WorldWideScience
 
 
1

Glutamate Excitotoxicity Inflicts Paranodal Myelin Splitting and Retraction  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting ...

Fu, Yan; Sun, Wenjing; Shi, Yunzhou; Shi, Riyi; Cheng, Ji-xin

2009-01-01

2

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mechanical injury causes myelin disruption and subsequent axonal conduction failure in the mammalian spinal cord. However, the underlying mechanism is not well understood. In mammalian myelinated axons, proper paranodal myelin structure is crucial for the generation and propagation of action potentials. The exposure of potassium channels at the juxtaparanodal region due to myelin disruption is thought to induce outward potassium currents and inhibit the genesis of the action potential, leadin...

Sun, Wenjing; Fu, Yan; Shi, Yuzhou; Cheng, Ji-xin; Cao, Peng; Shi, Riyi

2012-01-01

3

Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.  

Science.gov (United States)

This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity. PMID:23844090

Babbs, Charles F; Shi, Riyi

2013-01-01

4

Subtle Paranodal Injury Slows Impulse Conduction in a Mathematical Model of Myelinated Axons  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myeli...

2013-01-01

5

Real-Time CARS Imaging Reveals a Calpain-Dependent Pathway for Paranodal Myelin Retraction during High-Frequency Stimulation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retrac...

Huff, Terry B.; Shi, Yunzhou; Sun, Wenjing; Wu, Wei; Shi, Riyi; Cheng, Ji-xin

2011-01-01

6

Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers.  

Science.gov (United States)

In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na(+) currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS. PMID:19880143

Piao, Hua; Minohara, Motozumi; Kawamura, Nobutoshi; Li, Wei; Mizunoe, Yoshimitsu; Umehara, Fujio; Goto, Yoshinobu; Kusunoki, Susumu; Matsushita, Takuya; Ikenaka, Kazuhiro; Maejima, Takashi; Nabekura, Jun-ichi; Yamasaki, Ryo; Kira, Jun-ichi

2010-01-15

7

Electron tomography of paranodal septate-like junctions and the associated axonal and glial cytoskeletons in the central nervous system  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The polarized domains of myelinated axons are specifically organized to maximize the efficiency of saltatory conduction. The paranodal region is directly adjacent to the node of Ranvier and contains specialized septate-like junctions that provide adhesion between axons and glial cells and that pose a lateral diffusion barrier for nodal components. To complement and extend earlier studies on the peripheral nervous system, electron tomography was used to image paranodal regions from the central...

2011-01-01

8

Membrane domain organization of myelinated axons requires ?II spectrin.  

Science.gov (United States)

The precise and remarkable subdivision of myelinated axons into molecularly and functionally distinct membrane domains depends on axoglial junctions that function as barriers. However, the molecular basis of these barriers remains poorly understood. Here, we report that genetic ablation and loss of axonal ?II spectrin eradicated the paranodal barrier that normally separates juxtaparanodal K(+) channel protein complexes located beneath the myelin sheath from Na(+) channels located at nodes of Ranvier. Surprisingly, the K(+) channels and their associated proteins redistributed into paranodes where they colocalized with intact Caspr-labeled axoglial junctions. Furthermore, electron microscopic analysis of the junctions showed intact paranodal septate-like junctions. Thus, the paranodal spectrin-based submembranous cytoskeleton comprises the paranodal barriers required for myelinated axon domain organization. PMID:24217619

Zhang, Chuansheng; Susuki, Keiichiro; Zollinger, Daniel R; Dupree, Jeffrey L; Rasband, Matthew N

2013-11-11

9

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of ...

Cifuentes-diaz, Carmen; Chareyre, Fabrice; Garcia, Marta; Devaux, Je?ro?me; Carnaud, Miche?le; Levasseur, Gre?goire; Niwa-kawakita, Michiko; Harroch, Sheila; Girault, Jean-antoine; Giovannini, Marco; Goutebroze, Laurence

2011-01-01

10

MRI Characterization of Paranodal Junction Failure and Related Spinal Cord Changes in Mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the p...

Takano, Morito; Hikishima, Keigo; Fujiyoshi, Kanehiro; Shibata, Shinsuke; Yasuda, Akimasa; Konomi, Tsunehiko; Hayashi, Akiko; Baba, Hiroko; Honke, Koichi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

2012-01-01

11

CSF myelin basic protein  

Science.gov (United States)

CSF myelin basic protein is a test to measure the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF). The CSF ... less than 4 ng/mL of myelin basic protein in the CSF. Note: ng/mL = nanogram per ...

12

GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia  

Directory of Open Access Journals (Sweden)

Full Text Available White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD. Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155, and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1 on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group. HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05 and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05. Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties.

Y.P. Zhang

2011-06-01

13

Synthesis and incorporation of myelin polypeptides into CNS myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The distribution of newly synthesized proteolipid protein (PLP, 23 kdaltons) and myelin basic proteins (MBPs, 14-21.5 kdaltons) was determined in microsomal and myelin fractions prepared from the brainstems o1 10-30 d-old rats sacrificed at different times after an intracranial injection of 35S-methionine. Labeled MBPs were found in the myelin fraction 2 min after the injection, whereas PLP appeared first in the rough microsomal fraction and only after a lag of 30 min in the myelin fraction. ...

1982-01-01

14

GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of t [...] he paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P

Y.P., Zhang; Q.L., Huang; C.M., Zhao; J.L., Tang; Y.L., Wang.

15

Two types of fast K+ channels in rat myelinated nerve fibres and their sensitivity to dendrotoxin.  

Science.gov (United States)

The effect of dendrotoxin (DTX), a component of the venom of the Eastern green mamba snake, Dendroaspis angusticeps, on K+ currents in rat myelinated nerve fibres was studied in voltage clamp experiments, immunocytochemistry and binding experiments. The analysis of K+ tail currents in 160 mM KCl solution revealed that K+ channels with slow gating kinetics predominate in the intact node of Ranvier. These slow K+ channels were not blocked by DTX. Intact nerve fibres additionally showed fast K+ tail currents of small amplitude which could be blocked by DTX. After enzymatic demyelination with pronase, fast K+ currents of large amplitude appeared. Analysis of the non-monotonous voltage dependence of the fast K+ conductance and the partial pharmacological block by DTX suggest the presence of two subtypes of fast K+ channels in rat nerve fibres similar to the Kf1 and Kf2 channels previously described in the frog and toad node of Ranvier. The DTX concentration required for 50% inhibition (IC50) for the Kf1 component was 8 nM. The IC50 of the blocked Kf2 component was the same as that for Kf1, but the Kf2 component was only partially blocked (about 50%). In contrast to frog nerve, these two fast K+ channel subtypes are located predominantly in the paranodal region. Immunocytochemical staining experiments with DTX using the peroxidase-antiperoxidase technique confirmed the electrophysiological data. In intact nodes, either no staining or only slight staining in some fibres was found. After demyelination, extensive staining of paranodal and internodal regions occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1876485

Corrette, B J; Repp, H; Dreyer, F; Schwarz, J R

1991-05-01

16

Electrodiagnostic testing and histopathologic changes confirm peripheral nervous system myelin abnormalities in the feline model of niemann-pick disease type C.  

Science.gov (United States)

Niemann-Pick disease type C (NPC disease) is an incurable, neurodegenerative, autosomal recessive disease caused by mutations in either the NPC1 or the NPC2 gene. These mutations affect the intracellular trafficking of lipids and cholesterol, resulting in the intralysosomal accumulation of unesterified cholesterol and glycosphingolipids. These abnormalities are associated with clinical ataxia and impaired motor and intellectual development, and death frequently occurs in adolescence. The incidence of peripheral neuropathy in NPC patients is not known. We investigated peripheral nerves in the naturally occurring feline model of NPC disease, which has proven to be critical for understanding both disease pathogenesis and for evaluating experimental therapies. Electrodiagnostic studies revealed significantly slowed motor and sensory nerve conduction velocities in affected cats in the absence of altered M-wave amplitude. Histologic and ultrastructural analyses showed thin myelin sheaths, membranous debris, myelin figures, lipid vacuolization of Schwann cell cytoplasm, and expanded paranodal areas. Axonal degeneration was not identified. There was a shift to small myelinated fibers in affected cats, and there were significant decreases in fiber diameter, axon diameter, and myelin thickness. These changes were similar to those described in the murine NPC disease model and in rare patients in whom nerve biopsy has been performed. Characterization of the demyelinating neuropathy is necessary for evaluating clinical trials that target only the CNS aspects of NPC. PMID:23399903

Bagel, Jessica H; Sikora, Tracey U; Prociuk, Maria; Pesayco, Jill P; Mizisin, Andrew P; Shelton, G Diane; Vite, Charles H

2013-03-01

17

Electrodiagnostic testing and histopathological changes confirm peripheral nervous system myelin abnormalities in the feline model of Niemann-Pick disease type C  

Science.gov (United States)

Niemann-Pick disease type C (NPC disease) is an incurable, neurodegenerative, autosomal recessive disease caused by mutations in either the NPC1 or NPC2 gene. These mutations affect the intracellular trafficking of lipids and cholesterol resulting in the intralysosomal accumulation of unesterified cholesterol and glycosphingolipids, and clinical signs of ataxia and impaired motor and intellectual development with death frequently occurring in adolescence. The incidence of peripheral neuropathy in NPC patients is not known. We investigated peripheral nerves in the naturally-occurring feline model of NPC disease which has proven critical for understanding both disease pathogenesis and for evaluating experimental therapies. Electrodiagnostic studies revealed significantly slowed motor and sensory nerve conduction velocities in affected cats in the absence of altered M-wave amplitude. Histology showed demyelination characterized by thin myelin sheaths, membranous debris, myelin figures, lipid vacuolization of Schwann cell cytoplasm, and expanded paranodal areas. Axonal degeneration was not identified. A shift to small myelinated fibers was noted in affected cats and significant decreases in fiber diameter, axonal diameter, and myelin thickness was found. These changes were similar to those described in the murine model as well as in the rare patient in which nerve biopsy was performed. Characterization of the demyelinating neuropathy is necessary in NPC disease due to the clinical trial in patients scheduled for 2013 where cyclodextrin will be delivered into the cerebral ventricles in an attempt to control the CNS aspects of this disease.

Bagel, Jessica H.; Sikora, Tracey U; Prociuk, Maria; Pesayco, Jill P.; Mizisin, Andrew P.; Shelton, G. Diane; Vite, Charles H.

2013-01-01

18

Control of Schwann cell myelination.  

Science.gov (United States)

Schwann cells ensheath all axons of peripheral nerves. Only around large-diameter axons do they elaborate myelin, forming insulating sheaths that are vital for fast conduction of axon potentials. A series of recent papers has illuminated some of the ways in which the process of myelination is controlled, both by signals from axons and by positive and negative transcriptional mechanisms within the Schwann cells themselves. PMID:20948814

Jessen, Kristján R; Mirsky, Rhona

2010-01-01

19

Switching myelination on and off.  

Science.gov (United States)

Schwann cells are remarkably plastic cells that can both form and stably maintain myelin sheaths around axons and also rapidly dedifferentiate upon injury. New findings (Parkinson, D.B., A. Bhaskaran, P. Arthur-Farraj, L.A. Noon, A. Woodhoo, A.C. Lloyd, M.L. Feltri, L. Wrabetz, A. Behrens, R. Mirsky, and K.R. Jessen. 2008. J. Cell Biol. 181:625-637) indicate that the transition between these distinct states of differentiation is directed by the transcription factor Krox-20, which promotes and maintains myelination, and c-Jun, which antagonizes it. Cross-inhibition of these transcription factors serves to switch Schwann cells between the myelinated and dedifferentiated phenotypes, respectively. PMID:18490509

Salzer, James L

2008-05-19

20

Accelerated myelination associated with venous congestion  

International Nuclear Information System (INIS)

Magnetic resonance imaging is currently the gold standard in the assessment of brain myelination. The normal pattern of brain myelination conforms to a fixed chronological sequence. Focal accelerated myelination is a usual pathological state and previously has only been associated with Sturge-Weber syndrome. The purpose of our study is to describe alternate causes for accelerated myelination. We retrospectively reviewed serial MR scans, MR angiography, conventional angiography and the clinical progress of three children with accelerated myelination. Two patients with accelerated myelination had an underlying cerebral sinovenous thrombosis. The third patient had Sturge-Weber syndrome. Our study strongly suggests that cerebral venous thrombosis with the consequent restriction of venous outflow could be a key factor in the induction of accelerated myelination. We recommend that in patients with accelerated myelination, the search for an underlying etiology should include careful evaluation of the intracranial vascular pathology, especially cerebral venous thrombosis. (orig.)

2006-04-01

 
 
 
 
21

Accelerated myelination associated with venous congestion  

Energy Technology Data Exchange (ETDEWEB)

Magnetic resonance imaging is currently the gold standard in the assessment of brain myelination. The normal pattern of brain myelination conforms to a fixed chronological sequence. Focal accelerated myelination is a usual pathological state and previously has only been associated with Sturge-Weber syndrome. The purpose of our study is to describe alternate causes for accelerated myelination. We retrospectively reviewed serial MR scans, MR angiography, conventional angiography and the clinical progress of three children with accelerated myelination. Two patients with accelerated myelination had an underlying cerebral sinovenous thrombosis. The third patient had Sturge-Weber syndrome. Our study strongly suggests that cerebral venous thrombosis with the consequent restriction of venous outflow could be a key factor in the induction of accelerated myelination. We recommend that in patients with accelerated myelination, the search for an underlying etiology should include careful evaluation of the intracranial vascular pathology, especially cerebral venous thrombosis. (orig.)

Porto, L.; Yan, B.; Zanella, F.E.; Lanfermann, H. [Klinikum der Johann Wolfgang Goethe-Universitaet, Neuroradiology Department, Institut fuer Neuroradiologie, Frankfurt am Main (Germany); Kieslich, M. [Klinikum der Johann Wolfgang Goethe-Universitaet, Neuroradiology Department, Institut fuer Neuroradiologie, Frankfurt am Main (Germany); Neuropediatric Department, Frankfurt am Main (Germany)

2006-04-15

22

Effects of aging on myelinated nerve fibers in monkey primary visual cortex.  

Science.gov (United States)

In monkeys, myelin sheaths of the axons in the vertical bundles of nerve fibers passing through the deeper layers of primary visual cortex show age-related alterations in their structure. These alterations have been examined by comparing the myelin sheaths in young monkeys, 5-10 years old, with those in old monkeys, between 25 and 33 years of age. The age-related alterations are of four basic types. In some sheaths, there is local splitting of the major dense line to accommodate dense cytoplasm derived from the oligodendrocytes. Other sheaths balloon out, and in these locations, the intraperiod line in that part of the sheath opens up to surround a fluid-filled space. Other alterations are the formation of redundant myelin so that a sheath is too large for the enclosed axon and the formation of double sheaths in which one layer of compact myelin is surrounded by another one. These alterations in myelin increase in frequency with the ages of the monkeys, and there is a significant correlation between the breakdown of the myelin and the impairments in cognition exhibited by individual monkeys. This correlation also holds even when the old monkeys, 25 to 33 years of age, are considered as a group. It is suggested that the correlation between the breakdown of myelin in the old monkeys and their impairments in cognition has not to do specifically with visual function but to the role of myelin in axonal conduction throughout the brain. The breakdown of myelin could impair cognition by leading to a change in the conduction rates along axons, resulting in a loss of synchrony in cortical neuronal circuits. PMID:10723011

Peters, A; Moss, M B; Sethares, C

2000-04-10

23

Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Magnetic resonance imaging has previously demonstrated its potential for indirectly mapping myelin density, either by relaxometric detection of myelin water or magnetization transfer. Here, we investigated whether myelin can be detected and possibly quantified directly. We identified the spectrum of myelin in the spinal cord in situ as well as in myelin lipids extracted via a sucrose gradient method, and investigated its spectral properties. High-resolution solution NMR spectroscopy showed th...

Wilhelm, Michael J.; Ong, Henry H.; Wehrli, Suzanne L.; Li, Cheng; Tsai, Ping-huei; Hackney, David B.; Wehrli, Felix W.

2012-01-01

24

Splitting Leagues  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Splitting leagues or tournaments seems to be puzzling when agents are homogeneous and splitting leads to a negative competition effect. However, it can be shown that the principal can nevertheless benefit from splitting. First, splitting can be used as a divide-and-rule strategy by the principal to create additional incentives when collusion among the agents is possible. Second, splitting leagues gives the principal the opportunity to introduce promotions and relegations between nested tourna...

Kra?kel, Matthias

2003-01-01

25

Nogo, myelin and axonal regeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Adult mammalian central nervous system (CNS) axons have very limited capacity of regrowth after injury. In recent years, advances in the field of axonal regeneration have proved that neurons do not regenerate, mainly because of the presence of inhibitory molecules. Myelin-associated proteins limit axonal outgrowth and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo, MAG and OMgp, share a common neuronal receptor (NgR), and together represent one...

Mingorance Jime?nez, Alfredo; Soriano Garci?a, Eduardo; Ri?o Ferna?ndez, Jose? Antonio Del

2004-01-01

26

Split digraphs  

CERN Multimedia

We generalize the class of split graphs to directed graphs and show these split digraphs can be identified from their degree sequences. We end by discussing their use in characterizing a class of digraphs called directed 3-cycle anchored.

LaMar, M Drew

2010-01-01

27

Splitting Polytopes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A split of a polytope $P$ is a (regular) subdivision with exactly two maximal cells. It turns out that each weight function on the vertices of $P$ admits a unique decomposition as a linear combination of weight functions corresponding to the splits of $P$ (with a split prime remainder). This generalizes a result of Bandelt and Dress [Adv. Math. 92 (1992)] on the decomposition of finite metric spaces. Introducing the concept of compatibility of splits gives rise to a finite...

Herrmann, Sven; Joswig, Michael

2008-01-01

28

Split hypergraphs  

CERN Document Server

Generalizing the notion of split graphs to uniform hypergraphs, we prove that the class of these hypergraphs can be characterized by a finite list of excluded induced subhypergraphs. We show that a characterization by generalized degree sequences is impossible, unlike in the well-known case of split graphs. We also give an algorithm to decide whether a given uniform hypergraph is a split hypergraph. If it is, the algorithm gives a splitting of it; the running time is $O(N\\log N)$. These answer questions of Sloan, Gy. Tur\\'an and Peled.

Timar, Adam

2011-01-01

29

Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRP? (signal regulatory protein-?) on phagocytes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own ph...

Gitik Miri; Liraz-Zaltsman Sigal; Oldenborg Per-Arne; Reichert Fanny; Rotshenker Shlomo

2011-01-01

30

Nonenzymatic glycosylation of bovine myelin basic protein  

International Nuclear Information System (INIS)

In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with [14C]-galactose and [14C]-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 370C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the [14C]-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using [14C]-glucose and [14C]-mannose with HPLC values at 1/6 and 1/5 of the [14C]-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the [3H]-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general

1987-01-01

31

Split Decomp  

Science.gov (United States)

This worksheet performs split decomposition on a set of four DNA sequences and their associated amino acid sequences. The user can type in the sequences or paste them in from a text file. The program then translates the DNA sequences into amino acid sequences and calculates split indices and four-point conditions for each of the three possible unrooted phylogenies. The user can use these values to assess the data support for each of these topologies.

Tony Weisstein (Truman State University;Biology); John Jungck (Beloit College;Biology)

2007-04-20

32

A role of peripheral myelin protein 2 in lipid homeostasis of myelinating schwann cells.  

Science.gov (United States)

Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although Pmp2 is predominantly expressed in myelinated Schwann cells, its role in glia is currently unknown. To study its function in PNS biology, we have generated a complete Pmp2 knockout mouse (Pmp2(-/-) ). Comprehensive characterization of Pmp2(-/-) mice revealed a temporary reduction in their motor nerve conduction velocity (MNCV). While this change was not accompanied by any defects in general myelin structure, we detected transitory alterations in the myelin lipid profile of Pmp2(-/-) mice. It was previously proposed that Pmp2 and Mbp have comparable functions in the PNS suggesting that the presence of Mbp can partially mask the Pmp2(-/-) phenotype. Indeed, we found that Mbp lacking Shi(-/-) mice, similar to Pmp2(-/-) animals, have preserved myelin structure and reduced MNCV, but this phenotype was not aggravated in Pmp2(-/-) /Shi(-/-) mutants indicating that Pmp2 and Mbp do not substitute each other's functions in the PNS. These data, together with our observation that Pmp2 binds and transports fatty acids to membranes, uncover a role for Pmp2 in lipid homeostasis of myelinating Schwann cells. GLIA 2014;62:1502-1512. PMID:24849898

Zenker, Jennifer; Stettner, Mark; Ruskamo, Salla; Domènech-Estévez, Enric; Baloui, Hasna; Médard, Jean-Jacques; Verheijen, Mark H G; Brouwers, Jos F; Kursula, Petri; Kieseier, Bernd C; Chrast, Roman

2014-09-01

33

Split gland  

Energy Technology Data Exchange (ETDEWEB)

A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention.

Petranto, Joseph J. (Los Alamos, NM)

1989-01-01

34

Split gland  

Energy Technology Data Exchange (ETDEWEB)

A split gland having only three parts is described. The gland has substantially the same stability to the relative motion of the constituent half-gland members during the attachment process to a female fitting as have more complicated designs. Ease of manufacture and use result from the reduction in complexity of the present invention. 15 figs.

Petranto, J.J.

1989-09-05

35

Myelination of rodent hippocampal neurons in culture  

Science.gov (United States)

Axons of various hippocampal neurons are myelinated mainly postnatally, which is important for the proper function of neural circuits. Demyelination in the hippocampus has been observed in patients with multiple sclerosis, Alzheimer’s disease or temporal lobe epilepsy. However, very little is known about the mechanisms and exact functions of the interaction between the myelin-making oligodendrocytes and the axons within the hippocampus. This is mainly attributable to the lack of a system suitable for molecular studies. We recently established a new myelin coculture from embryonic day (E) 18 rat embryos consisting of hippocampal neurons and oligodendrocytes, with which we identified a novel intra-axonal signaling pathway regulating the juxtaparanodal clustering of Kv1.2 channels. Here we describe the detailed protocol for this new coculture. It takes about 5 weeks to set up and use the system. This coculture is particularly useful for studying myelin-mediated regulation of ion channel trafficking and for understanding how neuronal excitability and synaptic transmission are regulated by myelination.

Gardner, Asa; Jukkola, Peter; Gu, Chen

2012-01-01

36

MMP-28 as a regulator of myelination  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Matrix metalloproteinase-28 (MMP-28 is a poorly understood member of the matrix metalloproteinase family. Metalloproteinases are important mediators in the development of the nervous system and can contribute to the maturation of the neural micro-environment. Results MMP-28 added to myelinating rat dorsal root ganglion (DRG co-cultures reduces myelination and two antibodies targeted to MMP-28 (pAb180 and pAb183 are capable of binding MMP-28 and inhibiting its activity in a dose-dependent manner. Addition of 30 nM pAb180 or pAb183 to rat DRG cultures resulted in the 2.6 and 4.8 fold enhancement of myelination respectively while addition of MMP-28 to DRG co-cultures resulted in enhanced MAPK, ErbB2 and ErbB3 phosphorylation. MMP-28 protein expression was increased within demyelinated lesions of mouse experimental autoimmune encephalitis (EAE and human multiple sclerosis lesions compared to surrounding normal tissue. Conclusion MMP-28 is upregulated in conditions of demyelination in vivo, induces signaling in vitro consistent with myelination inhibition and, neutralization of MMP-28 activity can enhance myelination in vitro. These results suggest inhibition of MMP-28 may be beneficial under conditions of dysmyelination.

Dotzlaf Joseph E

2008-09-01

37

Evolution of a neuroprotective function of central nervous system myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to...

Yin, Xinghua; Baek, Rena C.; Kirschner, Daniel A.; Peterson, Alan; Fujii, Yasuhisa; Nave, Klaus-armin; Macklin, Wendy B.; Trapp, Bruce D.

2006-01-01

38

Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The cellular basis of myelin deficits detected by neuroimaging in long-term survivors of periventricular leukomalacia (PVL) is poorly understood. We tested the hypothesis that oligodendrocyte lineage (OL) cell density is reduced in PVL, thereby contributing to subsequent myelin deficits. Using computer-based methods, we determined OL cell density in sections from 18 PVL and 18 age-adjusted control cases, immunostained with the OL-lineage marker Olig2. Myelination was assessed with myelin basi...

2008-01-01

39

Disruption of Myelin Leads to Ectopic Expression of KV1.1 Channels with Abnormal Conductivity of Optic Nerve Axons in a Cuprizone-Induced Model of Demyelination  

Science.gov (United States)

The molecular determinants of abnormal propagation of action potentials along axons and ectopic conductance in demyelinating diseases of the central nervous system, like multiple sclerosis (MS), are poorly defined. Widespread interruption of myelin occurs in several mouse models of demyelination, rendering them useful for research. Herein, considerable myelin loss is shown in the optic nerves of cuprizone-treated demyelinating mice. Immuno-fluorescence confocal analysis of the expression and distribution of voltage-activated K+ channels (KV1.1 and 1.2 ? subunits) revealed their spread from typical juxta-paranodal (JXP) sites to nodes in demyelinated axons, albeit with a disproportionate increase in the level of KV1.1 subunit. Functionally, in contrast to monophasic compound action potentials (CAPs) recorded in controls, responses derived from optic nerves of cuprizone-treated mice displayed initial synchronous waveform followed by a dispersed component. Partial restoration of CAPs by broad spectrum (4-aminopyridine) or KV1.1-subunit selective (dendrotoxin K) blockers of K+ currents suggest enhanced KV1.1-mediated conductance in the demyelinated optic nerve. Biophysical profiling of K+ currents mediated by recombinant channels comprised of different KV1.1 and 1.2 stoichiometries revealed that the enrichment of KV1 channels KV1.1 subunit endows a decrease in the voltage threshold and accelerates the activation kinetics. Together with the morphometric data, these findings provide important clues to a molecular basis for temporal dispersion of CAPs and reduced excitability of demyelinated optic nerves, which could be of potential relevance to the patho-physiology of MS and related disorders.

Bagchi, Bandita; Al-Sabi, Ahmed; Kaza, Seshu; Scholz, Dimitri; O'Leary, Valerie B.; Dolly, J. Oliver; Ovsepian, Saak V.

2014-01-01

40

Myelin basic protein-dependent plasma membrane reorganization in the formation of myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

During vertebrate development, oligodendrocytes wrap their plasma membrane around axons to produce myelin, a specialized membrane highly enriched in galactosylceramide (GalC) and cholesterol. Here, we studied the formation of myelin membrane sheets in a neuron–glia co-culture system. We applied different microscopy techniques to visualize lipid packing and dynamics in the oligodendroglial plasma membrane. We used the fluorescent dye Laurdan to examine the lipid order with two-photon microsc...

2006-01-01

 
 
 
 
41

Evaluation of myelination and myelination disorders with turbo inversion recovery magnetic resonance imaging  

International Nuclear Information System (INIS)

The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p < 0.05). Forty-two neurologically abnormal patients displayed a normal myelination on all sequences, whereas 23 showed an abnormal myelination. The TIRSE sequence provided a sensitive and specific depiction of an abnormal myelination in all of these patients. The TIRSE sequence provided additional information to conventional pulse sequences in determining myelination disorders in children, especially in children older than 2 years. (orig.)

1997-12-01

42

Neuronal activity promotes myelination via a cAMP pathway.  

Science.gov (United States)

Neuronal activity promotes myelination in vivo and in vitro. However, the molecular events that mediate activity-dependent myelination are not completely understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM) promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG) neurons and oligodendrocytes (OLs); the increase in myelination was frequency-dependent. Myelin segment formation was also enhanced following exposure of DRGs to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP) levels in DRGs were increased three-fold following ESTIM, and artificially increasing cAMP mimicked the ability of ESTIM to promote myelination. Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination. We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs and assessed cell-type specific effects of ESTIM on myelination. A selective increase or decrease in DRG cAMP levels resulted in enhanced or suppressed myelination, respectively. This work describes a novel role for the cAMP pathway in neurons that results in enhanced myelination. PMID:23554117

Malone, Misti; Gary, Devin; Yang, In Hong; Miglioretti, Anna; Houdayer, Thierry; Thakor, Nitish; McDonald, John

2013-06-01

43

Axon-glia interaction and membrane traffic in myelin formation  

Directory of Open Access Journals (Sweden)

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

Eva-MariaKrämer-Albers

2014-01-01

44

Zebrafish myelination: a transparent model for remyelination?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

There is currently an unmet need for a therapy that promotes the regenerative process of remyelination in central nervous system diseases, notably multiple sclerosis (MS). A high-throughput model is, therefore, required to screen potential therapeutic drugs and to refine genomic and proteomic data from MS lesions. Here, we review the value of the zebrafish (Danio rerio) larva as a model of the developmental process of myelination, describing the powerful applications of zebrafish for genetic ...

Buckley, Clare E.; Goldsmith, Paul; Franklin, Robin J. M.

2008-01-01

45

Towards resolving the transcription factor network controlling myelin gene expression.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the central nervous system (CNS), myelin is produced from spirally-wrapped oligodendrocyte plasma membrane and, as exemplified by the debilitating effects of inherited or acquired myelin abnormalities in diseases such as multiple sclerosis, it plays a critical role in nervous system function. Myelin sheath production coincides with rapid up-regulation of numerous genes. The complexity of their subsequent expression patterns, along with recently recognized heterogeneity within the oligodend...

Fulton, Debra; Denarier, Eric; Friedman, Hana; Wasserman, Wyeth; Peterson, Alan

2011-01-01

46

Towards resolving the transcription factor network controlling myelin gene expression  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the central nervous system (CNS), myelin is produced from spirally-wrapped oligodendrocyte plasma membrane and, as exemplified by the debilitating effects of inherited or acquired myelin abnormalities in diseases such as multiple sclerosis, it plays a critical role in nervous system function. Myelin sheath production coincides with rapid up-regulation of numerous genes. The complexity of their subsequent expression patterns, along with recently recognized heterogeneity within the oligodend...

Fulton, Debra L.; Denarier, Eric; Friedman, Hana C.; Wasserman, Wyeth W.; Peterson, Alan C.

2011-01-01

47

Oligodendrocyte Precursor Cell Transplantation into Organotypic Cerebellar Shiverer Slices: A Model to Study Myelination and Myelin Maintenance  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Current in vitro models to investigate the consequence of oligodendrocyte-specific loss-of-function mutations on myelination are primarily limited to co-culture experiments, which do not accurately recapitulate the complex in vivo environment. Here, we describe the development of an in vitro model of myelination and myelin maintenance in which oligodendrocyte precursor cells are transplanted into organotypic cerebellar slice cultures derived from dysmyelinated shiverer mice. Compared to neuro...

Bin, Jenea M.; Leong, Soo Yuen; Bull, Sarah-jane; Antel, Jack P.; Kennedy, Timothy E.

2012-01-01

48

N-WASp is required for Schwann cell cytoskeletal dynamics, normal myelin gene expression and peripheral nerve myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate the Schwann cell cytoskeleton are poorly defined. Here, we show that the actin cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated in myelinating Schwann cells coincident with myelin elaboration. When N-WASp is conditionally deleted in Schwann cells at the...

Jin, Fuzi; Dong, Baoxia; Georgiou, John; Jiang, Qiuhong; Zhang, Jinyi; Bharioke, Arjun; Qiu, Frank; Lommel, Silvia; Feltri, M. Laura; Wrabetz, Lawrence; Roder, John C.; Eyer, Joel; Chen, Xiequn; Peterson, Alan C.; Siminovitch, Katherine A.

2011-01-01

49

c-Jun is a negative regulator of myelination.  

Science.gov (United States)

Schwann cell myelination depends on Krox-20/Egr2 and other promyelin transcription factors that are activated by axonal signals and control the generation of myelin-forming cells. Myelin-forming cells remain remarkably plastic and can revert to the immature phenotype, a process which is seen in injured nerves and demyelinating neuropathies. We report that c-Jun is an important regulator of this plasticity. At physiological levels, c-Jun inhibits myelin gene activation by Krox-20 or cyclic adenosine monophosphate. c-Jun also drives myelinating cells back to the immature state in transected nerves in vivo. Enforced c-Jun expression inhibits myelination in cocultures. Furthermore, c-Jun and Krox-20 show a cross-antagonistic functional relationship. c-Jun therefore negatively regulates the myelinating Schwann cell phenotype, representing a signal that functionally stands in opposition to the promyelin transcription factors. Negative regulation of myelination is likely to have significant implications for three areas of Schwann cell biology: the molecular analysis of plasticity, demyelinating pathologies, and the response of peripheral nerves to injury. PMID:18490512

Parkinson, David B; Bhaskaran, Ambily; Arthur-Farraj, Peter; Noon, Luke A; Woodhoo, Ashwin; Lloyd, Alison C; Feltri, M Laura; Wrabetz, Lawrence; Behrens, Axel; Mirsky, Rhona; Jessen, Kristján R

2008-05-19

50

Proposed Evolutionary Changes In The Role Of Myelin  

Directory of Open Access Journals (Sweden)

Full Text Available Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period. We hypothesize that myelin's first role was mainly energy conservation. During the later “Mesozoic marine revolution”, marine ecosystems changed towards an increase in marine predation pressure. We hypothesize that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution. To test this hypothesis, we optimized models of myelinated axons for a combination of AP conduction velocity and energy efficiency. We demonstrate that there is a trade-off between these objectives. We then compared the simulation results to empirical data and conclude that while the data are consistent with the theory, additional measurements are necessary for a complete evaluation of the proposed hypothesis.

JaySCoggan

2013-11-01

51

Disruption of myelin leads to ectopic expression of K(V)1.1 channels with abnormal conductivity of optic nerve axons in a cuprizone-induced model of demyelination.  

Science.gov (United States)

The molecular determinants of abnormal propagation of action potentials along axons and ectopic conductance in demyelinating diseases of the central nervous system, like multiple sclerosis (MS), are poorly defined. Widespread interruption of myelin occurs in several mouse models of demyelination, rendering them useful for research. Herein, considerable myelin loss is shown in the optic nerves of cuprizone-treated demyelinating mice. Immuno-fluorescence confocal analysis of the expression and distribution of voltage-activated K? channels (K(V)1.1 and 1.2 ? subunits) revealed their spread from typical juxta-paranodal (JXP) sites to nodes in demyelinated axons, albeit with a disproportionate increase in the level of K(V)1.1 subunit. Functionally, in contrast to monophasic compound action potentials (CAPs) recorded in controls, responses derived from optic nerves of cuprizone-treated mice displayed initial synchronous waveform followed by a dispersed component. Partial restoration of CAPs by broad spectrum (4-aminopyridine) or K(V)1.1-subunit selective (dendrotoxin K) blockers of K? currents suggest enhanced K(V)1.1-mediated conductance in the demyelinated optic nerve. Biophysical profiling of K? currents mediated by recombinant channels comprised of different K(V)1.1 and 1.2 stoichiometries revealed that the enrichment of K(V)1 channels K(V)1.1 subunit endows a decrease in the voltage threshold and accelerates the activation kinetics. Together with the morphometric data, these findings provide important clues to a molecular basis for temporal dispersion of CAPs and reduced excitability of demyelinated optic nerves, which could be of potential relevance to the patho-physiology of MS and related disorders. PMID:24498366

Bagchi, Bandita; Al-Sabi, Ahmed; Kaza, Seshu; Scholz, Dimitri; O'Leary, Valerie B; Dolly, J Oliver; Ovsepian, Saak V

2014-01-01

52

Myelin proteomics: the past, the unexpected and the future.  

