egg and larval model

    DEFF Research Database (Denmark)

    Christensen, Asbjørn; Jensen, Henrik; Mosegaard, Henrik

    2008-01-01

    We have calculated a time series of larval transport indices for the central and southern North Sea covering 1970-2004, using a combined three-dimensional hydrodynamic and individual-based modelling framework for studying sandeel (Ammodytes marinus) eggs, larval transport, and growth. The egg phase...... is modelled by a stochastic, nonlinear degree-day model describing the extended hatch period. The larval growth model is parameterized by individually back-tracking the local physical environment of larval survivors from their catch location and catch time. Using a detailed map of sandeel habitats...... analyzed, and we introduce novel a scheme to quantify direct and indirect connectivity on equal footings in terms of an interbank transit time scale....

  4. Flexible 2D layered material junctions

    Science.gov (United States)

    Balabai, R.; Solomenko, A.

    2018-03-01

    Within the framework of the methods of the electron density functional and the ab initio pseudopotential, we have obtained the valence electron density spatial distribution, the densities of electron states, the widths of band gaps, the charges on combined regions, and the Coulomb potentials for graphene-based flexible 2D layered junctions, using author program complex. It is determined that the bending of the 2D layered junctions on the angle α leads to changes in the electronic properties of these junctions. In the graphene/graphane junction, there is clear charge redistribution with different signs in the regions of junctions. The presence in the heterojunctions of charge regions with different signs leads to the formation of potential barriers. The greatest potential jump is in the graphene/fluorographene junction. The greatest value of the band gap width is in the graphene/graphane junction.

  5. Learning disabilities in neuromuscular disorders: a springboard for adult life.

    Science.gov (United States)

    Astrea, Guja; Battini, Roberta; Lenzi, Sara; Frosini, Silvia; Bonetti, Silvia; Moretti, Elena; Perazza, Silvia; Santorelli, Filippo M; Pecini, Chiara

    2016-10-01

    Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

  6. Neuromuscular deficits after peripheral joint injury: a neurophysiological hypothesis.

    Science.gov (United States)

    Ward, Sarah; Pearce, Alan J; Pietrosimone, Brian; Bennell, Kim; Clark, Ross; Bryant, Adam L

    2015-03-01

    In addition to biomechanical disturbances, peripheral joint injuries (PJIs) can also result in chronic neuromuscular alterations due in part to loss of mechanoreceptor-mediated afferent feedback. An emerging perspective is that PJI should be viewed as a neurophysiological dysfunction, not simply a local injury. Neurophysiological and neuroimaging studies have provided some evidence for central nervous system (CNS) reorganization at both the cortical and spinal levels after PJI. The novel hypothesis proposed is that CNS reorganization is the underlying mechanism for persisting neuromuscular deficits after injury, particularly muscle weakness. There is a lack of direct evidence to support this hypothesis, but future studies utilizing force-matching tasks with superimposed transcranial magnetic stimulation may be help clarify this notion. © 2014 Wiley Periodicals, Inc.

  7. Early appearance and possible roles of non-neuromuscular cholinesterases.

    Directory of Open Access Journals (Sweden)

    Carla eFalugi

    2012-04-01

    Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

  8. Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

    Science.gov (United States)

    Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

    1999-06-01

    Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

  9. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    Science.gov (United States)

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  10. Bloqueio neuromuscular residual após o uso de rocurônio ou cisatracúrio Bloqueo neuromuscular residual después del uso de rocuronio o cisatracúrio Residual neuromuscular block after rocuronium or cisatracurium

    Directory of Open Access Journals (Sweden)

    Bruno Salomé de Morais

    2005-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio neuromuscular residual na sala de recuperação pós-anestésica (SRPA é um fenômeno que pode aumentar a morbidade pós-operatória, com incidência variando entre 0% e 93%. O objetivo deste estudo foi avaliar a incidência do bloqueio neuromuscular residual na SRPA. MÉTODO: Foram estudados 93 pacientes submetidos à cirurgia geral com o uso de cisatracúrio ou rocurônio. Após a admissão na SRPA foi realizada a monitorização objetiva da função neuromuscular (aceleromiografia - TOF GUARD. O bloqueio neuromuscular residual foi definido como SQE JUSTIFICATIVA Y OBJETIVOS: El bloqueo neuromuscular residual en la sala de recuperación posanestésica (SRPA es un fenómeno que puede aumentar la morbidez posoperatoria, con incidencia variando entre 0% y 93%. La finalidad de este estudio fue evaluar la incidencia del bloqueo neuromuscular residual en la SRPA. MÉTODO: Fueron estudiados 93 pacientes sometidos a cirugía general con el uso de cisatracúrio o rocuronio. Después de la admisión en la SRPA fue realizada la monitorización objetiva de la función neuromuscular (aceleromiografia - TOF-GUARD. El bloqueo neuromuscular residual fue definido como TOF BACKGROUND AND OBJECTIVES: Residual neuromuscular block in the post-anesthetic recovery unit (PACU may increase postoperative morbidity from 0% to 93%. This study aimed at evaluating the incidence of residual neuromuscular block in the PACU. METHODS: Participated in this study 93 patients submitted to general anesthesia with cisatracurium or rocuronium. After PACU admission, neuromuscular function was objectively monitored (acceleromyography - TOF GUARD. Residual neuromuscular block was defined as TOF < 0.9. RESULTS: From 93 patients, 53 received cisatracurium and 40 rocuronium. Demographics, procedure length and the use of antagonists were comparable between groups. Residual neuromuscular block was 32% in subgroup C (cisatracurium and 30% in subgroup R

  11. Report on Adaptive Force, a specific neuromuscular function

    Directory of Open Access Journals (Sweden)

    Marko Hoff

    2015-08-01

    Full Text Available In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1 What is the peculiarity of this neuromuscular function, introduced as AF? 2 Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3 It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects’ option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso, the maximal isometric Adaptive Force (AFisomax and the maximal eccentric Adaptive Force (AFeccmax. Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities.

  12. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

  13. Neuromuscular Control of Rapid Linear Accelerations in Fish

    Science.gov (United States)

    2016-06-22

    sunfish, Lepomis macrochirus. Animals with flexible bodies, like fishes , face a tradeoff for rapid movements. To produce high forces, they must...2014 30-Apr-2015 Approved for Public Release; Distribution Unlimited Final Report: Neuromuscular Control of Rapid Linear Accelerations in Fish The...Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 swimming, acceleration, fish , muscle, stiffness REPORT DOCUMENTATION PAGE 11. SPONSOR

  14. Computed tomography of skeletal muscles in neuromuscular disease

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Kuether, G.; Muenchen Univ.

    1985-01-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions. (orig.) [de

  15. Computed tomography of skeletal muscles in neuromuscular disease

    Energy Technology Data Exchange (ETDEWEB)

    Rodiek, S.O.; Kuether, G.

    1985-06-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

  16. Josephson junctions and circle maps

    Energy Technology Data Exchange (ETDEWEB)

    Bak, P; Bohr, T; Jensen, M H; Christiansen, P V

    1984-01-01

    The return map of a differential equation for the current driven Josephson junction, or the damped driven pendulum, is shown numerically to be a circle map. Phase locking, noise and hysteresis, can thus be understood in a simple and coherent way. The transition to chaos is related to the development of a cubic inflection point. Recent theoretical results on universal behavior at the transition to chaos can readily be checked experimentally by studying I-V characteristics. 17 references, 1 figure.

  17. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    International Nuclear Information System (INIS)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-01-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen

  18. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  19. Neuromuscular dose-response studies: determining sample size.

    Science.gov (United States)

    Kopman, A F; Lien, C A; Naguib, M

    2011-02-01

    Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

  20. Neuromuscular interactions around the knee in children, adults and elderly

    Science.gov (United States)

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

  1. Bilateral neuromuscular and force differences during a plyometric task.

    Science.gov (United States)

    Ball, Nick B; Scurr, Joanna C

    2009-08-01

    The purpose of this article is to compare the bilateral neuromuscular and force contribution during a plyometric bounce drop jump task and to assess the affects of nonsimultaneous foot placement. Sixteen male participants performed bounce drop jumps from a height of 0.4 m. Mean peak electromyography activity of the soleus, medial, and lateral gastrocnemius of both legs was recorded from each phase of the drop jump and normalized to a reference dynamic muscle action. Resultant ground reaction force, ground contact time, and duration of the drop jumps were recorded from each leg. Multivariate analysis of variance was used to compare bilateral electromyographic activity, resultant peak ground reaction force, and contact duration. Pearson's correlations (r) ascertained relationships between normalized electromyographic activity and contact time. Significant differences were shown between left and right triceps surae normalized electromyography during precontact and contact40ms (p 0.01). Significant differences were found between normalized soleus electromyography and both gastrocnemii for both legs during precontact (p 0.01). Weak relationships were found between normalized electromyographic activity and nonsimultaneous foot contact (r < 0.2). This study showed differences between left and right triceps surae in neuromuscular strategies engaged in the early stages of a drop jump task. Differences in contact time initiation were present; however, they are not significant enough to cause neuromuscular differences in the plantar flexor muscles.

  2. Neuromuscular signs associated with acute hypophosphatemia in a dog.

    Science.gov (United States)

    Claus, Kimberly N; Day, Thomas K; Wolf, Christina

    2015-01-01

    The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

  3. CT in neuromuscular disorders: A comparison of CT and histology

    International Nuclear Information System (INIS)

    Vliet, A.M. van der; Thijssen, H.O.M.; Merx, J.L.; Joosten, E.

    1988-01-01

    The value of CT-examination of the muscles compared to histology was studied in a retrospective analysis of 30 patients with clinical suspicion of neuromuscular disorder. In the evaluation of the CT-results descriptive criteria were used. The histologic diagnosis came from needle-biopsies taken from the quadriceps muscle. Considering the whole group of neuromuscular disorders, CT has an overall accuracy of 84.8%, a positive predictive value of 95.5% and a negative predictive value of 63.6%. This makes the use of CT as a diagnostic tool in neuromuscular disorders a reliable examination technique. In patients with a polymyositis there is even a 100% correlation between CT findings and biopsy results. Discrepancy between the biopsy results is remarkable of the quadriceps muscle and the CT findings: The number of abnormal histological findings is twice the number of abnormal CT findings. Using the more proximal gluteal region as a biopsy site would have decreased this discrepancy and would therefore have given a better correlation between CT and histology. The choice of protocol in determining the levels to be scanned is of great importance in achieving good reproducability in follow-up CT examinations. (orig.)

  4. Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2018-01-01

    Full Text Available Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

  5. Magnetic resonance imaging (MRI) in the diagnosis of neuromuscular diseases

    International Nuclear Information System (INIS)

    Schalke, B.C.G.; Rohkamm, R.; Kaiser, W.

    1990-01-01

    In the last few years imaging procedures became also important in the diagnosis of neuromuscular diseases. We examined more than 150 patients with different neuromuscular diseases with MRI. Conventional diagnostic procedures like EMG, muscle biopsy can not be replaced by imaging procedures. MRI gives the chance to get additional diagnostic informations. It is possible to determine exact distribution and intensity of pathological changes in the muscle. Inflammatory muscle diseases can be differrentiated by T1/T2 values from atrophic/dystrophic diseases. The resolving power is very high and allows the exact detection of affected areas even in a single muscle. This can help to reduce false negative muscle biopsies. This is very useful in children and young adults. MRI can be used for the early detection of genetic myopathies and neuropathies. MRI allows to examine all muscles, including the heart, bone artefacts are absent. Heart muscle involvement in neuromuscular diseases can directly be shown by this method without any risk for the patient. In addition P-spectroscopy can be done for better understanding of pathogenesis, especially if the exact distribution of pathological changes is known. (author)

  6. Recent advances in neuromuscular block during anesthesia [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Martijn Boon

    2018-02-01

    Full Text Available Muscle relaxation is a routine part of anesthesia and has important advantages. However, the lingering effects of muscle relaxants in the postoperative period have historically been associated with postoperative adverse events. Neuromuscular reversal, together with neuromuscular monitoring, is a recognized strategy to reduce the rate of postoperative residual relaxation but has only marginally improved outcome in the past few decades. Sugammadex, a novel reversal agent with unique encapsulating properties, has changed the landscape of neuromuscular reversal and opened up new opportunities to improve patient care. By quickly and completely reversing any depth of neuromuscular block, it may reduce the rate of residual relaxation and improve respiratory recovery. In addition, sugammadex has made the use of deep neuromuscular block possible during surgery. Deep neuromuscular block may improve surgical working conditions and allow for a reduction in insufflation pressures during selected laparoscopic procedures. However, whether and how this may impact outcomes is not well established.

  7. Squeezed States in Josephson Junctions.

    Science.gov (United States)

    Hu, X.; Nori, F.

    1996-03-01

    We have studied quantum fluctuation properties of Josephson junctions in the limit of large Josephson coupling energy and small charging energy, when the eigenstates of the system can be treated as being nearly localized. We have considered(X. Hu and F. Nori, preprints.) a Josephson junction in a variety of situations, e.g., coupled to one or several of the following elements: a capacitor, an inductor (in a superconducting ring), and an applied current source. By solving an effective Shrödinger equation, we have obtained squeezed vacuum (coherent) states as the ground states of a ``free-oscillating'' (linearly-driven) Josephson junction, and calculated the uncertainties of its canonical momentum, charge, and coordinate, phase. We have also shown that the excited states of the various systems we consider are similar to the number states of a simple harmonic oscillator but with different fluctuation properties. Furthermore, we have obtained the time-evolution operators for these systems. These operators can make it easier to calculate the time-dependence of the expectation values and fluctuations of various quantities starting from an arbitrary initial state.

  8. Superconducting tunnel-junction refrigerator

    International Nuclear Information System (INIS)

    Melton, R.G.; Paterson, J.L.; Kaplan, S.B.

    1980-01-01

    The dc current through an S 1 -S 2 tunnel junction, with Δ 2 greater than Δ 1 , when biased with eV 1 +Δ 2 , will lower the energy in S 1 . This energy reduction will be shared by the phonons and electrons. This device is shown to be analogous to a thermoelectric refrigerator with an effective Peltier coefficient π* approx. Δ 1 /e. Tunneling calculations yield the cooling power P/sub c/, the electrical power P/sub e/ supplied by the bias supply, and the cooling efficiency eta=P/sub c//P/sub e/. The maximum cooling power is obtained for eV= +- (Δ 2 -Δ 1 ) and t 1 =T 1 /T/sub c/1 approx. 0.9. Estimates are made of the temperature difference T 2 -T 1 achievable in Al-Pb and Sn-Pb junctions with an Al 2 O 3 tunneling barrier. The performance of this device is shown to yield a maximum cooling efficiency eta approx. = Δ 1 /(Δ 2 -Δ 1 ) which can be compared with that available in an ideal Carnot refrigerator of eta=T 1 /(T 2 -T 1 ). The development of a useful tunnel-junction refrigerator requires a tunneling barrier with an effective thermal conductance per unit area several orders of magnitude less than that provided by the A1 2 O 3 barrier in the Al-Pb and Sn-Pb systems

  9. The relative frequency of common neuromuscular diagnoses in a reference center

    OpenAIRE

    Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista Junior, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

    2017-01-01

    ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded confir...

  10. Utilization of ACL Injury Biomechanical and Neuromuscular Risk Profile Analysis to Determine the Effectiveness of Neuromuscular Training.

    Science.gov (United States)

    Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

    2016-12-01

    The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).

  11. A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

    Science.gov (United States)

    Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

    2016-06-01

    We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

  12. Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

    Science.gov (United States)

    Naranjo, David; Wen, Hua; Brehm, Paul

    2015-01-01

    The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

  13. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

    2014-05-01

    Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

  14. The Dissolution of Double Holliday Junctions

    DEFF Research Database (Denmark)

    Bizard, Anna H; Hickson, Ian D

    2014-01-01

    as "double Holliday junction dissolution." This reaction requires the cooperative action of a so-called "dissolvasome" comprising a Holliday junction branch migration enzyme (Sgs1/BLM RecQ helicase) and a type IA topoisomerase (Top3/TopoIIIα) in complex with its OB (oligonucleotide/oligosaccharide binding......Double Holliday junctions (dHJS) are important intermediates of homologous recombination. The separate junctions can each be cleaved by DNA structure-selective endonucleases known as Holliday junction resolvases. Alternatively, double Holliday junctions can be processed by a reaction known......) fold containing accessory factor (Rmi1). This review details our current knowledge of the dissolution process and the players involved in catalyzing this mechanistically complex means of completing homologous recombination reactions....

  15. Geodynamical simulation of the RRF triple junction

    Science.gov (United States)

    Wang, Z.; Wei, D.; Liu, M.; Shi, Y.; Wang, S.

    2017-12-01

    Triple junction is the point at which three plate boundaries meet. Three plates at the triple junction form a complex geological tectonics, which is a natural laboratory to study the interactions of plates. This work studies a special triple junction, the oceanic transform fault intersects the collinear ridges with different-spreading rates, which is free of influence of ridge-transform faults and nearby hotspots. First, we build 3-D numerical model of this triple junction used to calculate the stead-state velocity and temperature fields resulting from advective and conductive heat transfer. We discuss in detail the influence of the velocity and temperature fields of the triple junction from viscosity, spreading rate of the ridge. The two sides of the oceanic transform fault are different sensitivities to the two factors. And, the influence of the velocity mainly occurs within 200km of the triple junction. Then, we modify the model by adding a ridge-transform fault to above model and directly use the velocity structure of the Macquarie triple junction. The simulation results show that the temperature at both sides of the oceanic transform fault decreases gradually from the triple junction, but the temperature difference between the two sides is a constant about 200°. And, there is little effect of upwelling velocity away from the triple junction 100km. The model results are compared with observational data. The heat flux and thermal topography along the oceanic transform fault of this model are consistent with the observed data of the Macquarie triple junction. The earthquakes are strike slip distributed along the oceanic transform fault. Their depths are also consistent with the zone of maximum shear stress. This work can help us to understand the interactions of plates of triple junctions and help us with the foundation for the future study of triple junctions.

  16. Hysteresis development in superconducting Josephson junctions

    International Nuclear Information System (INIS)

    Refai, T.F.; Shehata, L.N.

    1988-09-01

    The resistively and capacitive shunted junction model is used to investigate hysteresis development in superconducting Josephson junctions. Two empirical formulas that relate the hysteresis width and the quasi-particle diffusion length in terms of the junctions electrical parameters, temperature and frequency are obtained. The obtained formulas provide a simple tool to investigate the full potentials of the hysteresis phenomena. (author). 9 refs, 3 figs

  17. Larval dispersal in three coral reef decapod species: Influence of larval duration on the metapopulation structure

    Science.gov (United States)

    Zavala-Hidalgo, Jorge; Allende-Arandía, Eugenia; Hermoso-Salazar, Margarita

    2018-01-01

    Most coral-associated decapod species have non-migratory adult populations and depend on their planktonic larvae for dispersal. This study examined the metapopulation structure of three decapod species with different pelagic larval duration (PLD) from twelve coral reef complexes of the Gulf of Mexico. The dispersion of larvae was analyzed through the use of a realistic numerical simulation of the Gulf of Mexico with the Hybrid Coordinate Ocean Model. To study the transport and dispersion of particles in near-surface waters, a particle-tracking subroutine was run using as input the currents from the model. The simulation consisted of the launch of 100 passive particles (virtual larvae) every 24 hours from each reef throughout five years, and tracked for as long as 210 days. Results indicated that species with a short PLD, Mithraculus sculptus (PLD 8‒13 days), had a weak connection among the reefs, but higher self-recruitment, especially on the narrow western shelf. The species with a longer PLD, Dromia erythropus (28‒30 days), had a stronger connection among neighboring reefs (< 300 km). Finally, the species with an even longer PLD, Stenopus hispidus (123‒210 days), had a wider potential distribution than the other species. Circulation on synoptic, seasonal and interannual scales had differential effects on the larval dispersal of each species. The metapopulation structure of M. sculptus and D. erythropus seemed to combine features of the non-equilibrium and the patchy models, whereas that of S. hispidus presumably fit to a patchy model. These findings support previous observations that indicate that species with longer PLD tend to occupy larger areas than species with short PLD, although recruitment of juveniles to the adult populations will also depend on other factors, such as the availability of suitable habitats and the ability to colonize them. PMID:29558478

  18. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...

  19. Loss models for long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, O. H.; Samuelsen, Mogens Rugholm

    1984-01-01

    A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement.......A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement....

  20. Harmonic synchronization in resistively coupled Josephson junctions

    International Nuclear Information System (INIS)

    Blackburn, J.A.; Gronbech-Jensen, N.; Smith, H.J.T.

    1994-01-01

    The oscillations of two resistively coupled Josephson junctions biased only by a single dc current source are shown to lock harmonically in a 1:2 mode over a significant range of bias current, even when the junctions are identical. The dependence of this locking on both junction and coupling parameters is examined, and it is found that, for this particular two-junction configuration, 1:1 locking can never occur, and also that a minimum coupling coefficient is needed to support harmonic locking. Some issues related to subharmonic locking are also discussed

  1. Superconducting flux qubits with π-junctions

    International Nuclear Information System (INIS)

    Shcherbakova, Anastasia

    2014-01-01

    In this thesis, we present a fabrication technology of Al/AlO x /Al Josephson junctions on Nb pads. The described technology gives the possibility of combining a variety of Nb-based superconducting circuits, like pi-junction phase-shifters with sub-micron Al/AlO x /Al junctions. Using this approach, we fabricated hybrid Nb/Al flux qubits with and without the SFS-junctions and studied dispersive magnetic field response of these qubits as well as their spectroscopy characteristics.

  2. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  3. Effects of two stressors on amphibian larval development.

    Science.gov (United States)

    Stark, Karolina; Scott, David E; Tsyusko, Olga; Coughlin, Daniel P; Hinton, Thomas G

    2012-05-01

    In parallel with a renewed interest in nuclear power and its possible environmental impacts, a new environmental radiation protection system calls for environmental indicators of radiological stress. However, because environmental stressors seldom occur alone, this study investigated the combined effects of an ecological stressor (larval density) and an anthropogenic stressor (ionizing radiation) on amphibians. Scaphiopus holbrookii tadpoles reared at different larval densities were exposed to four low irradiation dose rates (0.13, 2.4, 21, and 222 mGy d(-1)) from (137)Cs during the sensitive period prior to and throughout metamorphosis. Body size at metamorphosis and development rate served as fitness correlates related to population dynamics. Results showed that increased larval density decreased body size but did not affect development rate. Low dose rate radiation had no impact on either endpoint. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Cellular localization of the atypical isoforms of protein kinase C (aPKCζ/PKMζ and aPKCλ/ι) on the neuromuscular synapse.

    Science.gov (United States)

    Besalduch, Núria; Lanuza, Maria A; Garcia, Neus; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Priego, Mercedes; Tomàs, Josep

    2013-11-27

    Several classic and novel protein kinase C (PKC) isoforms are selectively distributed in specific cell types of the adult neuromuscular junction (NMJ), in the neuron, glia and muscle components, and are involved in many functions, including neurotransmission. Here, we investigate the presence in this paradigmatic synapse of atypical PKCs, full-length atypical PKC zeta (aPKCζ), its separated catalytic part (PKMζ) and atypical lambda-iota PKC (aPKCλ/ι). High resolution immunohistochemistry was performed using a pan-atypical PKC antibody. Our results show moderate immunolabeling on the three cells (presynaptic motor nerve terminal, teloglial Schwann cell and postsynaptic muscle cell) suggesting the complex involvement of atypical PKCs in synaptic function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Effects of beach morphology and waves on onshore larval transport

    Science.gov (United States)

    Fujimura, A.; Reniers, A.; Paris, C. B.; Shanks, A.; MacMahan, J.; Morgan, S.

    2015-12-01

    Larvae of intertidal species grow offshore, and migrate back to the shore when they are ready to settle on their adult substrates. In order to reach the habitat, they must cross the surf zone, which is characterized as a semi-permeable barrier. This is accomplished through physical forcing (i.e., waves and current) as well as their own behavior. Two possible scenarios of onshore larval transport are proposed: Negatively buoyant larvae stay in the bottom boundary layer because of turbulence-dependent sinking behavior, and are carried toward the shore by streaming of the bottom boundary layer; positively buoyant larvae move to the shore during onshore wind events, and sink to the bottom once they encounter high turbulence (i.e., surf zone edge), where they are carried by the bottom current toward the shore (Fujimura et al. 2014). Our biophysical Lagrangian particle tracking model helps to explain how beach morphology and wave conditions affect larval distribution patterns and abundance. Model results and field observations show that larval abundance in the surf zone is higher at mildly sloped, rip-channeled beaches than at steep pocket beaches. Beach attributes are broken up to examine which and how beach configuration factors affect larval abundance. Modeling with alongshore uniform beaches with variable slopes reveal that larval populations in the surf zone are negatively correlated with beach steepness. Alongshore variability enhances onshore larval transport because of increased cross-shore water exchange by rip currents. Wave groups produce transient rip currents and enhance cross-shore exchange. Effects of other wave components, such as wave height and breaking wave rollers are also considered.

  6. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  7. Polycystic echinococcosis in Colombia: the larval cestodes in infected rodents.

    Science.gov (United States)

    Morales, G A; Guzman, V H; Wells, E A; Angel, D

    1979-07-01

    Described are the characteristics of the polycystic larval cestodes found in an endemic area of echinococcosis in the Easter Plains of Colombia and the tissue reaction evoked in infected rodents. Of 848 free-ranging animals examined, polycystic hydatids were found in 44/93 Cuniculus paca and 1/369 Proechimys sp. None of 20 Dasyprocta fuliginosa examined was infected, but hunters provided a heart with hydatid cysts and information about two additional animals with infected livers. Recognition of an endemic area of polycystic echinococcosis provides a means to investigate the life cycle of the parasites and to study the histogenesis of the larval cestodes in susceptible laboratory animals.

  8. The neural basis of visual behaviors in the larval zebrafish.

    Science.gov (United States)

    Portugues, Ruben; Engert, Florian

    2009-12-01

    We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future. Copyright 2009 Elsevier Ltd. All rights reserved.

  9. Organogénesis durante el periodo larval en peces

    OpenAIRE

    Zavala-Leal, I; Dumas, Silvie; Peña Martínez, Renato

    2011-01-01

    La presencia de un periodo larval caracteriza a los peces con ontogenia indirecta. Este periodo de desarrollo implica una serie de transformaciones encaminadas a la adquisición de las características biológicas y ecológicas propias de la especie; y en muchos casos culmina con cambios de distribución y hábitos alimenticios. El periodo larval incluye cuatro estadios de desarrollo: larva vitelina, larva pre-flexión, larva flexión y larva post-flexión. Cada estadio de desarrollo presenta caracter...

  10. Quality of life after surgery for neuromuscular scoliosis

    Directory of Open Access Journals (Sweden)

    Peter Obid

    2013-02-01

    Full Text Available Surgery in patients with neuromuscular scoliosis is associated with a higher rate of complications. It is still controversially discussed whether the patients truly benefit from deformity correction. The purpose of this study is to investigate if the quality of life has been improved and if the patients and their caregivers are satisfied with the results of surgery. This is a retrospective clinical outcome study of 46 patients with neuromuscular scoliosis which were treated with primary stable posterior pedicle screw instrumentation and correction. To achieve fusion only autologous bone was used. Follow up was minimum 2 years and maximum 5 years with an average of 36 months. The patients and/or their caregivers received a questionnaire based on the PEDI (pediatric disability inventory and the GMFS (gross motor function score. The patients (and their caregivers were also asked if the quality of life has improved after surgery. Only 32 of 46 patients answered the questionnaire. The answers showed a high approval-rate regarding the patients satisfaction with the surgery and the improvement of quality of life. The questionnaire could be answered from 1 (I do not agree to 4 (I completely agree. The average agreement to the following statements was: i the quality of life has improved: 3.35; ii I am satisfied with surgery: 3.95; iii the operation has fulfilled my expectations: 3.76. The average age at surgery was 12.7 years. The mean pre-operative cobb-angle of the main curve was 83.1° with a correction post-operatively to a mean of 36.9° and 42.6° at final follow-up. That is an average correction of 56.9%. Although spinal fusion in neuromuscular scoliosis is associated with a higher rate of complications our results show that the patients and their caregivers are satisfied with the operation and the quality of life has improved after surgery.

  11. Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

    Science.gov (United States)

    Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

    2014-01-01

    The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

  12. Running Economy: Neuromuscular and Joint Stiffness Contributions in Trained Runners.

    Science.gov (United States)

    Tam, Nicholas; Tucker, Ross; Santos-Concejero, Jordan; Prins, Danielle; Lamberts, Robert P

    2018-05-29

    It is debated whether running biomechanics make good predictors of running economy, with little known information about the neuromuscular and joint stiffness contributions to economical running gait. The aim of this study was to understand the relationship between certain neuromuscular and spatiotemporal biomechanical factors associated with running economy. Thirty trained runners performed a 6-minute constant-speed running set at 3.3 m∙s -1 , where oxygen consumption was assessed. Overground running trials were also performed at 3.3 m∙s -1 to assess kinematics, kinetics and muscle activity. Spatiotemporal gait variables, joint stiffness, pre-activation and stance phase muscle activity (gluteus medius; rectus femoris (RF); biceps femoris(BF); peroneus longus (PL); tibialis anterior (TA); gastrocnemius lateralis and medius (LG and MG) were variables of specific interest and thus determined. Additionally, pre-activation and ground contact of agonist:antagonist co-activation were calculated. More economical runners presented with short ground contact times (r=0.639, p<0.001) and greater strides frequencies (r=-0.630, p<0.001). Lower ankle and greater knee stiffness were associated with lower oxygen consumption (r=0.527, p=0.007 & r=0.384, p=0.043, respectively). Only LG:TA co-activation during stance were associated with lower oxygen cost of transport (r=0.672, p<0.0001). Greater muscle pre-activation and bi-articular muscle activity during stance were associated with more economical runners. Consequently, trained runners who exhibit greater neuromuscular activation prior to and during ground contact, in turn optimise spatiotemporal variables and joint stiffness, will be the most economical runners.

  13. Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

    Directory of Open Access Journals (Sweden)

    Corrêa da Silva Bruno Victor

    2014-12-01

    Full Text Available The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest. Neuromuscular performance was measured by the bench press throw (BPT and vertical counter movement jump (VCMJ tests, assessed before the 1st fight (Pre and after the last one (Post. Blood lactate (LA was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05 increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post, but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post were observed. LA concentration increased significantly (p < 0.05 at Post, both in the 1st min and the 15th min of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power was observed.

  14. An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

    Science.gov (United States)

    Fatehi, M; Rowan, E G; Harvey, A L

    2002-01-01

    The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

  15. The endocannabinoid anandamide regulates the peristaltic reflex by reducing neuro-neuronal and neuro-muscular neurotransmission in ascending myenteric reflex pathways in rats.

    Science.gov (United States)

    Sibaev, Andrei; Yuece, Birol; Allescher, Hans Dieter; Saur, Dieter; Storr, Martin; Kurjak, Manfred

    2014-04-01

    Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms. The effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileum segments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon. Anandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 μM). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected. CB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Diagnostics of neuromuscular diseases with the aid of computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Visser, M de; Verbeeten, Jr, B J

    1988-06-04

    In this article the diagnosis of neuromuscular diseases with the aid of computerized tomography is treated. Computerized tomography of skeletal muscles give no information which is pathognomonic for particular diseases. But the technique can be used in the following aspects: to choose a muscle for a biopsy; when it is not possible to examine the function of a muscle, a CT scan can visualize morphological deviations; in the differentiation of muscle hypertrophy and pseudo-hypertrophy. For some cases as Becker-type muscular dystrophy, facioscapulohumeral dystrophy and Kugelberg-Welander type spinal muscular atrophy computerized tomography gives characteristic images. 10 refs.; 6 figs.

  17. Diagnostics of neuromuscular diseases with the aid of computerized tomography

    International Nuclear Information System (INIS)

    Visser, M. de; Verbeeten, B.J. Jr.

    1988-01-01

    In this article the diagnosis of neuromuscular diseases with the aid of computerized tomography is treated. Computerized tomography of skeletal muscles give no information which is pathognomonic for particular diseases. But the technique can be used in the following aspects: to choose a muscle for a biopsy; when it is not possible to examine the function of a muscle, a CT scan can visualize morphological deviations; in the differentiation of muscle hypertrophy and pseudo-hypertrophy. For some cases as Becker-type muscular dystrophy, facioscapulohumeral dystrophy and Kugelberg-Welander type spinal muscular atrophy computerized tomography gives characteristic images. 10 refs.; 6 figs

  18. Cardiac involvement in children with neuro-muscular disorders

    Directory of Open Access Journals (Sweden)

    E. N. Arkhipova

    2015-01-01

    Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

  19. Preventing Ischial Pressure Ulcers: I. Review of Neuromuscular Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Hilton M. Kaplan

    2011-01-01

    Full Text Available Objective: Pressure ulcers (PUs are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Treatment is expensive and recurrence rates are high. Pathophysiological mechanisms include reduced bulk and perfusion of chronically atrophic muscles as well as prolonged occlusion of blood flow to soft tissues from lack of voluntary postural shifting of body weight. This has suggested that PUs might be prevented by reanimating the paralyzed muscles using neuromuscular electrical stimulation (NMES. A review of the published literature over the past 2 decades is detailed.

  20. Resúmenes de los trabajos sobre las Enfermedades Neuromusculares

    OpenAIRE

    Congreso Nacional de Neurología

    2010-01-01

    Las enfermedades neuromusculares constituyen un conjunto de afectaciones que afectan las neuronas motoras periférica, las vías motoras eferentes o los efectores (músculos esqueléticos). Sus manifestaciones clínicas son muy variadas y dependen de la causa y de los niveles de afectación. En este acápite se pueden encontrar los resúmenes de trabajos relacionados con el síndrome de Guillain Barre, polineuropatía diabética, Atrofia Muscular Espinal, Distrofia miotónica y otros todos presentados en...

  1. MRI in neuromuscular disorders; MRT bei neuromuskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Fischmann, Arne [Klinik St. Anna, Luzern (Switzerland). Inst. fuer Radiologie und Nuklearmedizin; Fischer, Dirk [Kantonsspital Bruderholz (Switzerland)

    2014-03-15

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  2. Factors affecting fungus-induced larval mortality in Anopheles gambiae and Anopheles stephensi

    NARCIS (Netherlands)

    Bukhari, S.T.; Middelman, A.; Koenraadt, C.J.M.; Takken, W.; Knols, B.G.J.

    2010-01-01

    Background Entomopathogenic fungi have shown great potential for the control of adult malaria vectors. However, their ability to control aquatic stages of anopheline vectors remains largely unexplored. Therefore, how larval characteristics (Anopheles species, age and larval density), fungus (species

  3. Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

  4. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  5. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.

    2010-01-01

    A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs

  6. Fatigue in neuromuscular disorders: Focus on Guillain-Barré syndrome and Pompe disease

    NARCIS (Netherlands)

    J.M. de Vries (Juna); M.L.C. Hagemans (Marloes); J.B.J. Bussmann (Hans); A.T. van der Ploeg (Ans); P.A. van Doorn (Pieter)

    2010-01-01

    textabstractFatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided

  7. The immediate effect of neuromuscular joint facilitation on the rotation of the tibia during walking.

    Science.gov (United States)

    Li, Desheng; Huang, Qiuchen; Huo, Ming; Hiiragi, Yukinobu; Maruyama, Hitoshi

    2017-01-01

    [Purpose] The aim of this study was to investigate the change in tibial rotation during walking among young adults after neuromuscular joint facilitation therapy. [Subjects and Methods] The subjects were twelve healthy young people (6 males, 6 females). A neuromuscular joint facilitation intervention and nonintervention were performed. The interventions were performed one after the other, separated by a 1-week interval. The order of the interventions was completely randomized. The rotation of the tibia during walking was evaluated before and after treatment. [Results] The neuromuscular joint facilitation group demonstrated increased lateral rotation of the tibia in the overall gait cycle and stance phase, and decreased medial rotation of the tibia in the overall gait cycle, stance phase, and swing phase after the neuromuscular joint facilitation intervention. In the control group, there were no significant differences. [Conclusion] These results suggest neuromuscular joint facilitation intervention has an immediate effect on the rotational function of the knee.

  8. Linker-dependent Junction Formation Probability in Single-Molecule Junctions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

    2015-01-15

    We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

  9. Cavity syncronisation of underdamped Josephson junction arrays

    DEFF Research Database (Denmark)

    Barbara, P.; Filatrella, G.; Lobb, C.

    2003-01-01

    the junctions in the array and an electromagnetic cavity. Here we show that a model of a one-dimensional array of Josephson junctions coupled to a resonator can produce many features of the coherent be havior above threshold, including coherent radiation of power and the shape of the array current...

  10. Functional anatomy of the human ureterovesical junction

    NARCIS (Netherlands)

    Roshani, H.; Dabhoiwala, N. F.; Verbeek, F. J.; Lamers, W. H.

    1996-01-01

    BACKGROUND: The valve function of the ureterovesical-junction (UVJ) is responsible for protection of the low pressure upper urinary tract from the refluxing of urine from the bladder. Controversy about the microanatomy of the human ureterovesical-junction persists. METHODS: Ten (3 male and 7 female)

  11. Spin, Vibrations and Radiation in Superconducting Junctions

    NARCIS (Netherlands)

    Padurariu, C.

    2013-01-01

    This thesis presents the theoretical study of superconducting transport in several devices based on superconducting junctions. The important feature of these devices is that the transport properties of the junction are modified by the interaction with another physical system integrated in the

  12. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the

  13. Multiplication in Silicon p-n Junctions

    DEFF Research Database (Denmark)

    Moll, John L.

    1965-01-01

    Multiplication values were measured in the collector junctions of silicon p-n-p and n-p-n transistors before and after bombardment by 1016 neutrons/cm2. Within experimental error there was no change either in junction fields, as deduced from capacitance measurements, or in multiplication values i...

  14. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... experiment showed a lower dye diffusion distance of Cx46 V44M cells, ... Studies of connexins show that channel gating and permeability .... have found that connexin assembled into gap junction plaques is not soluble in 1% ..... high glucose reduces gap junction activity in microvascular endothelial cells.

  15. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    LIJUAN CHEN

    2017-12-20

    Dec 20, 2017 ... showed a lower dye diffusion distance of Cx46 V44M cells, which indicates that the gap junction intercellular ... permeability could be affected by alterations of charged residues of .... bled into gap junction plaques is not soluble in 1% Triton ..... regulation of connexin 43 expression by high glucose reduces.