Science.gov (United States)

Myelin proteomics has been the subject of intense research over the last decade, and its profiling has achieved good results by both in-gel and mass spectrometry-based techniques. 1280 proteins have been identified, a number expected to increase. Some of the identified proteins are as yet not established as true components of myelin. There appears to be a limit in our ability to discover markers of myelin biogenesis, function and disease. Myelin can be easily isolated free of contaminants, thanks to its lipidic nature, which however necessitates pretreatment with detergents before mass spectrometry analysis. Here, the key issue of solubilization of myelin proteins for mass spectrometry measurements is addressed. An in-depth characterization of the myelin proteome would have a profound impact on our knowledge of its pathology and physiology. Future quantitative proteomic studies of the low-abundance myelin protein complement, likely representing key regulatory components, may in future provide molecular description of the dysmyelinating/demyelinating diseases. PMID:24702188

Panfoli, Isabella; Bruschi, Maurizio; Santucci, Laura; Calzia, Daniela; Ravera, Silvia; Petretto, Andrea; Candiano, Giovanni

2014-06-01

53

Aptamer Antagonists of Myelin-Derived Inhibitors Promote Axon Growth  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin of the adult central nervous system (CNS) is one of the major sources of inhibitors of axon regeneration following injury. The three known myelin-derived inhibitors (Nogo, MAG, and OMgp) bind with high affinity to the Nogo-66 receptor (NgR) on axons and limit neurite outgrowth. Here we show that RNA aptamers can be generated that bind with high affinity to NgR, compete with myelin-derived inhibitors for binding to NgR, and promote axon elongation of neurons in vitro even in the presenc...

Wang, Yuxuan; Khaing, Zin Z.; Li, Na; Hall, Brad; Schmidt, Christine E.; Ellington, Andrew D.

2010-01-01

54

Thermocouple split follower  

Energy Technology Data Exchange (ETDEWEB)

Thermoelectric generator assembly accommodating differential thermal expansion between thermoelectric elements by means of a cylindrical split follower forming a slot and having internal spring loaded wedges that permit the split follower to open and close across the slot.

Howell, deceased, Louis J. (late of Upper Merion Township, Montgomery County, PA)

1980-01-01

55

The lipid sulfatide is a novel myelin-associated inhibitor of CNS axon outgrowth  

Digital Repository Infrastructure Vision for European Research (DRIVER)

CNS myelin is strongly inhibitory to growing axons and is thought to be a major contributor to CNS axon regenerative failure. Although a number of proteins present in myelin, including Nogo, MAG, and OMgp, have been identified as myelin-associated inhibitors, studies of mice lacking these genes suggest that additional inhibitors present in CNS myelin remain to be identified. Here we have investigated the hypothesis that myelin lipids contribute to CNS regenerative failure. We identified sulfa...

Winzeler, Alissa M.; Mandemakers, Wim J.; Sun, Matthew Z.; Stafford, Melissa; Phillips, Carolyn T.; Barres, Ben A.

2011-01-01

56

Mapping early stage of myelin degradation at nanoscale resolution  

CERN Multimedia

To provide insight into the early process of degradation often occurring in severely debilitating diseases with myelin pathology an increased level of spatial structural resolution is needed to bear in the biological realm. Although many observations have connected changes in the periodicity of myelin with illness, few information exist about the microscopic process in the early period of damage of the nerve and how these changes time percolate in space. Here we fill this gap by using first, a short time scale for data collection of scanning micro X-ray diffraction microscopy and second, methods of statistical physics for the analysis of time evolution of this non-invasive local structure experimental approach. We have mapped the time evolution of the fluctuations in myelin period in the degradation nerve process in a freshly extracted sciatic nerve of Xenopus laevis with a spatial resolution of 1 micron. We identify the first stage of myelin degradation with the period evolving through a bimodal distribution...

Poccia, Nicola; Ricci, Alessandro; Caporale, Alessandra S; Di Cola, Emanuela; Hawkins, Thomas A; Bianconi, Antonio

2013-01-01

57

Analysis of Myelin Basic Protein Fragmentation by Proteasome  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The proteasome is a high molecular protein complex whose purpose is specific protein degradation in eukaryotic cells. One of the proteasome functions is to produce peptides, which will then be presented on the outer cell membrane using main histocompatibility complex (MHC) molecules of the first or second class. There are definite reasons to believe that proteasome directly takes part in the specific degradation of myelin basic protein (MBP), which make up to 30% of all proteins in the myelin...

Bacheva, A. V.; Belogurov, A. A.; Ponomarenko, N. A.; Knorre, V. D.; Govorun, V. M.; Serebryakova, M. V.; Gabibov, A. G.

2009-01-01

58

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-Å resolution and the complex of...

Breithaupt, Constanze; Schubart, Anna; Zander, Hilke; Skerra, Arne; Huber, Robert; Linington, Christopher; Jacob, Uwe

2003-01-01

59

Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation.  

Science.gov (United States)

Immature Schwann cells found in perinatal rodent nerves are generated from Schwann cell precursors (SCPs) that originate from the neural crest. Immature Schwann cells generate the myelinating and non-myelinating Schwann cells of adult nerves. When axons degenerate following injury, Schwann cells demyelinate, proliferate and dedifferentiate to assume a molecular phenotype similar to that of immature cells, a process essential for successful nerve regeneration. Increasing evidence indicates that Schwann cell dedifferentiation involves activation of specific receptors, intracellular signalling pathways and transcription factors in a manner analogous to myelination. We have investigated the roles of Notch and the transcription factor c-Jun in development and after nerve transection. In vivo, Notch signalling regulates the transition from SCP to Schwann cell, times Schwann cell generation, controls Schwann cell proliferation and acts as a brake on myelination. Notch is elevated in injured nerves where it accelerates the rate of dedifferentiation. Likewise, the transcription factor c-Jun is required for Schwann cell proliferation and death and is down-regulated by Krox-20 on myelination. Forced expression of c-Jun in Schwann cells prevents myelination, and in injured nerves, c-Jun is required for appropriate dedifferentiation, the re-emergence of the immature Schwann cell state and nerve regeneration. Thus, both Notch and c-Jun are negative regulators of myelination. The growing realisation that myelination is subject to negative as well as positive controls and progress in molecular identification of negative regulators is likely to impact on our understanding of demyelinating disease and mechanisms that control nerve repair. PMID:18601657

Mirsky, Rhona; Woodhoo, Ashwin; Parkinson, David B; Arthur-Farraj, Peter; Bhaskaran, Ambily; Jessen, Kristján R

2008-06-01

60

Myelinated Herring bodies in the median eminence of the cat  

Digital Repository Infrastructure Vision for European Research (DRIVER)

An electron-microscopic study was carried out on the median eminence of cats during post-natal development. From the moment of birth (observations performed 12 hours later) Herring bodies were seen in the fibrillary layer of the median eminence. At 45 days after birth, myelinated nerve fibres could be observed, some of them containing neurosecretory granules. The number of myelinated fibres in the median eminence increased with age and at 90 days some Herring b...

Pastor, F. E.; Blazquez, J. L.; Toranzo, D.; Pelaez, B.; Sanchez, A.; Alvarez-morujo, A. J.; Amat, P.

1991-01-01

 
 
 
 
61

Tube splitting furnace  

International Nuclear Information System (INIS)

The application concerns a methane splitting plant, in which the heat produced in a nuclear reactor is directly used (i.e. without an intermediate circuit) in a process requiring heat, in order to split a CH_4/H_2O mixture by supplying heat and using a catalyst, into H_2, CO and CO_2. Coal can be gasified into methane with the hydrogen of the split gas obtained, or the split gas is used as a heat carrier in transporting the heat energy obtained in the high temperature reactor to a remove energy consumption location, where the split gas is again converted to methane by catalysis and the heat released is used. The methane splitting furnace is accommodated in the prestressed concrete pressure vessel with the high temperature reactor and the steam raising unit. The splitting furnace consists of three cylindrical spaces above one another, the primary circuit helium coming from the blower and flowing back to the high temperature reactor flows through the lowest space, which gives up its heat to the methane splitting tube projecting into it from above. Above this space there is the methane space, which has methane supplied to it from outside by a pipeline and which distributes it to the splitting tubes leading downwards. Each splitting tube contains a coaxial inner tube, in which the split gas produced is taken upwards to the top cylindrical space, from which the split gas is taken away by a pipeline. The design of the splitting furnace according to the invention, is simple and compact, requires little space and makes quick catalyst change and easy fitting and removal of the tube splitting furnace possible. (RB)

1976-04-06

62

Myelination in the absence of galactolipids and proteolipid proteins.  

Science.gov (United States)

The galactolipids galactocerebroside and sulfatide and the proteolipid protein (PLP) and its splice variant DM20 are the most abundant lipid and protein components of central nervous system myelin. Recent studies have found that mice lacking either the galactolipids or PLP are able to form myelin sheaths with apparently normal periodicity and near normal compaction. Here, we have generated galactolipid/proteolipid double mutants to examine the possibility that these molecules have overlapping functions. We show that the absence of the galactolipids and PLP has pleotropic effects on myelin formation. While oligodendrocytes in the postnatal day 20 galactolipid/proteolipid-deficient mouse are able to elaborate myelin with close to normal intraperiod lines, there is an increased frequency of uncompacted myelin sheaths as well as unmyelinated axons. Moreover, the double mutants display extensive white matter vacuolization of the cerebellum that initiates around postnatal day 16, which correlates with the onset of a severe ataxic phenotype and an increased percentage of apoptotic nuclei in the cerebellar internal granule cell layer. These data indicate that the galactolipids and PLP/DM20 are not required for intraperiod line formation, but they suggest a role for these molecules in mediating myelin compaction and in maintaining the integrity of the cerebellum. PMID:10433816

Coetzee, T; Suzuki, K; Nave, K A; Popko, B

1999-07-01

63

Profilin 1 is required for peripheral nervous system myelination.  

Science.gov (United States)

Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization. Pfn1 is inhibited upon phosphorylation by ROCK, a downstream effector of the integrin linked kinase pathway. Thus, a dramatic reduction of radial lamellipodia formation is observed in SCs lacking integrin-linked kinase or treated with the Rho/ROCK activator lysophosphatidic acid. Knocking down Pfn1 expression by lentiviral-mediated shRNA delivery impairs SC lamellipodia formation in vitro, suggesting a direct role for this protein in PNS myelination. Indeed, SC-specific gene ablation of Pfn1 in mice led to profound radial sorting and myelination defects, confirming a central role for this protein in PNS development. Our data identify Pfn1 as a key effector of the integrin linked kinase/Rho/ROCK pathway. This pathway, acting in parallel with integrin ?1/LCK/Rac1 and their effectors critically regulates SC lamellipodia formation, radial sorting and myelination during peripheral nervous system maturation. PMID:24598164

Montani, Laura; Buerki-Thurnherr, Tina; de Faria, Joana Paes; Pereira, Jorge A; Dias, Nuno G; Fernandes, Rui; Gonçalves, Ana F; Braun, Attila; Benninger, Yves; Böttcher, Ralph T; Costell, Mercedes; Nave, Klaus-Armin; Franklin, Robin J M; Meijer, Dies; Suter, Ueli; Relvas, João B

2014-04-01

64

Overcoming inhibitors in myelin to promote axonal regeneration.  

Science.gov (United States)

The lack of axonal growth after injury in the adult central nervous system (CNS) is due to several factors including the formation of a glial scar, the absence of neurotrophic factors, the presence of growth-inhibitory molecules associated with myelin and the intrinsic growth-state of the neurons. To date, three inhibitors have been identified in myelin: Myelin-Associated Glycoprotein (MAG), Nogo-A, and Oligodendrocyte-Myelin glycoprotein (OMgp). In previous studies we reported that MAG inhibits axonal regeneration by high affinity interaction (K(D) 8 nM) with the Nogo66 receptor (NgR) and activation of a p75 neurotrophin receptor (p75NTR)-mediated signaling pathway. Similar to other axon guidance molecules, MAG is bifunctional. When cultured on MAG-expressing cells, dorsal root ganglia neurons (DRG) older than post-natal day 4 (PND4) extend neurites 50% shorter on average than when cultured on control cells. In contrast, MAG promotes neurite outgrowth from DRG neurons from animals younger than PND4. The response switch, which is also seen in retinal ganglia (RGC) and Raphe nucleus neurons, is concomitant with a developmental decrease in the endogenous neuronal cAMP levels. We report that artificially increasing cAMP levels in older neurons can alter their growth-state and induce axonal growth in the presence of myelin-associated inhibitors. PMID:15949495

Domeniconi, Marco; Filbin, Marie T

2005-06-15

65

Splitting White Light  

Science.gov (United States)

In this optics activity, learners split white light into all its component colors using three household items: a compact disc, dishwashing liquid, and a hose (outside). In each experiment, learners split light through a different color separation process, including dispersion, interference and diffraction. This resource includes an explanation of each process as well as links to three articles about color and light.

America, Optical S.

2008-01-01

66

Coded Splitting Tree Protocols  

DEFF Research Database (Denmark)

This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity.

Sørensen, Jesper Hemming; Stefanovic, Cedomir

2013-01-01

67

Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Multiple sclerosis (MS) is the most common demyelinating and an autoimmune disease of the central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. T cell subsets (Th1, Th2, Th17, CD8+, NKT, CD4+CD25+ T regulatory cells) and B cells are involved in this disorder, thus new MS therapies seek damage prevention by resetting multiple components of the immune system. The currently approved therapies are i...

Maria Podbielska; Banik, Naren L.; Ewa Kurowska; Hogan, Edward L.

2013-01-01

68

Evaluation of dermal myelinated nerve fibers in diabetes mellitus  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 29–73) underwent skin biopsy of the index finger, ne...

Peltier, Amanda C.; Myers, M. Iliza; Artibee, Kay J.; Hamilton, Audra D.; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

2013-01-01

69

A culture system to study oligodendrocyte myelination-processes using engineered nanofibers  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive for myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively un...

Lee, Seonok; Leach, Michelle K.; Redmond, Stephanie A.; Chong, S. Y. Christin; Mellon, Synthia H.; Tuck, Samuel J.; Feng, Zhang-qi; Corey, Joseph M.; Chan, Jonah R.

2012-01-01

70

Cultures of shiverer mutant cerebellum injected with normal oligodendrocytes make both normal and shiverer myelin.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Earlier reports suggested that injecting normal optic nerve into organotypic cerebellar cultures from three of the central nervous system hypomyelinated mutant mice resulted in striking local increases in myelination of mutant axons. It has been questioned whether this myelin was produced by the introduced normal glia because there was no "marker" by which the genotype of an individual myelin sheath could be rigorously determined. The present study shows that the myelin sheaths of the central...

Billings-gagliardi, S.; Hall, A. L.; Stanhope, G. B.; Altschuler, R. J.; Sidman, R. L.; Wolf, M. K.

1984-01-01

71

BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Current concepts of addiction focus on neuronal neurocircuitry and neurotransmitters and are largely based on animal model data, but the human brain is unique in its high myelin content and extended developmental (myelination) phase that continues until middle age. The biology of our exceptional myelination process and factors that influence it have been synthesized into a recently published myelin model of human brain evolution and normal development that cuts across the current symptom-base...

Bartzokis, George

2005-01-01

72

Impaired adult myelination in the prefrontal cortex of socially isolated mice  

Science.gov (United States)

Protracted social isolation of adult mice induced behavioral, transcriptional and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and impaired adult myelination. Social re-integration was sufficient to normalize behavioral and transcriptional changes. Short periods of isolation affected chromatin and myelin, but did not induce behavioral changes. Thus, myelinating oligodendrocytes in the adult PFC respond to social interaction with chromatin changes, suggesting that myelination acts as a form of adult plasticity.

Liu, Jia; Dietz, Karen; DeLoyht, Jacqueline M; Pedre, Xiomara; Kelkar, Dipti; Kaur, Jasbir; Vialou, Vincent; Lobo, Mary Kay; Dietz, David M; Nestler, Eric J; Dupree, Jeffrey; Casaccia, Patrizia

2013-01-01

73

Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes both in vitro and in an animal model of multiple sclerosis, but the possible role of LIF signaling in myelination during normal development has not been investigated. We find that LIF-/- mice have a pronounced myelination defect in optic nerve at postnatal day 10. Myelin basic protein (MBP)- and proteolipid protein (PLP)-positive myelin was evident throughout the optic nerve in the wild-type mice, but staining was pres...

Ishibashi, Tomoko; Lee, Philip R.; Baba, Hiroko; Fields, R. Douglas

2009-01-01

74

Photon splitting $\\gamma \\to \  

CERN Multimedia

The process of the photon splitting into the neutrino - antineutrino pair in a magnetic field is investigated. The amplitude and the probability are analysed in the limits of relatively small and strong fields. Possible astrophysical manifestations are briefly discussed.

Kuznetsov, A V; Vasilievskaya, L A

1998-01-01

75

Polarized Antenna Splitting Functions  

Energy Technology Data Exchange (ETDEWEB)

We consider parton showers based on radiation from QCD dipoles or 'antennae'. These showers are built from 2 {yields} 3 parton splitting processes. The question then arises of what functions replace the Altarelli-Parisi splitting functions in this approach. We give a detailed answer to this question, applicable to antenna showers in which partons carry definite helicity, and to both initial- and final-state emissions.

Larkoski, Andrew J.; Peskin, Michael E.; /SLAC

2009-10-17

76

Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination.  

Science.gov (United States)

Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP and analyzed the consequence of plasmalogen deficiency in peripheral nerves. We determined that plasmalogens are crucial for Schwann cell development and differentiation and that plasmalogen defects impaired radial sorting, myelination, and myelin structure. Plasmalogen insufficiency resulted in defective protein kinase B (AKT) phosphorylation and subsequent signaling, causing overt activation of glycogen synthase kinase 3? (GSK3?) in nerves of mutant mice. Treatment with GSK3? inhibitors, lithium, or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) restored Schwann cell defects, effectively bypassing plasmalogen deficiency. Our results demonstrate the requirement of plasmalogens for the correct and timely differentiation of Schwann cells and for the process of myelination. In addition, these studies identify a mechanism by which the lack of a membrane phospholipid causes neuropathology, implicating plasmalogens as regulators of membrane and cell signaling. PMID:24762439

da Silva, Tiago Ferreira; Eira, Jessica; Lopes, André T; Malheiro, Ana R; Sousa, Vera; Luoma, Adrienne; Avila, Robin L; Wanders, Ronald J A; Just, Wilhelm W; Kirschner, Daniel A; Sousa, Mónica M; Brites, Pedro

2014-06-01

77

Increased Th17 response to myelin peptides in pediatric MS.  

Science.gov (United States)

Studies of the underlying immune mechanisms of multiple sclerosis (MS) in children may shed light on the initial events of MS pathogenesis. We studied T cell responses to myelin peptides in 10 pediatric MS patients (PMS), 10 pediatric healthy controls (PHC), 10 adult MS patients (AMS) and 10 adult healthy controls (AHC). A significantly higher proportion of divided CD4+ T cell responses in response to myelin peptides by the CFSE assay in PMS compared to PHC at both concentrations of myelin peptide tested (t test, 95% CI, p=0.0067 for MP1; p=0.0086 for MP10), and between PMS and AMS (p=0.0012 at 1 ?g/mL of myelin peptides, p<0.0001 at 10 ?g/mL) was found. In addition, T cells with a central memory phenotype producing IL-17 were increased in PMS compared to PHC (p<0.05). IL-7 levels in culture supernatants were elevated in PMS compared to PHC and AMS (t test<0.01). PMID:23352968

Vargas-Lowy, David; Kivisäkk, Pia; Gandhi, Roopali; Raddassi, Khadir; Soltany, Pejvak; Gorman, Mark P; Khoury, Samia J; Chitnis, Tanuja

2013-03-01

78

Tibetan medical interpretation of myelin lipids and multiple sclerosis.  

Science.gov (United States)

Tibetan medicine integrates diet, lifestyle, herbs, and accessory therapies to increase health and longevity. A comparison of the three humor theory of Tibetan medicine and the three thermodynamic phase properties of myelin lipids exemplifies how integrating medical systems can increase understanding of complex chronic disabling conditions. As a correlative study to microscopically better understand multiple sclerosis (MS) from the view of Tibetan medicine, the physical disruption of central nervous system myelin membranes in MS is interpreted from the theory of the three humors (vital energies) of Tibetan medicine: rLung (Wind), MKhris pa (Bile), and Bad gen (Phlegm). The three classes of myelin lipids--phospholipids, sphingolipids, and cholesterol--are interpreted as one of three humors based on Langmuir isotherm thermodynamic measurements. The nature of rLung is movement or change. Myelin sphingolipids have rLung properties based on thermodynamic observations of changes in phase organization. MKhris pa is fire, energetic. Phospholipids have MKhris pa properties based on thermodynamic observations of being energetic membrane lipids with fast molecular motions and fluid-like properties. The nature of Bad gen is substance and form; it dominates body structure. Cholesterol relates to Bad gen because it dominates membrane structure. We propose a theoretical relationship whereby demyelination in MS is viewed as a continuum of imbalance of the three humors as understood in Tibetan medicine. Myelin lipid data is presented to support this theoretical relationship. Clinically, MS is, in general, a rLung-MKhrispa disorder in women and a Bad gen-MKhrispa disorder in men, with rLung-MKhrispa excess in both genders during exacerbation, inflammation, and demyelination. Studying Tibetan medicine in its traditional context will create an integrative model for the treatment of MS and other chronic conditions. PMID:19743559

Husted, Cynthia; Dhondup, Lobsang

2009-08-01

79

Effects of normal aging on myelin sheath ultrastructures in the somatic sensorimotor system of rats.  

Science.gov (United States)

Previous studies have presented qualitative and quantitative data regarding the morphological changes that occur peripherally in myelin sheaths and nerve fibers of rats during their lifespan. However, studies on ultrastructural features of myelinated fibers (MFs) in the central nervous system (CNS) remain limited. In the present study, morphological analyses of the somatic sensorimotor MFs in rats at time?points between postnatal day 14 and postnatal month (PNM) 26 were conducted using electron microscopy. Significant alterations in the myelin sheath were observed in the sensorimotor system of aging and aged rats, which became aggravated with age. The ultrastructural pattern of myelin lamellae also exhibited age dependence. The transformation of the myelin intraperiod line from complete to incomplete fusion occurred after PNM 5, leading to an expansion of periodicity in myelin lamellae. These pathological changes in the myelin structure occurred very early and showed a significant correlation with age, indicating that myelin was the part of the CNS with the highest susceptibility to the influence of aging, and may be the main target of aging effects. In addition to the myelin breakdown, continued myelin production and remyelination were observed in the aging sensorimotor system, suggesting the presence of endogenous mechanisms of myelin repair. PMID:24818843

Xie, Fang; Liang, Ping; Fu, Han; Zhang, Jiu-Cong; Chen, Jun

2014-07-01

80

Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths in vivo.  

Science.gov (United States)

The number of myelin sheaths made by individual oligodendrocytes regulates the extent of myelination, which profoundly affects central nervous system function. It remains unknown when, during their life, individual oligodendrocytes can regulate myelin sheath number in vivo. We show, using live imaging in zebrafish, that oligodendrocytes make new myelin sheaths during a period of just 5 hr, with regulation of sheath number after this time limited to occasional retractions. We also show that activation and reduction of Fyn kinase in oligodendrocytes increases and decreases sheath number per cell, respectively. Interestingly, these oligodendrocytes also generate their new myelin sheaths within the same period, despite having vastly different extents of myelination. Our data demonstrate a restricted time window relative to the lifetime of the individual oligodendrocyte, during which myelin sheath formation occurs and the number of sheaths is determined. PMID:23806617

Czopka, Tim; Ffrench-Constant, Charles; Lyons, David A

2013-06-24

 
 
 
 
81

Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling  

Science.gov (United States)

SUMMARY Oligodendrocyte precursors (OPs) continue to proliferate and generate myelinating oligodendrocytes (OLs) well into adulthood. It is not known whether adult-born OLs ensheath previously unmyelinated axons or remodel existing myelin. We quantified OP division and OL production in different regions of the adult mouse CNS including the 4-month-old optic nerve, in which practically all axons are already myelinated. Even there, all OPs were dividing and generating new OLs and myelin at a rate higher than can be explained by first-time myelination of naked axons. We conclude that adult-born OLs in the optic nerve are engaged in myelin remodeling, either replacing OLs that die in service or intercalating among existing myelin sheaths. The latter would predict that average internode length should decrease with age. Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life.

Young, Kaylene M.; Psachoulia, Konstantina; Tripathi, Richa B.; Dunn, Sara-Jane; Cossell, Lee; Attwell, David; Tohyama, Koujiro; Richardson, William D.

2013-01-01

82

Intracortical myelin links with performance variability across the human lifespan: results from T1- and T2-weighted MRI myelin mapping and diffusion tensor imaging.  

Science.gov (United States)

Cerebral myelin maturation and aging-related degradation constitute fundamental features of human brain integrity and functioning. Although mostly studied in the white matter, the cerebral cortex contains significant amounts of myelinated axons. However, how intracortical myelin content evolves during development, decays in aging, and links with cognition remain poorly understood. Several studies have shown the potential of mapping myelin in the cortex by use of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging signal intensity, which show inverse sensitivity to myelin. Here, we characterized cortical myelin in 339 participants 8-83 years of age using a recently introduced T1w/T2w ratio myelin mapping technique and mean diffusivity (MD) from diffusion tensor imaging. To test for cognitive correlates, we used intraindividual variability (IIV) in performance during a speeded task, a measure recently associated with white matter integrity. The results showed that intracortical myelin maturation was ongoing until the late 30s, followed by 20 relative stable years before declining from the late 50s. For MD, U-shaped paths showing similar patterns were observed, but with fewer maturational effects in some regions. IIV was correlated with both T1w/T2w ratio and MD, mainly indicating that the higher degree of intracortical myelin is associated with greater performance stability. The relations were more prominent with advancing age, suggesting that aging-related cortical demyelination contributes to increased IIV. The T1w/T2w ratio myelin-mapping technique thus seems sensitive to intracortical myelin content in normal development and aging, relates to cognitive functioning, and might constitute an important future tool in mapping normal and clinical brain changes. PMID:24259583

Grydeland, Håkon; Walhovd, Kristine B; Tamnes, Christian K; Westlye, Lars T; Fjell, Anders M

2013-11-20

83

On the number and nature of regenerating myelinated axons after lesions of cutaneous nerves in the cat.  

Science.gov (United States)

1. Electrophysiological and anatomical techniques were used to investigate normal and regenerating sural and posterior femoral cutaneous nerve fibres in the cat. 2. One and a half years after transection of these nerves it was found that the regenerating neurones supported multiple sprouts in the distal stump of the nerve. The branching occurred at or beyond the level of the neuroma and some of the branched fibres innervated split receptive fields on the skin. 3. Counts of the number of axons in the proximal stumps of transected nerves showed that the whole original population of myelinated fibres persisted for at least 18 months. About 75% of these fibres successfully crossed the unrepaired transection site and regenerated into the distal stump of the nerve to re-form functional connexions in the skin. 4. After nerve crush all the myelinated axons regenerated. None showed signs of abnormal branching. 5. After crush the conduction velocities of the regenerated axons in the distal stump of the nerve reached nearly normal values by 6 months. After nerve transection the distal conduction velocities were reduced to 50% of normal even 18 months after the injury. 6. The implications of these findings for the recovery of function after nerve injury in man are discussed. PMID:7277219

Horch, K W; Lisney, S J

1981-01-01

84

Distances of Heegaard splittings  

Digital Repository Infrastructure Vision for European Research (DRIVER)

J Hempel [Topology, 2001] showed that the set of distances of the Heegaard splittings (S,V, h^n(V)) is unbounded, as long as the stable and unstable laminations of h avoid the closure of V in PML(S). Here h is a pseudo-Anosov homeomorphism of a surface S while V is the set of isotopy classes of simple closed curves in S bounding essential disks in a fixed handlebody. With the same hypothesis we show the distance of the splitting (S,V, h^n(V)) grows linearly with n, answeri...

Abrams, Aaron; Schleimer, Saul

2003-01-01

85

Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons  

Science.gov (United States)

Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T.

2001-01-01

86

Organization of myelin in the mouse somatosensory barrel cortex and the effects of sensory deprivation.  

Science.gov (United States)

In rodents, the barrel cortex is a specialized area within the somatosensory cortex that processes signals from the mystacial whiskers. We investigated the normal development of myelination in the barrel cortex of mice, as well as the effects of sensory deprivation on this pattern. Deprivation was achieved by trimming the whiskers on one side of the face every other day from birth. In control mice, myelin was not present until postnatal day 14 and did not show prominence until postnatal day 30; adult levels of myelination were reached by the end of the second postnatal month. Unbiased stereology was used to estimate axon density in the interbarrel septal region and barrel walls as well as the barrel centers. Myelin was significantly more concentrated in the interbarrel septa/barrel walls than in the barrel centers in both control and sensory-deprived conditions. Sensory deprivation did not impact the onset of myelination but resulted in a significant decrease in myelinated axons in the barrel region and decreased the amount of myelin ensheathing each axon. Visualization of the oligodendrocyte nuclear marker Olig2 revealed a similar pattern of myelin as seen using histochemistry, but with no significant changes in Olig2+ nuclei following sensory deprivation. Consistent with the anatomical results showing less myelination, local field potentials revealed slower rise times following trimming. Our results suggest that myelination develops relatively late and can be influenced by sensory experience. PMID:23047707

Barrera, Kyrstle; Chu, Philip; Abramowitz, Jason; Steger, Robert; Ramos, Raddy L; Brumberg, Joshua C

2013-04-01

87

Split dynamics plasma simulations  

International Nuclear Information System (INIS)

I will talk about some aspects of a trans-Debye kinetic plasma modeling. A split dynamics scheme is employed for the simulation of processes complementary to PIC codes. Furthermore, I will briefly touch upon a recent result regarding the interaction between a prompt GRB photonic pulse and an assumed circumburst medium. (author)

2008-10-05

88

The Splitting Group  

Science.gov (United States)

Piagetian theory describes mathematical development as the construction and organization of mental operations within psychological structures. Research on student learning has identified the vital roles of two particular operations--splitting and units coordination--play in students' development of advanced fractions knowledge. Whereas Steffe and…

Norton, Anderson; Wilkins, Jesse L. M.

2012-01-01

89

Split image optical display  

Energy Technology Data Exchange (ETDEWEB)

A video image is displayed from an optical panel by splitting the image into a plurality of image components, and then projecting the image components through corresponding portions of the panel to collectively form the image. Depth of the display is correspondingly reduced.

Veligdan, James T. (Manorville, NY)

2007-05-29

90

Split Injection Gas Chromatography  

Science.gov (United States)

This animation site deals specifically with split injection in gas chromatography. The animations are short (one to two minutes each) and can easily be shown in class as part of a lecture. They are extremely helpful in illustrating key components and concepts of chromatographic systems. Users are encouraged to explore the site and the other brief animations as well.

2011-05-11

91

A role for nociceptive, myelinated nerve fibers in itch sensation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of non-histaminergic mechanisms. To investigate the role of small myelinated afferents in non-histaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plan...

Ringkamp, M.; Schepers, R. J.; Shimada, S. G.; Johanek, L. M.; Hartke, T. V.; Borzan, J.; Shim, B.; Lamotte, R. H.; Meyer, R. A.

2011-01-01

92

Retrograde growth of myelinated fibres in experimental neuromas.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Retrograde growth of myelinated fibre sprouts following section of mouse sural nerves has been investigated. The results indicate that many sprouts grow relatively long distances proximally along the nerve trunk. The largest number of such sprouts was observed at 10 weeks after nerve section, with a decrease by 9 months. It has been shown that the retrogradely growing sprouts arise within the neuroma and not more proximally on the nerve.

Scadding, J. W.; Thomas, P. K.

1983-01-01

93

Cholecalciferol (vitamin D?) improves myelination and recovery after nerve injury.  

Science.gov (United States)

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair. PMID:23741446

Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel; Decherchi, Patrick; Feron, Francois

2013-01-01

94

Synthesis of myelin glycosphingolipids by isolated oligodendrocytes in tissue culture  

International Nuclear Information System (INIS)

Isolated lamb oligodendrocytes in tissue culture were tested for their ability to express differentiated functions related to the synthesis of myelin. At selected times, monolayer cultures of cells were double labeled for 60-72 h with [3H]galactose and H235SO4. Glycosphingolipids were separated and identified by thin layer chromatography. During the first week in tissue culture, there was gradual decline in incorporation of both isotopes relative to the values obtained for freshly isolated cells. However, by 3 weeks high levels of H235SO4 incorporation into sulfatide and [3H]galactose into cerebrosides were found. A complex pattern of incorporation ensued after this peak which varied for each particular glycosphingolipid. It is concluded that: (1) cultured oligodendrocytes retain the capacity to synthesize components of myelin; (2) since the isolated cells have already been involved in myelination, these cultures afford a unique model to study remyelination; and (3) these cells provide a good system to study the properties of oligodendrocytes. (Auth.)

1981-06-09

95

Effect of benzene and lead on relationship between ?-aminolevulinic acid and brain myelin proteins  

International Nuclear Information System (INIS)

The aim of this investigation was to study binding of ALA by brain myelin under normal conditions and under the influence of lead and benzene. Rabbits of three different groups were given an intercranial injection of "1"4C-ALA (50 microCi) in physiological saline in a volume of 0.25 ml. The myelin fraction was obtained by differential centrifugation and the "1"4C-ALA in it was assayed on an LKB liquid scintillation counter. By determining the quantity of exogenous "1"4C-ALA bound with myelin, the authors found that myelin of white matter in the brain contains more of the acid than myelin of the gray matter. Data on binding of "1"4C-ALA calculated per milligram of each group of myelin proteins isolated is given

1986-03-01

96

Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Diffusion tensor imaging (DTI) using variable diffusion times (tdiff) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At tdiff = 30 ms, the diffusion anisotropy “volume ratio” (VR), diffusion perpendicular to the fibers (??), and mean apparent diffusion coefficient (?D?) of the corpus callosum of shi mice were significantly high...

Nair, Govind; Tanahashi, Yusuke; Low, Hoi Pang; Billings-gagliardi, Susan; Schwartz, William J.; Duong, Timothy Q.

2005-01-01

97

Late onset axonal Charcot?Marie?Tooth phenotype caused by a novel myelin protein zero mutation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A late onset axonal Charcot?Marie?Tooth phenotype is described, resulting from a novel mutation in the myelin protein zero (MPZ) gene. Comparative computer modelling of the three dimensional structure of the MPZ protein predicts that this mutation does not cause a significant structural change. The primary axonal disease process in these patients points to a function of MPZ in maintenance of the myelinated axons, apart from securing stability of the myelin layer.

Bienfait, H. M. E.; Faber, C. G.; Baas, F.; Gabree?ls-festen, A. A. W. M.; Koelman, J. H. T. M.; Hoogendijk, J. E.; Verschuuren, J. J.; Wokke, J. H. J.; Visser, M.

2006-01-01

98

A Thermodynamic and Structural Study of Myelin Basic Protein in Lipid Membrane Models  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin basic protein (MBP) is a major protein of the myelin membrane in the central nervous system. It is believed to play a relevant role in the structure and function of the myelin sheath and is a candidate autoantigen in demyelinating processes such as multiple sclerosis. MBP has many features typical of soluble proteins but is capable of strongly interacting with lipids, probably via a conformation change. Its structure in the lipid membrane as well as the details of its interaction with ...

Rispoli, P.; Carzino, R.; Svaldo-lanero, T.; Relini, A.; Cavalleri, O.; Fasano, A.; Liuzzi, G. M.; Carlone, G.; Riccio, P.; Gliozzi, A.; Rolandi, R.

2007-01-01

99

Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute to the absence of a single myelin protein. We hypothesized that secondary molecular changes in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions i...

Werner, Hauke B.; Kuhlmann, Katja; Shen, Siming; Uecker, Marina; Schardt, Anke; Dimova, Kalina; Orfaniotou, Foteini; Dhaunchak, Ajit; Brinkmann, Bastian G.; Mo?bius, Wiebke; Guarente, Lenny; Casaccia-bonnefil, Patrizia; Jahn, Olaf; Nave, Klaus-armin

2007-01-01

100

Integrin-mediated axoglial interactions initiate myelination in the central nervous system  

Digital Repository Infrastructure Vision for European Research (DRIVER)

All but the smallest-diameter axons in the central nervous system are myelinated, but the signals that initiate myelination are unknown. Our prior work has shown that integrin signaling forms part of the cell–cell interactions that ensure only those oligodendrocytes contacting axons survive. Here, therefore, we have asked whether integrins regulate the interactions that lead to myelination. Using homologous recombination to insert a single-copy transgene into the hypoxanthine phosphoribosyl...

Ca?mara, Joana; Wang, Zhen; Nunes-fonseca, Cristina; Friedman, Hana C.; Grove, Matthew; Sherman, Diane L.; Komiyama, Noboru H.; Grant, Seth G.; Brophy, Peter J.; Peterson, Alan; Ffrench-constant, Charles

2009-01-01

 
 
 
 
101

Myelin-associated glycoprotein-related neuropathy associated with psoriasis: a case report  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Introduction Psoriasis vulgaris is a common inflammatory disease of the skin, and myelin-associated glycoprotein-related neuropathy is a chronic sensory-predominant polyneuropathy. Although both of these diseases are considered autoimmune diseases, psoriasis with concomitant myelin-associated glycoprotein-related neuropathy is very rare. Here, we report a case of myelin-associated glycoprotein-related neuropathy associated with psoriasis. Case presentation...

2013-01-01

102

Antibody-independent complement activation by myelin via the classical complement pathway  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Murine or rabbit whole brain homogenates were shown to activate human complement via the classical pathway by an antibody-independent reaction. This activity required Ca++ ions. Anticomplementary activity in fractionated murine brain was found to reside in the myelin fraction and in purified myelin. It was absent, however, both from highly purified myelin basic protein (MBP) and from the MBP-free residue. Because purified MBP is a monomer and this protein exists in brain tissue largely as a d...

1982-01-01

103

Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In some cases of polyneuropathy and plasma cell dyscrasia, the monclonal antibodies react with human peripheral nerve myelin. To identify the myelin antigens involved, we separated the proteins of human central and peripheral nerve myelin by polyacrylamide gel electrophoresis, transferred the proteins onto nitrocellulose sheets, and used an immunoenzymatic technique to detect the reactive antigens. Serum IgM but not IgG from three patients with neuropathy and complement-fixing anti-human myel...

Latov, N.; Braun, P. E.; Gross, R. B.; Sherman, W. H.; Penn, A. S.; Chess, L.

1981-01-01

104

Surface bundles versus Heegaard splittings  

CERN Document Server

This paper studies Heegaard splittings of surface bundles via the curve complex of the fibre. The translation distance of the monodromy is the smallest distance it moves any vertex of the curve complex. We prove that the translation distance is bounded above in terms of the genus of any strongly irreducible Heegaard splitting. As a consequence, if a splitting surface has small genus compared to the translation distance of the monodromy, the splitting is standard.

Bachman, D C; Bachman, David; Schleimer, Saul

2002-01-01

105

The influence of Hericium erinaceus extract on myelination process in vitro.  

Science.gov (United States)

Myelin sheaths, wrapping axons, perform the following important functions: support, protection, feeding and isolation. Injury of myelin compact structure leads to an impairment and severe illness of the nerve system. Exact mechanisms underlying the myelination process and myelin sheaths damage have not established yet. Therefore search for substances, which provide regulatory and protective effects on the normal myelination as well as stimulating action on the remyelination after myelin damage, is of special interest. Recently it was shown that extract from mushroom Hericium erinaceus had activating action on the nerve tissue. So the aim of the present work was to study an influence of an extract from H. erinaceus on the cerebellar cells and the process of myelination in vitro. Obtained data revealed the normal growth of the nerve and glial cells with extract at cultivating. No pathologic or toxic action of the extract has been found. The cell ultrastructure was intact and similar to that observed in vivo. The process of myelination in the presence of the extract began earlier as compared to controls and was characterised by a higher rate. Thus, extract of H. erinaceus promoted normal development of cultivated cerebellar cells and demonstrated a regulatory effect on the process of myelin genesis process in vitro. PMID:12675022

Kolotushkina, E V; Moldavan, M G; Voronin, K Yu; Skibo, G G

2003-01-01

106

Mini-Split  

CERN Document Server

The lack of evidence for new physics beyond the standard model at the LHC points to a paucity of new particles near the weak scale. This suggests that the weak scale is tuned and that supersymmetry, if present at all, is realized at higher energies. The measured Higgs mass constrains the scalar sparticles to be below 10^5 TeV, while gauge coupling unification favors Higgsinos below 100 TeV. Nevertheless, in many models gaugino masses are suppressed and remain within reach of the LHC. Tuning the weak scale and the renormalization group evolution of the scalar masses constrain Split model building. Due to the small gaugino masses, either the squarks or the up-higgs often run tachyonic; in the latter case, successful electroweak breaking requires heavy higgsinos near the scalar sparticles. We discuss the consequences of tuning the weak scale and the phenomenology of several models of Split supersymmetry including anomaly mediation, U(1)_(B-L) mediation, and Split gauge mediation.

Arvanitaki, Asimina; Dimopoulos, Savas; Villadoro, Giovanni

2012-01-01

107

Rotational Splitting of Pulsational Modes  

CERN Multimedia

Mode splittings produced by uniform rotation and a particular form of differential rotation are computed for two-dimensional rotating 10 Mo ZAMS stellar models. The change in the character of the mode splitting is traced as a function of uniform rotation rate, and it is found that only relatively slow rotation rates are required before the mode splitting becomes asymmetric about the azimuthally symmetric (m=0) mode. Increased rotation produces a progressively altered pattern of the individual modes with respect to each other. Large mode splittings begin to overlap with the mode splittings produced by different radial and latitudinal modes at relatively low rotation rates. The mode splitting pattern for the differentially rotating stars we model is different than that for uniformly rotating stars, making the mode splitting a possible discriminant of the internal angular momentum distribution if one assumes the formidable challenge of mode identification can be overcome.

Deupree, Robert

2010-01-01

108

Collagen VI regulates peripheral nerve myelination and function.  

Science.gov (United States)

Collagen VI is an extracellular matrix protein with broad distribution in several tissues. Although Col6a1 is expressed by Schwann cells, the role of collagen VI in the peripheral nervous system (PNS) is yet unknown. Here we show that Schwann cells, but not axons, contribute to collagen VI deposition in peripheral nerves. By using Col6a1-null mice, in which collagen VI deposition is compromised, we demonstrate that lack of collagen VI leads to increased myelin thickness (Pvelocity and motor coordination (Pcritical component of PNS contributing to the structural integrity and proper function of peripheral nerves. PMID:24277578

Chen, Peiwen; Cescon, Matilde; Megighian, Aram; Bonaldo, Paolo

2014-03-01

109

PHOTOSYNTHESIS: Splitting Water  

Science.gov (United States)

Access to the article is free, however registration and sign-in are required. Photosynthetic water oxidation is the largest global source of atmospheric O2 and provided the impetus for the evolution of complex life on Earth. In his Perspective, Dismukes highlights the recent publication of a structural model of the polypeptide subunit organization of the enzyme responsible for this reaction. These results, which are based on x-ray crystallographic data, provide hope that a detailed atomic model of the water-splitting catalyst should be forthcoming.

G. C. Dismukes (Princeton University;Department of Chemistry and the Princeton Environmental Institute)

2001-04-20

110

Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men  

Science.gov (United States)

Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

2013-01-01

111

Axon-myelin transfer of glycerol-labeled lipids and inorganic phosphate during axonal transport  

International Nuclear Information System (INIS)

Axon-to-myelin transfer of lipids and lipid precursors have been studied in the rabbit optic system by intraocular injection of [32P]orthophosphate, [14C]glycerol and [3H]glycerol. Choline and ethanolamine phosphoglycerides and myelin showed increasing [32P]-radioactivity between 7 and 21 days following injection, while [3H]- and [14C]-radioactivities remained relatively constant. The latter radioactivities decreased, however, in all the axon- and axolemma-enriched fractions during the same period. These findings supported the concept that a portion of substances undergoing axonal transport enters the pool of myelin lipids by two mechanisms: transcellular transfer of intact lipid and axon-myelin transfer of precursors which are re-utilized for lipid biosynthesis by myelin-localized enzymes. The present study shows that inorganic phosphate, possibly generated by catabolic activity within the axon, is able to enter myelin and participate in the re-utilization mechanism as previously described for serine, choline and acyl chains. The relative invariance of the 3H:14C ratio suggested that the majority of glycerol is not re-utilized in this manner but probably enters myelin through transfer of intact lipid. These and earlier results suggest a possible form of metabolic dependence of myelin on trophic substances from the axon. (Auth.)

1983-06-20

112

A screen for mutations in zebrafish that affect myelin gene expression in Schwann cells and oligodendrocytes.  

Science.gov (United States)

Myelin is the multi-layered glial sheath around axons in the vertebrate nervous system. Myelinating glia develop and function in intimate association with neurons and neuron-glial interactions control much of the life history of these cells. However, many of the factors that regulate key aspects of myelin development and maintenance remain unknown. To discover new molecules that are important for glial development and myelination, we undertook a screen of zebrafish mutants with previously characterized neural defects. We screened for myelin basic protein (mbp) mRNA by in situ hybridization and identified four mutants (neckless, motionless, iguana and doc) that lacked mbp expression in parts of the peripheral and central nervous systems (PNS or CNS), despite the presence of axons. In all four mutants electron microscopy revealed that myelin-forming glia were present and had formed loose wraps around axons but did not form compact myelin. We found that addition of exogenous retinoic acid (RA) rescued mbp expression in neckless mutant embryos, which lack endogenous RA synthesis. Timed application of the RA synthesis inhibitor DEAB to wild type embryos showed that RA signalling is required at least 48 h before the onset of myelin protein synthesis in both CNS and PNS. PMID:16839543

Kazakova, Natalia; Li, Huiliang; Mora, Ana; Jessen, Kristjan R; Mirsky, Rhona; Richardson, William D; Smith, Hazel K

2006-09-01

113

The effects of normal aging on myelinated nerve fibers in monkey central nervous system  

Directory of Open Access Journals (Sweden)

Full Text Available The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter degenerate and are lost, leading to some disconnections between various parts of the central nervous system. Other myelinated nerve fibers are affected differently, because only their sheaths degenerate, leaving the axons intact. Such axons are remyelinated by a series of internodes that are much shorter than the original ones and are composed of thinner sheaths. Thus the myelin-forming cells of the central nervous system, the oligodendrocytes, remain active during aging. Indeed, not only do these neuroglial cell remyelinate axons, with age they also continue to add lamellae to the myelin sheaths of intact nerve fibers, so that sheaths become thicker. It is presumed that the degeneration of myelin sheaths is due to the degeneration of the parent oligodendrocyte, and that the production of increased numbers of internodes as a consequence of remyelination requires additional oligodendrocytes. Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of oligodendrocytes. While the loss of some myelinated nerve fibers leads to some disconnections, the degeneration of other myelin sheaths and the subsequent remyelination of axons by shorter internodes slow down the rate conduction along nerve fibers. These changes affect the integrity and timing in neuronal circuits, and there is evidence that they contribute to cognitive decline.

AlanPeters

2009-07-01

114

A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This study identifies novel mechanisms of Hes5 function in developmental myelination. We report here upregulation of myelin gene expression in Hes5?/? mice compared to wild-type siblings and downregulation in overexpressing progenitors. This effect was only partially explained by the ability to regulate the levels of Mash1 and bind to N boxes in myelin promoters, as deletion of the DNA-binding domain of Hes5 did not suppress its inhibitory role on myelin gene expression. Novel mechanisms ...

Liu, Aixiao; Li, Jiadong; Marin-husstege, Mireya; Kageyama, Ryochiro; Fan, Yongjun; Gelinas, Celine; Casaccia-bonnefil, Patrizia

2006-01-01

115

Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background The sphingolipids galactosylceramide (GalCer) and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt-/-) mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanie...

Meixner Marion; Jungnickel Julia; Grothe Claudia; Gieselmann Volkmar; Eckhardt Matthias

2011-01-01

116

Myelin-associated Glycoprotein gene and brain morphometry in schizophrenia  

Directory of Open Access Journals (Sweden)

Full Text Available Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin associated glycoprotein gene on brain morphometry in schizophrenia patients and healthy controls. 45 schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes along with subcortical structure volumes were calculated from T1-weighted MRI scans. Each subject was also genotyped for the two disease-associated MAG single nucleotide polymorphisms (rs720308 and rs720309. Repeated measures general linear model analysis found significant region by genotype and region by diagnosis interactions for the effects of MAG risk variants on lobar gray matter volumes. No significant associations were found with lobar white matter volumes or subcortical structure volumes. Follow-up univariate general linear models found the AA genotype of rs720308 predisposed schizophrenia patients to left temporal and parietal gray matter volume deficits. These results suggest that the effects of the MAG gene on cortical gray matter volume in schizophrenia patients can be localized to temporal and parietal cortices. Our results support a role for MAG gene variation in brain morphometry in schizophrenia, align with other lines of evidence implicating MAG in schizophrenia, and provide genetically-based insight into the heterogeneity of brain imaging findings in this disorder.

JamesKennedy

2012-05-01

117

Statistical physics approach to quantifying differences in myelinated nerve fibers  

Science.gov (United States)

We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross-sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum.

Comin, César H.; Santos, João R.; Corradini, Dario; Morrison, Will; Curme, Chester; Rosene, Douglas L.; Gabrielli, Andrea; da F. Costa, Luciano; Stanley, H. Eugene

2014-03-01

118

Myelinated afferents signal the hyperalgesia associated with nerve injury.  

Science.gov (United States)

Pain to light touching of the skin is a hallmark sign of causalgia. The purpose of this study was to determine whether myelinated or unmyelinated afferent fibers signal this hyperalgesia. Sensory testing was performed in 17 patients with long-standing hyperalgesia after nerve injury. The patients underwent a differential ischemic block of nerve function of the involved area. At a time when touch sensation in adjacent normal skin was eliminated, but when sensibility to warming and cooling stimuli was unaffected, the hyperalgesia to mechanical stimuli was abolished in 15 of the subjects. In 2 of these 15 patients, a differential local anesthetic block of the injured nerve was performed proximal to the site of injury. When temperature sensibility was absent, but when touch sensation was intact, hyperalgesia was present. In a third study, latency measurements in response to 400 micron stepped displacement stimuli were made in two patients who had hyperalgesia on the foot. The mean latency for detection of pain in the hyperalgesic region was 414 +/- 18 msec, compared to 458 +/- 16 msec for the detection of touch to the same stimuli applied to the opposite normal foot. These 3 lines of evidence indicate that myelinated primary afferents, perhaps A beta fibers, signal the hyperalgesic pain in causalgia. These fibers may be sensitized A beta nociceptors or low-threshold mechanoreceptors. PMID:3340426

Campbell, J N; Raja, S N; Meyer, R A; Mackinnon, S E

1988-01-01

119

A quantitative measure of myelination development in infants, using MR images  

International Nuclear Information System (INIS)

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

2004-09-01

120

Subclinical CNS inflammation as response to a myelin antigen in humanized mice.  

Science.gov (United States)

Multiple sclerosis is a demyelinating autoimmune disease of the CNS. Its animal model experimental autoimmune encephalomyelitis is commonly induced by active immunization with myelin antigens. To investigate human immune responses against myelin antigens in vivo we established a new subclinical experimental autoimmune encephalomyelitis model in humanized mice. NOD/Scid?c?/? animals were transferred with peripheral blood mononuclear cells from healthy human donors and immunized with myelin antigens in complete Freund's adjuvant and antigen-pulsed autologous dendritic cells. Human T cells recovered from these animals reacted specifically to the soluble domain of myelin oligodendrocyte glycoprotein and secreted proinflammatory cytokines. Furthermore, immunized animals developed subclinical CNS inflammation with infiltrating CD4? and CD8? T cells and production of encephalitogenic cytokines. Thus, this model of myelin-induced CNS inflammation by human T cells may allow testing of new human-specific therapeuticals for multiple sclerosis. PMID:23640521

Zayoud, Morad; El Malki, Khalifa; Frauenknecht, Katrin; Trinschek, Bettina; Kloos, Luise; Karram, Khalad; Wanke, Florian; Georgescu, Julia; Hartwig, Udo F; Sommer, Clemens; Jonuleit, Helmut; Waisman, Ari; Kurschus, Florian C

2013-09-01

 
 
 
 
121

Comet LINEAR Splits Further  

Science.gov (United States)

Third Nucleus Observed with the VLT Summary New images from the VLT show that one of the two nuclei of Comet LINEAR (C/2001 A2), now about 100 million km from the Earth, has just split into at least two pieces . The three fragments are now moving through space in nearly parallel orbits while they slowly drift apart. This comet will pass through its perihelion (nearest point to the Sun) on May 25, 2001, at a distance of about 116 million kilometres. It has brightened considerably due to the splitting of its "dirty snowball" nucleus and can now be seen with the unaided eye by observers in the southern hemisphere as a faint object in the southern constellation of Lepus (The Hare). PR Photo 18a/01 : Three nuclei of Comet LINEAR . PR Photo 18b/01 : The break-up of Comet LINEAR (false-colour). Comet LINEAR splits and brightens ESO PR Photo 18a/01 ESO PR Photo 18a/01 [Preview - JPEG: 400 x 438 pix - 55k] [Normal - JPEG: 800 x 875 pix - 136k] ESO PR Photo 18b/01 ESO PR Photo 18b/01 [Preview - JPEG: 367 x 400 pix - 112k] [Normal - JPEG: 734 x 800 pix - 272k] Caption : ESO PR Photo 18a/01 shows the three nuclei of Comet LINEAR (C/2001 A2). It is a reproduction of a 1-min exposure in red light, obtained in the early evening of May 16, 2001, with the 8.2-m VLT YEPUN (UT4) telescope at Paranal. ESO PR Photo 18b/01 shows the same image, but in a false-colour rendering for more clarity. The cometary fragment "B" (right) has split into "B1" and "B2" (separation about 1 arcsec, or 500 km) while fragment "A" (upper left) is considerably fainter. Technical information about these photos is available below. Comet LINEAR was discovered on January 3, 2001, and designated by the International Astronomical Union (IAU) as C/2001 A2 (see IAU Circular 7564 [1]). Six weeks ago, it was suddenly observed to brighten (IAUC 7605 [1]). Amateurs all over the world saw the comparatively faint comet reaching naked-eye magnitude and soon thereafter, observations with professional telescopes indicated the reason for this strange behaviour: the comet's "dirty snowball" nucleus had split into two pieces (IAUC 7616 [1]). During the splitting of the nucleus, fresh material from the interior of this frozen body is suddenly exposed to the sunlight, causing a rapid increase in the evaporation process. More cometary material is released and the overall brightness increases, as more sunlight is reflected off the dust around the nucleus. The VLT observes three fragments But Comet LINEAR has just shown that it is good for another surprise. When astronomers at ESO's Paranal Observatory [2] turned the 8.2-m VLT MELIPAL telescope (UT3) towards that object in the evening of May 14, they noted that one of the two pieces of the nucleus appeared somewhat elongated. The comet is rapidly approaching the Sun - it will pass through its perihelion (the point closest to the Sun) on May 25, and it was quite low in the sky (about 20° above the western horizon). Accordingly, the image quality was not perfect, but there was no doubt that something was going on with the fragment that was closest to the Sun (denoted "B"). And indeed, when the 8.2-m VLT YEPUN telescope (UT4) obtained another image of the comet in the evening of May 16, it was obvious that fragment "B" had split into two, see PR Photos 18a-b/01 . In fact, the astronomers suspect that there may be other, smaller pieces. The distance between the two pieces of nucleus "B" of Comet LINEAR (now denoted "B1" and "B2") was only about 1 arcsec, or approximately 500 km (projected) at the present distance of the comet from the Earth (about 100 million km). The distance between these and the other nucleus ("A") increased from about 6000 km (May 14) to 7000 km (May 16). The ESO astronomers have reported their detailed findings in IAU Circular 7627 [1]. They also note that the shape of the bright cloud (the "coma") around components "B1" and "B2" is quite unsual - this is well visible on

2001-05-01

122

Splittings and C-complexes  

CERN Multimedia

The intersection pattern of the translates of the limit set of a quasi-convex subgroup of a hyperbolic group can be coded in a natural incidence graph, which suggests connections with the splittings of the ambient group. A similar incidence graph exists for any subgroup of a group. We show that the disconnectedness of this graph for codimension one subgroups leads to splittings. We also reprove some results of Peter Kropholler on splittings of groups over malnormal subgroups and variants of them.

Mj, Mahan; Swarup, Gadde

2009-01-01

123

Splittings and C-complexes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The intersection pattern of the translates of the limit set of a quasi-convex subgroup of a hyperbolic group can be coded in a natural incidence graph, which suggests connections with the splittings of the ambient group. A similar incidence graph exists for any subgroup of a group. We show that the disconnectedness of this graph for codimension one subgroups leads to splittings. We also reprove some results of Peter Kropholler on splittings of groups over malnormal subgroups...

Mj, Mahan; Scott, Peter; Swarup, Gadde

2009-01-01

124

Splitting extended supersymmetry  

International Nuclear Information System (INIS)

We show how splitting supersymmetry reconciles a class of intersecting brane models with unification. The gauge sector in these models arises in multiplets of extended supersymmetry while matter states are in N=1 representations. A deformation of the angles between the branes gives large masses to squarks and sleptons, as well as supersymmetry breaking contributions to other string states. The latter generate at one-loop heavy Dirac masses for winos and gluinos and can induce a mass term for the higgsino doublets. We find that this scenario is compatible with gauge coupling unification at high scale for both cases where the gauge sector is N=2 and N=4 supersymmetric. Moreover a neutralino, combination of neutral higgsinos and binos, is a natural candidate for dark matter

2006-03-09

125

Evaluation of white matter myelin water fraction in chronic stroke?  

Science.gov (United States)

Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p < 0.001) and in the ipsilesional (p = 0.017) and contralesional (p = 0.037) posterior limb of internal capsule (PLIC) after stroke compared to whole-cerebrum and bilateral PLIC MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p < 0.001). MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke.

Borich, M.R.; MacKay, A.L.; Vavasour, I.M.; Rauscher, A.; Boyd, L.A.

2013-01-01

126

STEREOLOGY OF NEURONAL CONNECTIONS (MYELINATED FIBERS OF WHITE MATTER AND SYNAPSES OF NEOCORTEX IN HUMAN BRAIN  

Directory of Open Access Journals (Sweden)

Full Text Available Unbiased stereological sampling and counting techniques for estimating the total length, total volume and diameter distribution of myelinated nerve fibers in white matter and the total number of synapses in neocortex of human autopsy brains were described. Uniform random sampling of tissues from entire hemisphere was performed. The total volume and total length of myelinated fibers in white matter were estimated from the product of the volume of white matter obtained with the Cavalieri principle and the volume density and length density of myelinated fibers in white matter, respectively. The volume density of myelinated nerve fibers in white a matter was estimated with a point counting method. The length density of myelinated fibers in white matter was estimated from the isotropic, uniform random sections that were ensured by the sector. The diameter of myelinated fibers was derived by measuring the profile diameterperpendicular to its longest axis. The ethanolic phosphotungstic acid staining technique was modified for staining synapses in human autopsy brains. The total number of synapses in each neocortical region was estimated as the product of the volume of each neocortical region and the numerical density of synapses in each region. The numerical density of synapses in each neocortical region was obtained with the disector at the electron microscopical level. The presented methods will be useful for quantitative studies of the changes of myelinated nerve fibers and synapses in various distinct regions of the central nervous system due to development, aging and diseases.

Yong Tang

2011-05-01

127

Myelin and iron concentration in the human brain: A quantitative study of MRI contrast.  

Science.gov (United States)

During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T1 mapping and T2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1?m spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples. PMID:24607447

Stüber, Carsten; Morawski, Markus; Schäfer, Andreas; Labadie, Christian; Wähnert, Miriam; Leuze, Christoph; Streicher, Markus; Barapatre, Nirav; Reimann, Katja; Geyer, Stefan; Spemann, Daniel; Turner, Robert

2014-06-01

128

Modeling healthy male white matter and myelin development: 3 through 60months of age.  

Science.gov (United States)

An emerging hypothesis in developmental and behavioral disorders is that they arise from disorganized brain messaging or reduced connectivity. Given the importance of myelin to efficient brain communication, characterization of myelin development in infancy and childhood may provide salient information related to early connectivity deficits. In this work, we investigate regional and whole brain growth trajectories of the myelin water fraction, a quantitative magnetic resonance imaging measure sensitive and specific to myelin content, in data acquired from 122 healthy male children from 3 to 60months of age. We examine common growth functions to find the most representative model of myelin maturation and subsequently use the best of these models to develop a continuous population-averaged, four-dimensional model of normative myelination. Through comparisons with an independent sample of 63 male children across the same age span, we show that the developed model is representative of this population. This work contributes to understanding the trajectory of myelination in healthy infants and toddlers, furthering our knowledge of early brain development, and provides a model that may be useful for identifying developmental abnormalities. PMID:24095814

Dean, Douglas C; O'Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Walker, Lindsay; Han, Michelle; Deoni, Sean C L

2014-01-01

129

Modeling healthy male white matter and myelin development: 3 through 60 months of age?  

Science.gov (United States)

An emerging hypothesis in developmental and behavioral disorders is that they arise from disorganized brain messaging or reduced connectivity. Given the importance of myelin to efficient brain communication, characterization of myelin development in infancy and childhood may provide salient information related to early connectivity deficits. In this work, we investigate regional and whole brain growth trajectories of the myelin water fraction, a quantitative magnetic resonance imaging measure sensitive and specific to myelin content, in data acquired from 122 healthy male children from 3 to 60 months of age. We examine common growth functions to find the most representative model of myelin maturation and subsequently use the best of these models to develop a continuous population-averaged, four-dimensional model of normative myelination. Through comparisons with an independent sample of 63 male children across the same age span, we show that the developed model is representative of this population. This work contributes to understanding the trajectory of myelination in healthy infants and toddlers, furthering our knowledge of early brain development, and provides a model that may be useful for identifying developmental abnormalities.

Dean, Douglas C.; O'Muircheartaigh, Jonathan; Dirks, Holly; Waskiewicz, Nicole; Lehman, Katie; Walker, Lindsay; Han, Michelle; Deoni, Sean C.L.

2014-01-01

130

Developmental changes in myelin-induced proliferation of cultured Schwann cells  

Energy Technology Data Exchange (ETDEWEB)

Schwann cell proliferation induced by a myelin-enriched fraction was examined in vitro. Although nearly all the Schwann cells contained material that was recognized by antisera to myelin basic protein after 24 h, only 1% of the cells were synthesizing DNA. 72 h after the addition of the mitogen a maximum of 10% of the cells incorporated (/sup 3/H)thymidine. If the cultures were treated with the myelin-enriched fraction for 24 h and then washed, the number of proliferating Schwann cells decreased by 75% when compared with those cells that were incubated with the mitogen continuously. When Schwann cells were labeled with (/sup 14/C)thymidine followed by a pulse of (/sup 3/H)thymidine 24 h later, every Schwann cell labeled with (/sup 3/H)thymidine was also labeled with (/sup 14/C)thymidine. Although almost every Schwann cell can metabolize the myelin membranes within 24 h of exposure, a small population of cell initially utilizes the myelin as a mitogen, and this population continues to divide only if myelin is present in the extracellular media. The percentage of the Schwann cells that initially recognize the myelin-enriched fraction as a mitogen is dependent upon the age of the animal from which the cells were prepared.

Yoshino, J.E.; Mason, P.W.; DeVries, G.H.

1987-03-01

131

APPLICATION OF STEREOLOGICAL METHODS TO STUDY THE WHITE MATTER AND MYELINATED FIBERS THEREIN OF RAT BRAIN  

Directory of Open Access Journals (Sweden)

Full Text Available An efficient and unbiased stereological method was applied to estimate the white matter volume, the total volume, total length and mean diameter of the myelinated fibers in the white matter and the total volume of the myelin sheaths in the white matter of rat brain. The white matter volume was obtained with the Cavalieri principle. Four tissue blocks were sampled from the entire white matter in a uniform random fashion. The length density of the myelinated fibers in the white matter was obtained from the isotropic, uniform, random sections ensured by the isector. The volume density of the myelinated fibers in the white matter was estimated by point counting. The total length and the total volume of the myelinated fibers in the white matter were estimated by multiplying the white matter volume and the length density and the volume density of the myelinated fibers in the white matter, respectively. The size of nerve fibers was derived by measuring the profile diameter perpendicular to its longest axis. The results were satisfactory in the sense that the sampling variance introduced by the stereological estimation procedure was a minor fraction of the observed variance. The comparison of the white matter and the myelinated fibers in the white matter between rat brain and human brain was also made in the present study.

Shu Yang

2011-05-01

132

Proteolipid Protein Is Required for Transport of Sirtuin 2 into CNS Myelin  

Science.gov (United States)

Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute to the absence of a single myelin protein. We hypothesized that secondary molecular changes in PLPnull myelin contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions in this disease model. By gel-based proteome analysis, we identified >160 proteins in purified myelin membranes, which allowed us to systematically monitor the CNS myelin proteome of adult PLPnull mice, before the onset of disease. We identified three proteins of the septin family to be reduced in abundance, but the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 2 (SIRT2) was virtually absent. SIRT2 is expressed throughout the oligodendrocyte lineage, and immunoelectron microscopy revealed its association with myelin. Loss of SIRT2 in PLPnull was posttranscriptional, suggesting that PLP/DM20 is required for its transport into the myelin compartment. Because normal SIRT2 activity is controlled by the NAD+/NADH ratio, its function may be coupled to the axo-glial metabolism and the long-term support of axons by oligodendrocytes.

Werner, Hauke B.; Kuhlmann, Katja; Shen, Siming; Uecker, Marina; Schardt, Anke; Dimova, Kalina; Orfaniotou, Foteini; Dhaunchak, Ajit; Brinkmann, Bastian G.; Mobius, Wiebke; Guarente, Lenny; Casaccia-Bonnefil, Patrizia; Jahn, Olaf; Nave, Klaus-Armin

2009-01-01

133

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.  

Science.gov (United States)

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-?m penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis. PMID:22112117

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

2011-11-01

134

Ndrg1 in development and maintenance of the myelin sheath.  

Science.gov (United States)

CMT4D disease is a severe autosomal recessive demyelinating neuropathy with extensive axonal loss leading to early disability, caused by mutations in the N-myc downstream regulated gene 1 (NDRG1). NDRG1 is expressed at particularly high levels in the Schwann cell (SC), but its physiological function(s) are unknown. To help with their understanding, we characterise the phenotype of a new mouse model, stretcher (str), with total Ndrg1 deficiency, in comparison with the hypomorphic Ndrg1 knock-out (KO) mouse. While both models display normal initial myelination and a transition to overt pathology between weeks 3 and 5, the markedly more severe str phenotype suggests that even low Ndrg1 expression results in significant phenotype rescue. Neither model replicates fully the features of CMT4D: although axon damage is present, regenerative capacity is unimpaired and the mice do not display the early severe axonal loss typical of the human disease. The widespread large fibre demyelination coincides precisely with the period of rapid growth of the animals and the dramatic (160-500-fold) increase in myelin volume and length in large fibres. This is followed by stabilisation after week 10, while small fibres remain unaffected. Gene expression profiling of str peripheral nerve reveals non-specific secondary changes at weeks 5 and 10 and preliminary data point to normal proteasomal function. Our findings do not support the proposed roles of NDRG1 in growth arrest, terminal differentiation, gene expression regulation and proteasomal degradation. Impaired SC trafficking failing to meet the considerable demands of nerve growth, emerges as the likely pathogenetic mechanism in NDRG1 deficiency. PMID:21303696

King, Rosalind H M; Chandler, David; Lopaticki, Sash; Huang, Dexing; Blake, Julian; Muddle, John R; Kilpatrick, Trevor; Nourallah, Michelle; Miyata, Toshiyuki; Okuda, Tomohiko; Carter, Kim W; Hunter, Michael; Angelicheva, Dora; Morahan, Grant; Kalaydjieva, Luba

2011-06-01

135

The apolipoprotein A-I gene is actively expressed in the rapidly myelinating avian peripheral nerve  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The expression of the apolipoprotein A-I (apo A-I) gene was investigated in the myelinating sciatic nerve. Hybridization analysis with an apo A-I cDNA probe obtained from a cDNA library of mRNA isolated from rapidly myelinating chick sciatic nerve indicated that apo A-I coding transcripts increase during development in the chick sciatic nerve in parallel with the increase of myelin lamellae. Substantial apo A-I-like immunoreactivity in chick sciatic nerve homogenates was detected by Western b...

1989-01-01

136

Schwann cell precursors: a favourable cell for myelin repair in the Central Nervous System.  

Science.gov (United States)

Cell transplant therapies are currently under active consideration for a number of degenerative diseases. In the immune-mediated demyelinating-neurodegenerative disease multiple sclerosis (MS), only the myelin sheaths of the CNS are lost, while Schwann cell myelin of the PNS remains normal. This, and the finding that Schwann cells can myelinate CNS axons, has focussed interest on Schwann cell transplants to repair myelin in MS. However, the experimental use of these cells for myelin repair in animal models has revealed a number of problems relating to the incompatibility between peripheral glial cells and the CNS glial environment. Here, we have tested whether these difficulties can be avoided by using an earlier stage of the Schwann cell lineage, the Schwann cell precursor (SCP). For direct comparison of these two cell types, we implanted Schwann cells from post-natal rat nerves and SCPs from embryo day 14 (E14) rat nerves into the CNS under various experimental conditions. Examination 1 and 2 months later showed that in the presence of naked CNS axons, both types of cell form myelin that antigenically and ultrastructurally resembles that formed by Schwann cells in peripheral nerves. In terms of every other parameter we studied, however, the cells in these two implants behaved remarkably differently. As expected from previous work, Schwann cell implants survive poorly unless the cells find axons to myelinate, the cells do not migrate significantly from the implantation site, fail to integrate with host oligodendrocytes and astrocytes, and form little myelin when challenged with astrocyte-rich environment in the retina. Following SCP implantation, on the other hand, the cells survive well, migrate through normal CNS tissue, interface smoothly and intimately with host glial cells and myelinate extensively among the astrocytes of the retina. Furthermore, when implanted at a distance from a demyelinated lesion, SCPs but not Schwann cells migrate through normal CNS tissue to reach the lesion and generate new myelin. These features of SCP implants are all likely to be helpful attributes for a myelin repair cell. Since these cells also form Schwann cell myelin that is arguably likely to be resistant to MS pathology, they share some of the main advantages of Schwann cells without suffering from the disadvantages that render Schwann cells less than ideal candidates for transplantation into MS lesions. PMID:17550908

Woodhoo, A; Sahni, V; Gilson, J; Setzu, A; Franklin, R J M; Blakemore, W F; Mirsky, R; Jessen, K R

2007-08-01

137

Study Astrophysics in Split!  