  16. Diel and lunar variations in larval supply to Malindi Marine Park ...

    African Journals Online (AJOL)

    Understanding larval ecology and the mechanisms used in dispersal and habitat selection helps to better understand the population dynamics of coral reef communities. However, few studies have examined patterns of larval supply to reefs sites especially in the WIO region. Temporal patterns of fish larval occurrence in ...

  17. File list: InP.Lar.10.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lar.10.AllAg.Larval_brain dm3 Input control Larvae Larval brain SRX1426944,SRX1...426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Lar.10.AllAg.Larval_brain.bed ...

  18. File list: His.Lar.50.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lar.50.AllAg.Larval_brain dm3 Histone Larvae Larval brain SRX1426943,SRX1426945... http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/His.Lar.50.AllAg.Larval_brain.bed ...

  19. File list: ALL.Lar.50.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Lar.50.AllAg.Larval_brain dm3 All antigens Larvae Larval brain SRX1426944,SRX14...26943,SRX1426945,SRX1426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/ALL.Lar.50.AllAg.Larval_brain.bed ...

  20. File list: InP.Lar.20.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lar.20.AllAg.Larval_brain dm3 Input control Larvae Larval brain SRX1426944,SRX1...426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Lar.20.AllAg.Larval_brain.bed ...

  1. Vegetative substrates used by larval northern pike in Rainy and Kabetogama Lakes, Minnesota

    Science.gov (United States)

    Anne L. Timm; Rodney B. Pierce

    2015-01-01

    Our objective was to identify characteristics of aquatic vegetative communities used as larval northern pike nursery habitat in Rainy and Kabetogama lakes, glacial shield reservoirs in northern Minnesota. Quatrefoil light traps fished at night were used to sample larval northern pike in 11 potential nursery areas. Larval northern pike were most commonly sampled among...

  2. File list: InP.Lar.50.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lar.50.AllAg.Larval_brain dm3 Input control Larvae Larval brain SRX1426944,SRX1...426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Lar.50.AllAg.Larval_brain.bed ...

  3. File list: ALL.Lar.20.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Lar.20.AllAg.Larval_brain dm3 All antigens Larvae Larval brain SRX1426944,SRX14...26943,SRX1426945,SRX1426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/ALL.Lar.20.AllAg.Larval_brain.bed ...

  4. File list: ALL.Lar.05.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Lar.05.AllAg.Larval_brain dm3 All antigens Larvae Larval brain SRX1426945,SRX14...26944,SRX1426946,SRX1426943 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/ALL.Lar.05.AllAg.Larval_brain.bed ...

  5. File list: ALL.Lar.10.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Lar.10.AllAg.Larval_brain dm3 All antigens Larvae Larval brain SRX1426945,SRX14...26944,SRX1426943,SRX1426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/ALL.Lar.10.AllAg.Larval_brain.bed ...

  6. File list: InP.Lar.05.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lar.05.AllAg.Larval_brain dm3 Input control Larvae Larval brain SRX1426944,SRX1...426946 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.Lar.05.AllAg.Larval_brain.bed ...

  7. File list: His.Lar.10.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: His.Lar.20.AllAg.Larval_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. Fabrication of Josephson Junction without shadow evaporation

    Science.gov (United States)

    Wu, Xian; Ku, Hsiangsheng; Long, Junling; Pappas, David

    We developed a new method of fabricating Josephson Junction (Al/AlOX/Al) without shadow evaporation. Statistics from room temperature junction resistance and measurement of qubits are presented. Unlike the traditional ``Dolan Bridge'' technique, this method requires two individual lithographies and straight evaporations of Al. Argon RF plasma is used to remove native AlOX after the first evaporation, followed by oxidation and second Al evaporation. Junction resistance measured at room temperature shows linear dependence on Pox (oxidation pressure), √{tox} (oxidation time), and inverse proportional to junction area. We have seen 100% yield of qubits made with this method. This method is promising because it eliminates angle dependence during Junction fabrication, facilitates large scale qubits fabrication.

  10. Overlap junctions for high coherence superconducting qubits

    Science.gov (United States)

    Wu, X.; Long, J. L.; Ku, H. S.; Lake, R. E.; Bal, M.; Pappas, D. P.

    2017-07-01

    Fabrication of sub-micron Josephson junctions is demonstrated using standard processing techniques for high-coherence, superconducting qubits. These junctions are made in two separate lithography steps with normal-angle evaporation. Most significantly, this work demonstrates that it is possible to achieve high coherence with junctions formed on aluminum surfaces cleaned in situ by Ar plasma before junction oxidation. This method eliminates the angle-dependent shadow masks typically used for small junctions. Therefore, this is conducive to the implementation of typical methods for improving margins and yield using conventional CMOS processing. The current method uses electron-beam lithography and an additive process to define the top and bottom electrodes. Extension of this work to optical lithography and subtractive processes is discussed.

  11. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  12. Integrated mosquito larval source management reduces larval numbers in two highland villages in western Kenya

    Directory of Open Access Journals (Sweden)

    Imbahale Susan S

    2012-05-01

    Full Text Available Abstract Background In western Kenya, malaria remains one of the major health problems and its control remains an important public health measure. Malaria control is by either use of drugs to treat patients infected with malaria parasites or by controlling the vectors. Vector control may target the free living adult or aquatic (larval stages of mosquito. The most commonly applied control strategies target indoor resting mosquitoes. However, because mosquitoes spend a considerable time in water, targeting the aquatic stages can complement well with existing adult control measures. Methods Larval source management (LSM of malaria vectors was examined in two villages i.e. Fort Ternan and Lunyerere, with the aim of testing strategies that can easily be accessed by the affected communities. Intervention strategies applied include environmental management through source reduction (drainage of canals, land levelling or by filling ditches with soil, habitat manipulation (by provision of shading from arrow root plant, application of Bacillus thuringiensis var israelensis (Bti and the use of predatory fish, Gambusia affinis. The abundance of immature stages of Anopheles and Culex within intervention habitats was compared to that within non-intervention habitats. Results The findings show that in Fort Ternan no significant differences were observed in the abundance of Anopheles early and late instars between intervention and non-intervention habitats. In Lunyerere, the abundance of Anopheles early instars was fifty five times more likely to be present within non-intervention habitats than in habitats under drainage. No differences in early instars abundance were observed between non-intervention and habitats applied with Bti. However, late instars had 89 % and 91 % chance of being sampled from non-intervention rather than habitats under drainage and those applied with Bti respectively. Conclusion Most of these interventions were applied in habitats

  13. Larval diet affects mosquito development and permissiveness to Plasmodium infection.

    Science.gov (United States)

    Linenberg, Inbar; Christophides, George K; Gendrin, Mathilde

    2016-12-02

    The larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. Richness in the nutrient supply to larvae influences the development and metabolism of larvae and adults. Here, we investigated the effects of larval diet on the development, microbiota content and permissiveness to Plasmodium of Anopheles coluzzii. We tested three fish diets often used to rear mosquitoes in the laboratory, including two pelleted diets, Dr. Clarke's Pool Pellets and Nishikoi Fish Pellets, and one flaked diet, Tetramin Fish-Flakes. Larvae grow and develop faster and produce bigger adults when feeding on both types of pellets compared with flakes. This correlates with a higher microbiota load in pellet-fed larvae, in agreement with the known positive effect of the microbiota on mosquito development. Larval diet also significantly influences the prevalence and intensity of Plasmodium berghei infection in adults, whereby Nishikoi Fish Pellets-fed larvae develop into adults that are highly permissive to parasites and survive longer after infection. This correlates with a lower amount of Enterobacteriaceae in the midgut microbiota. Together, our results shed light on the influence of larval feeding on mosquito development, microbiota and vector competence; they also provide useful data for mosquito rearing.

  14. Larval biology of the crab Rhithropanopeus harrisii (Gould): a synthesis.

    Science.gov (United States)

    Forward, Richard B

    2009-06-01

    This synthesis reviews the physiological ecology and behavior of larvae of the benthic crab Rhithropanopeus harrisii, which occurs in low-salinity areas of estuaries. Larvae are released rhythmically around the time of high tide in tidal estuaries and in the 2-h interval after sunset in nontidal estuaries. As in most subtidal crustaceans, the timing of larval release is controlled by the developing embryos, which release peptide pheromones that stimulate larval release behavior by the female to synchronize the time of egg hatching. Larvae pass through four zoeal stages and a postlarval or megalopal stage that are planktonic before metamorphosis. They are retained near the adult population by means of an endogenous tidal rhythm in vertical migration. Larvae have several safeguards against predation: they undergo nocturnal diel vertical migration (DVM) and have a shadow response to avoid encountering predators, and they bear long spines as a deterrent. Photoresponses during DVM and the shadow response are enhanced by exposure to chemical cues from the mucus of predator fishes and ctenophores. The primary visual pigment has a spectral sensitivity maximum at about 500 nm, which is typical for zooplankton and matches the ambient spectrum at twilight. Larvae can detect vertical gradients in temperature, salinity, and hydrostatic pressure, which are used for depth regulation and avoidance of adverse environmental conditions. Characteristics that are related to the larval habitat and are common to other crab larval species are considered.

  15. Basolateral Cl- channels in the larval bullfrog skin epithelium

    DEFF Research Database (Denmark)

    Hillyard, Stanley D.; Rios, K.; Larsen, Erik Hviid

    2002-01-01

    The addition of 150 U/ml nystatin to the mucosal surface of isolated skin from larval bullfrogs increases apical membrane permeability and allows a voltage clamp to be applied to the basolateral membrane. With identical Ringer's solutions bathing either side of the tissue the short-circuit curren...

  16. Silk formation mechanisms in the larval salivary glands of Apis ...

    Indian Academy of Sciences (India)

    Unknown

    The mechanism of silk formation in Apis mellifera salivary glands, during the 5th instar, was studied. Larval salivary glands were dissected and prepared for light and polarized light microscopy, as well as for scanning and transmission electron microscopy. The results showed that silk formation starts at the middle of the 5th ...

  17. A larval hunger signal in the bumblebee Bombus terrestris

    DEFF Research Database (Denmark)

    Den Boer, Susanne Petronella A; Duchateau, Marie-Jose

    2006-01-01

    Larvae of Bombus terrestris, a pollen-storing bumblebee, are dependent on progressive provisioning by workers. We test the hypothesis that larval cuticular chemicals can act as a hunger signal. We first show with a new classical conditioning experiment, using a Y-shaped tube, that workers can...

  18. Estimation of larval density of Liriomyza sativae Blanchard (Diptera ...

    African Journals Online (AJOL)

    This study was conducted to develop sequential sampling plans to estimate larval density of Liriomyza sativae Blanchard (Diptera: Agromyzidae) at three precision levels in cucumber greenhouse. The within- greenhouse spatial patterns of larvae were aggregated. The slopes and intercepts of both Iwao's patchiness ...

  19. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Science.gov (United States)

    Heap, Lucy A.; Vanwalleghem, Gilles C.; Thompson, Andrew W.; Favre-Bulle, Itia; Rubinsztein-Dunlop, Halina; Scott, Ethan K.

    2018-01-01

    The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH) to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC)/stratum griseum periventriculare (SPV), and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil. PMID:29403362

  20. Study on Silkworm Bed Cleaning Frequency during Larval Growth ...

    African Journals Online (AJOL)

    Study on Silkworm Bed Cleaning Frequency during Larval Growth Period. Abiy Tilahun, Kedir Shifa, Ahmed Ibrahim, Metasebia Terefe. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/star.v4i2.5 · AJOL African ...

  1. Body shape, burst speed and escape behavior of larval anurans

    Science.gov (United States)

    Gage H. Dayton; Daniel Saenz; Kristen A. Baum; R. Brian Langerhans; Thomas J. DeWitt

    2005-01-01

    Variation in behavior, morphology and life history traits of larval anurans across predator gradients, and consequences of that variation, have been abundantly studied. Yet the functional link between morphology and burst-swimming speed is largely unknown. We conducted experiments with two divergent species of anurans, Scaphiopus holbrookii and

  2. Population dynamics and management implications of larval dispersal

    African Journals Online (AJOL)

    caused by the identified mechanism provides: (1) the basis for spatially explicit management, and (2) an explanation for the observed spatial variability in the degree of overfishing. Research on larval dispersal is also providing the information necessary to design spatially explicit management strategies involving either ...

  3. Mosquito larval habitats and public health implications in Abeokuta ...

    African Journals Online (AJOL)

    The larval habitats of mosquitoes were investigated in Abeokuta, Nigeria in order to determine the breeding sites of the existing mosquito fauna and its possible public health implications on the residents of the City. The habitats were sampled between August 2005 and July 2006 using plastic dippers and a pipette.

  4. Stretch-activated cation channel from larval bullfrog skin

    DEFF Research Database (Denmark)

    Hillyard, Stanley D; Willumsen, Niels J; Marrero, Mario B

    2010-01-01

    Cell-attached patches from isolated epithelial cells from larval bullfrog skin revealed a cation channel that was activated by applying suction (-1 kPa to -4.5 kPa) to the pipette. Activation was characterized by an initial large current spike that rapidly attenuated to a stable value and showed ...

  5. The larval development and population dynamics of Derocheilocaris ...

    African Journals Online (AJOL)

    Seven larval stages of Derocheilocaris algoensis have been described and appear to be identical with those of D. typica from North America. This stresses the remarkable conservativeness of this subclass of Crustacea. The population biology of D. algoensis has been studied over 16 months and reproduction has been ...

  6. Fruit Fly Liquid Larval Diet Technology Transfer and Update

    Science.gov (United States)

    Since October 2006, USDA-ARS has been implementing a fruit fly liquid larval diet technology transfer, which has proceeded according to the following steps: (1) Recruitment of interested groups through request; (2) Establishment of the Material Transfer Agreement (MTA) with ARS; (3) Fruit fly liquid...

  7. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Directory of Open Access Journals (Sweden)

    Lucy A. Heap

    2018-01-01

    Full Text Available The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC/stratum griseum periventriculare (SPV, and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil.

  8. Silk formation mechanisms in the larval salivary glands of Apis ...

    Indian Academy of Sciences (India)

    Unknown

    The mechanism of silk formation in Apis mellifera salivary glands, during the 5th instar, was studied. Larval salivary glands .... be used in the silk-manufacture industry. This paper analyses .... (figure 3C); and are highly birefringent (figure 3D).

  9. The role of individual variation in marine larval dispersal

    KAUST Repository

    Nanninga, Gerrit B.

    2014-12-08

    The exchange of individuals among patchy habitats plays a central role in spatial ecology and metapopulation dynamics. Dispersal is frequently observed to vary non-randomly within populations (e.g., short vs. long), indicating that variability among individuals may shape heterogeneity in patterns of connectivity. The concept of context- and condition-dependent dispersal describes the balance between the costs and benefits of dispersal that arises from the interaction of temporal and spatial landscape heterogeneity (the context) with phenotypic variability among individuals (the condition). While this hypothesis is widely accepted in terrestrial theory, it remains questionable to what extent the concept of adaptive dispersal strategies may apply to marine larval dispersal, a process that is largely determined by stochastic forces. Yet, larvae of many taxa exhibit strong navigational capabilities and there is mounting evidence of widespread intra-specific variability in biological traits that are potentially correlated with dispersal potential. While so far there are few known examples of real larval dispersal polymorphisms, intra-specifically variable dispersal strategies may be common in marine systems. Whether adaptive or not, it is becoming apparent that inter-individual heterogeneity in morphology, behavior, condition, and life history traits may have critical effects on population-level heterogeneity in dispersal. Here, we explore the eco-evolutionary causes and consequences of intrinsic and extrinsic variability on larval dispersal by synthesizing the existing literature and drawing conceptual parallels from terrestrial theory. We emphasize the potential importance of larval dispersal polymorphisms in marine population dynamics.

  10. Motor unit recruitment during neuromuscular electrical stimulation: a critical appraisal.

    Science.gov (United States)

    Bickel, C Scott; Gregory, Chris M; Dean, Jesse C

    2011-10-01

    Neuromuscular electrical stimulation (NMES) is commonly used in clinical settings to activate skeletal muscle in an effort to mimic voluntary contractions and enhance the rehabilitation of human skeletal muscles. It is also used as a tool in research to assess muscle performance and/or neuromuscular activation levels. However, there are fundamental differences between voluntary- and artificial-activation of motor units that need to be appreciated before NMES protocol design can be most effective. The unique effects of NMES have been attributed to several mechanisms, most notably, a reversal of the voluntary recruitment pattern that is known to occur during voluntary muscle contractions. This review outlines the assertion that electrical stimulation recruits motor units in a nonselective, spatially fixed, and temporally synchronous pattern. Additionally, it synthesizes the evidence that supports the contention that this recruitment pattern contributes to increased muscle fatigue when compared with voluntary actions and provides some commentary on the parameters of electrical stimulation as well as emerging technologies being developed to facilitate NMES implementation. A greater understanding of how electrical stimulation recruits motor units, as well as the benefits and limitations of its use, is highly relevant when using this tool for testing and training in rehabilitation, exercise, and/or research.

  11. Ultrastructural findings in noncompaction prevail with neuromuscular disorders.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia

    2013-01-01

    Little is known about the ultrastructural abnormalities of left ventricular hypertrabeculation/noncompaction (LVHT). This literature review aimed to summarize and discuss ultrastructural abnormalities described in LVHT so far. The literature search was conducted via MEDLINE using the search terms 'non-compaction', 'noncompaction', 'left ventricular hypertrabeculation', 'spongy myocardium' in combination with the terms 'ultra-structural', or 'electron microscopy'. Altogether, 11 studies reporting ultrastructural investigations of LVHT were retrieved. In these 11 studies, data on 13 patients with LVHT were presented. Ultrastructural abnormalities found in these study patients were generally nonspecific and included an increase in the number of mitochondria (n = 3), abnormally shaped mitochondria (n = 2), distorted cristae (n = 3), sarcomeric derangement (n = 3), immature cardiomyocytes (n = 1), lipid-like inclusions (n = 1), enlarged interstitial spaces (n = 1), increased interstitial collagen (n = 1), or increased glycogen (n = 1). The morphological abnormalities were most prominent in patients with a neuromuscular disorder like Barth syndrome or mitochondrial myopathy. Only in few patients with LVHT, ultrastructural investigations have been performed so far. Ultrastructural abnormalities in LVHT are nonspecific and most prominent in patients with a neuromuscular disorder. There is a strong need to carry out thorough ultrastructural investigations of LVHT to contribute to the understanding of this still unexplained myocardial abnormality.

  12. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

    2017-06-01

    Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

  13. Toward Balance Recovery With Leg Prostheses Using Neuromuscular Model Control

    Science.gov (United States)

    Geyer, Hartmut

    2016-01-01

    Objective Lower limb amputees are at high risk of falling as current prosthetic legs provide only limited functionality for recovering balance after unexpected disturbances. For instance, the most established control method used on powered leg prostheses tracks local joint impedance functions without taking the global function of the leg in balance recovery into account. Here we explore an alternative control policy for powered transfemoral prostheses that considers the global leg function and is based on a neuromuscular model of human locomotion. Methods We adapt this model to describe and simulate an amputee walking with a powered prosthesis using the proposed control, and evaluate the gait robustness when confronted with rough ground and swing leg disturbances. We then implement and partially evaluate the resulting controller on a leg prosthesis prototype worn by a non-amputee user. Results In simulation, the proposed prosthesis control leads to gaits that are more robust than those obtained by the impedance control method. The initial hardware experiments with the prosthesis prototype show that the proposed control reproduces normal walking patterns qualitatively and effectively responds to disturbances in early and late swing. However, the response to mid-swing disturbances neither replicates human responses nor averts falls. Conclusions The neuromuscular model control is a promising alternative to existing prosthesis controls, although further research will need to improve on the initial implementation and determine how well these results transfer to amputee gait. Significance This work provides a potential avenue for future development of control policies that help improve amputee balance recovery. PMID:26315935

  14. [Six-minute walk test in children with neuromuscular disease.