Science.gov (United States)

Beginning in autumn 2008 the first generation of astronomy master students will start a 2 year course in Astrophysics offered by the Physics department of the University of Split, Croatia (http://fizika.pmfst.hr/ astro/english/index.html). This unique master course in South-Eastern Europe, following the Bologna convention and given by astronomers from international institutions, offers a series of comprehensive lectures designed to greatly enhance students' knowledge and skills in astrophysics, and prepare them for a scientific career. An equally important aim of the course is to recognise the areas in which astronomy and astrophysics can serve as a national asset and to use them to prepare young people for real life challenges, enabling graduates to enter the modern society as a skilled and attractive work-force. I will present an example of a successful organisation of international astrophysics studies in a developing country, which aims to become a leading graduate program in astrophysics in the broader region. I will focus on the goals of the project showing why and in what way astronomy can be interesting for third world countries, what are the benefits for the individual students, nation and region, but also research, science and the astronomical community in general.

Krajnovic, D.

2006-08-01

138

Split-illumination electron holography  

Energy Technology Data Exchange (ETDEWEB)

We developed a split-illumination electron holography that uses an electron biprism in the illuminating system and two biprisms (applicable to one biprism) in the imaging system, enabling holographic interference micrographs of regions far from the sample edge to be obtained. Using a condenser biprism, we split an electron wave into two coherent electron waves: one wave is to illuminate an observation area far from the sample edge in the sample plane and the other wave to pass through a vacuum space outside the sample. The split-illumination holography has the potential to greatly expand the breadth of applications of electron holography.

Tanigaki, Toshiaki; Aizawa, Shinji; Suzuki, Takahiro; Park, Hyun Soon [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Inada, Yoshikatsu [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Sendai 980-8577 (Japan); Matsuda, Tsuyoshi [Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Taniyama, Akira [Corporate Research and Development Laboratories, Sumitomo Metal Industries, Ltd., Amagasaki, Hyogo 660-0891 (Japan); Shindo, Daisuke [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Sendai 980-8577 (Japan); Tonomura, Akira [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Okinawa Institute of Science and Technology, Graduate University, Onna-son, Okinawa 904-0495 (Japan); Central Research Laboratory, Hitachi, Ltd., Hatoyama, Saitama 350-0395 (Japan)

2012-07-23

139

Association of extensive myelinated nerve fibers and high degree myopia: case report.  

Science.gov (United States)

Unilateral extensive myelination of the peripapillary nerve fibers may be associated with anisometropic myopia, strabismus, and reduced vision. Myelination of optic nerve fibers terminate at lamina cribrosa. Yet in some patients, myelination progresses into the peripapillary retinal nerve fibers and may affect the visual acuity. In this report, we described 4 patients. All patients presented extensive peripapillary myelinated nerve fibers associated with myopic anisometropia. After routine ophthalmic and orthoptic examinations, all patients underwent treatment for amblyopia through correction with spectacles, contact lenses, and the occlusion of the good eye. Corrected visual acuity improved in 1 patient, but 3 patients had no increase in visual acuity despite treatment with full cycloplegic refraction and appropriate patching. Probably because of structural abnormalies of the macula, visual results are often disappointing with appropriate correction of the refractive error and occlusion. PMID:24088642

Yalc?n, Elvan; Balc?, Ozlem; Ak?ngol, Ziya

2013-10-01

140

Age- and brain-region-specific effects of dietary vitamin K on myelin sulfatides  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, dihydrophylloquinone for ...

Crivello, Natalia A.; Casseus, Sherley L.; Peterson, James W.; Smith, Donald E.; Booth, Sarah L.

2010-01-01

 
 
 
 
141

Biochemical changes in mouse brain myelin during experimental primary amoebic meningo-encephalitis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin membranes were purified from normal as well as experimental primary amoebic meningo-encephalitis-afflicted mouse brains. Infected myelin fractions were observed to form a floating fraction in 0.32 M sucrose. Total proteins, total lipids, phospholipids, cholesterol and galactolipids decreased markedly due to amoebic infection. Phosphatidyl choline, phosphatidyl ethanolamine plus phosphatidyl serine and sphingomyelin were decreased with a concomitant increase in lysophosphatidyl choline,...

1984-01-01

142

Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system.  

Science.gov (United States)

One of the most important developmental modifications of the nervous system is Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin segments to provide protection to the axon as well as increase the conduction of action potentials. In vitro neuronal systems provide a unique modality to study a variety of factors influencing myelination as well as diseases associated with myelin sheath degradation. This work details the development of a patterned in vitro myelinating dorsal root ganglion culture. This defined system utilized a serum-free medium in combination with a patterned substrate, utilizing the cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional outgrowth of the neurites and subsequent myelination was controlled by surface modifications, and conformity to the pattern was measured over the duration of the experiments. The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This tissue-engineered system provides a highly controlled, reproducible model for studying Schwann cell interactions with sensory neurons, as well as the myelination process, and its effect on neuronal plasticity and peripheral nerve regeneration. It is also compatible for use in bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the media combination used is the same that we have used previously for motoneurons, muscle, and for neuromuscular junction (NMJ) formation. This work could have application for the study of demyelinating diseases such as diabetes induced peripheral neuropathy and could rapidly translate to a role in the discovery of drugs promoting enhanced peripheral nervous system (PNS) remyelination. PMID:23949775

Rumsey, John W; McAleer, Christopher; Das, Mainak; Bhalkikar, Abhijeet; Wilson, Kerry; Stancescu, Maria; Lambert, Stephen; Hickman, James J

2013-09-01

143

Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adu...

Stricker, N. H.; Schweinsburg, B. C.; Delano-wood, L.; Wierenga, C. E.; Bangen, K. J.; Haaland, K. Y.; Frank, L. R.; Salmon, D. P.; Bondi, M. W.

2009-01-01

144

Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Effect of long-term (90–100 days) exposure of rats to soluble salt of aluminum (AlCl3) on myelin lipid profile was examined. The long-term exposure to AlCl3 resulted in a 60 % decrease in the total phospholipid (TPL) content while the cholesterol (CHL) content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically...

Pandya Jignesh D; Dave Kunjan R; Katyare Surendra S

2004-01-01

145

PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Platelet-derived growth factor a receptor (PDGFRA)/NG2-expressing glia are distributed throughout the adult CNS. They are descended from oligodendrocyte precursors (OLPs) in the perinatal CNS, but it is not clear whether they continue to generate myelinating oligodendrocytes or other differentiated cells during normal adult life. We followed the fates of adult OLPs in Pdgfra-creER(T2)/Rosa26-YFP double-transgenic mice and found that they generated many myelinating oligodendrocytes during adul...

Rivers, L. E.; Young, K. M.; Rizzi, M.; Jamen, F.; Psachoulia, K.; Wade, A.; Kessaris, N.; Richardson, W. D.

2008-01-01

146

A novel method to study the local mitochondrial fusion in myelinated axons in vivo  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mitochondrial remodeling (replication, fission/fusion) is a dynamically regulated process with diverse functions in neurons. A myelinated axon is an extension from the cell soma of a fully differentiated neuron. Mitochondria, once synthesized in the cell body, enter the axon displaying robust trafficking and accumulation at nodes of Ranvier to match metabolic needs. This long-distance deployment of mitochondria to axons raises the issue of whether myelinated axons can function independently o...

2012-01-01

147

Mouse schwann cells need both NRG1 and cyclic AMP to myelinate.  

Science.gov (United States)

Genetically modified mice have been a major source of information about the molecular control of Schwann-cell myelin formation, and the role of ?-neuregulin 1 (NRG1) in this process in vivo. In vitro, on the other hand, Schwann cells from rats have been used in most analyses of the signaling pathways involved in myelination. To correlate more effectively in vivo and in vitro data, we used purified cultures of mouse Schwann cells in addition to rat Schwann cells to examine two important myelin-related signals, cyclic adenosine monophosphate (cAMP), and NRG1 and to determine whether they interact to control myelin differentiation. We find that in mouse Schwann cells, neither cAMP nor NRG1, when used separately, induced markers of myelin differentiation. When combined, however, they induced strong protein expression of the myelin markers, Krox-20 and P(0) . Importantly, the level of cAMP signaling was crucial in switching NRG1 from a proliferative signal to a myelin differentiation signal. Also in cultured rat Schwann cells, NRG1 promoted cAMP-induced Krox-20 and P(0) expression. Finally, we found that cAMP/NRG1-induced Schwann-cell differentiation required the activity of the cAMP response element binding family of transcription factors in both mouse and rat cells. These observations reconcile observations in vivo and on neuron-Schwann-cell cultures with studies on purified Schwann cells. They demonstrate unambiguously the promyelin effects of NRG1 in purified cells, and they show that the cAMP pathway determines whether NRG1 drives proliferation or induces myelin differentiation. PMID:21322058

Arthur-Farraj, Peter; Wanek, Katharina; Hantke, Janina; Davis, Catherine M; Jayakar, Anuj; Parkinson, David B; Mirsky, Rhona; Jessen, Kristján R

2011-05-01

148

Negative regulation of myelination: relevance for development, injury, and demyelinating disease.  

Science.gov (United States)

Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury and demyelinating neuropathies. We review recent evidence that this dedifferentiation depends on activation of specific intracellular signaling molecules that drive the dedifferentiation program. In particular, we discuss the idea that Schwann cells contain negative transcriptional regulators of myelination that functionally complement positive regulators such as Krox-20, and that myelination is therefore determined by a balance between two opposing transcriptional programs. Negative transcriptional regulators should be expressed prior to myelination, downregulated as myelination starts but reactivated as Schwann cells dedifferentiate following injury. The clearest evidence for a factor that works in this way relates to c-Jun, while other factors may include Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular-related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating cells is also discussed. We also review evidence that neurotrophin 3 (NT3), purinergic signaling, and nitric oxide synthase are involved in suppressing myelination. The realization that myelination is subject to negative as well as positive controls contributes significantly to the understanding of Schwann cell plasticity. Negative regulators are likely to have a major role during injury, because they promote the transformation of damaged nerves to an environment that fosters neuronal survival and axonal regrowth. In neuropathies, however, activation of these pathways is likely to be harmful because they may be key contributors to demyelination, a situation which would open new routes for clinical intervention. PMID:18803323

Jessen, Kristján R; Mirsky, Rhona

2008-11-01

149

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Inadequate formation and maintenance of myelin is the basis for several neurodegenerative disorders, including leukodystrophy and multiple sclerosis. In mice, oligodendrocyte differentiation and subsequent formation of myelin requires the Quaking gene. Mutation of this gene leads to embryonic lethality or to a trembling phenotype characteristic of dysmyelination. Quaking encodes Qk1, a member of the highly conserved STAR/GSG family of RNA-binding proteins that function as master developmental...

Ryder, Sean P.; Williamson, James R.

2004-01-01

150

Gestational nicotine exposure modifies myelin gene expression in the brains of adolescent rats with sex differences  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3?mg?kg?1 per day; gestati...

Cao, J.; Wang, J.; Dwyer, J. B.; Gautier, N. M.; Wang, S.; Leslie, F. M.; Li, M. D.

2013-01-01

151

Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new F-actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation ...

Jung, Junyang; Cai, Wenting; Lee, Hyun Kyoung; Pellegatta, Marta; Shin, Yoon Kyung; Jang, So Young; Suh, Duk Joon; Wrabetz, Lawrence; Feltri, M. Laura; Park, Hwan Tae

2011-01-01

152

ISR split-field magnet  

CERN Multimedia

The experimental apparatus used at intersection 4 around the Split-Field Magnet by the CERN-Bologna Collaboration (experiment R406). The plastic scintillator telescopes are used for precise pulse-height and time-of-flight measurements.

1975-01-01

153

Splitting of the Family Index  

Science.gov (United States)

We establish a general splitting formula for index bundles of families of Dirac type operators. Among the applications, our result provides a positive answer to a question of Bismut and Cheeger [BC2].

Dai, Xianzhe; Zhang, Weiping

1996-12-01

154

ISR split-field magnet  

CERN Multimedia

The Split-Field-Magnet at the ISR with arrays of multiwire proportional chambers installed in its large aperture. The detection system is now in full action for experiments and the first results have been reported.

1974-01-01

155

Frobenius splittings of toric varieties  

CERN Document Server

We discuss a characteristic free version of Frobenius splittings for toric varieties and characterize those toric varieties X such that the diagonal is compatibly split in X x X. As an application, we show that lattice polytopes that are cut out by root systems of classical type are normal and Koszul, generalizing a well-known result of Bruns, Gubeladze, and Trung for A_n.

Payne, Sam

2008-01-01

156

Biphasic water splitting by osmocene  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The photochemical reactivity of osmocene in a biphasic water-organic solvent system has been investigated to probe its water splitting properties. The photoreduction of aqueous protons to hydrogen under anaerobic conditions induced by osmocene dissolved in 1,2-dichloroethane and the subsequent water splitting by the osmocenium metal-metal dimer formed during H-2 production were studied by electrochemical methods, UV-visible spectrometry, gas chromatography, and nuclear magnetic resonance spec...

Ge, Peiyu; Todorova, Tanya Kumanova; Hatay, Imren; Avendano, Olaya; Johana, Astrid; Vrubel, Heron; Agudelo, Me?ndez; Alejandro, Manuel; Hu, Xile; Corminboeuf, Clemence; Girault, Hubert

2012-01-01

157

Biphasic water splitting by osmocene  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The photochemical reactivity of osmocene in a biphasic water-organic solvent system has been investigated to probe its water splitting properties. The photoreduction of aqueous protons to hydrogen under anaerobic conditions induced by osmocene dissolved in 1,2-dichloroethane and the subsequent water splitting by the osmocenium metal-metal dimer formed during H2 production were studied by electrochemical methods, UV-visible spectrometry, gas chromatography, and nuclear magnetic resonance spect...

Ge, Peiyu; Todorova, Tanya K.; Patir, Imren Hatay; Olaya, Astrid J.; Vrubel, Heron; Mendez, Manuel; Hu, Xile; Corminboeuf, Cle?mence; Girault, Hubert H.

2012-01-01

158

Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence.  

Science.gov (United States)

Myelin water imaging, a magnetic resonance imaging technique capable of resolving the fraction of water molecules which are located between the layers of myelin, is a valuable tool for investigating both normal and pathological brain structure in vivo. There is a strong need for pulse sequences which improve the quality and applicability of myelin water imaging in a clinical setting. In this study, we validated the use of a fast multi echo T(2) relaxation sequence for myelin water imaging. Using a multiple combined gradient and spin echo (GRASE) technique, we attain whole cerebrum myelin water images in under 15 minutes. Region of interest analysis indicates that this fast GRASE imaging sequence produces results which are in good agreement with pure spin echo measurements (R(2)=0.95, p<0.0001). This drastic improvement in speed and brain coverage compared to current spin echo standards will allow increased inclusion of myelin water imaging in neurological research protocols and opens up the possibility of applications in a clinical setting. PMID:22776448

Prasloski, Thomas; Rauscher, Alexander; MacKay, Alex L; Hodgson, Madeleine; Vavasour, Irene M; Laule, Corree; Mädler, Burkhard

2012-10-15

159

Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin.  

Science.gov (United States)

Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered. PMID:24962806

Poccia, Nicola; Campi, Gaetano; Ricci, Alessandro; Caporale, Alessandra S; Di Cola, Emanuela; Hawkins, Thomas A; Bianconi, Antonio

2014-01-01

160

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria  

DEFF Research Database (Denmark)

BACKGROUND: Cerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context. METHODS: The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (nâ??=â??4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology. RESULTS: The infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages. CONCLUSIONS: EPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.

Hempel, Casper; Hyttel, Poul

2012-01-01

 
 
 
 
161

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient.  

Science.gov (United States)

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduced Digital Holographic Microscopy (DHM) as a useful method to calculate the precise dynamical volume, thickness, surface and length of the myelin figures. As an example of DHM imaging of myelin figures, their structure and growth rate in the presence and absence of temperature gradient have been studied in this work. We showed that the thickness of a myelin figure can be changed during the first few seconds. However, after approximately ten seconds, the thickness stabilizes and does not alter significantly. We further studied the effect of the thermal gradient on the length growth. The calculation of the length growth from the measurement of the myelin figure volume shows that the length (L) grows in time (t) as [Formula: see text]at the early stage of the myelin protrusion in both the presence and the absence of the thermal gradient. However, thermal gradient facilitates the growth and increases its rate. PMID:23760951

Fathi, Narges; Moradi, Ali-Reza; Habibi, Mehdi; Vashaee, Daryoosh; Tayebi, Lobat

2013-06-01

162

Development of the optic nerve in Xenopus laevis. II. Gliogenesis, myelination and metamorphic remodelling.  

Science.gov (United States)

We studied the time of origin, development and location of glial elements in the developing optic nerve of Xenopus with light and electron microscopy. The first cells acting as a primitive glia are ependymal cells lying dorsal to the chiasmatic optic nerve (CON) at Nieuwkoop & Faber (1956) NF stage 39. Later (stage 47/48), immature astrocyte cell bodies migrate from the periphery of the middle optic nerve (MON) into the central fibre mass along cytoplasmic processes extending from the outer glia limitans. Shortly thereafter, oligodendrocyte cell bodies appear in the centre of the fibre mass and myelination begins, first in the middle of the MON, spreading from the centre distally towards the chiasm and proximally to the retina. In late tadpoles myelinated fibres appear first in the CON then in the retinal optic nerve (RON) increasing markedly in juveniles and adults. Segment-specific patterns of glia and myelination appear during optic nerve development. During metamorphic climax, the optic nerve shortens (Cullen & Webster, 1979), a process involving myelin and axon remodelling primarily in the MON. Neither the profound changes during metamorphosis, nor the processes of gliogenesis and myelination significantly alter the underlying chronotopic ordering in the tadpole nerve. In juvenile and adult optic nerves, however, as myelination and gliogenesis increase, and as more axons mature and grow in diameter, the dorsoventral chronotopic arrangement of axons becomes less apparent. PMID:7183742

Cima, C; Grant, P

1982-12-01

163

Understanding glial abnormalities associated with myelin deficiency in the jimpy mutant mouse.  

Science.gov (United States)

Jimpy is a shortened life-span murine mutant showing recessive sex-linked inheritance. The genetic defect consists of a point mutation in the PLP gene and produces a severe CNS myelin deficiency that is associated with a variety of complex abnormalities affecting all glial populations. The myelin deficiency is primarily due to a failure to produce the normal amount of myelin during development. However, myelin destruction and oligodendrocyte death also account for the drastic myelin deficit observed in jimpy. The oligodendroglial cell line shows complex abnormalities in its differentiation pattern, including the degeneration of oligodendrocytes through an apoptotic mechanism. Oligodendrocytes seem to be the most likely candidate to be primarily altered in a disorder affecting myelination, but disturbances affecting astrocytes and microglia are also remarkable and may have a crucial significance in the development of the jimpy disorder. In fact, the jimpy phenotype may not be attributed to a defect in a single cell but rather to a deficiency in the normal relations between glial cells. Evidences from a variety of sources indicate that the jimpy mutant could be a model for disturbed glial development in the CNS. The accurate knowledge of the significance of PLP and its regulation during development must be of vital importance in order to understand glial abnormalities in jimpy. PMID:9600623

Vela, J M; González, B; Castellano, B

1998-03-01

164

Structure and expression of a novel compact myelin protein – Small VCP-interacting protein (SVIP)  

Energy Technology Data Exchange (ETDEWEB)

Highlights: •SVIP (small p97/VCP-interacting protein) co-localizes with myelin basic protein (MBP) in compact myelin. •We determined that SVIP is an intrinsically disordered protein (IDP). •The helical content of SVIP increases dramatically during its interaction with negatively charged lipid membrane. •This study provides structural insight into interactions between SVIP and myelin membranes. -- Abstract: SVIP (small p97/VCP-interacting protein) was initially identified as one of many cofactors regulating the valosin containing protein (VCP), an AAA+ ATPase involved in endoplasmic-reticulum-associated protein degradation (ERAD). Our previous study showed that SVIP is expressed exclusively in the nervous system. In the present study, SVIP and VCP were seen to be co-localized in neuronal cell bodies. Interestingly, we also observed that SVIP co-localizes with myelin basic protein (MBP) in compact myelin, where VCP was absent. Furthermore, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopic measurements, we determined that SVIP is an intrinsically disordered protein (IDP). However, upon binding to the surface of membranes containing a net negative charge, the helical content of SVIP increases dramatically. These findings provide structural insight into interactions between SVIP and myelin membranes.

Wu, Jiawen [Department of Neurology, Vanderbilt University School of Medicine (United States); Peng, Dungeng [Department of Biochemistry, Vanderbilt University School of Medicine (United States); Voehler, Markus [Center for Structural Biology, Vanderbilt University (United States); Sanders, Charles R. [Department of Biochemistry, Vanderbilt University School of Medicine (United States); Center for Structural Biology, Vanderbilt University (United States); Li, Jun, E-mail: jun.li.2@vanderbilt.edu [Department of Neurology, Vanderbilt University School of Medicine (United States); Tennessee Valley Healthcare System (TVHS) – Nashville VA (United States)

2013-10-11

165

Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally.  

Science.gov (United States)

Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg/day; GN) or saline (GS) via osmotic mini pumps from gestational days 4-18. Both male and female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36 (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected. The expression of genes encoding major myelin components was evaluated using quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles with brain region and sex differences. The pattern of alteration was different from that observed in adolescents. Although these genes were expressed normally in male adults, we observed decreased expression in GN-treated female adults, especially in the CPu. Thus, GN altered myelin gene expression throughout postnatal development and adulthood. The effect on adolescents was quite different from that at other ages, which correlated with the unique symptoms of many psychiatric disorders during adolescence. PMID:23962570

Cao, Junran; Dwyer, Jennifer B; Gautier, Nicole M; Leslie, Frances M; Li, Ming D

2013-10-11

166

Entropy Splitting and Numerical Dissipation  

Science.gov (United States)

A rigorous stability estimate for arbitrary order of accuracy of spatial central difference schemes for initial-boundary value problems of nonlinear symmetrizable systems of hyperbolic conservation laws was established recently by Olsson and Oliger (1994) and Olsson (1995) and was applied to the two-dimensional compressible Euler equations for a perfect gas by Gerritsen and Olsson (1996) and Gerritsen (1996). The basic building block in developing the stability estimate is a generalized energy approach based on a special splitting of the flux derivative via a convex entropy function and certain homogeneous properties. Due to some of the unique properties of the compressible Euler equations for a perfect gas, the splitting resulted in the sum of a conservative portion and a non-conservative portion of the flux derivative. hereafter referred to as the "Entropy Splitting." There are several potential desirable attributes and side benefits of the entropy splitting for the compressible Euler equations that were not fully explored in Gerritsen and Olsson. The paper has several objectives. The first is to investigate the choice of the arbitrary parameter that determines the amount of splitting and its dependence on the type of physics of current interest to computational fluid dynamics. The second is to investigate in what manner the splitting affects the nonlinear stability of the central schemes for long time integrations of unsteady flows such as in nonlinear aeroacoustics and turbulence dynamics. If numerical dissipation indeed is needed to stabilize the central scheme, can the splitting help minimize the numerical dissipation compared to its un-split cousin? Extensive numerical study on the vortex preservation capability of the splitting in conjunction with central schemes for long time integrations will be presented. The third is to study the effect of the non-conservative proportion of splitting in obtaining the correct shock location for high speed complex shock-turbulence interactions. The fourth is to determine if this method can be extended to other physical equations of state and other evolutionary equation sets. If numerical dissipation is needed, the Yee, Sandham, and Djomehri (1999) numerical dissipation is employed. The Yee et al. schemes fit in the Olsson and Oliger framework.

Yee, H. C.; Vinokur, M.; Djomehri, M. J.

1999-01-01

167

Radioimmunoassay of myelin basic protein. A methodological evaluation  

International Nuclear Information System (INIS)

Three techniques for separating free antigen from antigen-antibody complexes have been applied to radioimmunoassay of myelin basic protein: cold ethanol precipitation of complexes, dextran-coated charcoal precipitation of free antigen, and second antibody precipitation of complexes. After optimization of the incubation and separation steps, the 3 methods were evaluated for precision and accuracy when applied to both spinal fluid and brain tissue homogenates. For determinations in brain tissue all 3 methods showed the same precision and gave largely the same values, though the ethanol method gave slightly lower levels. For spinal fluid the ethanol and dextran-charcoal methods gave the same values, but the double antibody method gave values only 1/3 as high. With spinal fluid, the precision of the dextran-charcoal method was poor compared with that of the other two. The double antibody method proved to be the method of choice for brain tissue samples, when the results of the incubation and separation steps, and the precision and accuracy of the determinations were taken into account. However, for an unknown reason values for spinal fluid were too low by this method. Therefore the ethanol precipitation method is recommended for spinal fluid samples and the double antibody method for brain tissue samples. (Auth.)

1982-11-26

168

Combined genetic attenuation of myelin and Semaphorin-mediated growth inhibition is insufficient to promote serotonergic axon regeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Following CNS injuries, axon growth inhibitors from the myelin and the scar tissue at the injury site are considered major impediments to axon regeneration. The presence of several classes of inhibitors with multiple members in each class suggests functional redundancy in growth inhibition. To test redundancy within the myelin inhibitory pathway, we analyzed raphespinal serotonergic (5-HT) axon regeneration in mice deficient in two major myelin inhibitors, Nogo and MAG, and their common recep...

Lee, Jae K.; Chow, Renee; Xie, Fang; Chow, Sharon Y.; Tolentino, Kristine E.; Zheng, Binhai

2010-01-01

169

Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Rat Schwann cells cultured with dorsal root ganglion neurons in a serum- free defined medium fail to ensheathe or myelinate axons or assemble basal laminae. Replacement of defined medium with medium that contains human placental serum (HPS) and chick embryo extract (EE) results in both basal lamina and myelin formation. In the present study, the individual effects of HPS and EE on basal lamina assembly and on myelin formation by Schwann cells cultured with neurons have been examined. Some bat...

1987-01-01

170

Copper Uptake Induces Self-Assembly of 18.5 kDa Myelin Basic Protein (MBP)  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin basic protein (MBP) is predominantly found in the membranes of the myelin sheath of the central nervous system and is involved in important protein-protein and protein-lipid interactions in vivo and in vitro. Furthermore, divalent transition metal ions, especially Zn2+ and Cu2+, seem to directly affect the MBP-mediated formation and stabilization of the myelin sheath of the central nervous system. MBP belongs to the realm of intrinsically disordered proteins, and only fragmentary inf...

Bund, Timo; Boggs, Joan M.; Harauz, George; Hellmann, Nadja; Hinderberger, Dariush

2010-01-01

171

Corneal Cross-Linking for the Treatment of Keratoconus in a Patient with Ipsilateral Myelinated Retinal Nerve Fiber Layer  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Keratoconus associated with myelinated retinal nerve fibers is not frequent and the relationship between the two pathologies is difficult to explain, therefore studies and further investigation are required. The etiology of each condition may suggest the role of genetic factors. Follow-up is important to evaluate the progression of keratoconus and myelination. Here we describe the unusual coexistence of keratoconus and ipsilateral myelinated retinal nerve fiber layer and, for the first time, ...

2011-01-01

172

Lattice splitting under intermittent flows  

CERN Document Server

We study the splitting of regular square lattices subject to stochastic intermittent flows. By extensive Monte Carlo simulations we reveal how the time span until the occurence of a splitting depends on various flow patterns imposed on the lattices. Increasing the flow fluctuation frequencies shortens this time span which reaches a minimum before rising again due to inertia effects incorporated in the model. The size of the largest connected component after the splitting is rather independent of the flow fluctuations but sligthly decreases with the link capacities. Our results are relevant for assessing the robustness of real-life systems, such as electric power grids with a large share of renewable energy sources including wind turbines and photovoltaic systems.

Schläpfer, Markus

2010-01-01

173

Splitting methods for Levitron Problems  

CERN Document Server

In this paper we describe splitting methods for solving Levitron, which is motivated to simulate magnetostatic traps of neutral atoms or ion traps. The idea is to levitate a magnetic spinning top in the air repelled by a base magnet. The main problem is the stability of the reduced Hamiltonian, while it is not defined at the relative equilibrium. Here it is important to derive stable numerical schemes with high accuracy. For the numerical studies, we propose novel splitting schemes and analyze their behavior. We deal with a Verlet integrator and improve its accuracy with iterative and extrapolation ideas. Such a Hamiltonian splitting method, can be seen as geometric integrator and saves computational time while decoupling the full equation system. Experiments based on the Levitron model are discussed.

Geiser, Juergen

2012-01-01

174

Baryon asymmetry and split SUSY  

International Nuclear Information System (INIS)

It is one of the greatest mysteries that the baryon asymmetry in our universe is so small. It is argued that it may originate from some profound physics beyond the standard model. We investigate the Affleck-Dine baryogenesis in split supersymmetry, and find that the smallness of the baryon asymmetry is directly related to the hierarchy between the supersymmetry breaking squark/slepton masses and the weak scale. Put simply, the baryon asymmetry is small because of the split mass spectrum. LHC may prove or falsify our scenario

2005-12-02

175

Characterization of dodecylphosphocholine/myelin basic protein complexes  

International Nuclear Information System (INIS)

The stoichiometry of myelin basic protein (MBP)/dodecylphosphocholine (DPC) complexes and the location of protein segments in the micelle have been investigated by electron paramagnetic resonance (EPR), ultracentrifugation, photon correlation light scattering, 31P, 13C, and 1H nuclear magnetic resonance (NMR), and electron microscopy. Ultracentrifugation measurements indicate that MBP forms stoichiometrically well-defined complexes consisting of 1 protein molecule and approximately 140 detergent molecules. The spin-labels 5-, 12-, and 16-doxylstearate have been incorporated into DPC/MBP aggregates. EPR spectral parameters and 13C and 1H NMR relaxation times indicate that the addition of MBP does not affect the environment and location of the labels or the organization of the micelles except for a slight increase in size. Previous results indicating that the protein lies primarily near the surface of the micelle have been confirmed by comparing 13C NMR spectra of the detergent with and without protein with spectra of protein/detergent aggregates containing spin-labels. Electron micrographs of the complexes taken by using the freeze-fracture technique confirm that the estimated size obtained by light-scattering measurements. Overall, these results indicate that mixtures of MBP and DPC can form highly porous particles with well-defined protein and lipid stoichiometry. The structural integrity of these particles appears to be based on protein-lipid interactions. In addition, electron micrographs of aqueous DPC/MBP suspensions show the formation of a small amount of material consisting of large arrays of detergent micelles, suggesting that MBP is capable of inducing large changes in the overall organization of the detergent

1988-01-12

176

Internal nanosecond dynamics in the intrinsically disordered myelin basic protein.  

Science.gov (United States)

Intrinsically disordered proteins lack a well-defined folded structure and contain a high degree of structural freedom and conformational flexibility, which is expected to enhance binding to their physiological targets. In solution and in the lipid-free state, myelin basic protein belongs to that class of proteins. Using small-angle scattering, the protein was found to be structurally disordered similar to Gaussian chains. The combination of structural and hydrodynamic information revealed an intermediary compactness of the protein between globular proteins and random coil polymers. Modeling by a coarse-grained structural ensemble gave indications for a compact core with flexible ends. Neutron spin-echo spectroscopy measurements revealed a large contribution of internal dynamics to the overall diffusion. The experimental results showed a high flexibility of the structural ensemble. Displacement patterns along the first two normal modes demonstrated that collective stretching and bending motions dominate the internal modes. The observed dynamics represent nanosecond conformational fluctuations within the reconstructed coarse-grained structural ensemble, allowing the exploration of a large configurational space. In an alternative approach, we investigated if models from polymer theory, recently used for the interpretation of fluorescence spectroscopy experiments on disordered proteins, are suitable for the interpretation of the observed motions. Within the framework of the Zimm model with internal friction (ZIF), a large offset of 81.6 ns is needed as an addition to all relaxation times due to intrachain friction sources. The ZIF model, however, shows small but systematic deviations from the measured data. The large value of the internal friction leads to the breakdown of the Zimm model. PMID:24758710

Stadler, Andreas M; Stingaciu, Laura; Radulescu, Aurel; Holderer, Olaf; Monkenbusch, Michael; Biehl, Ralf; Richter, Dieter

2014-05-14

177

miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination.  

Science.gov (United States)

Duplication of the gene encoding lamin B1 (LMNB1) with increased mRNA and protein levels has been shown to cause severe myelin loss in the brains of adult-onset autosomal dominant leukodystrophy patients. Similar to many neurodegenerative disorders, patients with adult-onset autosomal dominant leukodystrophy are phenotypically normal until adulthood and the defect is specific to the central nervous system despite the ubiquitous expression pattern of lamin B1. We set out to dissect the molecular mechanisms underlying this demyelinating phenotype. Increased lamin B1 expression results in disturbances of inner nuclear membrane proteins, chromatin organization and nuclear pore transport in vitro. It also leads to premature arrest of oligodendrocyte differentiation, which might be caused by reduced transcription of myelin genes and by mislocalization of myelin proteins. We identified the microRNA miR-23 as a negative regulator of lamin B1 that can ameliorate the consequences of excessive lamin B1 at the cellular level. Our results indicate that regulation of lamin B1 is important for myelin maintenance and that miR-23 contributes to this process, at least in part, by downregulating lamin B1, therefore establishing novel functions of lamin B1 and miR-23 in the regulation of oligodendroglia development and myelin formation in vitro. PMID:19259393

Lin, Shu-Ting; Fu, Ying-Hui

2009-01-01

178

Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method  

DEFF Research Database (Denmark)

Regeneration of myelinated and unmyelinated sensory nerve fibres after a crush lesion of the rat sciatic nerve was investigated by means of retrograde labelling. The advantage of this method is that the degree of regeneration is estimated on the basis of sensory somata rather than the number of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate was 3.7 mm/day with no obvious differences between myelinated and unmyelinated axons. This contrasted with previous claims of two to three times faster regeneration rates of unmyelinated as compared to myelinated fibres. The initial delay was 0.55 days. Fewer small neurons were labelled relative to large neurons after crush and regeneration than in controls, indicating that regeneration of small neurons was less complete than that of large ones. This contrasted with the fact that unmyelinated axons in the regenerated sural nerve after 74 days were only slightly reduced.

Lozeron, Pierre; Krarup, Christian

2004-01-01

179

Oligodendrocyte-Encoded HIF Function Couples Postnatal Myelination and White Matter Angiogenesis.  

Science.gov (United States)

Myelin sheaths provide critical functional and trophic support for axons in white matter tracts of the brain. Oligodendrocyte precursor cells (OPCs) have extraordinary metabolic requirements during development as they differentiate to produce multiple myelin segments, implying that they must first secure adequate access to blood supply. However, mechanisms that coordinate myelination and angiogenesis are unclear. Here, we show that oxygen tension, mediated by OPC-encoded hypoxia-inducible factor (HIF) function, is an essential regulator of postnatal myelination. Constitutive HIF1/2? stabilization resulted in OPC maturation arrest through autocrine activation of canonical Wnt7a/7b. Surprisingly, such OPCs also show paracrine activity that induces excessive postnatal white matter angiogenesis in vivo and directly stimulates endothelial cell proliferation in vitro. Conversely, OPC-specific HIF1/2? loss of function leads to insufficient angiogenesis in corpus callosum and catastrophic axon loss. These findings indicate that OPC-intrinsic HIF signaling couples postnatal white matter angiogenesis, axon integrity, and the onset of myelination in mammalian forebrain. PMID:25018103

Yuen, Tracy J; Silbereis, John C; Griveau, Amelie; Chang, Sandra M; Daneman, Richard; Fancy, Stephen P J; Zahed, Hengameh; Maltepe, Emin; Rowitch, David H

2014-07-17

180

Labelling by axonal transport of myelin-associated proteins in the rabbit visual pathway  

International Nuclear Information System (INIS)

After intraocular injections of [3H]leucine, six regions of the visual pathway of adult rabbit were used to study the spatio-temporal pattern of the slow anterograde axonal transport of radioactive proteins associated with the particulate fraction, the water-soluble fraction and the myelin fraction. Unlike other fractions, myelin-associated labelled proteins represented a time-constant percentage of total tissue radioactivity. This percentage increased from the first half to the second half of the optic nerve and remained high in the chiasma and tract. The peak specific radioactivity of myelin decreased in the same direction. At the peak of myelin radioactivity of a given region the label was typically associated with four protein bands, L1-L4, of 40000-68000 mol.wt. The basic protein, the proteolipid protein and the W1 component of the Wolfgram proteins were not significantly labelled. The radioactivity associated with the W2 component could be derived from the closely migrating L3 component. At shorter survival times no clear labelling pattern could be detected. At longer survival times radioactivity was almost totally localized around band L3. The results presented underline the importance of choosing appropriate experimental conditions to obtain a consistent labelling pattern of myelin-associated proteins. (author)

1981-05-15

 
 
 
 
181

Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis.  

Science.gov (United States)

In mice with experimental autoimmune encephalomyelitis (EAE) pretreatment with progesterone improves clinical signs and decreases the loss of myelin basic protein (MBP) and proteolipid protein (PLP) measured by immunohistochemistry and in situ hybridization. Presently, we analyzed if progesterone effects in the spinal cord of EAE mice involved the decreased transcription of local inflammatory mediators and the increased transcription of myelin proteins and myelin transcription factors. C57Bl/6 female mice were divided into controls, EAE and EAE receiving progesterone (100mg implant) 7 days before EAE induction. Tissues were collected on day 17 post-immunization. Real time PCR technology demonstrated that progesterone blocked the EAE-induced increase of the proinflammatory mediators tumor necrosis factor alpha (TNF?) and its receptor TNFR1, the microglial marker CD11b and toll-like receptor 4 (TLR4) mRNAs, and increased mRNA expression of PLP and MBP, the myelin transcription factors NKx2.2 and Olig1 and enhanced CC1+oligodendrocyte density respect of untreated EAE mice. Immunocytochemistry demonstrated decreased Iba1+microglial cells. Confocal microscopy demonstrated that TNF? colocalized with glial-fibrillary acidic protein+astrocytes and OX-42+microglial cells. Therefore, progesterone treatment improved the clinical signs of EAE, decreased inflammatory glial reactivity and increased myelination. Data suggest that progesterone neuroprotection involves the modulation of transcriptional events in the spinal cord of EAE mice. PMID:23000619

Garay, L I; González Deniselle, M C; Brocca, M E; Lima, A; Roig, P; De Nicola, A F

2012-12-13

182

A spin label study of myelin fluidity with normal and pathological peripheral nerves.  

Science.gov (United States)

The myelin fluidity in peripheral nerves from normal subjects and patients with neuropathy has been studied. Nerve biopsies were made in subjects without neuropathy and in patients with Guillain-Barré, alcoholic or diabetic polyneuropathies and heredodegenerative diseases. The fluidity was studied using a stearic acid spin label with a nitroxide radical at C12 (12-doxylstearic acid) which was introduced by exchange between spin label-charged BSA and nerve myelin. Spectra was obtained with a VARIAN E 109 ESR spectrometer, at temperatures from 5 to 45 degrees C. The ultrastructure of biopsied nerves was also studied. The electron spin resonance (ESR) spectra were all typical of a partially immobilized nitroxide with a distance between outer hyperfine lines (2T//) of about 50 G, at room temperature. The curve 2T// against temperature shows two critical temperatures: 10 and 30 degrees C for all nerves. No correlation could be established between ultrastructure and fluidity of nerves. However, the myelin of nerves from diabetic patients showed a significant increase in viscosity. This physicochemical modification may represent an initial alteration of the myelin sheath, and demands further investigation. No modification of the myelin fluidity was observed in any of the other nerves studied. PMID:230319

Laporte, A; Richard, H; Bonnaud, E; Henry, P; Vital, A; Georgescauld, D

1979-11-01

183

Resurgent functions and splitting problems  

CERN Document Server

The present text is an introduction to \\'Ecalle's theory of resurgent functions and alien calculus, in connection with problems of exponentially small separatrix splitting. An outline of the resurgent treatment of Abel's equation for resonant dynamics in one complex variable is included. The emphasis is on examples of nonlinear difference equations, as a simple and natural way of introducing the concepts.

Sauzin, David

2006-01-01

184

Terminal maritime à Split (Croatie)  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Après 40 ans de statu quo provoqué par l'expérience autogestionnaire de Tito, puis la guerre civile, Split, épargnée par le conflit, reste une ville presque intacte. Aujourd'hui la ville prépare son futur. L'image de la guerre s'estompe, la Croatie négoci

Dubuis, Gilles; O Connell, Johann

2006-01-01

185

Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve.  

Science.gov (United States)

Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukemia antigen (CALLA), is a cell surface zinc metalloprotease that has the ability to hydrolyse a variety of physiologically active peptides. Interest in this enzyme is based on the view that it may play a role in the regulation of peptide signals in different tissues, including the nervous and immune systems. We have previously shown that endopeptidase-24.11 is present in Schwann cells in the peripheral nervous system of newborn pigs [Kioussi C. and Matsas R. (1991) J. Neurochem. 57, 431-440]. In the present study we have investigated the developmental expression of the endopeptidase by Schwann cells in the rat sciatic nerve, from embryonic day 16 to maturity. Endopeptidase-24.11 was monitored enzymatically as well as by immunoblotting and immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. We found an age-dependent decline in both the enzyme activity and the levels of immunoreactive protein. Endopeptidase-24.11 was first detected at embryonic day 18 and was present in all neonatal and early postnatal Schwann cells. However, as myelination proceeded the endopeptidase was gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. At this stage, only very few large diameter myelinated fibers expressed weakly endopeptidase-24.11. Schwann cells dissociated from postnatal day 5 nerves and cultured up to one week in the absence of axons expressed endopeptidase-24.11. These results show that the endopeptidase has a distinct developmental profile in the rat sciatic nerve, similar to that of a group of other Schwann cell surface antigens, including the cell adhesion molecules N-CAM and L1 and the nerve growth factor receptor. We suggest that, as is the case with these antigens, endopeptidase-24.11 may play a role in nerve development and/or regeneration. In addition, persistence of endopeptidase-24.11 in a minority of adult myelin-forming Schwann cells suggests a possible role for the enzyme in axon-myelin apposition and maintenance, especially of larger diameter axons. PMID:1407560

Kioussi, C; Crine, P; Matsas, R

1992-09-01

186

Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo.  

Science.gov (United States)

Inhibitors in myelin play a major role in preventing spontaneous axonal regeneration after CNS injury. Elevation of cAMP overcomes this inhibition, in a transcription-dependent manner, through the upregulation of Arginase I (Arg I) and increased synthesis of polyamines. Here, we show that the cAMP effect requires activation of the transcription factor cAMP response element binding protein (CREB) to overcome myelin inhibitors; a dominant-negative CREB abolishes the effect, and neurons expressing a constitutively active form of CREB are not inhibited. Activation of CREB is also required for cAMP to upregulate Arg I, and the ability of constitutively active CREB to overcome inhibition is blocked by an inhibitor of polyamine synthesis. Finally, expression of constitutively active CREB in DRG neurons is sufficient to promote regeneration of subsequently lesioned dorsal column axons. These results indicate that CREB plays a central role in overcoming myelin inhibitors and so encourages regeneration in vivo. PMID:15541310

Gao, Ying; Deng, Kangwen; Hou, Jianwei; Bryson, J Barney; Barco, Angel; Nikulina, Elena; Spencer, Tim; Mellado, Wilfredo; Kandel, Eric R; Filbin, Marie T

2004-11-18

187

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.  

Science.gov (United States)

Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesis. PMID:19525946

Woodhoo, Ashwin; Alonso, Maria B Duran; Droggiti, Anna; Turmaine, Mark; D'Antonio, Maurizio; Parkinson, David B; Wilton, Daniel K; Al-Shawi, Raya; Simons, Paul; Shen, Jie; Guillemot, Francois; Radtke, Freddy; Meijer, Dies; Feltri, M Laura; Wrabetz, Lawrence; Mirsky, Rhona; Jessen, Kristján R

2009-07-01

188

Incorporation of fucose and leucine into PNS myelin proteins in nerves undergoing early Wallerian degeneration  

International Nuclear Information System (INIS)

The simultaneous incorporation of [3H]fucose and [1-14C]leucine into normal rat sciatic nerve was examined using an in vitro incubation model. A linear rate of protein precursor uptake was found in purified myelin protein over 1/2-6 hr of incubation utilizing a supplemented medium containing amino acids. This model was then used to examine myelin protein synthesis in nerves undergoing degeneration at 1-4 days following a crush injury. Data showed a statistically significant decrease in the ratio of fucose to leucine at 2, 3, and 4 days of degeneration, which was the consequence of a significant increase in leucine uptake. These results, plus substantial protein recovery in axotomized nerves, are indicative of active synthesis of proteins that purify with myelin during early Wallerian degeneration

1981-01-01

189

Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent.  

Science.gov (United States)

In developing and regenerating peripheral nerve, Schwann cells interact with axons and extracellular matrix in order to ensheath and myelinate axons. Both of these interactions are likely to be mediated by adhesion molecules, including integrins, which mediate cell-cell and cell-extracellular matrix interactions. Recently, the beta 4 integrin subunit was reported to be expressed by Schwann cells in peripheral nerve. We have examined the expression of beta 4, beta 1 and their common heterodimeric partner, the alpha 6 integrin subunit, in developing and regenerating rat peripheral nerve. beta 4 and alpha 6 are enriched in peripheral nerve and they co-localize at the abaxonal surface of myelinating Schwann cells, opposite the Schwann cell basal lamina, which contains possible ligands of alpha 6 beta 4. In contrast, beta 4 and alpha 6 are expressed in a different pattern in non-myelinating Schwann cells. The level of beta 4, but not alpha 6 or beta 1 mRNAs, increases progressively in developing nerves, reaching a peak in adult nerves well after the peak of the myelin-specific mRNAs. After axotomy, the expression of beta 4 mRNA and protein, but not alpha 6 or beta 1 mRNAs, fall rapidly but subsequently are reinduced by regenerating axons. Similarly, in cultured Schwann cells, the expression of beta 4 mRNA, but not alpha 6 mRNA, is significantly modulated by forskolin, a drug that elevates cAMP and mimics some of the effects of axonal contact. beta 4 integrin expression in Schwann cells, therefore, is regulated by Schwann cell-axon interactions, which are known to be critical in determining the Schwann cell phenotype. Furthermore, the polarized expression of alpha 6 beta 4 to the abaxonal surface of myelinating Schwann cells suggests that alpha 6 beta 4 may mediate in part the morphological changes required of Schwann cells in the process of myelination in the peripheral nervous system. PMID:8026337

Feltri, M L; Scherer, S S; Nemni, R; Kamholz, J; Vogelbacker, H; Scott, M O; Canal, N; Quaranta, V; Wrabetz, L

1994-05-01

190

Locomotion, physical development, and brain myelination in rats treated with ionizing radiation in utero  

International Nuclear Information System (INIS)

Effects of ionizing radiation on the emergence of locomotion skill and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 R, 15 R, and 6.8 R) delivered on the 20th day of the prenatal life. Results indicated that relatively moderate (15 R) to high (150 R) doses of radiation have effects on certain locomotion and physical development parameters. Exposure to 150 R affected pivoting, cliff-avoidance, upper jaw tooth eruption, body weight, and organs, such as brain, cerebral cortex, ovary, kidney, heart and spleen weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption appeared to be affected in the 150 R treated animals. Exposure to 15 R affected pivoting and cliff-avoidance parameters. The cerebral cortex weight of the 15 R treated animals was found to be reduced at the age of day 30. Exposure to 6.8 R had no adverse effects on these parameters. Prenatal exposure to 150 R of radiation reduced the cerebral cortex weight by 22.07% at 30 days of age, and 20.15% at 52 days of age which caused a reduction in cerebral cortex myelin content by 20.16, and 22.89% at the ages of day 30 and day 52 respectively. Exposure to 150 R did not affect the myelin content of the cerebellum or the brain stem; or the myelin concentration (mg myelin/g brain tissue weight) of the cerebral cortex, cerebellum, and the brain stem. Exposure to 15 R, and 6.8 R did not affect either the myelin content or the myelin concentration of these brain areas

1989-01-01

191

Gene profiling in the dynamic regulation of the lifespan of the myelin sheath structure in the optic nerve of rats.  

Science.gov (United States)

Aging of the nervous system leads to impairments in cognition and motor skills, and is a major risk factor for several neurological disorders. Recently, numerous nerve function deficits that appear with aging have been found to be a consequence of myelin abnormalities; however, the genetic mechanism of the age?related alterations in the myelin sheath has not yet been fully elucidated. In the present study, the morphology of the myelin sheath in the optic nerve of rats was analyzed at 10 time?points throughout life. Marked alterations in the myelin sheath were observed in aging and aged optic nerves, and these became progressively more severe with time. To determine the biological processes affected by aging in the myelin sheath, the age?related profiling of the myelin sheath in rat optic nerves was established using microarray hybridization at 10 time?points throughout life, between birth and senescence. From the results, 3,826 transcripts associated with the age?related alterations in the myelin sheath of the optic nerve were identified. It was found that the biological processes most significantly altered by aging were lipid metabolism, the immune response and transmitter transport. This suggests that the downregulation of lipid synthesis genes and the upregulation of immune and neurotransmitter transport genes in aging may be the genetic basis for the age?related alterations observed in the myelin sheath. PMID:24818667

Xie, Fang; Fu, Han; Zhang, Jiu-Cong; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

2014-07-01

192

Nogo receptor is involved in the adhesion of dendritic cells to myelin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic ...

McDonald Claire L; Steinbach Karin; Kern Florian; Schweigreiter Rüdiger; Martin Roland; Bandtlow Christine E; Reindl Markus

2011-01-01

193

The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination.  

Science.gov (United States)

Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and these observations have spurred interest in the potential protective effects of androgens. Here, we demonstrate that testosterone treatment efficiently stimulates the formation of new myelin and reverses myelin damage in chronic demyelinated brain lesions, resulting from the long-term administration of cuprizone, which is toxic for oligodendrocytes. In addition to the strong effect of testosterone on myelin repair, the number of activated astrocytes and microglial cells returned to low control levels, indicating a reduction of neuroinflammatory responses. We also identify the neural androgen receptor as a novel therapeutic target for myelin recovery. After the acute demyelination of cerebellar slices in organotypic culture, the remyelinating actions of testosterone could be mimicked by 5?-dihydrotestosterone, a metabolite that is not converted to oestrogens, and blocked by the androgen receptor antagonist flutamide. Testosterone treatment also failed to promote remyelination after chronic cuprizone-induced demyelination in mice with a non-functional androgen receptor. Importantly, testosterone did not stimulate the formation of new myelin sheaths after specific knockout of the androgen receptor in neurons and macroglial cells. Thus, the neural brain androgen receptor is required for the remyelination effect of testosterone, whereas the presence of the receptor in microglia and in peripheral tissues is not sufficient to enhance remyelination. The potent synthetic testosterone analogue 7?-methyl-19-nortestosterone, which has been developed for long-term male contraception and androgen replacement therapy in hypogonadal males and does not stimulate prostate growth, also efficiently promoted myelin repair. These data establish the efficacy of androgens as remyelinating agents and qualify the brain androgen receptor as a promising drug target for remyelination therapy, thus providing the preclinical rationale for a novel therapeutic use of androgens in males with multiple sclerosis. PMID:23365095

Hussain, Rashad; Ghoumari, Abdel M; Bielecki, Bartosz; Steibel, Jérôme; Boehm, Nelly; Liere, Philippe; Macklin, Wendy B; Kumar, Narender; Habert, René; Mhaouty-Kodja, Sakina; Tronche, François; Sitruk-Ware, Regine; Schumacher, Michael; Ghandour, M Said

2013-01-01

194

EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans  

Science.gov (United States)

Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

Koprivica, Vuk; Cho, Kin-Sang; Park, Jong Bae; Yiu, Glenn; Atwal, Jasvinder; Gore, Bryan; Kim, Jieun A.; Lin, Estelle; Tessier-Lavigne, Marc; Chen, Dong Feng; He, Zhigang

2005-10-01

195

Porphyrin-heme biosynthesis in organotypic cultures of mouse dorsal root ganglia. Effects of heme and lead on porphyrin synthesis and peripheral myelin.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Well-myelinated cultures of mouse dorsal root ganglia incubated for 48 h with sigma-aminolevulinic acid (ALA) showed intense porphyrin fluorescence localized in myelin sheaths but not in axons or neuronal somata. When the cultures were continuously incubated with a high concentration of lead, focal swelling and segmental degeneration of myelin began to develop within 2 wk. Incubation of cultures with ALA after 3 wk of lead treatment revealed markedly decreased porphyrin fluorescence in myelin...

1984-01-01

196

Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism.  

Science.gov (United States)

MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the Gi protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a Gi protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo. PMID:10027292

Cai, D; Shen, Y; De Bellard, M; Tang, S; Filbin, M T

1999-01-01

197

Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation  

International Nuclear Information System (INIS)

In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated form the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24 h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. (Author)

1994-07-01

198

Some remarks to the nuclear splitting  

International Nuclear Information System (INIS)

Dynamics of the nuclear splitting is n + 23592U ? 23692U, 23692U ? Aa? + Bb? + 4.n. History of the nuclear splitting is mentioned. General remarks, dealing with the dynamics of physical processes in nature are made. (author)

2012-03-01

199

Salt splitting using ceramic membranes  

International Nuclear Information System (INIS)

Inorganic ceramic membranes for salt splitting of radioactively contaminated sodium salt solutions are being developed for treating US Department of Energy tank wastes. The process consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON) membranes. In contrast to conventional organic-based bipolar or ion exchange membranes used in salt splitting, NaSICON membranes are resistant to gamma/beta radiation and are highly selective for sodium ions. Potential applications include (1) caustic recycle for sludge leaching, regeneration of ion exchange resins, inhibition of corrosion in carbon steel tanks, or retrieval of tank wastes; (2) pH adjustment and reduction of competing cations to enhance cesium ion exchange processes; (3) sodium reduction in high-level waste sludges; and (4) sodium removal from acidic wastes to facilitate calcining. Initial experiments with dysprosium-based NaSICON membranes have demonstrated the feasibility of the process

1995-10-22

200

Finite bias Cooper pair splitting  

CERN Document Server

In a device with a superconductor coupled to two parallel quantum dots (QDs) the electrical tunability of the QD levels can be used to exploit non-classical current correlations due to the splitting of Cooper pairs. We experimentally investigate the effect of a finite potential difference across one quantum dot on the conductance through the other completely grounded QD in a Cooper pair splitter fabricated on an InAs nanowire. We demonstrate that the electrical transport through the device can be tuned by electrical means to be dominated either by Cooper pair splitting (CPS), or by elastic co-tunneling (EC). The basic experimental findings can be understood by considering the energy dependent density of states in a QD. The reported experiments add bias-dependent spectroscopy to the investigative tools necessary to develop CPS-based sources of entangled electrons in solid-state devices.

Hofstetter, L; Baumgartner, A; Fülöp,; d'Hollosy, S; Nygård, J; Schönenberger, C

2011-01-01

 
 
 
 
201

Empirical Methods for Compound Splitting  

CERN Document Server

Compounded words are a challenge for NLP applications such as machine translation (MT). We introduce methods to learn splitting rules from monolingual and parallel corpora. We evaluate them against a gold standard and measure their impact on performance of statistical MT systems. Results show accuracy of 99.1% and performance gains for MT of 0.039 BLEU on a German-English noun phrase translation task.

Koehn, P; Koehn, Philipp; Knight, Kevin

2003-01-01

202

Gluino decays in Split Supersymmetry  

Energy Technology Data Exchange (ETDEWEB)

We compute the gluino lifetime and branching ratios in Split Supersymmetry. Using an effective-theory approach, we resum the large logarithmic corrections controlled by the strong gauge coupling and the top Yukawa coupling. We find that the resummation of the radiative corrections has a sizeable numerical impact on the gluino decay width and branching ratios. Finally, we discuss the gluino decays into gravitino, relevant in models with direct mediation of supersymmetry breaking.

Gambino, P. [INFN and Dipartimento di Fisica Teorica, Universita di Torino, I-10125 Turin (Italy); Giudice, G.F. [CERN, Theory Division, CH-1211 Geneva 23 (Switzerland); Slavich, P. [Durham University, IPPP, DH1-3LE Durham (United Kingdom)]. E-mail: pietro.slavich@durham.ac.uk

2005-10-17

203

Gluon splitting in a shockwave  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluo...

Iancu, Edmond; Laidet, Julien

2013-01-01

204

Gluino Decays in Split Supersymmetry  

CERN Multimedia

We compute the gluino lifetime and branching ratios in Split Supersymmetry. Using an effective-theory approach, we resum the large logarithmic corrections controlled by the strong gauge coupling and the top Yukawa coupling. We find that the resummation of the radiative corrections has a sizeable numerical impact on the gluino decay width and branching ratios. Finally, we discuss the gluino decays into gravitino, relevant in models with direct mediation of supersymmetry breaking.

Gambino, P; Slavich, P

2005-01-01

205

Splitting Methods for Convex Clustering  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Clustering is a fundamental problem in many scientific applications. Standard methods such as $k$-means, Gaussian mixture models, and hierarchical clustering, however, are beset by local minima, which are sometimes drastically suboptimal. Recently introduced convex relaxations of $k$-means and hierarchical clustering shrink cluster centroids toward one another and ensure a unique global minimizer. In this work we present two splitting methods for solving the convex clusterin...

Chi, Eric C.; Lange, Kenneth

2013-01-01

206

7 CFR 51.2002 - Split shell.  

Science.gov (United States)

...2010-01-01 2010-01-01 false Split shell. 51.2002 Section 51.2002 Agriculture...States Standards for Grades of Filberts in the Shell 1 Definitions § 51.2002 Split shell. Split shell means a shell having...

2010-01-01

207

M2 muscarinic receptor activation regulates schwann cell differentiation and myelin organization.  

Science.gov (United States)

Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 676-691, 2014. PMID:24403178

Uggenti, Carolina; De Stefano, M Egle; Costantino, Michele; Loreti, Simona; Pisano, Annalinda; Avallone, Bice; Talora, Claudio; Magnaghi, Valerio; Tata, Ada Maria

2014-07-01

208

Oligodendrocyte development and the onset of myelination in the human fetal brain  

Directory of Open Access Journals (Sweden)

Full Text Available Oligodendrocytes are cells that myelinate axons, providing saltatory conduction of action potentials and proper function of the central nervous system. Myelination begins prenatally in the human, and the sequence of oligodendrocyte development and the onset of myelination are not thoroughly investigated. This knowledge is important to better understand human diseases, such as periventricular leukomalacia, one of the leading causes of motor deficit in premature babies, and demyelinating disorders such as multiple sclerosis (MS. In this review we discuss the spatial and temporal progression of oligodendrocyte lineage characterized by the expression of specific markers and transcription factors in the human fetal brain from the early embryonic period (5 gestational weeks, gw until midgestation (24 gw. Our in vitro evidence indicated that a subpopulation of human oligodendrocytes may have dorsal origin, from cortical radial glia cells, in addition to their ventral telencephalic origin. Furthermore, we demonstrated that the regulation of myelination in the human fetal brain includes positive and negative regulators. Chemokines, such as CXCL1, abundant in proliferative zones during brain development and in regions of remyelination in adult, are discussed in the view of their potential roles in stimulating oligodendrocyte development. Other signals are inhibitory and may include, but are not limited to, polysialic acid modification of the neural cell adhesion molecule on axons. Overall, important differences in temporal and spatial distribution and regulatory signals for oligodendrocyte differentiation exist in the human brain. Those differences may underlie the unique susceptibility of humans to demyelinating diseases, such as MS.

RadmilaFilipovic

2009-06-01

209

beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG and oligodendrocyte myelin glycoprotein (OMgp, can associate with a common GPI-linked protein Nogo-66 receptor (NgR. Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with ?1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of ?1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK, which in turn is required for MAG-induced growth cone turning. These studies identify ?1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.

Goh Eyleen LK

2008-10-01

210

Asymptotic construction of pulses in the Hodgkin Huxley model for myelinated nerves  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A quantitative description of pulses and wave trains in the spatially discrete Hodgkin-Huxley model for myelinated nerves is given. Predictions of the shape and speed of the waves and the thresholds for propagation failure are obtained. Our asymptotic predictions agree quite well with numerical solutions of the model and describe wave patterns generated by repeated firing at a boundary.

Carpio, A.

2005-01-01

211

AN INTEGRIN-CONTACTIN COMPLEX REGULATES CNS MYELINATION BY DIFFERENTIAL FYN PHOSPHORYLATION  

Science.gov (United States)

The understanding of how adhesion molecules mediate the axo-glia interactions in the CNS that ensure target-dependent survival of oligodendrocytes and initiate myelination remains incomplete. Here, we investigate how signals from adhesion molecules can be integrated to regulate these initial steps of myelination. We first demonstrate that the immunoglobulin superfamily molecule contactin is associated in oligodendrocytes with integrins, extracellular matrix receptors that regulate target-dependent survival by amplification of growth factor signaling. This amplification is inhibited by siRNA-mediated knockdown of contactin in oligodendrocytes. In contrast, the presence of L1-Fc, the extracellular portion of a contactin ligand expressed on axons, enhanced survival and additionally promoted myelination in co-cultures of neurons and oligodendrocytes. We further demonstrate that the signals from contactin and integrin are integrated by differential phosphorylation of the Src-family kinase Fyn. Integrin induced dephosphorylation of the inhibitory Tyr-531, while contactin increased phosphorylation of both Tyr-531 and the activating Tyr-420. The combined effect is an enhanced activity of Fyn and also a dynamic regulation of the phosphorylation/dephosphorylation balance of Fyn, as required for normal cell adhesion and spreading. We conclude, therefore, that a novel integrin/contactin complex coordinates signals from extracellular matrix and the axonal surface to regulate both oligodendrocyte survival and myelination by controlling Fyn activity.

Laursen, Lisbeth S.; Chan, Colin W.; ffrench-Constant, Charles

2014-01-01

212

Muscarinic receptor binding and muscarinic receptor-mediated inhibition of adenylate cyclase in rat brain myelin  

International Nuclear Information System (INIS)

ulated adenylate cyclase 10% of the values for total particulate fraction of whole brain stem. These levels in myelin are appreciably greater than would be predicted on the basis of contamination. Also, additional receptors and adenylate cyclase, added by mixing nonmyelin tissue with whole brain stem, were quantitatively removed during the purification procedure

1987-01-01

213

Degree of myelination (g-ratio) of the human recurrent laryngeal nerve.  

Science.gov (United States)

The g-ratio (estimated by dividing the axon diameter by the myelinated fiber diameter) can be useful to the evaluation of the relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration. However, there is little detailed information about the g-ratio of the human recurrent laryngeal nerve (RLN), especially between men and women. The objective of this study was to investigate the g-ratio of the RLN by quantifying histomorphometric data (axon diameter and myelinated fiber diameter) in the RLN of men and women. The RLN was bilaterally studied in human specimens obtained from necropsies (seven men and seven women). The nerves were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD, USA). When compared with the RLN of the women, the parameters of the RLN of the men are significantly larger, as shown by the axon diameter (19.0%) (P = 0.0001), myelinated fiber diameter (7.1%) (P = 0.0497), and g-ratio (12.5%) (P = 0.0005). Our findings demonstrated that there are morphological asymmetries between the g-ratio (degree of the myelination) of the masculine and feminine RLN. These morphological findings are probably related to physiological differences. PMID:24061571

de Campos, Deivis; Heck, Layana; Jotz, Geraldo Pereira; Xavier, Léder Leal

2014-05-01

214

Myelination process in preterm subjects with periventricular leucomalacia assessed by magnetization transfer ratio  

International Nuclear Information System (INIS)

Magnetization transfer imaging assesses the myelination status of the brain. To study the progress of myelination in children with periventricular leucomalacia (PVL) by measuring the magnetization transfer ratio (MTR) and to compare the MTR values with normal values. Brain MTR in 28 PVL subjects (16 males, 12 females, gestational age 30.7±2.5 weeks, corrected age 3.1±2.9 years) was measured using a 3D gradient echo sequence (TR/TE 32/8 ms, flip angle 60 , 4 mm/2 mm overlapping sections) without and with magnetization transfer prepulse and compared with normal values for preterm subjects. MTR of white-matter structures followed a monoexponential function model (y=A-B*exp(-x/C)) while the thalamus and caudate nucleus had a poor goodness of fit. MTR of the splenium of the corpus callosum reached a final value lower than normal (0.67 versus 0.70) at a younger age [t(99%) at 10.32 versus 18.90 months; P<0.05]. MTR of the normal-appearing occipital white matter and of the genu of the corpus callosum reached a normal final MTR but at a younger age than normal preterm infants [t(99%) at 8.51 versus 14.50 months and 12.51 versus 20.85 months, respectively]. In PVL subjects, myelination of the splenium is characterized by early arrest and deficient maturation. Accelerated myelination in unaffected white matter might suggest a compensatory process of reorganization. (orig.)

2006-09-01

215

Myelination process in preterm subjects with periventricular leucomalacia assessed by magnetization transfer ratio  

Energy Technology Data Exchange (ETDEWEB)

Magnetization transfer imaging assesses the myelination status of the brain. To study the progress of myelination in children with periventricular leucomalacia (PVL) by measuring the magnetization transfer ratio (MTR) and to compare the MTR values with normal values. Brain MTR in 28 PVL subjects (16 males, 12 females, gestational age 30.7{+-}2.5 weeks, corrected age 3.1{+-}2.9 years) was measured using a 3D gradient echo sequence (TR/TE 32/8 ms, flip angle 60 , 4 mm/2 mm overlapping sections) without and with magnetization transfer prepulse and compared with normal values for preterm subjects. MTR of white-matter structures followed a monoexponential function model (y=A-B*exp(-x/C)) while the thalamus and caudate nucleus had a poor goodness of fit. MTR of the splenium of the corpus callosum reached a final value lower than normal (0.67 versus 0.70) at a younger age [t(99%) at 10.32 versus 18.90 months; P<0.05]. MTR of the normal-appearing occipital white matter and of the genu of the corpus callosum reached a normal final MTR but at a younger age than normal preterm infants [t(99%) at 8.51 versus 14.50 months and 12.51 versus 20.85 months, respectively]. In PVL subjects, myelination of the splenium is characterized by early arrest and deficient maturation. Accelerated myelination in unaffected white matter might suggest a compensatory process of reorganization. (orig.)

Xydis, Vassilios; Astrakas, Loukas; Gassias, Dimitrios; Argyropoulou, Maria [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Drougia, Aikaterini; Andronikou, Styliani [University of Ioannina, Neonatology Clinic, Child Health Department, Medical School, Ioannina (Greece)

2006-09-15

216

Transfer of axonally transported phospholipids into myelin isolated from the rabbit optic pathway  

International Nuclear Information System (INIS)

The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: [1-_1_4C]palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and [2-_3H]glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or _3H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxonal transfer into myelin

1982-01-01

217

Novel method for studying myelination in vivo reveals that EDTA is a potent inhibitor of myelin protein and mRNA expression during development of the rat sciatic nerve.  

Science.gov (United States)

To probe the effects of possible inhibitors or enhancers of in vivo myelination, we have modified a technique widely used in studies of the developing neuromuscular system that involves incorporation of test compounds into a silicon rubber solution, which solidifies on contact with air. U-shaped rubber implants are inserted around the sciatic nerve of 1-day-old rats and left in place for 24-48 h. Sections from the region of the nerve lying within the implant, with or without the test compound, are then immunolabeled, examined with in situ hybridization or electron microscopy. Application of EDTA (440 microg/implant) in this way strongly suppressed the levels of the myelin-associated molecules protein P0, myelin basic protein (MBP), and galactocerebroside (Galc). mRNA levels for P0 and the myelin-related transcription factor Krox-20 were also reduced, further supporting association of the EDTA-induced effect with the myelinating Schwann cells. In contrast, no obvious differences were observed in either neurofilament (NF) protein or glial fibrillary acidic protein (GFAP) expression, suggesting absence of influence on axons or nonmyelinating Schwann cells. Despite the severely altered molecular composition of myelin in the presence of EDTA, examination in the electron microscope did not reveal any apparent ultrastructural changes in the myelin sheaths or nerve development. This work introduces a novel method for studying nerve development and shows that EDTA, which chelates divalent cations such as Ca(2+) and Mg(2+), strongly and selectively reduces levels of molecules, which, on postnatal days 1-4, are expressed in myelinating cells at much higher levels than in cells not engaged in myelination. PMID:15378656

Meintanis, Stathis; Thomaidou, Dimitra; Jessen, Kristjan R; Mirsky, Rhona; Matsas, Rebecca

2004-11-01

218

Mutation of sec63 in zebrafish causes defects in myelinated axons and liver pathology  

Science.gov (United States)

SUMMARY Mutations in SEC63 cause polycystic liver disease in humans. Sec63 is a member of the endoplasmic reticulum (ER) translocon machinery, although it is unclear how mutations in SEC63 lead to liver cyst formation in humans. Here, we report the identification and characterization of a zebrafish sec63 mutant, which was discovered in a screen for mutations that affect the development of myelinated axons. Accordingly, we show that disruption of sec63 in zebrafish leads to abnormalities in myelinating glia in both the central and peripheral nervous systems. In the vertebrate nervous system, segments of myelin are separated by the nodes of Ranvier, which are unmyelinated regions of axonal membrane containing a high density of voltage-gated sodium channels. We show that sec63 mutants have morphologically abnormal and reduced numbers of clusters of voltage-gated sodium channels in the spinal cord and along peripheral nerves. Additionally, we observed reduced myelination in both the central and peripheral nervous systems, as well as swollen ER in myelinating glia. Markers of ER stress are upregulated in sec63 mutants. Finally, we show that sec63 mutants develop liver pathology. As in glia, the primary defect, detectable at 5 dpf, is fragmentation and swelling of the ER, indicative of accumulation of proteins in the lumen. At 8 dpf, ER swelling is severe; other pathological features include disrupted bile canaliculi, altered cytoplasmic matrix and accumulation of large lysosomes. Together, our analyses of sec63 mutant zebrafish highlight the possible role of ER stress in polycystic liver disease and suggest that these mutants will serve as a model for understanding the pathophysiology of this disease and other abnormalities involving ER stress.