    Science.gov (United States)

    Cruz-Anleu, Israel Didier; Baños-Mejía, Benjamín Omar; Galicia-Amor, Susana

    2013-01-01

    Background: neuromuscular diseases affect the motor unit. When they evolve, respiratory complications are common; the six-minute walk test plays an important role in the assessment of functional capacity. Methods: prospective, transversal, descriptive and observational study. We studied seven children with a variety of neuromuscular diseases and spontaneous ambulation. We tested their lung function, and administered a six-minute walk test and a test of respiratory muscle strength to these children. Results: the age was 9.8 ± 2.4 years. All patients were males. Forced vital capacity decreased in three patients (42.8 %), forced expiratory volume during the first second (2.04 ± 1.4 L) and peak expiratory flow (4.33 ± 3.3 L/s) were normal. The maximum strength of respiratory muscles was less than 60 % of predicted values. The distance covered in the six-minute walk test was lower when compared with healthy controls (29.9 %). Conclusions: the six-minute walk test can be a useful tool in early stages of this disease, since it is easy to perform and well tolerated by the patients.

  15. Effect of salbutamol on neuromuscular function in endurance athletes.

    Science.gov (United States)

    Decorte, Nicolas; Bachasson, Damien; Guinot, Michel; Flore, Patrice; Levy, Patrick; Verges, Samuel; Wuyam, Bernard

    2013-10-01

    The potential ergogenic effects of therapeutic inhaled salbutamol doses in endurance athletes have been controversially discussed for decades. We hypothesized that salbutamol inhalation may increase peripheral muscle contractility, reduce fatigability, and improve force recovery after a localized exercise in endurance athletes. Eleven healthy, nonasthmatic male athletes with high aerobic capacities were recruited to be compared in a double-blinded, randomized crossover study of two dose levels of salbutamol (200 and 800 μg) and a placebo administered by inhalation before a quadriceps fatigue test. Subjects performed an incremental exercise protocol consisting in sets of 10 intermittent isometric contractions starting at 20% of maximum voluntary contraction (MVC) with 10% MVC increment until exhaustion. Femoral nerve magnetic stimulation was used during and after MVC to evaluate neuromuscular fatigue after each set, at task failure, and after 10 and 30 min of recovery. Initial MVC and evoked muscular responses were not modified with salbutamol (P > 0.05). The total number of submaximal contractions until task failure significantly differed between treatments (placebo, 72 ± 7; 200 µg, 78 ± 8; and 800 µg, 82 ± 7; P 0.05). Voluntary activation was unaffected by the fatiguing task and treatments (P > 0.05). Supratherapeutic inhaled doses of β2-agonists increased quadriceps endurance during an incremental and localized fatiguing task in healthy endurance-trained athletes without significant effect on neuromuscular fatigue. Further studies are needed to clarify the underlying mechanisms.

  16. Estimating neuromuscular stimulation within the human torso with Taser stimulus.

    Science.gov (United States)

    Sun, Hongyu; Webster, John G

    2007-11-07

    Designers of electromuscular incapacitation devices need to know efficacy. Which areas of nerve and muscle are stimulated and are these areas adequate to cause incapacitation? This paper focuses on efficacy, which used a torso-sized finite element model with a mesh of about 5 mm. To estimate the neuromuscular regions stimulated by the Taser X26, calculations of electric current density and field strength values with 1 A inserted into the torso using the Utah 3D mesh were made. Field-times-duration values for given Taser stimulation were calculated. Then the region where the motor nerve was stimulated by the Taser was estimated by using a field-times-duration threshold from Reilly (1998 'Applied Bioelectricity: From Electrical Stimulation to Electropathology ' (New York: Springer)). Neuromuscular stimulation occurred up to about 19 cm away from the darts and included the spinal cord. The current density at the heart for dart separation less than 10 cm was smaller than for larger dart separation. Users of finite element computer models will find information for torso models and their creation, meshing and operation.

  17. Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

    Science.gov (United States)

    Dewan, Karuna; Vahabzadeh-Hagh, Andrew; Soofer, Donna; Chhetri, Dinesh K

    2017-07-01

    Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. In vivo canine model. In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. NA Laryngoscope, 127:1633-1638, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Emerging modalities in dysphagia rehabilitation: neuromuscular electrical stimulation.

    Science.gov (United States)

    Huckabee, Maggie-Lee; Doeltgen, Sebastian

    2007-10-12

    The aim of this review article is to advise the New Zealand medical community about the application of neuromuscular electrical stimulation (NMES) as a treatment for pharyngeal swallowing impairment (dysphagia). NMES in this field of rehabilitation medicine has quickly emerged as a widely used method overseas but has been accompanied by significant controversy. Basic information is provided about the physiologic background of electrical stimulation. The literature reviewed in this manuscript was derived through a computer-assisted search using the biomedical database Medline to identify all relevant articles published until from the initiation of the databases up to January 2007. The reviewers used the following search strategy: [(deglutition disorders OR dysphagia) AND (neuromuscular electrical stimulation OR NMES)]. In addition, the technique of reference tracing was used and very recently published studies known to the authors but not yet included in the database systems were included. This review elucidates not only the substantive potential benefit of this treatment, but also potential key concerns for patient safety and long term outcome. The discussion within the clinical and research communities, especially around the commercially available VitalStim stimulator, is objectively explained.

  19. Macroscopic quantum tunneling in Josephson tunnel junctions and Coulomb blockade in single small tunnel junctions

    International Nuclear Information System (INIS)

    Cleland, A.N.

    1991-04-01

    Experiments investigating the process of macroscopic quantum tunneling in a moderately-damped, resistively shunted, Josephson junction are described, followed by a discussion of experiments performed on very small capacitance normal-metal tunnel junctions. The experiments on the resistively-shunted Josephson junction were designed to investigate a quantum process, that of the tunneling of the Josephson phase variable under a potential barrier, in a system in which dissipation plays a major role in the dynamics of motion. All the parameters of the junction were measured using the classical phenomena of thermal activation and resonant activation. Theoretical predictions are compared with the experimental results, showing good agreement with no adjustable parameters; the tunneling rate in the moderately damped (Q ∼ 1) junction is seen to be reduced by a factor of 300 from that predicted for an undamped junction. The phase is seen to be a good quantum-mechanical variable. The experiments on small capacitance tunnel junctions extend the measurements on the larger-area Josephson junctions from the region in which the phase variable has a fairly well-defined value, i.e. its wavefunction has a narrow width, to the region where its value is almost completely unknown. The charge on the junction becomes well-defined and is predicted to quantize the current through the junction, giving rise to the Coulomb blockade at low bias. I present the first clear observation of the Coulomb blockade in single junctions. The electrical environment of the tunnel junction, however, strongly affects the behavior of the junction: higher resistance leads are observed to greatly sharpen the Coulomb blockade over that seen with lower resistance leads. I present theoretical descriptions of how the environment influences the junctions; comparisons with the experimental results are in reasonable agreement

  20. Resonance Transport of Graphene Nanoribbon T-Shaped Junctions

    International Nuclear Information System (INIS)

    Xiao-Lan, Kong; Yong-Jian, Xiong

    2010-01-01

    We investigate the transport properties of T-shaped junctions composed of armchair graphene nanoribbons of different widths. Three types of junction geometries are considered. The junction conductance strongly depends on the atomic features of the junction geometry. When the shoulders of the junction have zigzag type edges, sharp conductance resonances usually appear in the low energy region around the Dirac point, and a conductance gap emerges. When the shoulders of the junction have armchair type edges, the conductance resonance behavior is weakened significantly, and the metal-metal-metal junction structures show semimetallic behaviors. The contact resistance also changes notably due to the various interface geometries of the junction

  1. Remotely Sensing Larval Population Dynamics of Rice Field Anophelines

    Science.gov (United States)

    Beck, Louisa R.; Dister, Sheri W.; Wood, Byron L.; Washino, Robert K.

    1997-01-01

    The primary objective of both studies was to determine if RS and GIS techniques could be used to distinguish between high and low larval-producing rice fields in California. Results of the first study suggested that early-season green-up and proximity to livestock pastures were positively correlated with high larval abundance. Based on the early-season spectral differences between high and low larval-producing fields, it appeared that canopy development and tillering influenced mosquito habitat quality. At that time, rice fields consisted of a mixture of plants and water, a combination that allowed An. freeborni females to lay eggs in partial sunlight, protected from both predators and wind. This established a population earlier in the season than in other, 'less-green' fields where tillering and plant emergence was too minimal for ovipositioning. The study also indicated the importance of the distance that a mosquito would have to fly in order to take a bloodmeal prior to ovipositing. These associations were fully explored in an expanded study two years later. The second study confirmed the positive relationship between early season canopy development and larval abundance, and also demonstrated the relationship between abundance and distance-to-pasture. The association between greenness (as measured using NDVI), distance-to-pasture, and abundance is illustrated. The second study also indicated the siginificance of the landscape context of rice fields for larval production. Fields that included opportunities for feeding and resting within the flight range of the mosquito had higher abundances than did fields that were in a homogeneous rice area.

  2. Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.

    Science.gov (United States)

    Ohno, Kinji; Ohkawara, Bisei; Ito, Mikako

    2017-10-01

    Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.

  3. Fitness consequences of larval exposure to Beauveria bassiana on adults of the malaria vector Anopheles stephensi.

    Science.gov (United States)

    Vogels, Chantal B F; Bukhari, Tullu; Koenraadt, Constantianus J M

    2014-06-01

    Entomopathogenic fungi have shown to be effective in biological control of both larval and adult stages of malaria mosquitoes. However, a small fraction of mosquitoes is still able to emerge after treatment with fungus during the larval stage. It remains unclear whether fitness of these adults is affected by the treatment during the larval stage and whether they are still susceptible for another treatment during the adult stage. Therefore, we tested the effects of larval exposure to the entomopathogenic fungus Beauveria bassiana on fitness of surviving Anopheles stephensi females. Furthermore, we tested whether larval exposed females were still susceptible to re-exposure to the fungus during the adult stage. Sex ratio, survival and reproductive success were compared between non-exposed and larval exposed A. stephensi. Comparisons were also made between survival of non-exposed and larval exposed females that were re-exposed to B. bassiana during the adult stage. Larval treatment did not affect sex ratio of emerging mosquitoes. Larval exposed females that were infected died significantly faster and laid equal numbers of eggs from which equal numbers of larvae hatched, compared to non-exposed females. Larval exposed females that were uninfected had equal survival, but laid a significantly larger number of eggs from which a significantly higher number of larvae hatched, compared to non-exposed females. Larval exposed females which were re-exposed to B. bassiana during the adult stage had equal survival as females exposed only during the adult stage. Our results suggest that individual consequences for fitness of larval exposed females depended on whether a fungal infection was acquired during the larval stage. Larval exposed females remained susceptible to re-exposure with B. bassiana during the adult stage, indicating that larval and adult control of malaria mosquitoes with EF are compatible. Copyright © 2014. Published by Elsevier Inc.

  4. Food selection in larval fruit flies: dynamics and effects on larval development

    Science.gov (United States)

    Schwarz, Sebastian; Durisko, Zachary; Dukas, Reuven

    2014-01-01

    Selecting food items and attaining a nutritionally balanced diet is an important challenge for all animals including humans. We aimed to establish fruit fly larvae ( Drosophila melanogaster) as a simple yet powerful model system for examining the mechanisms of specific hunger and diet selection. In two lab experiments with artificial diets, we found that larvae deprived of either sucrose or protein later selectively fed on a diet providing the missing nutrient. When allowed to freely move between two adjacent food patches, larvae surprisingly preferred to settle on one patch containing yeast and ignored the patch providing sucrose. Moreover, when allowed to move freely between three patches, which provided either yeast only, sucrose only or a balanced mixture of yeast and sucrose, the majority of larvae settled on the yeast-plus-sucrose patch and about one third chose to feed on the yeast only food. While protein (yeast) is essential for development, we also quantified larval success on diets with or without sucrose and show that larvae develop faster on diets containing sucrose. Our data suggest that fruit fly larvae can quickly assess major nutrients in food and seek a diet providing a missing nutrient. The larvae, however, probably prefer to quickly dig into a single food substrate for enhanced protection over achieving an optimal diet.

  5. Electron optics with ballistic graphene junctions

    Science.gov (United States)

    Chen, Shaowen

    Electrons transmitted across a ballistic semiconductor junction undergo refraction, analogous to light rays across an optical boundary. A pn junction theoretically provides the equivalent of a negative index medium, enabling novel electron optics such as negative refraction and perfect (Veselago) lensing. In graphene, the linear dispersion and zero-gap bandstructure admit highly transparent pn junctions by simple electrostatic gating, which cannot be achieved in conventional semiconductors. Robust demonstration of these effects, however, has not been forthcoming. Here we employ transverse magnetic focusing to probe propagation across an electrostatically defined graphene junction. We find perfect agreement with the predicted Snell's law for electrons, including observation of both positive and negative refraction. Resonant transmission across the pn junction provides a direct measurement of the angle dependent transmission coefficient, and we demonstrate good agreement with theory. Comparing experimental data with simulation reveals the crucial role played by the effective junction width, providing guidance for future device design. Efforts toward sharper pn junction and possibility of zero field Veselago lensing will also be discussed. This work is supported by the Semiconductor Research Corporations NRI Center for Institute for Nanoelectronics Discovery and Exploration (INDEX).

  6. Valley dependent transport in graphene L junction

    Science.gov (United States)

    Chan, K. S.

    2018-05-01

    We studied the valley dependent transport in graphene L junctions connecting an armchair lead and a zigzag lead. The junction can be used in valleytronic devices and circuits. Electrons injected from the armchair lead into the junction is not valley polarized, but they can become valley polarized in the zigzag lead. There are Fermi energies, where the current in the zigzag lead is highly valley polarized and the junction is an efficient generator of valley polarized current. The features of the valley polarized current depend sensitively on the widths of the two leads, as well as the number of dimers in the armchair lead, because this number has a sensitive effect on the band structure of the armchair lead. When an external potential is applied to the junction, the energy range with high valley polarization is enlarged enhancing its function as a generator of highly valley polarized current. The scaling behavior found in other graphene devices is also found in L junctions, which means that the results presented here can be extended to junctions with larger dimensions after appropriate scaling of the energy.

  7. The Preparation Period in Basketball: Training Load and Neuromuscular Adaptations.

    Science.gov (United States)

    Ferioli, Davide; Bosio, Andrea; Bilsborough, Johann C; Torre, Antonio La; Tornaghi, Michele; Rampinini, Ermanno

    2018-01-18

    To investigate the 1) effect of the preparation period on the neuromuscular characteristics of 12 professional (PRO) and 16 semi-professional (SEMI-PRO) basketball players; 2) relationships between training load indices and changes in neuromuscular physical performance. Prior to and following the preparation period, players underwent a counter-movement jump (CMJ) test, followed by a repeated change of direction (COD) test consisting of 4 levels with increasing intensities. The peripheral neuromuscular functions of the knee extensors (peak torque, PT) were measured using electrical stimulations after each level (PT1, PT2, PT3 and PT4). Furthermore, PT Max (the highest value of PT) and PT Dec (PT decrement from PT Max to PT4) were calculated. Trivial-to-small (effect size, ES: -0.17 to 0.46) improvements were found in CMJ variables, regardless of the competitive levels. After the preparation period, peripheral fatigue induced by a COD test was similarly reduced in both PRO (PT Dec: from 27.8±21.3% to 11.4±13.7%, ES±90%CI= -0.71±0.30) and SEMI-PRO (PT Dec: from 26.1±21.9% to 10.2±8.2%, ES±90%CI= -0.69±0.32). Moderate-to-large relationships were found between session rating of perceived exertion training load and changes in PPO measured during the CMJs (r s ±90%CI: PPOabs, -0.46±0.26; PPOrel, -0.53±0.23) and in some PTs measured during the COD test (PT1, -0.45±0.26; PT2, -0.44±0.26; PT3, -0.40±0.27 and PT Max, -0.38±0.28). Preparation period induced minimal changes in the CMJ, while the ability to sustain repeated COD efforts was improved. Reaching high session rating of perceived exertion training loads might partially and negatively affect the ability to produce strength and power.

  8. Immunocytochemistry and metamorphic fate of the larval nervous system of Triphyllozoon mucronatum (Ectoprocta: Gymnolaemata: Cheilostomata)

    DEFF Research Database (Denmark)

    Wanninger, Andreas; Koop, Demian; Degnan, Bernard M.

    2005-01-01

    The development of gymnolaemate Ectoprocta includes a larval stage of either the coronate or the cyphonautes type. Herein, we provide the first description of the larval neural anatomy of a coronate larva using immunocytochemical methods. We used antibodies against the neurotransmitters serotonin...... that the larval neuroanatomy and the processes that underlie the reorganization of larval organ systems during metamorphosis may vary much more among lophotrochozoan taxa than previously thought....... and FMRFamide and followed the fate of immunoreactive cells through metamorphosis. The larval serotonergic nervous system of Triphyllozoon mucronatum consists of an apical commissure, one pair of lateral axons, a coronate nerve net, an internal nerve mesh, and one pair of axons innervating the frontal organ....... FMRFamide is only found in the larval commissure and in the lateral axons. The entire serotonergic and FMRFamidergic nervous system is lost during metamorphosis and the adult neural structures form independent of the larval ones. In the postlarval zooid, both neurotransmitters are detected in the cerebral...

  9. Shot noise in YBCO bicrystal Josephson junctions

    DEFF Research Database (Denmark)

    Constantinian, K.Y.; Ovsyannikov, G.A.; Borisenko, I.V.

    2003-01-01

    We measured spectral noise density in YBCO symmetric bicrystal Josephson junctions on sapphire substrates at bias voltages up to 100 mV and T 4.2 K. Normal state resistance of the Josephson junctions, R-N = 20-90 Omega and ICRN up to 2.2 mV have been observed in the experimental samples. Noise...... may explain the experimentally measured linewidth broadening of Josephson oscillations at mm and submm wave frequencies in high-Tc superconducting junctions. Experimental results are discussed in terms of bound states existing at surfaces of d-wave superconducting electrodes....

  10. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.

    2010-01-01

    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...... the persistent currents circulating in a superconducting loop. Analytical and numerical results indicate that the presence of fractional vortices leads to remarkable differences from the conventional case of uniformly distributed dc bias current. The theoretical findings are supported by detailed measurements...

  11. Parametric frequency conversion in long Josephson junctions

    International Nuclear Information System (INIS)

    Irie, F.; Ashihara, S.; Yoshida, K.

    1976-01-01

    Current steps at voltages corresponding to the parametric coupling between an applied r.f. field and junction resonant modes have been observed in long Josephson tunnel junctions in the flux-flow state. The observed periodic variations of the step height due to the applied magnetic field are explained quantitatively by a perturbational analysis using Josephson phase equations. The present study demonstrates that the moving vortex array can serve as a coherent pump wave for signal waves propagating in the barrier region, which indicates, as a result, the possibility of traveling-wave parametric devices with long Josephson tunnel junctions. (author)

  12. A splice isoform of DNedd4, DNedd4-long, negatively regulates neuromuscular synaptogenesis and viability in Drosophila.

    Directory of Open Access Journals (Sweden)

    Yunan Zhong

    Full Text Available Neuromuscular (NM synaptogenesis is a tightly regulated process. We previously showed that in flies, Drosophila Nedd4 (dNedd4/dNedd4S is required for proper NM synaptogenesis by promoting endocytosis of commissureless from the muscle surface, a pre-requisite step for muscle innervation. DNedd4 is an E3 ubiquitin ligase comprised of a C2-WW(x3-Hect domain architecture, which includes several splice isoforms, the most prominent ones are dNedd4-short (dNedd4S and dNedd4-long (dNedd4Lo.We show here that while dNedd4S is essential for NM synaptogenesis, the dNedd4Lo isoform inhibits this process and causes lethality. Our results reveal that unlike dNedd4S, dNedd4Lo cannot rescue the lethality of dNedd4 null (DNedd4(T121FS flies. Moreover, overexpression of UAS-dNedd4Lo specifically in wildtype muscles leads to NM synaptogenesis defects, impaired locomotion and larval lethality. These negative effects of dNedd4Lo are ameliorated by deletion of two regions (N-terminus and Middle region unique to this isoform, and by inactivating the catalytic activity of dNedd4Lo, suggesting that these unique regions, as well as catalytic activity, are responsible for the inhibitory effects of dNedd4Lo on synaptogenesis. In accord with these findings, we demonstrate by sqRT-PCR an increase in dNedd4S expression relative to the expression of dNedd4Lo during embryonic stages when synaptogenesis takes place.Our studies demonstrate that splice isoforms of the same dNedd4 gene can lead to opposite effects on NM synaptogenesis.

  13. Neuromuscular blockade for improvement of surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Scheppan, Susanne; Kissmeyer, Peter

    2015-01-01

    INTRODUCTION: During laparotomy, surgeons frequently experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. This issue is particularly pertinent while closing the fascia and placing the intestines into the abdominal cavity. Establishment of a deep neuromus......INTRODUCTION: During laparotomy, surgeons frequently experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. This issue is particularly pertinent while closing the fascia and placing the intestines into the abdominal cavity. Establishment of a deep...... neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS...

  14. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    Science.gov (United States)

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

  15. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

    Science.gov (United States)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

    2017-10-06

    Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. The e

  16. Neuromuscular training in construction workers: a longitudinal controlled pilot study.

    Science.gov (United States)

    Faude, Oliver; Donath, Lars; Bopp, Micha; Hofmann, Sara; Erlacher, Daniel; Zahner, Lukas

    2015-08-01

    Many accidents at construction sites are due to falls. An exercise-based workplace intervention may improve intrinsic fall risk factors. In this pilot study, we aimed at evaluating the effects of neuromuscular exercise on static and functional balance performance as well as on lower limb explosive power in construction workers. Healthy middle-aged construction workers were non-randomly assigned to an intervention [N = 20, age = 40.3 (SD 8.3) years] or a control group [N = 20, age = 41.8 (9.9) years]. The intervention group performed static and dynamic balance and strength exercises (13 weeks, 15 min each day). Before and after the intervention and after an 8-week follow-up, unilateral postural sway, backward balancing (on 3- and 4.5-cm-wide beams) as well as vertical jump height were assessed. We observed a group × time interaction for postural sway (p = 0.002) with a reduction in the intervention group and no relevant change in the control group. Similarly, the number of successful steps while walking backwards on the 3-cm beam increased only in the intervention group (p = 0.047). These effects were likely to most likely practically beneficial from pretest to posttest and to follow-up test for postural sway (+12%, standardized mean difference (SMD) = 0.65 and 17%, SMD = 0.92) and backward balancing on the 3-cm beam (+58%, SMD = 0.59 and 37%, SMD = 0.40). Fifteen minutes of neuromuscular training each day can improve balance performance in construction workers and, thus, may contribute to a decreased fall risk.

  17. EFFECT OF NEUROMUSCULAR TRAINING ON BALANCE AMONG UNIVERSITY ATHLETES

    Directory of Open Access Journals (Sweden)

    Mohansundar Sankaravel

    2016-06-01

    Full Text Available Background: Proprioceptive deficiency followed by lateral ankle sprain leads to poor balance is not uncommon. It has been linked with increased injury risk among young athletes. Introducing neuromuscular training programs for this have been believed as one of the means of injury prevention. Hence, this study was aimed to determine the effects of six weeks progressive neuromuscular training (PNM Training on static balance gains among the young athletes with a previous history of ankle sprains. Methods: This study was an experimental study design, with pre and post test method to determine the effects of PNM Training on static balance gains. All data were collected at university’s sports rehabilitation lab before and after six weeks of intervention period. There were 20 male and female volunteer young athletes (20.9 ± 0.85 years of age with a previous history of ankle sprain involving various sports were recruited from the University community. All the subjects were participated in a six week PNM Training that included stability, strength and power training. Outcome measures were collected by calculating the errors on balance error scoring system made by the athletes on static balance before and after the six weeks of intervention period. Static balance was tested in firm and foam surfaces and recorded accordingly. Results: The researchers found a significant decrease (2.40 ± 0.82 in total errors among the samples at the post test compared with their pre test (P >0.05. Conclusions: The study demonstrates that a PNM Training can improve the static balance on both the firm and foam surfaces among the young athletes with a previous history of ankle sprains.

  18. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

    Directory of Open Access Journals (Sweden)

    Peter C Rowe

    Full Text Available Chronic fatigue syndrome (CFS is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04 and concentration difficulties (P = 0.02 as well as increased composite symptom scores (all P = 0.03 during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001 and for the composite symptom score (P = 0.005. During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical

  19. Tunnel junctions with multiferroic barriers

    Science.gov (United States)

    Gajek, Martin; Bibes, Manuel; Fusil, Stéphane; Bouzehouane, Karim; Fontcuberta, Josep; Barthélémy, Agnès; Fert, Albert

    2007-04-01

    Multiferroics are singular materials that can exhibit simultaneously electric and magnetic orders. Some are ferroelectric and ferromagnetic and provide the opportunity to encode information in electric polarization and magnetization to obtain four logic states. However, such materials are rare and schemes allowing a simple electrical readout of these states have not been demonstrated in the same device. Here, we show that films of La0.1Bi0.9MnO3 (LBMO) are ferromagnetic and ferroelectric, and retain both ferroic properties down to a thickness of 2nm. We have integrated such ultrathin multiferroic films as barriers in spin-filter-type tunnel junctions that exploit the magnetic and ferroelectric degrees of freedom of LBMO. Whereas ferromagnetism permits read operations reminiscent of magnetic random access memories (MRAM), the electrical switching evokes a ferroelectric RAM write operation. Significantly, our device does not require the destructive ferroelectric readout, and therefore represents an advance over the original four-state memory concept based on multiferroics.

  20. Chirality effect in disordered graphene ribbon junctions

    International Nuclear Information System (INIS)

    Long Wen

    2012-01-01

    We investigate the influence of edge chirality on the electronic transport in clean or disordered graphene ribbon junctions. By using the tight-binding model and the Landauer-Büttiker formalism, the junction conductance is obtained. In the clean sample, the zero-magnetic-field junction conductance is strongly chirality-dependent in both unipolar and bipolar ribbons, whereas the high-magnetic-field conductance is either chirality-independent in the unipolar or chirality-dependent in the bipolar ribbon. Furthermore, we study the disordered sample in the presence of magnetic field and find that the junction conductance is always chirality-insensitive for both unipolar and bipolar ribbons with adequate disorders. In addition, the disorder-induced conductance plateaus can exist in all chiral bipolar ribbons provided the disorder strength is moderate. These results suggest that we can neglect the effect of edge chirality in fabricating electronic devices based on the magnetotransport in a disordered graphene ribbon. (paper)

  1. Josephson tunnel junctions in niobium films

    International Nuclear Information System (INIS)

    Wiik, Tapio.

    1976-12-01

    A method of fabricating stable Josephson tunnel junctions with reproducible characteristics is described. The junctions have a sandwich structure consisting of a vacuum evaporated niobium film, a niobium oxide layer produced by the glow discharge method and a lead film deposited by vacuum evaporation. Difficulties in producing thin-film Josephson junctions are discussed. Experimental results suggest that the lower critical field of the niobium film is the most essential parameter when evaluating the quality of these junctions. The dependence of the lower critical field on the film thickness and on the Ginzburg-Landau parameter of the film is studied analytically. Comparison with the properties of the evaporated films and with the previous calculations for bulk specimens shows that the presented model is applicable for most of the prepared samples. (author)

  2. Transparency of atom-sized superconducting junctions

    International Nuclear Information System (INIS)

    Van-der-Post, N.; Peters, E.T.; Van Ruitenbeek, J.M.; Yanson, I.K.

    1995-01-01

    We discuss the transparency of atom-size superconducting tunnel junctions by comparing experimental values of the normal resistance and Subgap Structure with the theoretical predictions for these phenomena by Landauer's formula and Multiple Andreev Reflection, respectively

  3. Josephson junction arrays and superconducting wire networks

    International Nuclear Information System (INIS)

    Lobb, C.J.

    1992-01-01

    Techniques used to fabricate integrated circuits make it possible to construct superconducting networks containing as many as 10 6 wires or Josephson junctions. Such networks undergo phase transitions from resistive high-temperature states to ordered low-resistance low-temperature states. The nature of the phase transition depends strongly on controllable parameters such as the strength of the superconductivity in each wire or junction and the external magnetic field. This paper will review the physics of these phase transitions, starting with the simplest zero-magnetic field case. This leads to a Kosterlitz-Thouless transition when the junctions or wires are weak, and a simple mean-field fransition when the junctions or wires are strong. Rich behavior, resulting from frustration, occurs in the presence of a magnetic field. (orig.)

  4. Effects of moisture content of food waste on residue separation, larval growth and larval survival in black soldier fly bioconversion.

    Science.gov (United States)

    Cheng, Jack Y K; Chiu, Sam L H; Lo, Irene M C

    2017-09-01

    In order to foster sustainable management of food waste, innovations in food waste valorization technologies are crucial. Black soldier fly (BSF) bioconversion is an emerging technology that can turn food waste into high-protein fish feed through the use of BSF larvae. The conventional method of BSF bioconversion is to feed BSF larvae with food waste directly without any moisture adjustment. However, it was reported that difficulty has been experienced in the separation of the residue (larval excreta and undigested material) from the insect biomass due to excessive moisture. In addition to the residue separation problem, the moisture content of the food waste may also affect the growth and survival aspects of BSF larvae. This study aims to determine the most suitable moisture content of food waste that can improve residue separation as well as evaluate the effects of the moisture content of food waste on larval growth and survival. In this study, pre-consumer and post-consumer food waste with different moisture content (70%, 75% and 80%) was fed to BSF larvae in a temperature-controlled rotary drum reactor. The results show that the residue can be effectively separated from the insect biomass by sieving using a 2.36mm sieve, for both types of food waste at 70% and 75% moisture content. However, sieving of the residue was not feasible for food waste at 80% moisture content. On the other hand, reduced moisture content of food waste was found to slow down larval growth. Hence, there is a trade-off between the sieving efficiency of the residue and the larval growth rate. Furthermore, the larval survival rate was not affected by the moisture content of food waste. A high larval survival rate of at least 95% was achieved using a temperature-controlled rotary drum reactor for all treatment groups. The study provides valuable insights for the waste management industry on understanding the effects of moisture content when employing BSF bioconversion for food waste recycling

  5. Neutron induced permanent damage in Josephson junctions

    International Nuclear Information System (INIS)

    Mueller, G.P.; Rosen, M.

    1982-01-01

    14 MeV neutron induced permanent changes in the critical current density of Josephson junctions due to displacement damage in the junction barrier are estimated using a worst case model and the binary collision simulation code MARLOWE. No likelihood of single event hard upsets is found in this model. It is estimated that a fluence of 10 18 -10 19 neutrons/cm 2 are required to change the critical current density by 5%

  6. Exotic hadron and string junction model

    International Nuclear Information System (INIS)

    Imachi, Masahiro

    1978-01-01

    Hadron structure is investigated adopting string junction model as a realization of confinement. Besides exotic hadrons (M 4 , B 5 etc.), unconventional hadrons appear. A mass formula for these hadrons is proposed. New selection rule is introduced which requires the covalence of constituent line at hadron vertex. New duality appears due to the freedom of junction, especially in anti BB→anti BB reaction. A possible assignment of exotic and unconventional hadrons to recently observed narrow meson states is presented. (auth.)

  7. Construction of tunable peptide nucleic acid junctions.

    Science.gov (United States)

    Duan, Tanghui; He, Liu; Tokura, Yu; Liu, Xin; Wu, Yuzhou; Shi, Zhengshuang

    2018-03-15

    We report here the construction of 3-way and 4-way peptide nucleic acid (PNA) junctions as basic structural units for PNA nanostructuring. The incorporation of amino acid residues into PNA chains makes PNA nanostructures with more structural complexity and architectural flexibility possible, as exemplified by building 3-way PNA junctions with tunable nanopores. Given that PNA nanostructures have good thermal and enzymatic stabilities, they are expected to have broad potential applications in biosensing, drug delivery and bioengineering.

  8. Molecular Diffusion through Cyanobacterial Septal Junctions.

    Science.gov (United States)

    Nieves-Morión, Mercedes; Mullineaux, Conrad W; Flores, Enrique

    2017-01-03

    Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N 2 -fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO 2 through oxygenic photosynthesis provide the heterocysts with reduced carbon and heterocysts provide the vegetative cells with fixed nitrogen. Intercellular molecular transfer has been traced with fluorescent markers, including calcein, 5-carboxyfluorescein, and the sucrose analogue esculin, which are observed to move down their concentration gradient. In this work, we used fluorescence recovery after photobleaching (FRAP) assays in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 to measure the temperature dependence of intercellular transfer of fluorescent markers. We find that the transfer rate constants are directly proportional to the absolute temperature. This indicates that the "septal junctions" (formerly known as "microplasmodesmata") linking the cells in the filament allow molecular exchange by simple diffusion, without any activated intermediate state. This constitutes a novel mechanism for molecular transfer across the bacterial cytoplasmic membrane, in addition to previously characterized mechanisms for active transport and facilitated diffusion. Cyanobacterial septal junctions are functionally analogous to the gap junctions of metazoans. Although bacteria are frequently considered just as unicellular organisms, there are bacteria that behave as true multicellular organisms. The heterocyst-forming cyanobacteria grow as filaments in which cells communicate. Intercellular molecular exchange is thought to be mediated by septal junctions. Here, we show that intercellular transfer of fluorescent markers in the cyanobacterial filament has the physical properties of simple diffusion. Thus, cyanobacterial septal junctions are functionally analogous to metazoan gap junctions

  9. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  10. Social coercion of larval development in an ant species.

    Science.gov (United States)

    Villalta, Irene; Amor, Fernando; Cerdá, Xim; Boulay, Raphaël

    2016-04-01

    Ants provide one of the best examples of the division of labor in animal societies. While the queens reproduce, workers generally refrain from laying eggs and dedicate themselves exclusively to domestic tasks. In many species, the small diploid larvae are bipotent and can develop either into workers or queens depending mostly on environmental cues. This generates a conflicting situation between the adults that tend to rear a majority of larvae into workers and the larvae whose individual interest may be to develop into reproductive queens. We tested the social regulation of larval caste fate in the fission-performing ant Aphaenogaster senilis. We first observed interactions between resident workers and queen- and worker-destined larvae in presence/absence of the queen. The results show that workers tend to specifically eliminate queen-destined larvae when the queen is present but not when she is absent or imprisoned in a small cage allowing for volatile pheromone exchanges. In addition, we found that the presence of already developed queen-destined larvae does not inhibit the development of younger still bipotent larvae into queens. Finally, we analyzed the cuticular hydrocarbon profiles of queen- and worker-destined larvae and found no significant quantitative or qualitative difference. Interestingly, the total amount of hydrocarbons on both larval castes is extremely low, which lends credence on the chemical insignificance hypothesis of larval ants. Overall, our results suggest that workers control larval development and police larvae that would develop into queens instead of workers. Such policing behavior is similar in many aspects to what is known of worker policing among adults.

  11. Social coercion of larval development in an ant species

    Science.gov (United States)

    Villalta, Irene; Amor, Fernando; Cerdá, Xim; Boulay, Raphaël

    2016-04-01

    Ants provide one of the best examples of the division of labor in animal societies. While the queens reproduce, workers generally refrain from laying eggs and dedicate themselves exclusively to domestic tasks. In many species, the small diploid larvae are bipotent and can develop either into workers or queens depending mostly on environmental cues. This generates a conflicting situation between the adults that tend to rear a majority of larvae into workers and the larvae whose individual interest may be to develop into reproductive queens. We tested the social regulation of larval caste fate in the fission-performing ant Aphaenogaster senilis. We first observed interactions between resident workers and queen- and worker-destined larvae in presence/absence of the queen. The results show that workers tend to specifically eliminate queen-destined larvae when the queen is present but not when she is absent or imprisoned in a small cage allowing for volatile pheromone exchanges. In addition, we found that the presence of already developed queen-destined larvae does not inhibit the development of younger still bipotent larvae into queens. Finally, we analyzed the cuticular hydrocarbon profiles of queen- and worker-destined larvae and found no significant quantitative or qualitative difference. Interestingly, the total amount of hydrocarbons on both larval castes is extremely low, which lends credence on the chemical insignificance hypothesis of larval ants. Overall, our results suggest that workers control larval development and police larvae that would develop into queens instead of workers. Such policing behavior is similar in many aspects to what is known of worker policing among adults.

  12. Rapid effects of marine reserves via larval dispersal.

    Directory of Open Access Journals (Sweden)

    Richard Cudney-Bueno

    Full Text Available Marine reserves have been advocated worldwide as conservation and fishery management tools. It is argued that they can protect ecosystems and also benefit fisheries via density-dependent spillover of adults and enhanced larval dispersal into fishing areas. However, while evidence has shown that marine reserves can meet conservation targets, their effects on fisheries are less understood. In particular, the basic question of if and over what temporal and spatial scales reserves can benefit fished populations via larval dispersal remains unanswered. We tested predictions of a larval transport model for a marine reserve network in the Gulf of California, Mexico, via field oceanography and repeated density counts of recently settled juvenile commercial mollusks before and after reserve establishment. We show that local retention of larvae within a reserve network can take place with enhanced, but spatially-explicit, recruitment to local fisheries. Enhancement occurred rapidly (2 yrs, with up to a three-fold increase in density of juveniles found in fished areas at the downstream edge of the reserve network, but other fishing areas within the network were unaffected. These findings were consistent with our model predictions. Our findings underscore the potential benefits of protecting larval sources and show that enhancement in recruitment can be manifested rapidly. However, benefits can be markedly variable within a local seascape. Hence, effects of marine reserve networks, positive or negative, may be overlooked when only focusing on overall responses and not considering finer spatially-explicit responses within a reserve network and its adjacent fishing grounds. Our results therefore call for future research on marine reserves that addresses this variability in order to help frame appropriate scenarios for the spatial management scales of interest.