Monk, Kelly R.; Voas, Matthew G.; Franzini-Armstrong, Clara; Hakkinen, Ian S.; Talbot, William S.

2013-01-01

219

Treatment with Thyroxine Restores Myelination and Clinical Recovery after Intraventricular Hemorrhage  

Science.gov (United States)

Intraventricular hemorrhage (IVH) remains a major cause of white matter injury in preterm infants with no viable therapeutic strategy to restore myelination. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling, which is mediated by TH receptor ? (TR?) and TR?. In the brain, cellular levels of TH are regulated by deiodinases, with deiodinase-2 mediating TH activation and deiodinase-3 TH inactivation. Therefore, we hypothesized that IVH would decrease TH signaling via changes in the expression of deiodinases and/or TRs, and normalization of TH signaling would enhance maturation of oligodendrocytes and myelination in preterm infants with IVH. These hypotheses were tested using both autopsy materials from human preterm infants and a rabbit model of IVH. We found that deiodinase-2 levels were reduced, whereas deiodinase-3 levels were increased in brain samples of both humans and rabbits with IVH compared with controls without IVH. TR? expression was also increased in human infants with IVH. Importantly, treatment with TH accelerated the proliferation and maturation of oligodendrocytes, increased transcription of Olig2 and Sox10 genes, augmented myelination, and restored neurological function in pups with IVH. Consistent with these findings, the density of myelinating oligodendrocytes was almost doubled in TH-treated human preterm infants compared with controls. Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TR?. Given that TH promotes neurological recovery in IVH, TH treatment might improve the neurodevelopmental outcome of preterm infants with IVH.

Vose, Linnea R.; Vinukonda, Govindaiah; Jo, Sungro; Miry, Omid; Diamond, Daniel; Korumilli, Ritesh; Arshad, Arslan; Zia, Muhammad T. K.; Hu, Furong; Kayton, Robert J.; La Gamma, Edmund F.; Bansal, Rashmi; Bianco, Antonio C.

2013-01-01

220

Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping  

Science.gov (United States)

The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or ‘disconnectivity’) arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays, few imaging studies have specifically examined its maturation throughout early infancy and childhood. Thus, direct investigations of the relationship(s) between evolving behavioral and cognitive functions and the myelination of the supporting neural systems have been sparse. Further, without knowledge of the ‘normative’ developmental time-course, identification of early abnormalities associated with developmental disorders remains challenging. In this work, we examined the use of longitudinal (T1) and transverse (T2) relaxation time mapping, and myelin water fraction (MWF) imaging to investigate white matter and myelin development in 153 healthy male and female children, 3 months through 60 months in age. Optimized age-specific acquisition protocols were developed using the DESPOT and mcDESPOT imaging techniques; and mean T1, T2 and MWF trajectories were determined for frontal, temporal, occipital, parietal and cerebellar white matter, and genu, body and splenium of the corpus callosum. MWF results provided a spatio-temporal pattern in-line with prior histological studies of myelination. Comparison of T1, T2 and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information.

Deoni, Sean C.L.; Dean, Douglas C.; O'Muircheartaigh, Jonathan; Dirks, Holly; Jerskey, Beth A.

2012-01-01

 
 
 
 
221

Npc1 acting in neurons and glia is essential for the formation and maintenance of CNS myelin.  

Science.gov (United States)

Cholesterol availability is rate-limiting for myelination, and prior studies have established the importance of cholesterol synthesis by oligodendrocytes for normal CNS myelination. However, the contribution of cholesterol uptake through the endocytic pathway has not been fully explored. To address this question, we used mice with a conditional null allele of the Npc1 gene, which encodes a transmembrane protein critical for mobilizing cholesterol from the endolysosomal system. Loss of function mutations in the human NPC1 gene cause Niemann-Pick type C disease, a childhood-onset neurodegenerative disorder in which intracellular lipid accumulation, abnormally swollen axons, and neuron loss underlie the occurrence of early death. Both NPC patients and Npc1 null mice exhibit myelin defects indicative of dysmyelination, although the mechanisms underlying this defect are incompletely understood. Here we use temporal and cell-type-specific gene deletion in order to define effects on CNS myelination. Our results unexpectedly show that deletion of Npc1 in neurons alone leads to an arrest of oligodendrocyte maturation and to subsequent failure of myelin formation. This defect is associated with decreased activation of Fyn kinase, an integrator of axon-glial signals that normally promotes myelination. Furthermore, we show that deletion of Npc1 in oligodendrocytes results in delayed myelination at early postnatal days. Aged, oligodendocyte-specific null mutants also exhibit late stage loss of myelin proteins, followed by secondary Purkinje neuron degeneration. These data demonstrate that lipid uptake and intracellular transport by neurons and oligodendrocytes through an Npc1-dependent pathway is required for both the formation and maintenance of CNS myelin. PMID:23593041

Yu, Ting; Lieberman, Andrew P

2013-04-01

222

CBM split title in Alberta  

Energy Technology Data Exchange (ETDEWEB)

Coalbed methane (CBM) coal underlies most of central and southern Alberta. This article discussed disputes surrounding CBM ownership and split-titles. Historically, ownership of lands in Alberta implied possession and rights of all under- and overground substances. Surface estates are now typically separated from the subsurface estate, and subsurface estates are further divided either on the basis of substances or stratigraphically to create a split-title. Mineral severances are used to separate respective mineral rights among owners. While there is a relative certainty that under provincial Crown tenure CBM is included in natural gas tenure, there is currently no Canadian jurisprudence in respect of CBM entitlement on split-title private lands. Where compressed natural gas (CNG) and coal are separately held, and CBM ownership is not specifically addressed in the mineral severance, there is no Canadian law respecting CBM ownership. Resolution of ownership issues has proceeded on a case by case basis. Coal owners argue that there is a distinct interrelationship between CBM and its host coal strata. Gas owners argue that the chemical composition of CBM is identical to CNG, and that the recovery method is similar to that of CNG. Courts have historically applied the vernacular test to resolve mineral substance ownership disputes, which considers the meanings of the word coal and coalbed methane as defined by industry. The most recent and relevant application of the vernacular test were the Borys/Anderson, which effectively implemented a gas-oil interface ownership determination, which if applied to a coal grant or reservation, may lead to the conclusion that the coal strata includes CBM. It was concluded that there are 26,000 individual mineral owners in Alberta that may become involved in CBM litigation. and could become parties to litigation. refs., tabs., figs.

Campbell, L.M. [EnCana Corp., Calgary, AB (Canada); Laurin, W.

2006-07-01

223

Frequency splitting in Ap stars  

International Nuclear Information System (INIS)

We generalize the oblique pulsator model by Kurtz to account for the observed properties of rapidly oscillating Ap stars. In our model, which includes advection and an oblique magnetic field, the modes are represented, in general, by a superposition of all spherical harmonics having the appropriate degree, l. We predict that an observer will report a mode splitting into (2l+1)--frequency components with the spacing equal to the rotation frequency of the star. The relative amplitudes at these frequencies are predicted following from a postulated selective excitation mechanism due to the field, and the diagnostic potential of the data on these Ap stars is discussed

1985-09-15

224

Quantum Teleportation and Beam Splitting  

CERN Document Server

Following the previous paper in which quantum teleportation is rig orously discussed with coherent entangled states given by beam splittings, we further discuss two types of models, perfect teleportation model and non-perfect teleportation model, in general scheme. Then the difference among several models, i.e., the perfect models and the non-perfect models, is studied. Our teleportation models are constructed by means of coherent states in some Fock space with counting measures, so that our model can be treated in the frame of usual optical communication.

Fichtner, K H; Fichtner, Karl-Heinz; Ohya, Masanori

2000-01-01

225

Split-mode ultrasonic transducer.  

Science.gov (United States)

A split-mode ultrasonic transducer is investigated in both theory and experiment. This transducer is a two-dimensional structure of periodically poled domains in a ferroelectric wafer with free surfaces. The acoustic vibrations are excited by a radio frequency electric current applied along the length of the wafer, which allows the basal-plane surfaces to be free of metal coatings and thus ready for further biomedical applications. A specific physical property of this transducer consists of the multiple acousto-electric resonances, which occur due to an acoustic mode split when the acoustic half-wavelength is equal to the domain length. Possible applications include ultrasonic generation and detection at the micro-scale, intravascular sonification and visualization, ultrasound therapy of localized small areas such as the eye, biomedical applications for cell cultures, and traditional nondestructive testing including bones and tissues. A potential use of a non-metallized wafer is a therapeutic application with double action that is both ultrasound itself and an electric field over the wafer. The experimental measurements and theoretical calculations are in good agreement. PMID:23927212

Ostrovskii, Igor; Cremaldi, Lucien

2013-08-01

226

Lysosomal delivery of the major myelin glycoprotein in the absence of myelin assembly: posttranslational regulation of the level of expression by Schwann cells  

International Nuclear Information System (INIS)

The major myelin protein, P0, has been shown to have decreased levels of expression and altered oligosaccharide processing after the disruption of Schwann cell-axon interaction. We show here that lysosomal degradation of the glycoprotein shortly after its synthesis accounts for much of its decreased expression in the permanently transected adult rat sciatic nerve, a denervated preparation where there is no axonal regeneration or myelin assembly. If ["3H]mannose incorporation into sciatic nerve endoneurial slices is examined in the presence of the lysosomotropic agent, NH_4Cl, a marked increase in the level of newly synthesized P0 is seen. Pulse-chase analysis of ["3H]mannose-labeled P0 in the presence of NH_4Cl indicates that this increase is a consequence of inhibition of P0 degradation that normally occurs 1-2 h after biosynthesis in the transected nerve. P0 degradation can also be inhibited if lysosomal function is disturbed by dilation of secondary lysosomes with L-methionine methyl ester. The addition of deoxymannonojirimycin or swainsonine (SW), inhibitors of oligosaccharide-processing mannosidases I and II, respectively, also results in a decrease in P0 degradation. This inhibition is presumably caused by a blockage of transport to the lysosomes due to altered processing of the glycoprotein, although the direct inhibition of lysosomal mannosidases cannot be excluded. In contrast to the transected nerve, addition of NH_4Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs. The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing

1987-01-01

227

Telugu Bigram Splitting using Consonant-based and Phrase-based Splitting  

Directory of Open Access Journals (Sweden)

Full Text Available Splitting is a conventional process in most of Indian languages according to their grammar rules. It is called ‘pada vicchEdanam’ (a Sanskrit term for word splitting and is widely used by most of the Indian languages. Splitting plays a key role in Machine Translation (MT particularly when the source language (SL is an Indian language. Though this splitting may not succeed completely in extracting the root words of which the compound is formed, but it shows considerable impact in Natural Language Processing (NLP as an important phase. Though there are many types of splitting, this paper considers only consonant based and phrase based splitting.

T. Kameswara Rao

2014-06-01

228

Valley splitting in strained silicon quantum wells  

CERN Document Server

A theory based on localized-orbital approaches is developed to describe the valley splitting observed in silicon quantum wells. The theory is appropriate in the limit of low electron density and relevant for proposed quantum computing architectures. The valley splitting is computed for realistic devices using the quantitative nanoelectronic modeling tool NEMO. A simple, analytically solvable tight-binding model is developed, it yields much physical insight, and it reproduces the behavior of the splitting in the NEMO results. The splitting is in general nonzero even in the absence of electric field in contrast to previous works. The splitting in a square well oscillates as a function of S, the number of layers in the quantum well, with a period that is determined by the location of the valley minimum in the Brillouin zone. The envelope of the splitting decays as $S^3$. Finally the feasibility of observing such oscillations experimentally in modern Si/SiGe heterostructures is discussed.

Boykin, T B; Eriksson, M A; Friesen, M; Coppersmith, S N; Von Allmen, P; Oyafuso, F; Lee, S; Boykin, Timothy B.; Klimeck, Gerhard; Friesen, Mark; Allmen, Paul von; Oyafuso, Fabiano; Lee, Seungwon

2003-01-01

229

Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro.  

Science.gov (United States)

Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibition by MAG and by myelin in general. While MAG/myelin support the growth of young DRG neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are high in young DRGs but drop spontaneously at an age that coincides with the switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury. PMID:12194870

Cai, Dongming; Deng, Kangwen; Mellado, Wilfredo; Lee, Junghee; Ratan, Rajiv R; Filbin, Marie T

2002-08-15

230

Optical Stark splitting of rotational Raman transitions  

Energy Technology Data Exchange (ETDEWEB)

The first observation of optical Stark splitting of a molecular Raman transition is reported. The splitting is observed in inverse Raman rotational spectra of diatomic nitrogen, measured in the presence of a pulsed 1.06-..mu..m laser field. The line positions and intensities of the Stark-split multiplets are in good agreement with calculations of the quadratic Stark effect associated with the optical polarizability anisotropy.

Farrow, R.L.; Rahn, L.A.

1982-02-08

231

Optical Stark splitting of rotational Raman transitions  

International Nuclear Information System (INIS)

The first observation of optical Stark splitting of a molecular Raman transition is reported. The splitting is observed in inverse Raman rotational spectra of diatomic nitrogen, measured in the presence of a pulsed 1.06-?m laser field. The line positions and intensities of the Stark-split multiplets are in good agreement with calculations of the quadratic Stark effect associated with the optical polarizability anisotropy

1982-02-08

232

Iterative Splitting Methods for Differential Equations  

CERN Document Server

Iterative Splitting Methods for Differential Equations explains how to solve evolution equations via novel iterative-based splitting methods that efficiently use computational and memory resources. It focuses on systems of parabolic and hyperbolic equations, including convection-diffusion-reaction equations, heat equations, and wave equations. In the theoretical part of the book, the author discusses the main theorems and results of the stability and consistency analysis for ordinary differential equations. He then presents extensions of the iterative splitting methods to partial differential

Geiser, Juergen

2011-01-01

233

Split general quasi-variational inequality problem  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In this paper, we introduce a split general quasi-variational inequality problem which is a natural extension of split variational inequality problem, quasi-variational and variational inequality problems in Hilbert spaces. Using projection method, we propose an iterative algorithm for the split general quasi-variational inequality problem and discuss some its special cases. Further, we discuss the convergence criteria of these iterative algorithms. The results presented in ...

Kazmi, Kaleem Raza

2013-01-01

234

Scalable Splitting of Massive Data Streams  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Scalable execution of continuous queries over massive data streams often requires splitting input streams into parallel sub-streams over which query operators are executed in parallel. Automatic stream splitting is in general very difficult, as the optimal parallelization may depend on application semantics. To enable application specific stream splitting, we introduce splitstream functions where the user specifies non-procedural stream partitioning and replication. For high-volume streams, t...

Zeitler, Erik; Risch, Tore

2010-01-01

235

Tube splitting furnace surrounded by cylindrical jacket  

International Nuclear Information System (INIS)

The application concerns a methane splitting plant, in which heat generated in a nuclear reactor is used directly, without an intermediate circuit in a process requiring heat, i.e. a CH_4/H_2O mixture is split into H_2, CO and CO_2 by supplying heat and using a catalyst. This split gas is used as heat carrier in transport of the heat energy obtained in a high temperature reactor to a remote energy consumption location, where the split gas is again converted to methane by catalysis and the heat released is used. The methane splitting furnace is a tall vertical cylinder, which contains 313 splitting tubes. The helium coming from the high temperature reactor reaches the cylinder from below at 950"0C and 39 bar, and gives up heat to the splitting tubes projecting down from above; it is taken away at 800"0C and is taken to the steam raising unit and the blower after it. The helium is returned from the blower at 300"0C and is taken through an annular space above the hot gas space mentioned above, in order to cool the support plate for the splitting tubes above it. From here, the cold helium returns to the high temperature reactor. The CH_4/H_2O mixture enters the space above the support plate at 500"0C and 44 bar, where it is distributed to the individual splitting tubes. It flows down in these, where it is split into H_2, CO and CO_2 by hot helium using a catalytic effect. The split gas flows upwards through the coaxial return pipes in the splitting tubes, where it is collected in a space above the gas mixture distribution space and is returned to the remote gas pipe at 680"0C. (RB)

1976-04-06

236

Additive operator-difference schemes splitting schemes  

CERN Document Server

Applied mathematical modeling isconcerned with solving unsteady problems. This bookshows how toconstruct additive difference schemes to solve approximately unsteady multi-dimensional problems for PDEs. Two classes of schemes are highlighted: methods of splitting with respect to spatial variables (alternating direction methods) and schemes of splitting into physical processes. Also regionally additive schemes (domain decomposition methods)and unconditionally stable additive schemes of multi-component splitting are considered for evolutionary equations of first and second order as well as for sy

Vabishchevich, Petr N

2013-01-01

237

Genetic variants of Nogo-66 Receptor with possible association to schizophrenia block myelin inhibition of axon growth  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In schizophrenia, genetic predisposition has been linked to chromosome 22q11 and myelin-specific genes are misexpressed in schizophrenia. Nogo-66 Receptor 1 (NGR or RTN4R) has been considered as a 22q11 candidate gene for schizophrenia susceptibility since it encodes an axonal protein that mediates myelin inhibition of axonal sprouting. Confirming previous studies, we found that variation at the NGR locus is associated with schizophrenia in a Caucasian case-control analysis and this associati...

Budel, Ste?phane; Padukkavidana, Thihan; Liu, Betty P.; Feng, Zeny; Hu, Fenghua; Johnson, Sam; Lauren, Juha; Park, James H.; Mcgee, Aaron W.; Liao, Ji; Stillman, Althea; Kim, Ji-eun; Yang, Bao-zhu; Sodi, Stefano; Gelernter, Joel

2008-01-01

238

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina.  

Science.gov (United States)

Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2'-, 3'-cyclic-nucleotide-3'-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. PMID:23680456

Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

2013-12-01

239

Anterograde transport and secretion of brain-derived neurotrophic factor along sensory axons promote schwann cell myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits Schwann cell (SC) migration and promotes myelination via the p75 neurotrophin receptor (NTR). Despite these recent findings, the expression, localization, and mechanism of BDNF action has yet to be determined. Here we demonstrate that the sensory neurons of the dorsal root ganglion (DRG) are a major source of BDNF during postnatal development. The expression of BDNF is initially elevated before myelination and decreases dramat...

Ng, Benjamin K.; Chen, Lian; Mandemakers, Wilhelm; Cosgaya, Jose? Miguel; Chan, Jonah R.

2007-01-01

240

Gangliosides and Nogo Receptors Independently Mediate Myelin-associated Glycoprotein Inhibition of Neurite Outgrowth in Different Nerve Cells*  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the injured nervous system, myelin-associated glycoprotein (MAG) on residual myelin binds to receptors on axons, inhibits axon outgrowth, and limits functional recovery. Conflicting reports identify gangliosides (GD1a and GT1b) and glycosylphosphatidylinositol-anchored Nogo receptors (NgRs) as exclusive axonal receptors for MAG. We used enzymes and pharmacological agents to distinguish the relative roles of gangliosides and NgRs in MAG-mediated inhibition of neurite outgrowth from three ne...

Mehta, Niraj R.; Lopez, Pablo H. H.; Vyas, Alka A.; Schnaar, Ronald L.

2007-01-01

 
 
 
 
241

Ex vivo and in vivo imaging of myelin fibers in mouse brain by coherent anti-Stokes Raman scattering microscopy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Coherent anti-Stokes Raman scattering (CARS) microscopy was applied to image myelinated fibers in different regions of a mouse brain. The CARS signal from the CH2 symmetric stretching vibration allows label-free imaging of myelin sheath with 3D sub-micron resolution. Compared with two-photon excited fluorescence imaging with lipophilic dye labeling, CARS microscopy provides sharper contrast and avoids photobleaching. The CARS signal exhibits excitation polarization dependence which can be eli...

Fu, Yan; Huff, T. Brandon; Wang, Han-wei; Wang, Haifeng; Cheng, Ji-xin

2008-01-01

242

Pubertal ovarian hormone exposure reduces the number of myelinated axons in the splenium of the rat corpus callosum  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The size of the female rat corpus callosum decreases in response to pubertal ovarian hormone exposure, but the underlying changes in axonal composition have not been examined. In the current study, animals underwent ovariectomy or sham surgery at day 20, and the number of myelinated and unmyelinated axons were examined in young adulthood (2 mo.) using electron microscopy. Ovariectomized animals had a greater number of myelinated axons compared to intact animals, while total axon number was no...

Yates, M. A.; Juraska, J. M.

2008-01-01

243

Salt splitting with ceramic membranes  

International Nuclear Information System (INIS)

The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures

1996-01-16

244

Gluon splitting in a shockwave  

CERN Document Server

The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark-gluon production in the literature. We consider in more detail two special kinematical limits: the "back-to-back correlation limit", where the transver...

Iancu, Edmond

2013-01-01

245

Dark matter from split seesaw  

Energy Technology Data Exchange (ETDEWEB)

The seesaw mechanism in models with extra dimensions is shown to be generically consistent with a broad range of Majorana masses. The resulting democracy of scales implies that the seesaw mechanism can naturally explain the smallness of neutrino masses for an arbitrarily small right-handed neutrino mass. If the scales of the seesaw parameters are split, with two right-handed neutrinos at a high scale and one at a keV scale, one can explain the matter-antimatter asymmetry of the universe, as well as dark matter. The dark matter candidate, a sterile right-handed neutrino with mass of several keV, can account for the observed pulsar velocities and for the recent data from Chandra X-ray Observatory, which suggest the existence of a 5 keV sterile right-handed neutrino.

Kusenko, Alexander [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States); Institute for the Physics and Mathematics of the Universe, University of Tokyo, Chiba 277-8583 (Japan); Takahashi, Fuminobu, E-mail: fuminobu.takahashi@ipmu.j [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Chiba 277-8583 (Japan); Yanagida, Tsutomu T. [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Chiba 277-8583 (Japan); Department of Physics, University of Tokyo, Tokyo 113-0033 (Japan)

2010-09-27

246

Relativistic electron drift shell splitting  

Science.gov (United States)

A survey of equatorial outer radiation belt relativistic electron pitch angle distributions measured on the Polar satellite shows anisotropies that are consistent with the effects of drift shell splitting. Simulations based on the observed radial intensity gradients and on drift shell calculations in a magnetospheric field model show that for low geomagnetic activity levels, the measured average anisotropies are similar to those predicted. With increasing geomagnetic activity the anisotropies do not change as much as is predicted, particularly on the nightside where the pitch angle distributions have local minima in the direction perpendicular to the magnetic field. At a given location and activity level there is substantial variability in the measured anisotropies about their long-term averages.

Selesnick, R. S.; Blake, J. B.

2002-09-01

247

Minimal Doubling and Point Splitting  

Energy Technology Data Exchange (ETDEWEB)

Minimally-doubled chiral fermions have the unusual property of a single local field creating two fermionic species. Spreading the field over hypercubes allows construction of combinations that isolate specific modes. Combining these fields into bilinears produces meson fields of specific quantum numbers. Minimally-doubled fermion actions present the possibility of fast simulations while maintaining one exact chiral symmetry. They do, however, introduce some peculiar aspects. An explicit breaking of hyper-cubic symmetry allows additional counter-terms to appear in the renormalization. While a single field creates two different species, spreading this field over nearby sites allows isolation of specific states and the construction of physical meson operators. Finally, lattice artifacts break isospin and give two of the three pseudoscalar mesons an additional contribution to their mass. Depending on the sign of this mass splitting, one can either have a traditional Goldstone pseudoscalar meson or a parity breaking Aoki-like phase.

Creutz, M.

2010-06-14

248

Selection Rules for Splitting Strings  

Energy Technology Data Exchange (ETDEWEB)

It has been pointed out that Nielsen-Olesen vortices may be able to decay by pair production of black holes. We show that when the Abelian-Higgs model is embedded in a larger theory, the additional fields may lead to selection rules for this process{emdash}even in the absence of fermions{emdash}due to the failure of a charge quantization condition. We show that when there is topology change, the criterion based on the charge quantization condition supplements the usual criterion based on {pi}{sub 0}(H). In particular, we find that unless 2sin{sup 2}{theta}{sub W} is a rational number, the thermal splitting of electroweak Z strings by magnetically neutral black holes is {ital impossible,} even though {pi}{sub 0}(H) is trivial. {copyright} {ital 1997} {ital The American Physical Society}

Achucarro, A.; Achucarro, A.; Achucarro, A. [Department of Mathematics, Tufts University, Medford, Massachusetts 02155 (United States); Gregory, R. [Centre for Particle Theory, Durham University, South Road, Durham, DH1 3LE, United Kingdom] [STRING MODELS:T1, SELECTION RULES:Q1, VORTICES, PAIR PRODUCTION:Q2, BLACK HOLES:T2, HIGGS MODEL, QUANTIZATION, TOPOLOGY] [Centre for Particle Theory, Durham University, South Road, Durham, DH1 3LE (United Kingdom)

1997-09-01

249

Salt splitting using ceramic membranes  

International Nuclear Information System (INIS)

Many radioactive aqueous wastes in the DOE complex have high concentrations of sodium that can negatively affect waste treatment and disposal operations. Sodium can decrease the durability of waste forms such as glass and is the primary contributor to large disposal volumes. Waste treatment processes such as cesium ion exchange, sludge washing, and calcination are made less efficient and more expensive because of the high sodium concentrations. Pacific Northwest National Laboratory (PNNL) and Ceramatec Inc. (Salt Lake City UT) are developing an electrochemical salt splitting process based on inorganic ceramic sodium (Na), super-ionic conductor (NaSICON) membranes that shows promise for mitigating the impact of sodium. In this process, the waste is added to the anode compartment, and an electrical potential is applied to the cell. This drives sodium ions through the membrane, but the membrane rejects most other cations (e.g., Sr+2, Cs+). The charge balance in the anode compartment is maintained by generating H+ from the electrolysis of water. The charge balance in the cathode is maintained by generating OH-, either from the electrolysis of water or from oxygen and water using an oxygen cathode. The normal gaseous products of the electrolysis of water are oxygen at the anode and hydrogen at the cathode. Potentially flammable gas mixtures can be prevented by providing adequate volumes of a sweep gas, using an alternative reductant or destruction of the hydrogen as it is generated. As H+ is generated in the anode compartment, the pH drops. The process may be operated with either an alkaline (pH>12) or an acidic anolyte (pH <1). The benefits of salt splitting using ceramic membranes are (1) waste volume reduction and reduced chemical procurement costs by recycling of NaOH; and (2) direct reduction of sodium in process streams, which enhances subsequent operations such as cesium ion exchange, calcination, and vitrification

1997-01-28

250

Invariant Natural Killer T-cell anergy to endogenous myelin acetyl-glycolipids in multiple sclerosis.  

Science.gov (United States)

To extend our studies on glycolipid-reactive invariant Natural Killer T-cell (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory activities of two myelin-derived glycolipids that are poly-acetylated derivatives of ?-galactosylceramide designated as fast-migrating cerebrosides (FMC) by thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral blood cells significantly expanded iNKT-cells similar to ?-GalCer and induced significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS patients failed to respond to FMCs or to ?-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS. PMID:23537888

Gately, Carol M; Podbielska, Maria; Counihan, Timothy; Hennessy, Michael; Leahy, Teresa; Moran, Anthony P; Hogan, Edward L; O'Keeffe, Joan

2013-06-15

251

A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players  

Science.gov (United States)

This study identifies novel mechanisms of Hes5 function in developmental myelination. We report here upregulation of myelin gene expression in Hes5?/? mice compared to wild-type siblings and downregulation in overexpressing progenitors. This effect was only partially explained by the ability to regulate the levels of Mash1 and bind to N boxes in myelin promoters, as deletion of the DNA-binding domain of Hes5 did not suppress its inhibitory role on myelin gene expression. Novel mechanisms of Hes5 function in the oligodendrocyte lineage include the regulation of feedback loops with the cell-specific transcriptional activator Sox10. In progenitors with low levels of Sox10, Hes5 further decreases the bioavailability of this protein by transcriptional inhibition and direct sequestration of this activator. Increasing levels of Sox10 in progenitors, in turn, bind to Hes5 and titrate out its inhibitory effect by sequestration and displacement of the repressive complexes from myelin promoters. Thus, Hes5-dependent modulation of myelin gene expression involves old players (i.e. Mash1) and novel mechanisms of transcriptional regulation that include cell-specific regulatory loops with transcriptional activators (i.e. Sox10).

Liu, Aixiao; Li, Jiadong; Marin-Husstege, Mireya; Kageyama, Ryochiro; Fan, Yongjun; Gelinas, Celine; Casaccia-Bonnefil, Patrizia

2006-01-01

252

Myelin-associated glycoprotein is altered in a familial late-onset orthochromatic leukodystrophy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Adult-onset dominant leukodystrophies are a heterogeneous group of rare disorders, whose etiology, pathogenesis and molecular background are still unknown. We report the neuropathological and biochemical investigations of the brains and their myelin proteins components in 2 members of an Italian family affected by an adult-onset autosomal dominant leukoencephalopathy. Clinical signs included spastic paraparesis, pseudobulbar syndrome, action tremor of head and hands, and moderate memory impai...

Giordana, Maria Teresa; Rinaudo, Maria Teresa; Buccinna, Barbara; Piccinini, Marco; Palmucci, Laura Maria; Brusco, Alfredo; Mongini, Tiziana Enrica

2005-01-01

253

Cerebrospinal fluid myelin basic protein as a prognostic biomarker in dogs with thoracolumbar intervertebral disk herniation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

BACKGROUND: Release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF) is associated with active demyelination and correlates with outcome in various neurological diseases. HYPOTHESIS/OBJECTIVES: To describe associations between CSF MBP concentration, initial neurological dysfunction, and long-term ambulatory outcome in dogs with acute thoracolumbar intervertebral disk herniation (IVDH). ANIMALS: 574 dogs with acute thoracolumbar IVDH and 16 clinically normal d...

Levine, Gwendolyn J.; Levine, Jonathan M.; Witsberger, Tige H.; Kerwin, Sharon C.; Russell, Karen E.; Suchodolski, Jan; Steiner, Jorg M.; Fosgate, Geoffrey T.

2010-01-01

254

A myelin gene causative of a catatonia-depression syndrome upon aging  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Severe mental illnesses have been linked to white matter abnormalities, documented by postmortem studies. However, cause and effect have remained difficult to distinguish. CNP (2?,3?-cyclic nucleotide 3?-phosphodiesterase) is among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA and protein level in brains of schizophrenic, bipolar or major depressive patients. This suggests that CNP reduction might be critical for a more general disease process and not restric...

Hagemeyer, Nora; Goebbels, Sandra; Papiol, Sergi; Ka?stner, Anne; Hofer, Sabine; Begemann, Martin; Gerwig, Ulrike C.; Boretius, Susann; Wieser, Georg L.; Ronnenberg, Anja; Gurvich, Artem; Heckers, Stephan H.; Frahm, Jens; Nave, Klaus-armin; Ehrenreich, Hannelore

2012-01-01

255

Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Misexpression and cytosolic retention of peripheral myelin protein 22 (PMP22) within Schwann cells (SCs) is associated with a genetically heterogeneous group of demyelinating peripheral neuropathies. PMP22 overproducer C22 and spontaneous mutant Trembler J (TrJ) mice display neuropathic phenotypes and affected nerves contain abnormally localized PMP22. Nutrient deprivation-induced autophagy is able to suppress the formation of PMP22 aggregates in a toxin-induced cellular model, and improve lo...

Rangaraju, Sunitha; Verrier, Jonathan D.; Madorsky, Irina; Nicks, Jessica; Dunn, William A.; Notterpek, Lucia

2010-01-01

256

Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture  

Energy Technology Data Exchange (ETDEWEB)

Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

Cho, Yun Kyung; Kim, Gunha; Park, Serah; Sim, Ju Hee; Won, You Jin [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hwang, Chang Ho [Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714 (Korea, Republic of); Yoo, Jong Yoon, E-mail: jyyoo@amc.seoul.kr [Department of Rehabilitation Medicine, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hong, Hea Nam, E-mail: hnhong@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of)

2012-01-13

257

A myelin gene causative of a catatonia-depression syndrome upon aging  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Severe mental illnesses have been linked to white matter abnormalities, documented by postmortem studies. However, cause and effect have remained difficult to distinguish. CNP (20,30-cyclic nucleotide 30-phosphodiesterase) is among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA and protein level in brains of schizophrenic, bipolar or major depressive patients. This suggests that CNP reduction might be critical for a more general disease process and...

Hagemeyer, Nora; Goebbels, Sandra; Papiol, Sergi; Ka?stner, Anne; Hofer, Sabine; Begemann, Martin; Gerwig, Ulrike C.; Boretius, Susann; Wieser, Georg L.; Ronnenberg, Anja; Gurvich, Artem; Heckers, Stephan H.; Frahm, Jens; Nave, Klaus-armin; Ehrenreich, Hannelore

2012-01-01

258

Mutation of sec63 in zebrafish causes defects in myelinated axons and liver pathology  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mutations in SEC63 cause polycystic liver disease in humans. Sec63 is a member of the endoplasmic reticulum (ER) translocon machinery, although it is unclear how mutations in SEC63 lead to liver cyst formation in humans. Here, we report the identification and characterization of a zebrafish sec63 mutant, which was discovered in a screen for mutations that affect the development of myelinated axons. Accordingly, we show that disruption of sec63 in zebrafish leads to abnormalities in myelinatin...

Monk, Kelly R.; Voas, Matthew G.; Franzini-armstrong, Clara; Hakkinen, Ian S.; Talbot, William S.

2013-01-01

259

Repair of astrocytes, blood vessels, and myelin in the injured brain: possible roles of blood monocytes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Inflammation in injured tissue has both repair functions and cytotoxic consequences. However, the issue of whether brain inflammation has a repair function has received little attention. Previously, we demonstrated monocyte infiltration and death of neurons and resident microglia in LPS-injected brains (Glia. 2007. 55:1577; Glia. 2008. 56:1039). Here, we found that astrocytes, oligodendrocytes, myelin, and endothelial cells disappeared in the damage core within 1–3 d and then re-appeared at...

Jeong, Hey-kyeong; Ji, Kyung-min; Kim, Jun; Jou, Ilo; Joe, Eun-hye

2013-01-01

260

Myelin Basic Protein Priming Reduces the Expression of Foxp3 in T Cells via Nitric Oxide  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Regulatory T cells (Tregs) play a vital role in autoimmune disorders. Among several markers, forkhead box p3 (Foxp3) is the most specific with regard to Treg activity. Therefore, understanding mechanisms that regulate Foxp3 expression is a critical step for unraveling the complicacy of autoimmune pathophysiology. The present study was undertaken to investigate the crosstalk between NO and Tregs. Interestingly, after myelin basic protein (MBP) priming, the expression of Foxp3 decreased in MBP-...

Brahmachari, Saurav; Pahan, Kalipada

2010-01-01

 
 
 
 
261

Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.  

Science.gov (United States)

Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time. PMID:23246926

Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

2013-02-01

262

Digital holographic microscopy of the myelin figure structural dynamics and the effect of thermal gradient  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin figures (MFs) are cylindrical multilamellar lipid tubes that can be found in various healthy and diseased living cells. Their formation and dynamics involve some of the most mysterious configurations that lipid molecules can adopt under certain conditions. They have been studied with different microscopy methods. Due to the frequent coiling of their structure, the usual methods of microscopy fail to give precise quantitative information about their dynamics. In this paper, we introduce...

Fathi, Narges; Moradi, Ali-reza; Habibi, Mehdi; Vashaee, Daryoosh; Tayebi, Lobat

2013-01-01

263

Mouse olfactory ensheathing glia enhance axon outgrowth on a myelin substrate in vitro  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Olfactory ensheathing glia (OEG) express cell adhesion molecules and secrete growth factors that support newly generated olfactory axons and are a promising therapeutic treatment to facilitate axonal regeneration after spinal cord injury (SCI). To study the molecular mechanisms underlying the ability of OEG to enhance axonal outgrowth, we designed an outgrowth assay using spinal cord myelin as a substrate to mimic an injury environment. We asked if olfactory bulb-derived OEG could enhance out...

Runyan, Stephen A.; Phelps, Patricia E.

2009-01-01

264

Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury  

Science.gov (United States)

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.

Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

2013-01-01

265

Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination.  

Science.gov (United States)

Although commonly considered a disease of white matter, gray matter demyelination is increasingly recognized as an important component of multiple sclerosis (MS) pathogenesis, particularly in the secondary progressive disease phase. Extent of damage to gray matter is strongly correlated to decline in memory and cognitive dysfunction in MS patients. Aging likewise occurs with cognitive decline from myelin loss, and age-associated failure to remyelinate significantly contributes to MS progression. However, recent evidence demonstrates that parabiotic exposure of aged animals to a youthful systemic milieu can promote oligodendrocyte precursor cell (OPC) differentiation and improve remyelination. In the current study, we focus on this potential for stimulating remyelination, and show it involves serum exosomes that increase OPCs and their differentiation into mature myelin-producing cells-both under control conditions and after acute demyelination. Environmental enrichment (EE) of aging animals produced exosomes that mimicked this promyelinating effect. Additionally, stimulating OPC differentiation via exosomes derived from environmentally enriched animals is unlikely to deplete progenitors, as EE itself promotes proliferation of neural stem cells. We found that both young and EE serum-derived exosomes were enriched in miR-219, which is necessary and sufficient for production of myelinating oligodendrocytes by reducing the expression of inhibitory regulators of differentiation. Accordingly, protein transcript levels of these miR-219 target mRNAs decreased following exosome application to slice cultures. Finally, nasal administration of exosomes to aging rats also enhanced myelination. Thus, peripheral circulating cells in young or environmentally enriched animals produce exosomes that may be a useful therapy for remyelination. PMID:24339157

Pusic, Aya D; Kraig, Richard P

2014-02-01

266

Modification of sodium channel inactivation in single myelinated nerve fibers by methionine-reactive chemicals.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Several methionine-reactive reagents, including N-bromoacetamide, N-bromosuccinimide, chloramine-T, and N-chlorosuccinimide, irreversibly slowed and prevented Na channel inactivation in single myelinated nerve fibers, whereas sulfhydryl- or tyrosine-modifying reagents had little effect. The activation process was not modified by the reagents that altered inactivation and could be modulated normally by Ca++ ions and Centruroides scorpion toxin II alpha. These results suggest that externally ap...

Wang, G. K.

1984-01-01

267

Myelin-associated glycoprotein is altered in a familial late-onset orthochromatic leukodystrophy.  

Science.gov (United States)

Adult-onset dominant leukodystrophies are a heterogeneous group of rare disorders, whose etiology, pathogenesis and molecular background are still unknown. We report the neuropathological and biochemical investigations of the brains and their myelin proteins components in 2 members of an Italian family affected by an adult-onset autosomal dominant leukoencephalopathy. Clinical signs included spastic paraparesis, pseudobulbar syndrome, action tremor of head and hands, and moderate memory impairment. No mental deterioration or neuropathy was present. Onset was subacute (range 42-53 years) and progression spanned 4 to 7 years. The neuropathological phenotype overlapped that of orthochromatic leukodystrophies. The biochemical analysis revealed an abnormal myelin-associated glycoprotein (MAG); the defect was localized at the C-terminal domain of the L-MAG isoform, resulting in a protein approximately 5 kDa shorter than the normal counterpart. No mutation in the MAG gene-coding regions was uncovered, and linkage analysis formally excluded the entire MAG locus. We show that the identified MAG protein alteration is probably due to an abnormal post-translational event. Considering MAG function in the maintenance of myelin, the abnormal protein may have a role in the pathogenesis of this disease. This is the first report of a possible pathogenetic role of MAG in a hereditary disease affecting the central white matter. PMID:15912883

Giordana, Maria Teresa; Piccinini, Marco; Palmucci, Laura; Buccinnà, Barbara; Ramondetti, Cristina; Brusco, Alfredo; Mongini, Tiziana; Vaula, Giovanna; Rinaudo, Maria Teresa

2005-04-01

268

Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system.  

Science.gov (United States)

The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi/zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases. PMID:11209055

Kuramoto, T; Kitada, K; Inui, T; Sasaki, Y; Ito, K; Hase, T; Kawagachi, S; Ogawa, Y; Nakao, K; Barsh, G S; Nagao, M; Ushijima, T; Serikawa, T

2001-01-16

269

Results of occlusion therapy in anisomyopic amblyopia with myelinated nerve fibers.  

Science.gov (United States)

The combination of anisomyopia and myelinated nerve fibers in the highly myopic eye is often correlated with severe and therapy-resistant amblyopia. There are very few reports on successful amblyopia therapy in patients with this constellation of symptoms. We report on six patients aged 6, 7, 9 (two cases), and 28 years (two cases) who presented with anisomyopia, myelinated nerve fibers, and severe amblyopia in the highly myopic eye. The four younger patients took part in a therapeutic trial with contact lens correction and occlusion. The six patients suffered from varying degrees of anisomyopia, which ranged between -3.5 and -18.5 D. Four patients underwent strict occlusion therapy. The best visual improvement was from 1/25 to 0.2 (factor of 5) and the best final visual acuity was 0.4. Two patients had microstrabismus, three displayed exotropia, and one patient showed no strabismus. The combination of unilateral high-grade myopia and myelinated nerve fibers represents a special conjunction that is usually correlated with severe amblyopia. The amblyopia is practically resistant to therapy, even under strict treatment regimen with contact lenses and forced occlusion. The goal must be to diagnose this constellation in the first 2 years of life. As case reports show in the literature, consistent therapy at this age can lead to good visual acuity. PMID:8854109

Käsmann, B; Höh, H; Ruprecht, K W

1996-07-01

270

A Few Splitting Criteria for Vector Bundles  

CERN Multimedia

We prove a few splitting criteria for vector bundles on a quadric hypersurface and Grassmannians. We give also some cohomological splitting conditions for rank 2 bundles on multiprojective spaces. The tools are monads and a Beilinson's type spectral sequence generalized by Costa and Mir\\'o-Roig.

Malaspina, Francesco

2008-01-01

271

Split mesencephalon: Diplomyelia of the basicranium.  

Science.gov (United States)

Abstract We report a novel case of congenitally split mesencephalon, in a 3-year old with hydrocephalus. We speculate that the ontogenetic mechanism is shared with split cord malformations (SCM). Our case adds to the two other cases of basicranial SCM which involved more caudal brainstem. PMID:23957778

Jayasekera, Bodiabaduge A P; Pereira, Erlick A C; Magdum, Shailendra

2014-06-01

272

Distinguishing division algebras by finite splitting fields  

CERN Multimedia

This paper is concerned with the problem of determining the number of division algebras which share the same collection of finite splitting fields. As a corollary we are able to determine when two central division algebras may be distinguished by their finite splitting fields over certain fields.

Krashen, Daniel

2010-01-01

273

Regular Splittings and the Discrete Neumann Problem.  

Science.gov (United States)

Iterative methods are discussed for approximating a solution to a singular but consistent square linear system Ax=b. The methods are based upon splitting A=M-N with M nonsingular. Monotonicity and the concept of regular splittings, introduced by Varga, ar...

R. J. Plemmons

1974-01-01

274

Splitting and Projection at Work in Schools  

Science.gov (United States)

Purpose: The purpose of this paper is to report research into the social defence of splitting and projection in schools. In splitting and projection, organisational members separate their unbearable feelings from the more acceptable ones and project them, typically towards other individuals and groups. Design/methodology/approach: The research was…

Dunning, Gerald; James, Chris; Jones, Nicola

2005-01-01

275

Split Dimensional Regularization for the Temporal Gauge  

CERN Multimedia

A split dimensional regularization, which was introduced for the Coulomb gauge by Leibbrandt and Williams, is used to regularize the spurious singularities of Yang-Mills theory in the temporal gauge. Typical one-loop split dimensionally regularized temporal gauge integrals, and hence the renormalization structure of the theory are shown to be the same as those calculated with some nonprincipal-value prescriptions.

Chen, Y H; Lin, C; Chen, Yaw-Hwang; Hsieh, Ron-Jou; Lin, Chilong

1996-01-01

276

Operator splitting for nonlinear delay equations  

CERN Multimedia

We investigate operator splitting methods for a special class of nonlinear partial differential equation with delay. Using results from the theory of nonlinear contraction semigroups in Hilbert spaces, we explain the convergence of the splitting procedure. The order of the convergence is also given in some important, linear special cases.

Bátkai, András; Farkas, Bálint

2010-01-01

277

Cheating More when the Spoils Are Split  

Science.gov (United States)

Four experiments demonstrated that people are more likely to cheat when the benefits of doing so are split with another person, even an anonymous stranger, than when the actor alone captures all of the benefits. In three of the studies, splitting the benefits of over-reporting one's performance on a task made such over-reporting seem less…

Wiltermuth, Scott S.

2011-01-01

278

The Split Domination in Product Graphs  

Directory of Open Access Journals (Sweden)

Full Text Available The paper concentrates on the theory of domination in graphs. The split domination in graphs was introduced by Kulli and Janakirm. In this paper; we have investigated some properties of the split domination number of some product graphs and obtained several interesting results.

K.V. Suryanarayana Rao

2013-10-01

279

Line splitting in the Schumann resonance oscillations  

Science.gov (United States)

We discuss detection of line splitting in the global electromagnetic (Schumann) resonances. The lifting of resonance degeneracy is usually not visible in the ordinary power spectrum of either the electric or magnetic field components since splitting is small in comparison with the natural width of the resonance lines. Splitting may be detected by exploiting the spatial structure of the fields and/or the elliptical polarization of the magnetic field. The spatial properties were utilized in synchronous and coherent measurements of the vertical electric field at two longitudinally separated observatories. The results were attributed to line splitting. An alternative interpretation was also advanced that takes into account the source-receiver separation. The lifting of degeneracy also appears as a frequency-dependent elliptical polarization of the horizontal magnetic field vector, which has been found experimentally. We compare measurement and computational data, and their reciprocity proves the detection of Schumann resonance line splitting.

Nickolaenko, A. P.; Sentman, Davis D.

2007-04-01

280

The structure of a solvmanifold's Heegaard splittings  

CERN Document Server

We classify isotopy classes of irreducible Heegaard splittings of solvmanifolds. If the monodromy of the solvmanifold can be expressed as a 2 x 2 matrix with 0 in the lower right hand corner (as always is true when the absolute value of the trace is 3), then any irreducible splitting is strongly irreducible and of genus two. If furthermore the absolute value of the trace is 4 or greater, then any two such splittings are isotopic. If the absolute value of the trace is 3 then, up to isotopy, there are exactly two irreducible splittings, their associated hyperelliptic involutions commute, and the product of the involutions is the central involution of the solvmanifold. If the monodromy cannot be expressed as a 2 x 2 matrix with 0 in the lower right hand corner, then the splitting is weakly reducible, of genus three and unique up to isotopy.

Cooper, D; Cooper, Daryl; Scharlemann, Martin

1998-01-01

 
 
 
 
281

Quasiperiodic Tip Splitting in Directional Solidification  

CERN Document Server

We report experimental results on the tip splitting dynamics of seaweed growth in directional solidification of succinonitrile alloys with poly(ethylene oxide) or acetone as solutes. The seaweed or dense branching morphology was selected by solidifying grains which are oriented close to the {111} plane. Despite the random appearance of the growth, a quasiperiodic tip splitting morphology was observed in which the tip alternately splits to the left and to the right. The tip splitting frequency f was found to be related to the growth velocity V as a power law f V^{1.5}. This finding is consistent with the predictions of a tip splitting model that is also presented. Small anisotropies are shown to lead to different kinds of seaweed morphologies.

Utter, B C; Bodenschatz, E

2001-01-01

282

Determinação de Anticorpos Anti-Mielina na Esclerose Múltipla / Anti-Myelin Autoantibodies in Multiple Sclerosis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Portugal | Language: Portuguese Abstract in portuguese Introdução: A Esclerose Múltipla é uma doença desmielinizante primária de carácter autoimune, envolvendo diferentes mecanismos imunopatológicos. Pensa-se que anticorpos dirigidos contra antigénios da mielina podem estar associados aos danos na mielina ou surgirem devido a estes, pelo que, o seu dose [...] amento poderá constituir um marcador de evolução da doença. No entanto, a positividade desta pesquisa pode levantar dúvidas em termos de valorização clínica dada a descrição destes auto-anticorpos também em indivíduos sem doença. O objectivo deste trabalho foi a avaliação da presença de auto-anticorpos para a mielina em pacientes com o diagnóstico de Esclerose Múltipla, comparativamente a amostras de controlo, avaliando a sua associação com sintomas clínicos em pacientes com diferentes formas clínicas da Esclerose Múltipla. Métodos: A pesquisa de anticorpos para a mielina foi realizada por uma técnica de imuno?uorescência indirecta usando como substrato, nervo periférico de primata (EUROIMMUN®). Foram estudados 34 doentes (14M/11H), observados no serviço de Neurologia do Hospital de São João: 8 com forma monosintomática em surto, 11 com forma Surto/Remissão (SR) em remissão, 11 com forma SR em surto e 4 com forma Primária Progressiva (PP) em remissão. A população de controlo foi constituída por 25 amostras de indivíduos saudáveis (26M/8H). Resultados: Encontraram-se diferenças signi?cativas nas duas populações em relação à presença de anticorpos para a mielina (p Abstract in english Introduction: Multiple Sclerosis (MS) is a primary demyelinating disease of autoimmune ethiology with different immunopathologic mechanisms. Anti-myelin autoantibodies may be associated with myelin damage and a possible marker of the disease evolution. However, the clinical usefulness of these autoa [...] ntibodies is questionable as they may be present in healthy individuals. The aim of this work was the evaluation of autoantibodies against myelin in patients with MS comparatively with control samples, and their association with differents clinical types. Methology: For the search of anti-myelin antibodies we used indirect immunofluorescence in primate peripheral nerves (EUROIMMUN®). Thirty four patients (14 female/11 male) followed in the Neurology department were studied: 8 with the Clinically Isolated Syndrome (CIS) with relapse, 11 with Relapsing/Remitting (RR) in remission, 11 with RR with relapse and 4 with Primary Progressive (PP); 25 samples of healthy individuals (26 female/8 male) were studied as controls. Results: The presence of autoantibodies to myelin was signifiantly different in the two studied populations (p

Eduardo, Lima; Joana, Guimarães; Ana, Pereira; Abília, Bodas; Luís, Delgado; Maria José, Sá.

283

Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The nosology of the inborn errors of myelin metabolism has been stymied by the lack of molecular genetic analysis. Historically, Pelizaeus-Merzbacher disease has encompassed a host of neurologic disorders that present with a deficit of myelin, the membrane elaborated by glial cells that encircles and successively enwraps axons. We describe here a Pelizaeus-Merzbacher pedigree of the classical type, with X-linked inheritance, a typical clinical progression, and a pathologic loss of myelinating...

Gencic, S.; Abuelo, D.; Ambler, M.; Hudson, L. D.

1989-01-01

284

Autoimmune T cell repertoire in optic neuritis and multiple sclerosis: T cells recognising multiple myelin proteins are accumulated in cerebrospinal fluid.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Monosymptomatic unilateral optic neuritis is a common first manifestation of multiple sclerosis. Abnormal T cell responses to myelin components including myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated glycoprotein (MAG) have been implicated in the pathogenesis of multiple sclerosis. Antigen-reactive T helper type 1 (Th1)-like cells that responded by interferon gamma (IFN-gamma) secretion on antigen stimulation in vitro were counted. Untreated patients with optic ...

So?derstro?m, M.; Link, H.; Sun, J. B.; Fredrikson, S.; Wang, Z. Y.; Huang, W. X.

1994-01-01

285

Lightweight electrical connector split backshell  

Science.gov (United States)

An electrical connector split backshell is provided, comprising two substantially identical backshell halves. Each half includes a first side and a cam projecting therefrom along an axis perpendicular thereto, the cam having an alignment tooth with a constant radius and an engagement section with a radius that increases with angular distance from the alignment tooth. Each half further includes a second side parallel to the first side and a circular sector opening disposed in the second side, the circular sector opening including an inner surface configured as a ramp with a constant radius, the ramp being configured to engage with an engagement section of a cam of the other half, the circular sector opening further including a relieved pocket configured to receive an alignment tooth of the cam of the other half. Each half further includes a back side perpendicular to the first and second sides and a wire bundle notch disposed in the back side, the wire bundle notch configured to align with a wire bundle notch of the other half to form a wire bundle opening. The two substantially identical halves are rotatably coupled by engaging the engagement section of each half to the ramp of the other half.

Goldman, Elliot (Inventor)

2009-01-01

286

Innovative solar thermochemical water splitting.  

Energy Technology Data Exchange (ETDEWEB)

Sandia National Laboratories (SNL) is evaluating the potential of an innovative approach for splitting water into hydrogen and oxygen using two-step thermochemical cycles. Thermochemical cycles are heat engines that utilize high-temperature heat to produce chemical work. Like their mechanical work-producing counterparts, their efficiency depends on operating temperature and on the irreversibility of their internal processes. With this in mind, we have invented innovative design concepts for two-step solar-driven thermochemical heat engines based on iron oxide and iron oxide mixed with other metal oxides (ferrites). The design concepts utilize two sets of moving beds of ferrite reactant material in close proximity and moving in opposite directions to overcome a major impediment to achieving high efficiency--thermal recuperation between solids in efficient counter-current arrangements. They also provide inherent separation of the product hydrogen and oxygen and are an excellent match with high-concentration solar flux. However, they also impose unique requirements on the ferrite reactants and materials of construction as well as an understanding of the chemical and cycle thermodynamics. In this report the Counter-Rotating-Ring Receiver/Reactor/Recuperator (CR5) solar thermochemical heat engine and its basic operating principals are described. Preliminary thermal efficiency estimates are presented and discussed. Our ferrite reactant material development activities, thermodynamic studies, test results, and prototype hardware development are also presented.

Hogan, Roy E. Jr.; Siegel, Nathan P.; Evans, Lindsey R.; Moss, Timothy A.; Stuecker, John Nicholas (Robocasting Enterprises, Albuquerque, NM); Diver, Richard B., Jr.; Miller, James Edward; Allendorf, Mark D. (Sandia National Laboratories, Livermore, CA); James, Darryl L. (Texas Tech University, Lubbock, TX)

2008-02-01

287

Regulation of Myelination in the Central Nervous System by Nuclear Lamin B1 and Non-coding RNAs.  

Science.gov (United States)

Adult-onset autosomal dominant leukodystrophy (ADLD) is a progressive and fatal hereditary demyelination disorder characterized initially by autonomic dysfunction and loss of myelin in the central nervous system (CNS). Majority of ADLD is caused by a genomic duplication of the nuclear lamin B1 gene (LMNB1) encoding lamin B1 protein, resulting in increased gene dosage in brain tissue. In vitro, excessive lamin B1 at the cellular level reduces transcription of myelin genes, leading to premature arrest of oligodendrocyte differentiation. Murine models of ADLD overexpressing LMNB1 exhibited age-dependent motor deficits and myelin defects, which are associated with reduced occupancy of the Yin Yang 1 transcription factor at the promoter region of the proteolipid protein gene. Lamin B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and suggests lamin B1 as an important regulator of myelin formation and maintenance during aging. Identification of microRNA-23 (miR-23) as a negative regulator of lamin B1 can ameliorate the consequences of excessive lamin B1 at the cellular level. miR-23a-overexpressing mice display enhanced oligodendrocyte differentiation and myelin synthesis. miR-23a targets include a protein coding transcript PTEN (phosphatase and tensin homolog on chromosome 10), and a long noncoding RNA (2700046G09Rik), indicating a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin. Here, we provide a concise review of the current literature on clinical presentations of ADLD and how lamin B1 affects myelination and other developmental processes. Moreover, we address the emerging role of non-coding RNAs (ncRNAs) in modulating gene networks, specifically investigating miR-23 as a potential target for the treatment of ADLD and other demyelinating disorders. PMID:24495672

Lin, Shu-Ting; Heng, Mary Y; Ptá?ek, Louis J; Fu, Ying-Hui

2014-01-01

288

Characterization of the M2 autoantigen of central nervous system (CNS) myelin as a glycoproteins(s) also expressed on oligodendrocyte membrane  

International Nuclear Information System (INIS)

Guinea pigs immunized with homologous brain tissue develop an acute experimental allergic encephalomyelitis and their sera contain demyelinating antibodies. These antibodies were used to characterize the target: the unidentified autoantigen M2. Using both the Dot immunobinding technique and autoradiography of immunoprecipitates formed with radiolabelled guinea-pig myelin and analyzed in SDS acrylamide gel electrophoresis, M2 was found to be a component of CNS myelin and not peripheral nervous system (PNS) myelin. In the Dot technique anti-M2 serum did not react with myelin basic protein (BP), proteolipid and galactocerebroside (GC). On electrophoresis, in reducing and non reducing conditions, M2 appeared as two CNS myelin protein bands at the 27,000 and 54,000 molecular weight levels, distinct from the CNS myelin major protein bands of proteolipid protein and BP. Affinity chromatography of CNS myelin on wheat germ agglutinin Sepharose showed that M2 bands were of glycoprotein nature. The same M2 bands were formed with guinea pig antibodies and rat, rabbit or bovine CNS myelin. The same type of anti-M2 antibodies were induced in rabbits immunized with homologous CNS tissue. As a component of myelin, M2 was present in white matter tracts of CNS tissue sections tested by immunofluorescence. Furthermore, M2 was expressed on rat oligodendrocyte membrane in one day and 8 day in vitro cultures

1986-03-01

289

Repression and splitting in the psychoanalytic process.  

Science.gov (United States)

The authors examine the concepts of repression and splitting and their interplay during the psychoanalytic process. Initially, repression was introduced by the clinical phenomenon of resistance, leading to the formulation of the association between intrapsychic conflicts and neurotic symptoms. Later, repression was linked to normal development and to personality organization. Splitting, on the other hand, has been defined in quite diverse ways. The two main definitions are of splitting within the ego, and splitting of representations of the self, and of internal and external objects. Repression and splitting are compared developmentally, dynamically, and with respect to their relationship to psychic functioning and energic conditions. Clinical material is presented from the analysis of a patient who presented with borderline personality organization and narcissistic features. During the initial phase of analysis, splitting associated with projection, projective identification and idealization were the main defence mechanisms. As the analysis progressed and the themes of omnipotence and mourning were explored with the simultaneous working through of drive derivatives expressed in the transference, repression gained ground over the more primitive defence mechanisms. The evolution of the case showed a gradual shift from splitting to repression and the association of repression with a more advanced psychic organization. This development reflected the dynamic movement from borderline to hysterical organization in psychoanalytic nosology. PMID:21323879

Savvopoulos, Savvas; Manolopoulos, Sotiris; Beratis, Stavroula

2011-02-01

290

Photoinduced water splitting with oxotitanium tetraphenylporphyrin.  

Science.gov (United States)

Photocatalytic splitting of water was investigated in a heterogeneous system consisting of micro-crystallites of oxotitanium tetraphenylporphyrin deposited on fused silica plates, immersed in water and excited within the visible range of their absorption spectra. The water photolysis was evidenced by the spectroscopic detection of hydroxyl radicals generated in the reaction. The experimental results confirm the mechanism of water splitting and generation of OH? radicals proposed theoretically by Sobolewski and Domcke [Phys. Chem. Chem. Phys., 2012, 14, 12807] for the oxotitaniumporphyrin-water complex. It is shown that photocatalytic water splitting occurs in pure water, and neither pH-bias nor external voltage is required to promote the reaction. PMID:24938429

Morawski, O; Izdebska, K; Karpiuk, E; Nowacki, J; Suchocki, A; Sobolewski, A L

2014-08-01

291

The solar internal rotation from GOLF splittings  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The low degree splittings obtained from one year of GOLF data analysis are combined with the MDI medium-l 144-day splittings in order to infer the solar internal rotation as a function of the radius down to $0.2R_\\odot$. Several inverse methods are applied to the same data and the uncertainties on the solution as well as the resolution reachable are discussed. The results are compared with the one obtained from the low degree splittings estimated from GONG network.

Corbard, T.; Di Mauro, M. P.; Sekii, T.; Team, The Golf

1998-01-01

292

Chow motives of generically split varieties  

CERN Multimedia

Let G be an anisotropic linear algebraic group which splits by a field extension of a prime degree. Let X be a projective homogeneous G-variety such that G splits over the function field of X. We prove that under certain conditions the Chow motive of X is isomorphic to a direct sum of twisted copies of an indecomposable motive R. This covers all known examples of motivic decompositions of generically split projective homogeneous varieties (Severi-Brauer varieties, Pfister quadrics, maximal orthogonal Grassmannians) as well as provides new ones (exceptional varieties of types E6 and E8).

Petrov, V; Zainoulline, K; Petrov, Victor; Semenov, Nikita; Zainoulline, Kirill

2006-01-01

293

Axonal spectrins: all-purpose fences.  

Science.gov (United States)

A membrane barrier important for assembly of the nodes of Ranvier is found at the paranodal junction. This junction is comprised of axonal and glial adhesion molecules linked to the axonal actin-spectrin membrane cytoskeleton through specific adaptors. In this issue, Zhang et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201308116) show that axonal ?II spectrin maintains the diffusion barrier at the paranodal junction. Thus, ?II spectrin serves to compartmentalize the membrane of myelinated axons at specific locations that are determined either intrinsically (i.e., at the axonal initial segment), or by axoglial contacts (i.e., at the paranodal junction). PMID:24217615

Eshed-Eisenbach, Yael; Peles, Elior

2013-11-11

294

Promoting myelination in an in vitro mouse model of the peripheral nerve system: the effect of wine ingredients.  

Science.gov (United States)

Protective properties of moderate wine consumption against cancers, cardiovascular, metabolic and degenerative diseases have been reported in various clinical studies. Here, we analysed the effect of red wine (RW) and white wine (WW) on myelination using an in vitro embryonic co-culture mouse model. The total amount of myelin was found to be significantly increased after RW and WW treatment, while only RW significantly increased the number of internodes. Both types of wine increased rat Schwann cell- (rSC) expression of the NAD+-dependent deacetylase sirtuin-two-homolog 2 (Sirt2), a protein known to be involved in myelination. Detailed chemical analysis of RW revealed a broad spectrum of anthocyanins, piceids, and phenolics, including resveratrol (RSV). In our assay system RSV in low concentrations induced myelination. Furthermore RSV raised intracellular glutathione concentrations in rSCs and in co-cultures and therefore augmented antioxidant capacity. We conclude that wine promotes myelination in a rodent in vitro model by controlling intracellular metabolism and SC plasticity. During this process, RSV exhibits protective properties; however, the fostering effect on myelinaton during exposure to wine appears to be a complex interaction of various compounds. PMID:23762469

Stettner, Mark; Wolffram, Kathleen; Mausberg, Anne K; Albrecht, Philipp; Derksen, Angelika; Methner, Axel; Dehmel, Thomas; Hartung, Hans-Peter; Dietrich, Helmut; Kieseier, Bernd C

2013-01-01

295

Peptidylarginine deiminase 2 (PAD2) overexpression in transgenic mice leads to myelin loss in the central nervous system.  

Science.gov (United States)

Demyelination in the central nervous system is the hallmark feature in multiple sclerosis (MS). The mechanism resulting in destabilization of myelin is a complex multi-faceted process, part of which involves deimination of myelin basic protein (MBP). Deimination, the conversion of protein-bound arginine to citrulline, is mediated by the peptidylarginine deiminase (PAD) family of enzymes, of which the PAD2 and PAD4 isoforms are present in myelin. To test the hypothesis that PAD contributes to destabilization of myelin in MS, we developed a transgenic mouse line (PD2) containing multiple copies of the cDNA encoding PAD2, under the control of the MBP promoter. Using previously established criteria, clinical signs were more severe in PD2 mice than in their normal littermates. The increase in PAD2 expression and activity in white matter was demonstrated by immunohistochemistry, reverse transcriptase-PCR, enzyme activity assays, and increased deimination of MBP. Light and electron microscopy revealed more severe focal demyelination and thinner myelin in the PD2 homozygous mice compared with heterozygous PD2 mice. Quantitation of the disease-associated molecules GFAP and CD68, as measured by immunoslot blots, were indicative of astrocytosis and macrophage activation. Concurrently, elevated levels of the pro-inflammatory cytokine TNF-alpha and nuclear histone deimination support initiation of demyelination by increased PAD activity. These data support the hypothesis that elevated PAD levels in white matter represents an early change that precedes demyelination. PMID:19093029

Musse, Abdiwahab A; Li, Zhen; Ackerley, Cameron A; Bienzle, Dorothee; Lei, Helena; Poma, Roberto; Harauz, George; Moscarello, Mario A; Mastronardi, Fabrizio G

2008-01-01

296

Irrational beliefs, attitudes about competition, and splitting.  

Science.gov (United States)

Rational-Emotive Behavior Therapy (REBT) theoretically promotes actualization of both individualistic and social-oriented potentials. In a test of this assumption, the Belief Scale and subscales from the Survey of Personal Beliefs served as measures of what REBT presumes to be pathogenic irrationalities. These measures were correlated with the Hypercompetitive Attitude Scale (HCAS), the Personal Development Competitive Attitude Scale (PDCAS), factors from the Splitting Index, and self-esteem. Results for the HCAS and Self-Splitting supported the REBT claim about individualistic self-actualization. Mostly nonsignificant and a few counterintuitive linkages were observed for irrational beliefs with the PDCAS, Family-Splitting, and Other-Splitting, and these data suggested that REBT may be less successful in capturing the "rationality" of a social-oriented self-actualization. PMID:11241364

Watson, P J; Morris, R J; Miller, L

2001-03-01

297

Solar activity and oscillation frequency splittings  

Science.gov (United States)

Solar p-mode frequency splittings, parameterized by the coefficients through order N = 12 of a Legendre polynomial expansion of the mode frequencies as a function of m/L, were obtained from an analysis of helioseismology data taken at Big Bear Solar Observatory during the 4 years 1986 and 1988-1990 (approximately solar minimum to maximum). Inversion of the even-index splitting coefficients confirms that there is a significant contribution to the frequency splittings originating near the solar poles. The strength of the polar contribution is anti correlated with the overall level or solar activity in the active latitudes, suggesting a relation to polar faculae. From an analysis of the odd-index splitting coefficients we infer an uppor limit to changes in the solar equatorial near-surface rotatinal velocity of less than 1.9 m/s (3 sigma limit) between solar minimum and maximum.

Woodard, M. F.; Libbrecht, K. G.

1993-01-01

298

Divided Opinions on the Split Fovea  

Science.gov (United States)

We explain once again the distinction between the "split fovea theory" and the "bilateral projection theory", and consider the implications of the two theories for understanding the processing of centrally fixated words and faces.

Ellis, Andrew W.; Brysbaert, Marc

2010-01-01

299

Spacetime Splitting, Admissible Coordinates and Causality  

CERN Document Server

To confront relativity theory with observation, it is necessary to split spacetime into its temporal and spatial components. The (1+3) timelike threading approach involves restrictions on the gravitational potentials $(g_{\\mu \

Bini, D; Mashhoon, B

2012-01-01

300

Splitting of separatrices for (fast) quasiperiodic forcing  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We consider fast quasiperiodic perturbations of a pendulum with two frequencies $(1,\\gamma)$, where $\\gamma$ is the golden mean number. For small perturbations such that its Fourier coefficients (the ones associated to Fibonacci numbers), are separated from zero, it is announced that the invariant manifolds split, and the value of the splitting, that turns out to be exponentially small with respect to the perturbation parameter, is correctly predicted by the Melnikov function. An explicit exa...

Delshams Valde?s, Amadeu; Gelfreich, Vassili; Jorba, Angel; Marti?nez-seara Alonso, M. Teresa

1996-01-01

 
 
 
 
301

Split-Quaternions and the Dirac Equation  

CERN Document Server

We show that Dirac 4-spinors admit an entirely equivalent formulation in terms of 2-spinors defined over the split-quaternions. In this formalism, a Lorentz transformation is represented as a $2 \\times 2$ unitary matrix over the split-quaternions. The corresponding Dirac equation is then derived in terms of these 2-spinors. In this framework the $SO(3,2; {\\bf R})$ symmetry of the Lorentz invariant scalar $\\overline{\\psi}\\psi$ is manifest.

Antonuccio, Francesco

2014-01-01

302

Normalizing Heegaard-Scharlemann-Thompson Splittings  

CERN Document Server

We define a Heegaard-Scharlemann-Thompson (HST) splitting of a 3-manifold M to be a sequence of pairwise-disjoint, embedded surfaces, {F_i}, such that for each odd value of i, F_i is a Heegaard splitting of the submanifold of M cobounded by F_{i-1} and F_{i+1}. Our main result is the following: Suppose M (\

Bachman, D C

2003-01-01

303

The splitting of branes on orientifold planes  

International Nuclear Information System (INIS)

Continuing the study in hep-th/0004092, we investigate a non-trivial string dynamical process related to orientifold planes, i.e., the splitting of physical NS-branes and D(p+2)-branes on orientifold Op-planes. Creation or annihilation of physical Dp-branes usually accompanies the splitting process. In the particular case p=4, we use Seiberg-Witten curves as an independent method to check the results. (author)

2002-04-01

304

Gravitino production from reheating in split supersymmetry  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We discuss gravitino production from reheating in models where the splitting between particle and sparticle masses can be larger than TeV, as naturally arising in the context of split supersymmetry. We show that such a production typically dominates over thermal contributions arising from the interactions of gauginos, squarks and sleptons. We constrain the supersymmetry breaking scale of the relevant sector for a given reheat temperature. However the situation changes when the gravitinos domi...

2004-01-01

305

Kondo spin splitting with slave boson  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english The slave boson (SB) technique is employed to study the Zeeman spin splitting in a quantum dot. Unlike traditional SB method, each spin is renormalized differently. Two geometries are compared: side connected and embedded. In both cases, it's shown a non linear behavior of the splitting as a functio [...] n of the magnetic field applied. The results are in line with the latest experiments.