  13. Ballistic Josephson junctions based on CVD graphene

    Science.gov (United States)

    Li, Tianyi; Gallop, John; Hao, Ling; Romans, Edward

    2018-04-01

    Josephson junctions with graphene as the weak link between superconductors have been intensely studied in recent years, with respect to both fundamental physics and potential applications. However, most of the previous work was based on mechanically exfoliated graphene, which is not compatible with wafer-scale production. To overcome this limitation, we have used graphene grown by chemical vapour deposition (CVD) as the weak link of Josephson junctions. We demonstrate that very short, wide CVD-graphene-based Josephson junctions with Nb electrodes can work without any undesirable hysteresis in their electrical characteristics from 1.5 K down to a base temperature of 320 mK, and their gate-tuneable critical current shows an ideal Fraunhofer-like interference pattern in a perpendicular magnetic field. Furthermore, for our shortest junctions (50 nm in length), we find that the normal state resistance oscillates with the gate voltage, consistent with the junctions being in the ballistic regime, a feature not previously observed in CVD-graphene-based Josephson junctions.

  14. Junction depth measurement using carrier illumination

    International Nuclear Information System (INIS)

    Borden, Peter

    2001-01-01

    Carrier Illumination [trade mark] (CI) is a new method recently developed to meet the need for a non-destructive, high throughput junction depth measurement on patterned wafers. A laser beam creates a quasi-static excess carrier profile in the semiconductor underlying the activated junction. The excess carrier profile is fairly constant below the junction, and drops rapidly in the junction, creating a steep index of refraction gradient at the junction edge. Interference with light reflected from this index gradient provides a signal that is analyzed to determine the junction depth. The paper summarizes evaluation of performance in full NMOS and PMOS process flows, on both bare and patterned wafers. The aims have been to validate (1) performance in the presence of underlying layers typically found at the source/drain (S/D) process steps and (2) measurement on patterned wafers. Correlation of CI measurements to SIMS and transistor drive current are shown. The data were obtained from NMOS structures using As S/D and LDD implants. Correlations to SRP, SIMS and sheet resistance are shown for PMOS structures using B 11 LDD implants. Gage capability measurements are also presented

  15. Characterisation of Culex quinquefasciatus (Diptera: Culicidae larval habitats at ground level and temporal fluctuations of larval abundance in Córdoba, Argentina

    Directory of Open Access Journals (Sweden)

    Marta Grech

    2013-09-01

    Full Text Available The aims of this study were to characterise the ground-level larval habitats of the mosquito Culex quinquefasciatus, to determine the relationships between habitat characteristics and larval abundance and to examine seasonal larval-stage variations in Córdoba city. Every two weeks for two years, 15 larval habitats (natural and artificial water bodies, including shallow wells, drains, retention ponds, canals and ditches were visited and sampled for larval mosquitoes. Data regarding the water depth, temperature and pH, permanence, the presence of aquatic vegetation and the density of collected mosquito larvae were recorded. Data on the average air temperatures and accumulated precipitation during the 15 days prior to each sampling date were also obtained. Cx. quinquefasciatus larvae were collected throughout the study period and were generally most abundant in the summer season. Generalised linear mixed models indicated the average air temperature and presence of dicotyledonous aquatic vegetation as variables that served as important predictors of larval densities. Additionally, permanent breeding sites supported high larval densities. In Córdoba city and possibly in other highly populated cities at the same latitude with the same environmental conditions, control programs should focus on permanent larval habitats with aquatic vegetation during the early spring, when the Cx. quinquefasciatus population begins to increase.

  16. Strong links between metal contamination, habitat modification and estuarine larval fish distributions

    Energy Technology Data Exchange (ETDEWEB)

    McKinley, Andrew C., E-mail: andrew.mckinley@hotmail.com [Evolution and Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales 2052 (Australia); Miskiewicz, Anthony [Environment and Recreation, Wollongong City Council, 41 Burelli Street, Wollongong, New South Wales 2500 (Australia); Taylor, Matthew D.; Johnston, Emma L. [Evolution and Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales 2052 (Australia)

    2011-06-15

    Changes to larval fish assemblages may have far reaching ecological impacts. Correlations between habitat modification, contamination and marine larval fish communities have rarely been assessed in situ. We investigated links between the large-scale distribution of stressors and larval fish assemblages in estuarine environments. Larval fish communities were sampled using a benthic sled within the inner and outer zones of three heavily modified and three relatively unmodified estuaries. Larval abundances were significantly greater in modified estuaries, and there were trends towards greater diversity in these systems. Differences in larval community composition were strongly related to sediment metal levels and reduced seagrass cover. The differences observed were driven by two abundant species, Paedogobius kimurai and Ambassis jacksoniensis, which occurred in large numbers almost exclusively in highly contaminated and pristine locations respectively. These findings suggest that contamination and habitat alteration manifest in substantial differences in the composition of estuarine larval fish assemblages. - Highlights: > We examine contamination/habitat modification impacts on larval fish. > Larvae communities differ between modified/unmodified estuaries. > Larvae are more abundant/diverse in modified areas. > Trends are strongly related to sediment metals/seagrass cover. > Larval impacts have wider ecological importance. - We describe strong links between sediment metals contamination, habitat modification and substantial differences in the composition of the estuarine larval fish assemblage.

  17. Strong links between metal contamination, habitat modification and estuarine larval fish distributions

    International Nuclear Information System (INIS)

    McKinley, Andrew C.; Miskiewicz, Anthony; Taylor, Matthew D.; Johnston, Emma L.

    2011-01-01

    Changes to larval fish assemblages may have far reaching ecological impacts. Correlations between habitat modification, contamination and marine larval fish communities have rarely been assessed in situ. We investigated links between the large-scale distribution of stressors and larval fish assemblages in estuarine environments. Larval fish communities were sampled using a benthic sled within the inner and outer zones of three heavily modified and three relatively unmodified estuaries. Larval abundances were significantly greater in modified estuaries, and there were trends towards greater diversity in these systems. Differences in larval community composition were strongly related to sediment metal levels and reduced seagrass cover. The differences observed were driven by two abundant species, Paedogobius kimurai and Ambassis jacksoniensis, which occurred in large numbers almost exclusively in highly contaminated and pristine locations respectively. These findings suggest that contamination and habitat alteration manifest in substantial differences in the composition of estuarine larval fish assemblages. - Highlights: → We examine contamination/habitat modification impacts on larval fish. → Larvae communities differ between modified/unmodified estuaries. → Larvae are more abundant/diverse in modified areas. → Trends are strongly related to sediment metals/seagrass cover. → Larval impacts have wider ecological importance. - We describe strong links between sediment metals contamination, habitat modification and substantial differences in the composition of the estuarine larval fish assemblage.

  18. Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

    Science.gov (United States)

    Shenoi, V N; Ali, S Z; Prasad, N G

    2016-02-01

    In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  19. Dutch pediatricians' views on the use of neuromuscular blockers for dying neonates: a qualitative study

    NARCIS (Netherlands)

    ten Cate, K.; van de Vathorst, S.

    2015-01-01

    To assess Dutch pediatricians' views on neuromuscular blockers for dying neonates. Qualitative study involving in-depth interviews with 10 Dutch pediatricians working with severely ill neonates. Data were analyzed using appropriate qualitative research techniques. Participants explained their view

  20. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Science.gov (United States)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  1. Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

    Science.gov (United States)

    Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

    2015-05-01

    [Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

  2. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults

    DEFF Research Database (Denmark)

    Hristovska, Ana-Marija; Duch, Patricia; Allingstrup, Mikkel

    2017-01-01

    , and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety......, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. OBJECTIVES: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents......-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. DATA...

  3. Novel vibration-exercise instrument with dedicated adaptive filtering for electromyographic investigation of neuromuscular activation

    NARCIS (Netherlands)

    Xu, L.; Rabotti, C.; Mischi, M.

    2012-01-01

    Vibration exercise (VE) has been suggested as an effective methodology to improve muscle strength and power performance. Several studies link the effects of vibration training to enhanced neuromuscular demand, typically ascribed to involuntary reflex mechanisms. However, the underlying mechanisms

  4. A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

    NARCIS (Netherlands)

    Mullender, M.G.; Blom, N.; de Kleuver, M.; Fock, J.; Hitters, W.; Horemans, A.; Kalkman, C.; Pruijs, J.; Timmer, R.; Titarsolej, P.; van Haasteren, N.; Jager, M.V.; van Vught, A.; van Royen, B.J.

    2008-01-01

    Background: Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is

  5. Efficiency of selection methods for increased ratio of pupal-larval to adult-larval weight gains in Tribolium.

    Science.gov (United States)

    Campo, J L; Cobos, P

    1994-01-12

    Four lines of Tribolium castaneum were selected in each of three replicates for increased ratio of (pupal-larval) to (adult-larval) weight gains, using selection for increased (pupal-larval) weight gain (PL), selection for decreased (adult-larval) weight gain (AL), direct selection for the ratio (R) and linear selection index of larval, pupal and adult weights (I), respectively, for four generations. Linear index was calculated with economic weights of m(2) -m(3) , m(3) -m(1) and m(1) -m(2) , respectively, with m(1) , m(2) and m(3) being the means for larval, pupal and adult weights. Selection to increase the ratio is considered to be a method to maximize the mean response in (adult-larval) weight while controlling the response in (pupal-adult) weight, and as a form of antagonistic selection to increase the weight gain during a given age period relative to the gain at another age period. Larval, pupal and adult weights were measured at 14, 21 and 28 days after adult emergence, respectively. The selected proportion was 20 % in all lines. The response observed for the ratio differed significantly among lines (p adulto-peso de larva en Tribolium Cuatro líneas de Tribolium castaneum fueron seleccionadas en cada una de tres repeticiones para incrementar el cociente (peso de pupa-peso de larva)/(peso de adulto-peso de larva); la línea PL fue seleccionada para aumentar la diferencia (peso de pupa-pesp de larva), la línea AL fue seleccionada para disminuir la diferencia (peso de adulto-peso de larva), fa línea R fue seleccionada directamente para el cociente, y la línea I fue seleccionada por medio de un índice lineal basado en los pesos de larva, pupa y adulto, durante cuatro generaciones. El índice lineal se calculó con pesos económicos de (m(2) -m(3) ), (m(3) -m(1) ), y (m(1) -m(2) ) respectivamentee, siendo m(1) , m(2) , y m(3) los valores medios para el peso de larva, pupa y adulto. La selección para aumentar el cociente indicado es un método para maximizar

  6. Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency

    DEFF Research Database (Denmark)

    Thomsen, J L; Nielsen, C V; Palmqvist, D F

    2015-01-01

    , neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation prematurely awakened if anaesthesia had been terminated while the patient was still...... paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored...

  7. Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study

    OpenAIRE

    Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

    2017-01-01

    If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF a...

  8. Isolation and culture of larval cells from C. elegans.

    Directory of Open Access Journals (Sweden)

    Sihui Zhang

    Full Text Available Cell culture is an essential tool to study cell function. In C. elegans the ability to isolate and culture cells has been limited to embryonically derived cells. However, cells or blastomeres isolated from mixed stage embryos terminally differentiate within 24 hours of culture, thus precluding post-embryonic stage cell culture. We have developed an efficient and technically simple method for large-scale isolation and primary culture of larval-stage cells. We have optimized the treatment to maximize cell number and minimize cell death for each of the four larval stages. We obtained up to 7.8×10(4 cells per microliter of packed larvae, and up to 97% of adherent cells isolated by this method were viable for at least 16 hours. Cultured larval cells showed stage-specific increases in both cell size and multinuclearity and expressed lineage- and cell type-specific reporters. The majority (81% of larval cells isolated by our method were muscle cells that exhibited stage-specific phenotypes. L1 muscle cells developed 1 to 2 wide cytoplasmic processes, while L4 muscle cells developed 4 to 14 processes of various thicknesses. L4 muscle cells developed bands of myosin heavy chain A thick filaments at the cell center and spontaneously contracted ex vivo. Neurons constituted less than 10% of the isolated cells and the majority of neurons developed one or more long, microtubule-rich protrusions that terminated in actin-rich growth cones. In addition to cells such as muscle and neuron that are high abundance in vivo, we were also able to isolate M-lineage cells that constitute less than 0.2% of cells in vivo. Our novel method of cell isolation extends C. elegans cell culture to larval developmental stages, and allows use of the wealth of cell culture tools, such as cell sorting, electrophysiology, co-culture, and high-resolution imaging of subcellular dynamics, in investigation of post-embryonic development and physiology.

  9. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-12-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

  10. Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives.

    Science.gov (United States)

    Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

    2018-01-01

    The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed.

  11. Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

    Science.gov (United States)

    Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

    2016-12-01

    To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Proprioceptive Neuromuscular Facilitation (PNF): Its Mechanisms and Effects on Range of Motion and Muscular Function

    Science.gov (United States)

    Hindle, Kayla B.; Whitcomb, Tyler J.; Briggs, Wyatt O.; Hong, Junggi

    2012-01-01

    Proprioceptive neuromuscular facilitation (PNF) is common practice for increasing range of motion, though little research has been done to evaluate theories behind it. The purpose of this study was to review possible mechanisms, proposed theories, and physiological changes that occur due to proprioceptive neuromuscular facilitation techniques. Four theoretical mechanisms were identified: autogenic inhibition, reciprocal inhibition, stress relaxation, and the gate control theory. The studies suggest that a combination of these four mechanisms enhance range of motion. When completed prior to exercise, proprioceptive neuromuscular facilitation decreases performance in maximal effort exercises. When this stretching technique is performed consistently and post exercise, it increases athletic performance, along with range of motion. Little investigation has been done regarding the theoretical mechanisms of proprioceptive neuromuscular facilitation, though four mechanisms were identified from the literature. As stated, the main goal of proprioceptive neuromuscular facilitation is to increase range of motion and performance. Studies found both of these to be true when completed under the correct conditions. These mechanisms were found to be plausible; however, further investigation needs to be conducted. All four mechanisms behind the stretching technique explain the reasoning behind the increase in range of motion, as well as in strength and athletic performance. Proprioceptive neuromuscular facilitation shows potential benefits if performed correctly and consistently. PMID:23487249

  13. Josephson junctions of multiple superconducting wires

    Science.gov (United States)

    Deb, Oindrila; Sengupta, K.; Sen, Diptiman

    2018-05-01

    We study the spectrum of Andreev bound states and Josephson currents across a junction of N superconducting wires which may have s - or p -wave pairing symmetries and develop a scattering matrix based formalism which allows us to address transport across such junctions. For N ≥3 , it is well known that Berry curvature terms contribute to the Josephson currents; we chart out situations where such terms can have relatively large effects. For a system of three s -wave or three p -wave superconductors, we provide analytic expressions for the Andreev bound-state energies and study the Josephson currents in response to a constant voltage applied across one of the wires; we find that the integrated transconductance at zero temperature is quantized to integer multiples of 4 e2/h , where e is the electron charge and h =2 π ℏ is Planck's constant. For a sinusoidal current with frequency ω applied across one of the wires in the junction, we find that Shapiro plateaus appear in the time-averaged voltage across that wire for any rational fractional multiple (in contrast to only integer multiples in junctions of two wires) of 2 e /(ℏ ω ) . We also use our formalism to study junctions of two p -wave and one s -wave wires. We find that the corresponding Andreev bound-state energies depend on the spin of the Bogoliubov quasiparticles; this produces a net magnetic moment in such junctions. The time variation of these magnetic moments may be controlled by an external voltage applied across the junction. We discuss experiments which may test our theory.

  14. Josephson tunnel junctions with ferromagnetic interlayer

    International Nuclear Information System (INIS)

    Weides, M.P.

    2006-01-01

    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al 2 O 3 tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or π coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, π) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-π Josephson junction. At a certain temperature this 0-π junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum Φ 0 . Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T → 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  15. Josephson tunnel junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M.P.

    2006-07-01

    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al{sub 2}O{sub 3} tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or {pi} coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, {pi}) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-{pi} Josephson junction. At a certain temperature this 0-{pi} junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum {phi}{sub 0}. Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T {yields} 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  16. Macroscopic quantum tunneling in Josephson tunnel junctions and Coulomb blockade in single small tunnel junctions

    International Nuclear Information System (INIS)

    Cleland, A.N.

    1991-01-01

    Experiments investigated the process of macroscopic quantum tunneling in a moderately-damped, resistively shunted, Josephson junction are described, followed by a discussion of experiments performed on very-small-capacitance normal-metal tunnel junctions. The experiments on the resistively-shunted Josephson junction were designed to investigate a quantum process, that of the tunneling of the Josephson-phase variable under a potential barrier, in a system in which dissipation plays a major role in the dynamics of motion. All the parameters of the junction were measured using the classical phenomena of thermal activation and resonant activation. Theoretical predictions are compared with the experimental results, showing good agreement with no adjustable parameters. The experiments on small-capacitance tunnel junctions extend the measurements on the large-area Josephson junctions from the region in which the phase variable has a fairly well-defined value, i.e. its wave function has a narrow width, to the region where its value is almost completely unknown. The charge on the junction becomes well-defined and is predicted to quantize the current through the junction, giving rise to the Coulomb blockade at low bias

  17. Ballistic Graphene Josephson Junctions from the Short to the Long Junction Regimes.

    Science.gov (United States)

    Borzenets, I V; Amet, F; Ke, C T; Draelos, A W; Wei, M T; Seredinski, A; Watanabe, K; Taniguchi, T; Bomze, Y; Yamamoto, M; Tarucha, S; Finkelstein, G

    2016-12-02

    We investigate the critical current I_{C} of ballistic Josephson junctions made of encapsulated graphene-boron-nitride heterostructures. We observe a crossover from the short to the long junction regimes as the length of the device increases. In long ballistic junctions, I_{C} is found to scale as ∝exp(-k_{B}T/δE). The extracted energies δE are independent of the carrier density and proportional to the level spacing of the ballistic cavity. As T→0 the critical current of a long (or short) junction saturates at a level determined by the product of δE (or Δ) and the number of the junction's transversal modes.

  18. Increasing gap junctional coupling: a tool for dissecting the role of gap junctions

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Haugan, Ketil; Stahlhut, Martin

    2007-01-01

    Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions are important in many physiological processes....... In a number of cases, gap junctions have been implicated in the initiation and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing...... the role of gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide and its synthetic analogs...

  19. Immunohistochemical and ultrastructural properties of the larval ciliary band-associated strand in the sea urchin Hemicentrotus pulcherrimus.

    Science.gov (United States)

    Katow, Hideki; Katow, Tomoko; Yoshida, Hiromi; Kiyomoto, Masato; Uemura, Isao

    2016-01-01

    The swimming activity of sea urchin larvae is dependent on the ciliary band (CB) on the larval surface and is regulated by several neurotransmitters, including serotonin (5HT), dopamine, and γ-aminobutyric acid (GABA). However, the CB signal transmission mechanism remains unknown. The present study investigated the structural relationship between the CB and external signal receptors by immunohistochemical and transmission electron microscopic analyses of sea urchin, Hemicentrotus pulcherrimus, larvae. Glutamate decarboxylase (GAD; GABA synthetase) was detected in a strand of multiple cells along the circumoral CB in 6-arm plutei. The GAD-expressing strand was closely associated with the CB on the oral ectoderm side. The ciliary band-associated strand (CBAS) also expressed the 5HT receptor (5HThpr) and encephalopsin (ECPN) throughout the cytoplasm and comprised 1- to 2-μm diameter axon-like long stretched regions and sporadic 6- to 7-μm diameter bulbous nucleated regions (perikarya) that protruded into the oral ectoderm side. Besides the laterally polarized morphology of the CBAS cells, Epith-2, which is the epithelial lateral cell surface-specific protein of the sea urchin embryo and larva, was expressed exclusively by perikarya but not by the axon-like regions. The CBAS exposed its narrow apical surface on the larval epithelium between the CB and squamous cells and formed adherens junctions (AJs) on the apical side between them. Despite the presence of the CBAS axon-like regions, tubulins, such as α-, β-, and acetylated α-tubulins, were not detected. However, the neuroendocrine cell marker protein synaptophysin was detected in the axon-like regions and in bouton-like protrusions that contained numerous small ultrastructural vesicles. The unique morphology of the CBAS in the sea urchin larva epithelium had not been reported. The CBAS expresses a remarkable number of receptors to environmental stimuli and proteins that are probably involved in signal

  20. A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

    International Nuclear Information System (INIS)

    Hadley, Austin; Ding, George X.

    2014-01-01

    Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fields and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans

  1. Particle detection with superconducting tunnel junctions

    International Nuclear Information System (INIS)

    Jany, P.

    1990-08-01

    At the Institute of Experimental Nuclear Physics of the University of Karlsruhe (TH) and at the Institute for Nuclear Physics of the Kernforschungszentrum Karlsruhe we started to produce superconducting tunnel junctions and to investigate them for their suitability as particle detectors. The required facilities for the production of tunnel junctions and the experimental equipments to carry out experiments with them were erected. Experiments are presented in which radiations of different kinds of particles could successfully be measured with the tunnel junctions produced. At first we succeeded in detectioning light pulses of a laser. In experiments with alpha-particles of an energy of 4,6 MeV the alpha-particles were detected with an energy resolution of 1,1%, and it was shown in specific experiments that the phonons originating from the deposition of energy by an alpha-particle in the substrate can be detected with superconducting tunnel junctions at the surface. On that occasion it turned out that the signals could be separated with respect to their point of origin (tunnel junction, contact leads, substrate). Finally X-rays with an energy of 6 keV were detected with an energy resolution of 8% in a test arrangement that makes use of the so-called trapping effect to read out a larger absorber volume. (orig.) [de

  2. Joint diseases: from connexins to gap junctions.

    Science.gov (United States)

    Donahue, Henry J; Qu, Roy W; Genetos, Damian C

    2017-12-19

    Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

  3. Location Isn't Everything: Timing of Spawning Aggregations Optimizes Larval Replenishment.

    Directory of Open Access Journals (Sweden)

    Megan J Donahue

    Full Text Available Many species of reef fishes form large spawning aggregations that are highly predictable in space and time. Prior research has suggested that aggregating fish derive fitness benefits not just from mating at high density but, also, from oceanographic features of the spatial locations where aggregations occur. Using a probabilistic biophysical model of larval dispersal coupled to a fine resolution hydrodynamic model of the Florida Straits, we develop a stochastic landscape of larval fitness. Tracking virtual larvae from release to settlement and incorporating changes in larval behavior through ontogeny, we found that larval success was sensitive to the timing of spawning. Indeed, propagules released during the observed spawning period had higher larval success rates than those released outside the observed spawning period. In contrast, larval success rates were relatively insensitive to the spatial position of the release site. In addition, minimum (rather than mean larval survival was maximized during the observed spawning period, indicating a reproductive strategy that minimizes the probability of recruitment failure. Given this landscape of larval fitness, we take an inverse optimization approach to define a biological objective function that reflects a tradeoff between the mean and variance of larval success in a temporally variable environment. Using this objective function, we suggest that the length of the spawning period can provide insight into the tradeoff between reproductive risk and reward.

  4. Redescription of the early larval stages of the pandalid shrimp Chlorotocus crassicornis (Decapoda: Caridea: Pandalidae).

    Science.gov (United States)

    Landeira, Jose M; Jiang, Guo-Chen; Chan, Tin-Yam; Shih, Tung-Wei; Gozález-Gordillo, J Ignacio

    2015-09-07

    The first four larval stages of the pandalid shrimp Chlorotocus crassicornis (A. Costa, 1871) are described and illustrated from laboratory-reared material obtained from ovigerous females collected in the southwestern Spain and south Taiwan. The second to fourth larval stages of this species are reported for the first time to science. Detailed examination of the first larval stages reveals that previous description misidentified some key larval characters which have prevented its identification in plankton samples. It is found that the zoeal morphology of Chlorotocus is not very different from other pandalid larvae, and in fact closely resembles Plesionika and Heterocarpus.

  5. Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap.

    Science.gov (United States)

    Wiest, Matheus J; Bergquist, Austin J; Schimidt, Helen L; Jones, Kelvin E; Collins, David F

    2017-04-01

    In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017. © 2016 Wiley Periodicals, Inc.

  6. Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

    Science.gov (United States)

    Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

    1998-01-01

    VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

  7. Neuromuscular factors related to success in Olympic wrestling

    Directory of Open Access Journals (Sweden)

    Alfonso Martínez-Moreno

    2011-03-01

    Full Text Available Abstract This study was undertaken to determine the relationship between maximum dynamic and isometric strength and success in male and female Olympic wrestling. Thirty-five female and thirty-seven male wrestlers were assigned into 4 groups according to their gender and competitive level: men elite (♂ ET, n = 18 and amateur (AT ♂, n = 19 and female elite (♀ ET n = 13 and amateur (AT ♀, n = 22. All subjects underwent assessments of body composition, countermovement jump, maximum dynamic strength test in full squat and bench press exercises and maximum isometric strength test of grip and hip extension. All the neuromuscular markers studied showed significantly higher values in the two elite groups compared to their respective amateur groups results, except the jump height between ♀ET y ♀AT, where no significant differences were detected. The present results suggest that the higher maximum isometric and dynamic strength values, explained in part by the differences in lean mass, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling.  Key  Words: bench press; squat; maximum dynamic strength; maximum isometric strength; combat.

  8. Neuromuscular factors related to success in Olympic wrestling

    Directory of Open Access Journals (Sweden)

    Alfonso Martínez-Moreno

    2011-03-01

    Full Text Available AbstractThis study was undertaken to determine the relationship between maximum dynamic and isometric strength and success in male and female Olympic wrestling. Thirty-five female and thirty-seven male wrestlers were assigned into 4 groups according to their gender and competitive level: men elite (♂ ET, n = 18 and amateur (AT ♂, n = 19 and female elite (♀ ET n = 13 and amateur (AT ♀, n = 22. All subjects underwent assessments of body composition, countermovement jump, maximum dynamic strength test in full squat and bench press exercises and maximum isometric strength test of grip and hip extension. All the neuromuscular markers studied showed significantly higher values in the two elite groups compared to their respective amateur groups results, except the jump height between ♀ET y ♀AT, where no significant differences were detected. The present results suggest that the higher maximum isometric and dynamic strength values, explained in part by the differences in lean mass, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling. Key  Words: bench press; squat; maximum dynamic strength; maximum isometric strength; combat.

  9. Neuromuscular adjustments of the quadriceps muscle after repeated cycling sprints.

    Directory of Open Access Journals (Sweden)

    Olivier Girard

    Full Text Available PURPOSE: This study investigated the supraspinal processes of fatigue of the quadriceps muscle in response to repeated cycling sprints. METHODS: Twelve active individuals performed 10 × 6-s "all-out" sprints on a cycle ergometer (recovery = 30 s, followed 6 min later by 5 × 6-s sprints (recovery = 30 s. Transcranial magnetic and electrical femoral nerve stimulations during brief (5-s and sustained (30-s isometric contractions of the knee extensors were performed before and 3 min post-exercise. RESULTS: Maximal strength of the knee extensors decreased during brief and sustained contractions (~11% and 9%, respectively; P0.05. While cortical voluntary activation declined (P 40% reduced (P<0.001 following exercise. CONCLUSION: The capacity of the motor cortex to optimally drive the knee extensors following a repeated-sprint test was shown in sustained, but not brief, maximal isometric contractions. Additionally, peripheral factors were largely involved in the exercise-induced impairment in neuromuscular function, while corticospinal excitability was well-preserved.

  10. Alterations in neuromuscular function in girls with generalized joint hypermobility.

    Science.gov (United States)

    Jensen, Bente Rona; Sandfeld, Jesper; Melcher, Pia Sandfeld; Johansen, Katrine Lyders; Hendriksen, Peter; Juul-Kristensen, Birgit

    2016-10-03

    Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions (90°) at 20 % Maximum Voluntary Contraction, and explosive isometric knee flexions while sitting. EMG was recorded from knee flexor and extensor muscles. Early rate of torque development was 53 % faster for GJH. Reduced hamstring muscle activation in girls with GJH was found while knee extensor and calf muscle activation did not differ between groups. Flexion-extension and medial-lateral co-activation ratio during flexions were higher for girls with GJH than NGJH girls. Girls with GJH had higher capacity to rapidly generate force than NGJH girls which may reflect motor adaptation to compensate for hypermobility. Higher medial muscle activation indicated higher levels of medial knee joint compression in girls with GJH. Increased flexion-extension co-activation ratios in GJH were explained by decreased agonist drive to the hamstrings.

  11. Long-term neuromuscular training and ankle joint position sense.

    Science.gov (United States)

    Kynsburg, A; Pánics, G; Halasi, T

    2010-06-01

    Preventive effect of proprioceptive training is proven by decreasing injury incidence, but its proprioceptive mechanism is not. Major hypothesis: the training has a positive long-term effect on ankle joint position sense in athletes of a high-risk sport (handball). Ten elite-level female handball-players represented the intervention group (training-group), 10 healthy athletes of other sports formed the control-group. Proprioceptive training was incorporated into the regular training regimen of the training-group. Ankle joint position sense function was measured with the "slope-box" test, first described by Robbins et al. Testing was performed one day before the intervention and 20 months later. Mean absolute estimate errors were processed for statistical analysis. Proprioceptive sensory function improved regarding all four directions with a high significance (pneuromuscular training has improved ankle joint position sense function in the investigated athletes. This joint position sense improvement can be one of the explanations for injury rate reduction effect of neuromuscular training.

  12. Kinematic and neuromuscular relationships between lower extremity clinical movement assessments.

    Science.gov (United States)

    Mauntel, Timothy C; Cram, Tyler R; Frank, Barnett S; Begalle, Rebecca L; Norcross, Marc F; Blackburn, J Troy; Padua, Darin A

    2018-06-01

    Lower extremity injuries have immediate and long-term consequences. Lower extremity movement assessments can assist with identifying individuals at greater injury risk and guide injury prevention interventions. Movement assessments identify similar movement characteristics and evidence suggests large magnitude kinematic relationships exist between movement patterns observed across assessments; however, the magnitude of the relationships for electromyographic (EMG) measures across movement assessments remains largely unknown. This study examined relationships between lower extremity kinematic and EMG measures during jump landings and single leg squats. Lower extremity three-dimensional kinematic and EMG data were sampled from healthy adults (males = 20, females = 20) during the movement assessments. Pearson correlations examined the relationships of the kinematic and EMG measures and paired samples t-tests compared mean kinematic and EMG measures between the assessments. Overall, significant moderate correlations were observed for lower extremity kinematic (r avg  = 0.41, r range  = 0.10-0.61) and EMG (r avg  = 0.47, r range  = 0.32-0.80) measures across assessments. Kinematic and EMG measures were greater during the jump landings. Jump landings and single leg squats place different demands on the body and necessitate different kinematic and EMG patterns, such that these measures are not highly correlated between assessments. Clinicians should, therefore, use multiple assessments to identify aberrant movement and neuromuscular control patterns so that comprehensive interventions can be implemented.

  13. Validity of the Neuromuscular Recovery Scale: a measurement model approach.

    Science.gov (United States)

    Velozo, Craig; Moorhouse, Michael; Ardolino, Elizabeth; Lorenz, Doug; Suter, Sarah; Basso, D Michele; Behrman, Andrea L

    2015-08-01

    To determine how well the Neuromuscular Recovery Scale (NRS) items fit the Rasch, 1-parameter, partial-credit measurement model. Confirmatory factor analysis (CFA) and principal components analysis (PCA) of residuals were used to determine dimensionality. The Rasch, 1-parameter, partial-credit rating scale model was used to determine rating scale structure, person/item fit, point-measure item correlations, item discrimination, and measurement precision. Seven NeuroRecovery Network clinical sites. Outpatients (N=188) with spinal cord injury. Not applicable. NRS. While the NRS met 1 of 3 CFA criteria, the PCA revealed that the Rasch measurement dimension explained 76.9% of the variance. Ten of 11 items and 91% of the patients fit the Rasch model, with 9 of 11 items showing high discrimination. Sixty-nine percent of the ratings met criteria. The items showed a logical item-difficulty order, with Stand retraining as the easiest item and Walking as the most challenging item. The NRS showed no ceiling or floor effects and separated the sample into almost 5 statistically distinct strata; individuals with an American Spinal Injury Association Impairment Scale (AIS) D classification showed the most ability, and those with an AIS A classification showed the least ability. Items not meeting the rating scale criteria appear to be related to the low frequency counts. The NRS met many of the Rasch model criteria for construct validity. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. The rapid evolution of molecular genetic diagnostics in neuromuscular diseases.

    Science.gov (United States)

    Volk, Alexander E; Kubisch, Christian

    2017-10-01

    The development of massively parallel sequencing (MPS) has revolutionized molecular genetic diagnostics in monogenic disorders. The present review gives a brief overview of different MPS-based approaches used in clinical diagnostics of neuromuscular disorders (NMDs) and highlights their advantages and limitations. MPS-based approaches like gene panel sequencing, (whole) exome sequencing, (whole) genome sequencing, and RNA sequencing have been used to identify the genetic cause in NMDs. Although gene panel sequencing has evolved as a standard test for heterogeneous diseases, it is still debated, mainly because of financial issues and unsolved problems of variant interpretation, whether genome sequencing (and to a lesser extent also exome sequencing) of single patients can already be regarded as routine diagnostics. However, it has been shown that the inclusion of parents and additional family members often leads to a substantial increase in the diagnostic yield in exome-wide/genome-wide MPS approaches. In addition, MPS-based RNA sequencing just enters the research and diagnostic scene. Next-generation sequencing increasingly enables the detection of the genetic cause in highly heterogeneous diseases like NMDs in an efficient and affordable way. Gene panel sequencing and family-based exome sequencing have been proven as potent and cost-efficient diagnostic tools. Although clinical validation and interpretation of genome sequencing is still challenging, diagnostic RNA sequencing represents a promising tool to bypass some hurdles of diagnostics using genomic DNA.

  15. HEMODYNAMIC AND LACTIC ACID RESPONSES TO PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION EXERCISE

    Directory of Open Access Journals (Sweden)

    Zuhal Gültekin

    2006-09-01

    Full Text Available The hemodynamic and metabolic responses to proprioceptive neuromuscular facilitation (PNF exercise were examined in 32 male university students (aged 19-28 years. Ten repetitions of PNF exercises were applied to the subjects' dominant upper extremities in the following order: as an agonist pattern flexion, adduction and external rotation; and as an antagonist pattern extension, abduction and internal rotation. Heart rate (HR, systolic blood pressure (SBP, diastolic blood pressure (DBP, double product (DP, and blood lactate concentration (La were determined before, immediately after, and at 1st, 3rd, and 5th minutes after PNF exercise. A one-way ANOVA with repeated measures indicated significant differences in HR, SBP, DBP, DP and La immediately after PNF exercise. HR increased from 81 (±10 to 108 (±15 b·min-1 (p < 0.01, SBP increased from 117 (±10 to 125 (±11 mmHg (p < 0.01, DBP increased from 71 (±10 to 75 (±8 mmHg (p < 0.01, DP increased from 96 (±16 to 135 (±24 (p < 0.01, and La increased from 0.69 (±0.31 to 3.99 (±14.63 mmol·L-1 (p < 0.01. Thus PNF exercise resulted in increased hemodynamic responses and blood lactate concentration that indicate a high strain on the cardiovascular system and anaerobic metabolism in healthy subjects

  16. Neurologic and neuromuscular functional disorders of the pharynx and esophagus

    International Nuclear Information System (INIS)

    Wuttge-Hannig, A.; Hannig, C.

    2007-01-01

    Neurologic swallowing disorders are an increasing diagnostic problem in our overaged population. Undiagnosed chronic aspiration pneumonia is the cause of death in 20-40% of all inhabitants of nursing homes. In neurologic diseases of the pharynx, the physiologic interaction of pharyngeal contraction, closure of the pharynx, and esophageal motility are frequently disturbed. This may be due to cortical, bulbar, or cerebellar brain damage of ischemic or traumatic origin. Furthermore diseases or peripheral nerves, muscles, and synapses cause disturbances. The most life-threatening complication of these disturbances is tracheal aspiration, which requires an iso-osmolar contrast medium for imaging studies that cause no or minimal pulmonary problems. Utilizing fast dynamic documentation we can analyze the swallowing act in 35 images within the passage time of 0.7 s. This requires digital frame sequences from 15-50 images/s, which can be provided by DSI or videofluoroscopy. Neurologic and neuromuscular patterns are demonstrated with and without tracheal aspiration. The differentiation of aspiration in a so-called pre-, intra-, and postdeglutitive form is possible. We distinguish four grades of severity of aspiration, which is also of great clinical impact for the differential rehabilitation therapy. The efficiency of the rehabilitation protocol can be assessed by the dynamic swallowing studies. (orig.) [de

  17. Role of analgesics, sedatives, neuromuscular blockers, and delirium.

    Science.gov (United States)

    Hall, Jesse B; Schweickert, William; Kress, John P

    2009-10-01

    A major focus on critical care medicine concerns the institution of life-support therapies, such as mechanical ventilation, during periods of organ failure to permit a window of opportunity to diagnose and treat underlying disorders so that patients may be returned to their prior functional status upon recovery. With the growing success of these intensive care unit-based therapies and longer-term follow-up of patients, severe weakness involving the peripheral nervous system and muscles has been identified in many recovering patients, often confounding the time course or magnitude of recovery. Mechanical ventilation is often accompanied by pharmacologic treatments including analgesics, sedatives, and neuromuscular blockers. These drugs and the encephalopathies accompanying some forms of critical illness result in a high prevalence of delirium in mechanically ventilated patients. These drug effects likely contribute to an impaired ability to assess the magnitude of intensive care unit-acquired weakness, to additional time spent immobilized and mechanically ventilated, and to additional weakness from the patient's relative immobility and bedridden state. This review surveys recent literature documenting these relationships and identifying approaches to minimize pharmacologic contributions to intensive care unit-acquired weakness.

  18. Peripheral neuromuscular dysfunction and falls in an elderly cohort.

    Science.gov (United States)

    Sorock, G S; Labiner, D M

    1992-09-01

    In a prospective study of 169 tenants of senior citizen housing in New Jersey in 1986-1987, the relations between tests of peripheral sensory and motor functions in the lower extremities and the rate of first falls were evaluated. The mean age of the cohort was 79.8 years. Fifty-seven persons fell at least once during the follow-up period (mean, 5.6 months). After adjustment for history of stroke, heart failure, emphysema, and use of a walker or cane, rate ratios for first falls were elevated in subjects with reduced toe joint position sense (rate ratio (RR) = 2.2) and sharp-dull discrimination (RR = 2.0), but to a lesser extent for reduced ankle strength (RR = 1.5). Presence of one or more of these three deficits was defined as a peripheral neuromuscular dysfunction and was associated with first falls after adjustment for multiple covariates (RR = 2.4, 95% confidence interval 1.3-4.5). Having two or all three sensory or motor deficits increased the rate of falling 3.9 times (95% confidence interval 2.1-7.0) compared with persons without these deficits. These data suggest that impaired sensory and motor function of the lower extremities plays an important role in falls in the elderly.

  19. Applications of Shape Memory Alloys for Neurology and Neuromuscular Rehabilitation

    Directory of Open Access Journals (Sweden)

    Simone Pittaccio

    2015-05-01

    Full Text Available Shape memory alloys (SMAs are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE, shape memory effect (SME and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous.

  20. Noninvasive Respiratory Management of Patients With Neuromuscular Disease.

    Science.gov (United States)

    Bach, John R

    2017-08-01

    This review article describes definitive noninvasive respiratory management of respiratory muscle dysfunction to eliminate need to resort to tracheotomy. In 2010 clinicians from 22 centers in 18 countries reported 1,623 spinal muscular atrophy type 1 (SMA1), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis users of noninvasive ventilatory support (NVS) of whom 760 required it continuously (CNVS). The CNVS sustained their lives by over 3,000 patient-years without resort to indwelling tracheostomy tubes. These centers have now extubated at least 74 consecutive ventilator unweanable patients with DMD, over 95% of CNVS-dependent patients with SMA1, and hundreds of others with advanced neuromuscular disorders (NMDs) without resort to tracheotomy. Two centers reported a 99% success rate at extubating 258 ventilator unweanable patients without resort to tracheotomy. Patients with myopathic or lower motor neuron disorders can be managed noninvasively by up to CNVS, indefinitely, despite having little or no measurable vital capacity, with the use of physical medicine respiratory muscle aids. Ventilator-dependent patients can be decannulated of their tracheostomy tubes.

  1. Evaluation of ventilators for mouthpiece ventilation in neuromuscular disease.

    Science.gov (United States)

    Khirani, Sonia; Ramirez, Adriana; Delord, Vincent; Leroux, Karl; Lofaso, Frédéric; Hautot, Solène; Toussaint, Michel; Orlikowski, David; Louis, Bruno; Fauroux, Brigitte

    2014-09-01

    Daytime mouthpiece ventilation is a useful adjunct to nocturnal noninvasive ventilation (NIV) in patients with neuromuscular disease. The aims of the study were to analyze the practice of mouthpiece ventilation and to evaluate the performance of ventilators for mouthpiece ventilation. Practice of mouthpiece ventilation was assessed by a questionnaire, and the performance of 6 home ventilators with mouthpiece ventilation was assessed in a bench test using 24 different conditions per ventilator: 3 mouthpieces, a child and an adult patient profile, and 4 ventilatory modes. Questionnaires were obtained from 30 subjects (mean age 33 ± 11 y) using NIV for 12 ± 7 y. Fifteen subjects used NIV for > 20 h/day, and 11 were totally ventilator-dependent. The subject-reported benefits of mouthpiece ventilation were a reduction in dyspnea (73%) and fatigue (93%) and an improvement in speech (43%) and eating (27%). The bench study showed that none of the ventilators, even those with mouthpiece ventilation software, were able to deliver mouthpiece ventilation without alarms and/or autotriggering in each condition. Alarms and/or ineffective triggering or autotriggering were observed in 135 of the 198 conditions. The occurrence of alarms was more common with a large mouthpiece without a filter compared to a small mouthpiece with a filter (P ventilator. Subjects are satisfied with mouthpiece ventilation. Alarms are common with home ventilators, although less common in those with mouthpiece ventilation software. Improvements in home ventilators are needed to facilitate the expansion of mouthpiece ventilation. Copyright © 2014 by Daedalus Enterprises.

  2. Supervised neuromuscular exercise prior to hip and knee replacement

    DEFF Research Database (Denmark)

    Fernandes, Linda; Roos, Ewa M; Overgaard, Søren

    2017-01-01

    was analysed to estimate the probability for the intervention being cost effective for a range of threshold values. A health care sector perspective was applied. RESULTS: HOOS/KOOS quality of life [8.25 (95% CI, 0.42 to 16.10)] and QALYs [0.04 (95% CI, 0.01 to 0.07)] were statistically significantly improved....... Effect-sizes ranged between 0.09-0.59 for HOOS/KOOS subscales. Despite including an intervention cost of €326 per patient, there was no difference in total cost between groups [€132 (95% CI -3942 to 3679)]. At a threshold of €40,000, preoperative exercise was found to be cost effective at 84% probability....... CONCLUSION: Preoperative supervised neuromuscular exercise for 8 weeks was found to be cost-effective in patients scheduled for THR and TKR surgery at conventional thresholds for willingness to pay. One-year clinical effects were small to moderate and favoured the intervention group, but only statistically...

  3. Lower Limb Neuromuscular Asymmetry in Volleyball and Basketball Players.

    Science.gov (United States)

    Fort-Vanmeerhaeghe, Azahara; Gual, Gabriel; Romero-Rodriguez, Daniel; Unnitha, Viswanath

    2016-04-01

    The primary objective of the present study was to evaluate the agreement between the dominant leg (DL) (determined subjectively) and the stronger leg (SL) (determined via a functional test) in a group of basketball and volleyball players. The secondary objective was to calculate lower limb neuromuscular asymmetry when comparing the DL vs the non-dominant leg (NDL) and the SL vs the weaker (WL) leg in the whole group and when differentiating by sex. Seventy-nine male and female volleyball and basketball players (age: 23.7 ± 4.5 years) performed three single-leg vertical countermovement jumps (SLVCJ) on a contact mat. Vertical jump height and an inter-limb asymmetry index (ASI) were determined. Only 32 (40%) of the subjects had a concordance between the perception of their dominant leg and the limb reaching the highest jump height. Using the DL as the discriminating variable, significant (pjump performance. Vertical jump asymmetry of 10-15% exists and this can be considered as a reference value for male and female basketball and volleyball players.

  4. An examination of neuromuscular and metabolic fatigue thresholds

    International Nuclear Information System (INIS)

    Bergstrom, Haley C; Housh, Terry J; Cochrane, Kristen C; Jenkins, Nathaniel D M; Lewis, Robert W Jr; Traylor, Daniel A; Schmidt, Richard J; Johnson, Glen O; Cramer, Joel T; Zuniga, Jorge M

    2013-01-01

    This study examined the relationships among the physical working capacity at the fatigue threshold (PWC FT ), the power outputs associated with the gas exchange threshold (PGET) and the respiratory compensation point (PRCP), and critical power (CP) to identify possible physiological mechanisms underlying the onset of neuromuscular fatigue. Ten participants (mean ± SD age: 20 ± 1 years) performed a maximal incremental cycle ergometer test to determine the PWC FT , PGET, and PRCP. CP was determined from the 3 min all-out test. The PWC FT (197 ± 55 W), PRCP (212 ± 50 W), and CP (208 ± 63 W) were significantly greater than the PGET (168 ± 40 W), but there were no significant differences among the PWC FT , PRCP, and CP. All thresholds were significantly inter-4 (r = 0.794–0.958). The 17% greater estimates for the PWC FT than PGET were likely related to differences in the physiological mechanisms that underlie these fatigue thresholds, while the non-significant difference and high correlation between the PWC FT and the PRCP suggested that hyperkalemia may underlie both thresholds. Furthermore, it is possible that the 5% lower estimate of the PWC FT than CP could more accurately reflect the demarcation of the heavy from severe exercise intensity domains. (paper)

  5. A family of neuromuscular stimulators with optical transcutaneous control.

    Science.gov (United States)

    Jarvis, J C; Salmons, S

    1991-01-01

    A family of miniature implantable neuromuscular stimulators has been developed using surface-mounted Philips 4000-series integrated circuits. The electronic components are mounted by hand on printed circuits (platinum/gold on alumina) and the electrical connections are made by reflow soldering. The plastic integrated-circuit packages, ceramic resistors and metal interconnections are protected from the body fluids by a coating of biocompatible silicone rubber. This simple technology provides reliable function for at least 4 months under implanted conditions. The circuits have in common a single lithium cell power-supply (3.2 V) and an optical sensor which can be used to detect light flashes through the skin after the device has been implanted. This information channel may be used to switch the output of a device on or off, or to cycle through a series of pre-set programs. The devices are currently finding application in studies which provide an experimental basis for the clinical exploitation of electrically stimulated skeletal muscle in cardiac assistance, sphincter reconstruction or functional electrical stimulation of paralysed limbs.

  6. Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

    Science.gov (United States)

    Pallarés, J G; López-Samanes, Á; Fernández-Elías, V E; Aguado-Jiménez, R; Ortega, J F; Gómez, C; Ventura, R; Segura, J; Mora-Rodríguez, R

    2015-12-01

    This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Terahertz Responses of Intrinsic Josephson Junctions in High TC Superconductors

    International Nuclear Information System (INIS)

    Wang, H. B.; Wu, P. H.; Yamashita, T.

    2001-01-01

    High frequency responses of intrinsic Josephson junctions up to 2.5THz, including the observation of Shapiro steps under various conditions, are reported and discussed in this Letter. The sample was an array of intrinsic Josephson junctions singled out from inside a high T C superconducting Bi 2 Sr 2 CaCu 2 O 8+x single crystal, with a bow-tie antenna integrated to it. The number of junctions in the array was controllable, the junctions were homogeneous, the distribution of applied irradiation among the junctions was even, and the junctions could synchronously respond to high frequency irradiation

  8. Phase-dependent noise in Josephson junctions

    Science.gov (United States)

    Sheldon, Forrest; Peotta, Sebastiano; Di Ventra, Massimiliano

    2018-03-01

    In addition to the usual superconducting current, Josephson junctions (JJs) support a phase-dependent conductance related to the retardation effect of tunneling quasi-particles. This introduces a dissipative current with a memory-resistive (memristive) character that should also affect the current noise. By means of the microscopic theory of tunnel junctions we compute the complete current autocorrelation function of a Josephson tunnel junction and show that this memristive component gives rise to both a previously noted phase-dependent thermal noise, and an undescribed non-stationary, phase-dependent dynamic noise. As experiments are approaching ranges in which these effects may be observed, we examine the form and magnitude of these processes. Their phase dependence can be realized experimentally as a hysteresis effect and may be used to probe defects present in JJ based qubits and in other superconducting electronics applications.

  9. Phonon spectroscopy with superconducting tunnel junctions

    International Nuclear Information System (INIS)

    Grimshaw, J.M.

    1984-02-01

    Superconducting tunnel junctions can be used as generators and detectors of monochromatic phonons of frequency larger than 80 GHz, as was first devised by Eisenmenger and Dayem (1967) and Kinder (1972a, 1973). In this report, we intend to give a general outline of this type of spectroscopy and to present the results obtained so far. The basic physics underlying phonon generation and detection are described in chapter I, a wider approach being given in the references therein. In chapter II, the different types of junctions are considered with respect to their use. Chapter III deals with the evaporation technique for the superconducting junctions. The last part of this report is devoted to the results that we have obtained on γ-irradiated LiF, pure Si and Phosphorous implanted Si. In these chapters, the limitations of the spectrometer are brought out and suggestions for further work are given [fr

  10. Silicon fiber with p-n junction

    International Nuclear Information System (INIS)

    Homa, D.; Cito, A.; Pickrell, G.; Hill, C.; Scott, B.

    2014-01-01

    In this study, we fabricated a p-n junction in a fiber with a phosphorous doped silicon core and fused silica cladding. The fibers were fabricated via a hybrid process of the core-suction and melt-draw techniques and maintained overall diameters ranging from 200 to 900 μm and core diameters of 20–800 μm. The p-n junction was formed by doping the fiber with boron and confirmed via the current-voltage characteristic. The demonstration of a p-n junction in a melt-drawn silicon core fiber paves the way for the seamless integration of optical and electronic devices in fibers.

  11. Tunnel magnetoresistance in double spin filter junctions

    International Nuclear Information System (INIS)

    Saffarzadeh, Alireza

    2003-01-01

    We consider a new type of magnetic tunnel junction, which consists of two ferromagnetic tunnel barriers acting as spin filters (SFs), separated by a nonmagnetic metal (NM) layer. Using the transfer matrix method and the free-electron approximation, the dependence of the tunnel magnetoresistance (TMR) on the thickness of the central NM layer, bias voltage and temperature in the double SF junction are studied theoretically. It is shown that the TMR and electron-spin polarization in this structure can reach very large values under suitable conditions. The highest value of the TMR can reach 99%. By an appropriate choice of the thickness of the central NM layer, the degree of spin polarization in this structure will be higher than that of the single SF junctions. These results may be useful in designing future spin-polarized tunnelling devices

  12. Josephson junctions with ferromagnetic alloy interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Himmel, Nico

    2015-07-23

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO{sub x} vertical stroke Nb vertical stroke Ni{sub 60}Cu{sub 40} vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially

  13. Electrical analog of a Josephson junction

    International Nuclear Information System (INIS)

    Goldman, A.M.

    1979-01-01

    It is noted that a mathematical description of the phase-coupling of two oscillators synchronized by a phase-lock-loop under the influence of thermal white noise is analogous to that of the phase coupling of two superconductors in a Josephson junction also under the influence of noise. This analogy may be useful in studying threshold instabilities of the Josephson junction in regimes not restricted to the case of large damping. This is of interest because the behavior of the mean voltage near the threshold current can be characterized by critical exponents which resemble those exhibited by an order parameter of a continuous phase transition. As it is possible to couple a collection of oscillators together in a chain, the oscillator analogy may also be useful in exploring the dynamics and statistical mechanics of coupled junctions

  14. Thermionic refrigeration at CNT-CNT junctions

    Science.gov (United States)

    Li, C.; Pipe, K. P.

    2016-10-01

    Monte Carlo (MC) simulation is used to study carrier energy relaxation following thermionic emission at the junction of two van der Waals bonded single-walled carbon nanotubes (SWCNTs). An energy-dependent transmission probability gives rise to energy filtering at the junction, which is predicted to increase the average electron transport energy by as much as 0.115 eV, leading to an effective Seebeck coefficient of 386 μV/K. MC results predict a long energy relaxation length (˜8 μm) for hot electrons crossing the junction into the barrier SWCNT. For SWCNTs of optimal length, an analytical transport model is used to show that thermionic cooling can outweigh parasitic heat conduction due to high SWCNT thermal conductivity, leading to a significant cooling capacity (2.4 × 106 W/cm2).

  15. Josephson junctions with ferromagnetic alloy interlayer

    International Nuclear Information System (INIS)

    Himmel, Nico

    2015-01-01

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO x vertical stroke Nb vertical stroke Ni 60 Cu 40 vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially a variation of

  16. Do effects of mercury in larval amphibians persist after metamorphosis?

    Science.gov (United States)

    Todd, Brian D; Willson, John D; Bergeron, Christine M; Hopkins, William A

    2012-01-01

    Despite widespread concern about the role of environmental contaminants in global amphibian declines, and evidence that post-metamorphic life stages contribute disproportionately to amphibian population dynamics, most studies in amphibian ecotoxicology focus on larval life stages. Studies that focus solely on early life stages may miss important effects of contaminant exposure, such as latent effects that manifest some time after previous exposure. Moreover, it is often assumed that effects observed in amphibian larvae will persist to affect survival or reproduction later in life. We used terrestrial enclosures to determine whether exposure to mercury (Hg) through maternal transfer and/or larval diet had any adverse effects in post-metamorphic American toads (Bufo americanus). We found a 5% difference in size at metamorphosis that was attributed to maternal Hg exposure persisted for 1 year in the terrestrial environment, resulting in a 7% difference at the conclusion of the study. Although patterns of survival differed among treatments through time, we found no overall difference in survival after 1 year. We also found no evidence of emergent latent effects in the terrestrial toads that could be attributed to earlier exposure. Our results indicate that adverse effects of maternal Hg exposure that were observed in larval amphibians may persist to affect later terrestrial life stages but that no novel adverse effects developed when animals were raised in a semi-natural environment. Moreover, we found no evidence of persistent effects of dietary Hg exposure in larvae, highlighting a need for greater focus on maternal effects in amphibian ecotoxicology. Finally, we suggest an increase in the use of longitudinal studies to better understand contaminant impacts to amphibian populations via effects in both aquatic and terrestrial life stages.

  17. Ocean acidification alters temperature and salinity preferences in larval fish.

    Science.gov (United States)

    Pistevos, Jennifer C A; Nagelkerken, Ivan; Rossi, Tullio; Connell, Sean D

    2017-02-01

    Ocean acidification alters the way in which animals perceive and respond to their world by affecting a variety of senses such as audition, olfaction, vision and pH sensing. Marine species rely on other senses as well, but we know little of how these might be affected by ocean acidification. We tested whether ocean acidification can alter the preference for physicochemical cues used for dispersal between ocean and estuarine environments. We experimentally assessed the behavioural response of a larval fish (Lates calcarifer) to elevated temperature and reduced salinity, including estuarine water of multiple cues for detecting settlement habitat. Larval fish raised under elevated CO 2 concentrations were attracted by warmer water, but temperature had no effect on fish raised in contemporary CO 2 concentrations. In contrast, contemporary larvae were deterred by lower salinity water, where CO 2 -treated fish showed no such response. Natural estuarine water-of higher temperature, lower salinity, and containing estuarine olfactory cues-was only preferred by fish treated under forecasted high CO 2 conditions. We show for the first time that attraction by larval fish towards physicochemical cues can be altered by ocean acidification. Such alterations to perception and evaluation of environmental cues during the critical process of dispersal can potentially have implications for ensuing recruitment and population replenishment. Our study not only shows that freshwater species that spend part of their life cycle in the ocean might also be affected by ocean acidification, but that behavioural responses towards key physicochemical cues can also be negated through elevated CO 2 from human emissions.

  18. Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives

    Directory of Open Access Journals (Sweden)

    Carron M

    2017-12-01

    Full Text Available Michele Carron, Francesco Bertoncello, Giovanna Ieppariello Department of Medicine, Anesthesiology, and Intensive Care, University of Padova, Padua, Italy Abstract: The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed. Keywords: sugammadex, aging, elderly, neuromuscular blockade, rocuronium, anesthesia, safety

  19. Characterization of cervical neuromuscular response to head-neck perturbation in active young adults.

    Science.gov (United States)

    Alsalaheen, Bara; Bean, Ryan; Almeida, Andrea; Eckner, James; Lorincz, Matthew

    2018-04-01

    The majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response. Nineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: (1) Anticipated perturbation with no preload (A-NP), (2) Unanticipated perturbation with no preload (U-NP), (3) Anticipated perturbation with preload (A-P), and (4) Unanticipated perturbation with preload (U-P). None of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM. The findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Parasites of larval black flies (Diptera: Simuliidae in Thailand

    Directory of Open Access Journals (Sweden)

    Sanae Jitklang

    2012-12-01

    Full Text Available Parasites of larval black flies are reported for the first time from Thailand, including mermithid nematodes(Mermithidae, microsporidian fungi (Zygomycota, and the fungus Coelomycidium simulii Debaisieux (Blastocladiomycetes.The following nine species of black flies were infected with one or more parasites: Simulium asakoae, S. chamlongi,S. chiangmaiense, S. fenestratum, S. feuerborni, S. nakhonense, S. nodosum, S. quinquestriatum, and S. tani. The prevalenceof patent infections per host species per season was 0.1–7.1% for mermithids, 0.1–6.0% for microsporidia, and 0.1–3.0% forC. simulii.