J. M. Aguiar, Hualde; G., Chiappe; E.V., Anda.

306

Ink Film Splitting Acoustics in Offset Printing  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This thesis claims a relationship between the film splitting sound emission from the printing press nip and the dynamic interaction occurring there between ink, fountain solution and substrate in offset lithography. The film splitting sound derives from the cavitation formed by the pressure drop in the second half of the print nip flow passage. As the ink film is strained, the cavities expand and eventually implode into breaking filaments at the nip exit, while emitting a partly audible, broa...

2006-01-01

307

Multiple Spectral Splits of Supernova Neutrinos  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Collective oscillations of supernova neutrinos swap the electron neutrino and antineutrino spectra with those of another flavor in certain energy intervals bounded by sharp spectral splits. This phenomenon is far more general than previously appreciated: typically one finds one or more swaps and accompanying splits in the neutrino and antineutrino channels for both inverted and normal neutrino mass hierarchies. Depending on an instability condition, swaps develop around spec...

Dasgupta, Basudeb; Dighe, Amol; Raffelt, Georg G.; Smirnov, Alexei Yu

2009-01-01

308

Smallness of baryon asymmetry from split supersymmetry  

International Nuclear Information System (INIS)

The smallness of the baryon asymmetry in our universe is one of the greatest mysteries and may originate from some profound physics beyond the standard model. We investigate the Affleck-Dine baryogenesis in split supersymmetry, and find that the smallness of the baryon asymmetry is directly related to the hierarchy between the supersymmetry breaking squark/slepton masses and the weak scale. Put simply, the baryon asymmetry is small because of the split mass spectrum

2005-06-15

309

Antenna Splitting Functions for Massive Particles  

Energy Technology Data Exchange (ETDEWEB)

An antenna shower is a parton shower in which the basic move is a color-coherent 2 {yields} 3 parton splitting process. In this paper, we give compact forms for the spin-dependent antenna splitting functions involving massive partons of spin 0 and spin 1/2. We hope that this formalism we have presented will be useful in describing the QCD dynamics of the top quark and other heavy particles at LHC.

Larkoski, Andrew J.; Peskin, Michael E.; /SLAC

2011-06-22

310

Splitting tensile test for fibre reinforced concrete  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The splitting tensile test is a much used method to determine the tensile strength of concrete. The conventional test procedure is known to have a number of limitations related to size effect and boundary conditions. Furthermore, it has been reported to be impossible to determine the tensile strength of Fibre Reinforced Concrete (FRC) using the standard splitting tensile test method. The objective of this paper is to present a methodology to obtain a close estimate of the true tensile strengt...

Denneman, Erik; Kearsley, Elsabe P.; Visser, Alex T.

2011-01-01

311

Macroscopic tunnel splittings in superconducting phase qubits.  

Science.gov (United States)

Prototype Josephson-junction based qubit coherence times are too short for quantum computing. Recent experiments probing superconducting phase qubits have revealed previously unseen fine splittings in the transition energy spectra. These splittings have been attributed to new microscopic degrees of freedom (microresonators), a previously unknown source of decoherence. We show that macroscopic resonant tunneling in the extremely asymmetric double-well potential of the phase qubit can have observational consequences that are strikingly similar to the observed data. PMID:15904404

Johnson, Philip R; Parsons, William T; Strauch, Frederick W; Anderson, J R; Dragt, Alex J; Lobb, C J; Wellstood, F C

2005-05-13

312

P-wave Cooper pair splitting  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Background: Splitting of Cooper pairs has recently been realized experimentally for s-wave Cooper pairs. A split Cooper pair represents an entangled two-electron pair state, which has possible application in on-chip quantum computation. Likewise the spin-activity of interfaces in nanoscale tunnel junctions has been investigated theoretically and experimentally in recent years. However, the possible implications of spin-active interfaces in Cooper pair splitters so far have not been inv...

Henning Soller; Andreas Komnik

2012-01-01

313

Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely re...

D Apos Antonio, Maurizio; Musner, Nicolo; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M. Laura; Wrabetz, Lawrence

2013-01-01

314

Short-lived complexes between myelin basic protein peptides and IAk.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Kinetic rate constants and the equilibrium dissociation constant have been determined for the reaction between an affinity-purified class II major histocompatibility complex molecule IAk and a myelin basic protein analogue peptide, fluorescein-labeled Ac(1-14)A4C15. Under the experimental conditions used, the lifetime of the peptide-free IAk molecule with respect to inactivation is 3.1 hr. The equilibrium dissociation constant, 3.3 +/- 1.7 microM, is determined from measurements of the kineti...

Mason, K.; Mcconnell, H. M.

1994-01-01

315

CHARACTERIZATION OF MYELIN LIGAND COMPLEXES WITH THE NEURONAL NOGO-66 RECEPTOR FAMILY  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Nogo, MAG, and OMgp are myelin-associated proteins that bind to a neuronal Nogo-66 receptor (NgR/NgR1) to limit axonal regeneration after central nervous system (CNS) injury. Within Nogo-A two separate domains are known interact with NgR1. NgR1 is the founding member of three-member NgR family, whereas Nogo-A (RTN4-A) belongs to a four-member reticulon family. Here, we systematically map the interactions between these superfamilies, demonstrating novel nanomolar interactions of RTN2 and RTN3 ...

Laure?n, Juha; Hu, Fenghua; Chin, Joanna; Liao, Ji; Airaksinen, Matti S.; Strittmatter, Stephen M.

2007-01-01

316

Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the adult mammalian CNS, the growth inhibitors oligodendrocyte-myelin glycoprotein (OMgp) and the reticulon RTN4 (Nogo) are broadly expressed in oligodendrocytes and neurons. Nogo and OMgp complex with the neuronal cell surface receptors Nogo receptor-1 (NgR1) and paired immunoglobulin-like receptor-B (PirB) to regulate neuronal morphology. In the healthy CNS, NgR1 regulates dendritic spine shape and attenuates activity-driven synaptic plasticity at Schaffer collateral-CA1 synapses. Here w...

Raiker, Stephen J.; Lee, Hakjoo; Baldwin, Katherine T.; Duan, Yuntao; Shrager, Peter; Giger, Roman J.

2010-01-01

317

Childhood steroid-responsive acute erythromelalgia with axonal neuropathy of large myelinated fibers: a dysimmune neuropathy?  

Science.gov (United States)

A 12-year-old girl developed acute erythromelalgia of distal extremities. Physical, imaging and laboratory examinations failed to find an infective, systemic autoimmune, metabolic, endocrine, and vascular origin. The severe pain and allodynia indicated small-fiber neuropathy but muscle weakness suggested an involvement of large myelinated nerve fibers. This was confirmed by electrophysiological testing. High-dose then slowly tapered methylprednisolone resulted in rapid remission of painful erythromelalgia and complete electrophysiological recovery. Our case may suggest an additional variant to recently described steroid-responsive erythromelalgia with small-fiber axonopathy and may denote a transitory variant to Guillain-Barré syndrome or chronic dysimmune neuropathies. PMID:19056270

Pfund, Zoltan; Stankovics, Jozsef; Decsi, Tamas; Illes, Zsolt

2009-01-01

318

Detection of flux emergence, splitting, merging, and cancellation of network field. I Splitting and Merging  

CERN Multimedia

Frequencies of magnetic patch processes on supergranule boundary, namely flux emergence, splitting, merging, and cancellation, are investigated through an automatic detection. We use a set of line of sight magnetograms taken by the Solar Optical Telescope (SOT) on board Hinode satellite. We found 1636 positive patches and 1637 negative patches in the data set, whose time duration is 3.5 hours and field of view is 112" \\times 112". Total numbers of magnetic processes are followed: 493 positive and 482 negative splittings, 536 positive and 535 negative mergings, 86 cancellations, and 3 emergences. Total numbers of emergence and cancellation are significantly smaller than those of splitting and merging. Further, frequency dependences of merging and splitting processes on flux content are investigated. Merging has a weak dependence on flux content only with a power- law index of 0.28. Timescale for splitting is found to be independent of parent flux content before splitting, which corresponds to \\sim 33 minutes. ...

Iida, Y; Yokoyama, T

2012-01-01

319

DETECTION OF FLUX EMERGENCE, SPLITTING, MERGING, AND CANCELLATION OF NETWORK FIELD. I. SPLITTING AND MERGING  

International Nuclear Information System (INIS)

Frequencies of magnetic patch processes on the supergranule boundary, namely, flux emergence, splitting, merging, and cancellation, are investigated through automatic detection. We use a set of line-of-sight magnetograms taken by the Solar Optical Telescope (SOT) on board the Hinode satellite. We found 1636 positive patches and 1637 negative patches in the data set, whose time duration is 3.5 hr and field of view is 112'' × 112''. The total numbers of magnetic processes are as follows: 493 positive and 482 negative splittings, 536 positive and 535 negative mergings, 86 cancellations, and 3 emergences. The total numbers of emergence and cancellation are significantly smaller than those of splitting and merging. Further, the frequency dependence of the merging and splitting processes on the flux content are investigated. Merging has a weak dependence on the flux content with a power-law index of only 0.28. The timescale for splitting is found to be independent of the parent flux content before splitting, which corresponds to ?33 minutes. It is also found that patches split into any flux contents with the same probability. This splitting has a power-law distribution of the flux content with an index of –2 as a time-independent solution. These results support that the frequency distribution of the flux content in the analyzed flux range is rapidly maintained by merging and splitting, namely, surface processes. We suggest a model for frequency distributions of cancellation and emergence based on this idea.

2012-06-20

320

p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination.  

Science.gov (United States)

Physical damage to the peripheral nerves triggers Schwann cell injury response in the distal nerves in an event termed Wallerian degeneration: the Schwann cells degrade their myelin sheaths and dedifferentiate, reverting to a phenotype that supports axon regeneration and nerve repair. The molecular mechanisms regulating Schwann cell plasticity in the PNS remain to be elucidated. Using both in vivo and in vitro models for peripheral nerve injury, here we show that inhibition of p38 mitogen-activated protein kinase (MAPK) activity in mice blocks Schwann cell demyelination and dedifferentiation following nerve injury, suggesting that the kinase mediates the injury signal that triggers distal Schwann cell injury response. In myelinating cocultures, p38 MAPK also mediates myelin breakdown induced by Schwann cell growth factors, such as neuregulin and FGF-2. Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin breakdown and drives differentiated Schwann cells to acquire phenotypic features of immature Schwann cells. We also show that p38 MAPK concomitantly functions as a negative regulator of Schwann cell differentiation: enforced p38 MAPK activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but induces expression of c-Jun. As expected of its role as a negative signal for myelination, inhibition of p38 MAPK in cocultures promotes myelin formation by increasing the number as well as the length of individual myelin segments. Altogether, our data identify p38 MAPK as an important regulator of Schwann cell plasticity and differentiation. PMID:22623660

Yang, David P; Kim, Jihyun; Syed, Neeraja; Tung, Young-John; Bhaskaran, Ambily; Mindos, Thomas; Mirsky, Rhona; Jessen, Kristjan R; Maurel, Patrice; Parkinson, David B; Kim, Haesun A

2012-05-23

 
 
 
 
321

p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination  

Science.gov (United States)

Physical damage to the peripheral nerves triggers Schwann cell injury response in the distal nerves in an event termed Wallerian degeneration: the Schwann cells degrade their myelin sheaths and de-differentiate, reverting to a phenotype that supports axon regeneration and nerve repair. The molecular mechanisms regulating Schwann cell plasticity in the PNS remain to be elucidated. Using both in vivo and in vitro models for peripheral nerve injury, here we show that inhibition of p38 MAPK activity in mice blocks Schwann cell demyelination and de-differentiation following nerve injury, suggesting that the kinase mediates the injury signal that triggers distal Schwann cell injury response. In myelinating co-cultures, p38 MAPK also mediates myelin breakdown induced by Schwann cell growth factors, such as neuregulin and FGF-2. Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin breakdown and drives differentiated Schwann cells to acquire phenotypic features of immature Schwann cells. We also show that p38 MAPK concomitantly functions as a negative regulator of Schwann cell differentiation: enforced p38 MAPK activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but induces expression of c-Jun. As expected of its role as a negative signal for myelination, inhibition of p38 MAPK in co-cultures promotes myelin formation by increasing the number as well as the length of individual myelin segments. Altogether, our data identify p38 MAPK as an important regulator of Schwann cell plasticity and differentiation.

Yang, David P.; Kim, Jihyun; Syed, Neeraja; Tung, Young-john; Bhaskaran, Ambily; Mindos, Thomas; Mirsky, Rhona; Jessen, Kristjan R.; Maurel, Patrice; Parkinson, David B.; Kim, Haesun A.

2012-01-01

322

Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme  

International Nuclear Information System (INIS)

Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma

2007-11-07

323

Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp-/- mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models — a severe complete transection or a milder dorsal hemisec...

Ji, Benxiu; Case, Lauren C.; Liu, Kai; Shao, Zhaohui; Lee, Xinhua; Yang, Zhongshu; Wang, Joy; Tian, Tim; Shulga-morskaya, Svetlana; Scott, Martin; He, Zhigang; Relton, Jane K.; Mi, Sha

2008-01-01

324

Clinical implications of peripheral myelin protein 22 for nerve compression and neural regeneration: a review.  

Science.gov (United States)

Peripheral myelin protein 22 (PMP22) is a major component of the peripheral myelin sheath. The PMP22 gene is located on chromosome 17p11.2, and defects in PMP22 gene have been implicated in several common inherited peripheral neuropathies. Hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy are all associated with defects in PMP22 gene. The disease phenotypes mirror the range of expression of PMP22 due to the corresponding genetic defect. HNPP, characterized by a milder recurrent episodic focal demyelinating neuropathy, is attributed to a deletion leading to PMP22 underexpression. On the other end of the spectrum, CMT1A leads to a more uniform demyelination and axonal loss, resulting in severe progressive distal weakness and paresthesias; it is due to a duplication at 17p11.2 leading to PMP22 overexpression. Additional point mutations result in varying phenotypes due to dysfunction of the resultant PMP22 protein. All inherited neuropathies are diagnosed with a combination of physical findings on examination, electromyography, sural nerve biopsies, and genetic testing. Treatment and management of these disorders differ depending on the underlying genetic defect, nerves involved, and resulting functional impairments. A review of current literature elucidates clinical, microsurgical implications, and management of patients with PMP22-related neuropathy. PMID:20976668

Hui-Chou, Helen G; Hashemi, Sharyhar S; Hoke, Ahmet; Dellon, A Lee

2011-01-01

325

A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy.  

Science.gov (United States)

Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy. Familial narcolepsy accounts for less than 10% of all narcolepsy cases. However, documented multiplex families are very rare and causative mutations have not been identified to date. To identify a causative mutation in familial narcolepsy, we performed linkage analysis in the largest ever reported family, which has 12 affected members, and sequenced coding regions of the genome (exome sequencing) of three affected members with narcolepsy and cataplexy. We successfully mapped a candidate locus on chromosomal region 6p22.1 (LOD score ¼ 3.85) by linkage analysis. Exome sequencing identified a missense mutation in the second exon of MOG within the linkage region. A c.398C>G mutation was present in all affected family members but absent in unaffected members and 775 unrelated control subjects. Transient expression of mutant myelin oligodendrocyte glycoprotein (MOG) in mouse oligodendrocytes showed abnormal subcellular localization, suggesting an altered function of the mutant MOG. MOG has recently been linked to various neuropsychiatric disorders and is considered as a key autoantigen in multiple sclerosis and in its animal model, experimental autoimmune encephalitis. Our finding of a pathogenic MOG mutation highlights a major role for myelin and oligodendrocytes in narcolepsy and further emphasizes glial involvement in neurodegeneration and neurobehavioral disorders. [corrected]. PMID:21907016

Hor, Hyun; Bartesaghi, Luca; Kutalik, Zoltán; Vicário, José L; de Andrés, Clara; Pfister, Corinne; Lammers, Gert J; Guex, Nicolas; Chrast, Roman; Tafti, Mehdi; Peraita-Adrados, Rosa

2011-09-01

326

Differential roles of astrocyte and microglia in supporting oligodendrocyte development and myelination in vitro.  

Science.gov (United States)

Oligodendrocyte (OL) development relies on many extracellular cues, most of which are secreted cytokines from neighboring neural cells. Although it is generally accepted that both astrocytes and microglia are beneficial for OL development, there is a lack of understanding regarding whether astrocytes and microglia play similar or distinct roles. The current study examined the effects of astrocytes and microglia on OL developmental phenotypes including cell survival, proliferation, differentiation, and myelination in vitro. Our data reveal that, although both astrocytes- and microglia-conditioned medium (ACDM and MCDM, respectively) protect OL progenitor cells (OPCs) against growth factor withdrawal-induced apoptosis, ACDM is significantly more effective than MCDM in supporting long-term OL survival. In contrast, MCDM preferentially promotes OL differentiation and myelination. These differential effects of ACDM and MCDM on OL development are highlighted by distinct pattern of cytokine/growth factors in the conditioned medium, which correlates with differentially activated intracellular signaling pathways in OPCs upon exposure to the conditioned medium. PMID:24392271

Pang, Yi; Fan, Lir-Wan; Tien, Lu-Tai; Dai, Xuemei; Zheng, Baoying; Cai, Zhengwei; Lin, Rick C S; Bhatt, Abhay

2013-09-01

327

Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. II  

International Nuclear Information System (INIS)

The classes of radioactive phospholipids appearing in the ciliary ganglion (CG) and especially in the myelin sheath of the intraorbital part of the oculomotor nerve (OMN) were determined after the intracerebral injection of [2-3H]glycerol and [methyl-14C]choline to chickens. Analysis of the radioactive compounds in water-soluble fractions and chloroform-methanol extracts was performed by thin-layer chromatography (TLC). The water-soluble content of the OMN and CG was much poorer in [2-3H]glycerol and metabolites than in [methyl-14C]choline and derivatives. All classes of glycerophospholipids were found to be axonally transported along the OMN and into the CG, but choline-phosphoglycerides (CPG) were largely predominant. In myelin fractions from the OMN, the specific radioactivity (SRA) of CPG labeled with [2-3H]glycerol reached a maximum earlier (40 h) than the SRA of CPG labeled with [methyl-14C]choline. A 25-fold enhancement of the [14C]SRA of sphingomyelin (SM) was observed between 12 h and 7 days. (Auth.)

1981-08-24

328

Analysis of main dynamic parameters of split power transmission  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The review carried out had shown one basic approach of split power transmission to the organization of drive which is applied to stepless transmissions of tractors and parallel hybrid cars. In the split power transmission the power split device uses a planetary gear. Tractor engine power in the split power transmission is transmitted to the drive shaft via a mechanical and hydraulic path. The theoretical analysis of main parameters of the split power transmission of the tractor is presented....

2008-01-01

329

On the additive splitting procedures and their computer realization  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Two additive splitting procedures are defined and studied in this paper. It is shown that these splitting procedures have good stability properties. Some other splitting procedures, which are traditionally used in mathematical models used in many scientific and engineering fields, are sketched. All splitting procedures are tested by using six different numerical methods for solving differential equations. Many conclusions, which are related both to the comparison of the additive splitting pro...

Farago, I.; Thomsen, Per Grove; Zlatev, Z.

2008-01-01

330

High efficiency beam splitting for H"- accelerators  

International Nuclear Information System (INIS)

Beam splitting for high energy accelerators has typically involved a significant loss of beam and radiation. This paper reports on a new method of splitting beams for H"- accelerators. This technique uses a high intensity flash of light to strip a fraction of the H"- beam to H"0 which are then easily separated by a small bending magnet. A system using a 900-watt (average electrical power) flashlamp and a highly efficient collector will provide 10"-"3 to 10"-"2 splitting of a 50 MeV H"- beam. Results on the operation and comparisons with stripping cross sections are presented. Also discussed is the possibility for developing this system to yield a higher stripping fraction

1985-05-13

331

Collider phenomenology of split-UED  

Energy Technology Data Exchange (ETDEWEB)

Split-universal extra dimension (split-UED), a recently suggested modification of universal extra dimension (UED) model, can nicely explain recent anomalies in cosmic-ray positrons and electrons observed by PAMELA and Fermi. In this model, Kaluza-Klein (KK) dark matters mainly annihilate into leptons because the hadronic branching fraction is highly suppressed by large KK quark masses and the antiproton flux agrees very well with the observation where no excess is found. Collider signatures of the colored KK particles at the LHC, especially q{sub 1}q{sub 1} production, are studied in detail. Due to the large split in masses of KK quarks and other particles, hard p{sub T} jets and missing E{sub T} are generated, which make it possible to suppress the standard model background and to discover the signals.

Chen, Chuan-Ren; Park, Seong Chang; Shu, Jing [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa-no Ha, Kashiwa City, Chiba (Japan); Nojiri, Mihoko M. [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa-no Ha, Kashiwa City, Chiba (Japan); Theory Group, KEK 1-1 Oho, Tsukuba, Ibaraki (Japan); Graduate University for Advanced Studies (SOKENDAI), Tsukuba, Ibaraki (Japan); Takeuchi, Michihisa [Theory Group, KEK 1-1 Oho, Tsukuba, Ibaraki (Japan); Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto (Japan)

2010-07-01

332

A Split Sprint mission to Mars  

Science.gov (United States)

Comprehensive infrastructure analysis is central to developing architectures necessary to support the Space Exploration Initiative. In the ``Split Sprint'' architecture, the cargo is split from the crew. An efficient low thrust ``slow boat'' is used for the cargo and a high thrust ``sprint'' vehicle is used for the crew. Infrastructure analysis is utilized in developing initial element designs to meet the transportation system requirements of the slit sprint architecture. Infrastructure analysis considers technology availability, launch vehicle volume and lift requirements, on orbit assembly, trajectory design and optimization, system reduncancy requirements and evolutionary capability. The resulting infrastructure includes propulsion system options for the crew and cargo space transfer vehicles. For the cargo, an SP-100 derived nuclear electric propulsion system was developed. For the crew, either a conventional cryogenic (LO2/LH2) propulsion system or nuclear thermal propulsion system is utilized. It is shown that the split sprint mission competes effectively with conventional approaches to the Mars mission.

Shepard, Kyle; Duffey, Jack; D'Annible, Dom; Holdridge, Jeff; Thompson, Walter; Armstrong, Robert C.

1992-01-01

333

Fermion localization on a split brane  

CERN Document Server

In this work we analyze the localization of fermions on a brane embedded in five-dimensional, warped and non-warped, space-time. In both cases we use the same nonlinear theoretical model with a non-polynomial potential featuring a self-interacting scalar field whose minimum energy solution is a soliton (a kink) which can be continuously deformed into a two-kink. Thus a single brane splits into two branes. The behavior of spin 1/2 fermions wavefunctions on the split brane depends on the coupling of fermions to the scalar field and on the geometry of the space-time.

Chumbes, A E R; Hott, M B

2010-01-01

334

Fermion localization on a split brane  

International Nuclear Information System (INIS)

In this work we analyze the localization of fermions on a brane embedded in five-dimensional, warped and nonwarped, space-time. In both cases we use the same nonlinear theoretical model with a nonpolynomial potential featuring a self-interacting scalar field whose minimum energy solution is a soliton (a kink) which can be continuously deformed into a two-kink. Thus a single brane splits into two branes. The behavior of spin 1/2 fermions wave functions on the split brane depends on the coupling of fermions to the scalar field and on the geometry of the space-time.

2011-05-15

335

Macroscopic tunnel splittings in superconducting phase qubits  

CERN Multimedia

Many prototype Josephson-junction based qubits have unacceptably short coherence times. Recent experiments probing a superconducting phase qubit with an extremely asymmetric double well potential have revealed previously unseen fine splittings in the transition energy spectra. These splittings have been attributed to new microscopic degrees of freedom (microresonators), a previously unknown source of decoherence. We show that the macroscopic resonant tunneling of states in an extremely asymmetric double well has some observational consequences that are strikingly similar to the observed data, suggesting a possible alternative explanation to microresonators. Our analysis indicates that macroscopic resonant tunneling may be unavoidable for double well phase qubits and thus must be taken into account.

Johnson, P R; Strauch, F W; Anderson, J R; Dragt, A J; Lobb, C J; Wellstood, F C; Johnson, Philip R.; Parsons, William T.; Strauch, Frederick W.; Dragt, Alex J.

2004-01-01

336

Splitting methods for the nonlocal Fowler equation  

CERN Multimedia

We consider a nonlocal scalar conservation law proposed by Andrew C. Fowler to describe the dynamics of dunes, and we develop a numerical procedure based on splitting methods to approximate its solutions. We begin by proving the convergence of the well-known Lie formula, which is an approximation of the exact solution of order one in time. We next use the split-step Fourier method to approximate the continuous problem using the fast Fourier transform and the finite difference method. Our numerical experiments confirm the theoretical results.

Bouharguane, Afaf

2011-01-01

337

Lecture notes on generalized Heegaard splittings  

CERN Document Server

These notes grew out of a lecture series given at RIMS in the summer of 2001. The lecture series was aimed at a broad audience that included many graduate students. Its purpose lay in familiarizing the audience with the basics of 3-manifold theory and introducing some topics of current research. The first portion of the lecture series was devoted to standard topics in the theory of 3-manifolds. The middle portion was devoted to a brief study of Heegaaard splittings and generalized Heegaard splittings. The latter portion touched on a brand new topic: fork complexes.

Saitô, T; Schultens, J; Saito, Toshio; Scharlemann, Martin; Schultens, Jennifer

2005-01-01

338

The transversely split gracilis twin free flaps  

Directory of Open Access Journals (Sweden)

Full Text Available The gracilis muscle is a Class II muscle that is often used in free tissue transfer. The muscle has multiple secondary pedicles, of which the first one is the most consistent in terms of position and calibre. Each pedicle can support a segment of the muscle thus yielding multiple small flaps from a single, long muscle. Although it has often been split longitudinally along the fascicles of its nerve for functional transfer, it has rarely been split transversely to yield multiple muscle flaps that can be used to cover multiple wounds in one patient without subjecting him/her to the morbidity of multiple donor areas .

Upadhyaya Divya

2010-01-01

339

Distribution of radioactivity among total myelin protein amino acids following administration of labeled glycine, leucine, or methionine  

Energy Technology Data Exchange (ETDEWEB)

This paper analyzes the distribution of radioactivity in the different amino acids of brain myelin protein for up to 6-7 weeks after an intracranial pulse administration of radioactive leucine, glycine, or methionine. Results show that there is no significant accumulation or reutilization of protein radioactivity in any form other than the one administered.

Wiggins, R.C.; Morell, P.

1983-01-01

340

[Peripheral nerve abnormalities of mutant (PMA) mouse--myelinated fiber counts of sciatic, peroneal, sural and tibial nerves].  

Science.gov (United States)

A mutant mouse characterized by peroneal muscular atrophy and congenital absence of the peroneal nerve has been described by Esaki et al. and investigated as a possible animal model of Charcot-Marie-Tooth disease or spinal muscular atrophy. However, the nature of the peripheral nerve abnormality of this mutant mouse has not been precisely defined yet. In this study, in addition to the qualitative evaluation of teased fiber and Epon-embedded preparations, the total transverse fascicular area and the total numbers of myelinated fibers per nerve in sciatic, peroneal (proximal and distal), sural (proximal and distal) and tibial (proximal and distal) nerves on both right and left sides were compared between six peroneal muscular atrophy (pma) mice with autosomal recessive gene manifesting mainly the peroneal muscular atrophy and their six control mice to understand and define the peripheral nerve abnormalities. The pma mice showed pes equinovarus bilaterally and their peroneal nerves were absent. No myelinated fibers showing axonal degeneration or segmental demyelination were found on teased fiber preparation. Onion bulb, demyelinated or remyelinated axons and myelin ovoids were not observed in Epon-embedded sections. The mean total transverse fascicular area and mean total number of myelinated fibers per nerve in the sciatic nerve in pma mice was significantly less (p less than 0.02) than that in control mice. On the other hand they were significantly greater (p less than 0.0001) in the sural nerve in pma mice than in control mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3707778

Ohnishi, A; Kuroiwa, Y; Esaki, K

1986-03-01

 
 
 
 
341

Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury  

Science.gov (United States)

Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp-/- mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models — a severe complete transection or a milder dorsal hemisection. OMgp-/- mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp+/+ littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT+ descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp-/- mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp-/- mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection.

Ji, Benxiu; Case, Lauren C.; Liu, Kai; Shao, Zhaohui; Lee, Xinhua; Yang, Zhongshu; Wang, Joy; Tian, Tim; Shulga-Morskaya, Svetlana; Scott, Martin; He, Zhigang; Relton, Jane K.; Mi, Sha

2009-01-01

342

Molecular characterization of myelin protein zero in Xenopus laevis peripheral nerve  

Science.gov (United States)

Myelin protein zero (P0), a glycosylated single-pass transmembrane protein, is essential in the formation and maintenance of peripheral nervous system (PNS) compact myelin. P0 in Xenopus (xP0) exists primarily as a dimeric form that remains stable after various physical and chemical treatments. In exploring the nature of the interactions underlying the dimer stability, we found that xP0 dimer dissociated into monomer during continuous elution gel electrophoresis and conventional SDS-PAGE, indicating that the dimer is stabilized by non-covalent interactions. Furthermore, as some of the gel-purified monomer re-associated into dimer on SDS-PAGE gels, there is likely a dynamic equilibrium between xP0 dimer and monomer in vivo. Because the carbohydrate and fatty acyl moieties may be crucial for the adhesion role of P0, we used sensitive mass spectrometry approaches to elucidate the detailed N-glycosylation and S-acylation profiles of xP0. Asn92 was determined to be the single, fully-occupied glycosylation site of xP0, and a total of 12 glycans was detected that exhibited new structural features compared with those observed from P0 in other species: (1) the neutral glycans were composed mainly of high mannose and hybrid types; (2) 5 of 12 were acidic glycans, among which three were sialylated and the other two were sulfated; (3) none of the glycans had core fucosylation; and (4) no glucuronic acid, hence no HNK-1 epitope, was detected. The drastically different carbohydrate structures observed here support the concept of the species-specific variation in N-glycosylation of P0. Cys152 was found to be acylated with stearoyl (C18:0), whereas palmitoyl (C16:0) is the corresponding predominant fatty acyl group on P0 from higher vertebrates. We propose that the unique glycosylation and acylation patterns of Xenopus P0 may underlie its unusual dimerization behavior. Our results should shed light on the understanding of the phylogenetic development of P0's adhesion role in PNS compact myelin.

Xie, Bo; Luo, Xiaoyang; Zhao, Cheng; Priest, Christina Marie; Chan, Shiu-Yung; O'Connor, Peter B.; Kirschner, Daniel A.; Costello, Catherine E.

2007-12-01

343

Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Multiple sclerosis (MS varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression. Attention was focused on markers of myelination (MBP and PDGF?R and neuronal distress and/or damage (GABA synthesis enzymes, GAD65 and GAD67, NGF, BDNF and related receptors, in two CNS areas, i.e. spinal cord and cerebellum, which are respectively severely and mildly affected by inflammation and demyelination. Tissues were sampled during acute, relapse/remission and chronic phases and results were analysed by two-way ANOVA. Results 1. A strong gender-dependent difference in myelin (MBP and myelin precursor (PDGF?R marker mRNA expression levels is observed in control animals in the spinal cord, but not in the cerebellum. This is the only gender-dependent difference in the expression level of the indicated markers in healthy animals; 2. both PDGF?R and MBP mRNAs in the spinal cord and MBP in the cerebellum are down-regulated during EAE in gender-dependent manner; 3. in the cerebellum, the expression profile of neuron-associated markers (GAD65, GAD67 is characterized by a substantial down-regulation during the inflammatory phase of the disease, which does not differ between male and female rats (two-way ANOVA; 4. there is an up-regulation of NGF, trkA and p75 mRNA expression in the early phases of the disease (14 and 21 days post-immunization, which is not different between male and female. Conclusions It is reported herein that the regulation of markers involved in demyelination and neuroprotection processes occurring during EAE, a well-established MS animal model, is gender- and time-dependent. These findings might contribute to gender- and phase disease-based therapy strategies.

Massella Alessandro

2012-01-01

344

Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons  

Science.gov (United States)

Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (?26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea.

Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

2013-01-01

345

Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro.  

Science.gov (United States)

Schwann cells, the myelin-forming cells of the PNS, are attractive candidates for remyelination therapy as they can remyelinate CNS axons. Yet their integration in CNS tissue appears hampered, at least in part, by their limited motility in the CNS environment. As the polysialylated (PSA) form of NCAM regulates migration of neural precursors in the CNS and is not expressed by developing Schwann cells, we investigated whether conferring sustained expression of PSA to Schwann cells derived from postnatal rats enhances their motility. Cells were transduced with a retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on NCAM. Migration of wild type and transduced cells expressing STX or the marker gene alkaline phosphatase was examined using a gap bridging assay in dissociated cells and by grafting cells in slice cultures of postnatal brain. Migration of PSA expressing cells was significantly increased in both models, as compared to control cells, and this effect was abolished by endoneuraminidase-N stripping of PSA. PSA-positive Schwann cells retained the ability to differentiate in vitro and expressed the Krox20 and P zero myelination markers. When grafted in neonatal cerebellar slices, STX-transduced cells started to myelinate Purkinje cell axons like control cells and make myelin internodes after 2 to 3 weeks. PSA was redistributed on the cell membrane and downregulated during differentiation in pure Schwann cell cultures and slice co-cultures. Thus, migratory properties of PNS myelin-forming cells within the CNS can be enhanced without altering their differentiation program. This finding may be beneficial for the development of remyelination therapies. PMID:16598779

Lavdas, Alexandros A; Franceschini, Isabelle; Dubois-Dalcq, Monique; Matsas, Rebecca

2006-06-01

346

DETECTION OF FLUX EMERGENCE, SPLITTING, MERGING, AND CANCELLATION OF NETWORK FIELD. I. SPLITTING AND MERGING  

Energy Technology Data Exchange (ETDEWEB)

Frequencies of magnetic patch processes on the supergranule boundary, namely, flux emergence, splitting, merging, and cancellation, are investigated through automatic detection. We use a set of line-of-sight magnetograms taken by the Solar Optical Telescope (SOT) on board the Hinode satellite. We found 1636 positive patches and 1637 negative patches in the data set, whose time duration is 3.5 hr and field of view is 112'' Multiplication-Sign 112''. The total numbers of magnetic processes are as follows: 493 positive and 482 negative splittings, 536 positive and 535 negative mergings, 86 cancellations, and 3 emergences. The total numbers of emergence and cancellation are significantly smaller than those of splitting and merging. Further, the frequency dependence of the merging and splitting processes on the flux content are investigated. Merging has a weak dependence on the flux content with a power-law index of only 0.28. The timescale for splitting is found to be independent of the parent flux content before splitting, which corresponds to {approx}33 minutes. It is also found that patches split into any flux contents with the same probability. This splitting has a power-law distribution of the flux content with an index of -2 as a time-independent solution. These results support that the frequency distribution of the flux content in the analyzed flux range is rapidly maintained by merging and splitting, namely, surface processes. We suggest a model for frequency distributions of cancellation and emergence based on this idea.

Iida, Y.; Yokoyama, T. [Department of Earth and Planetary Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Hagenaar, H. J. [Lockheed Martin Advanced Technology Center, Org. ADBS, Building 252, 3251 Hanover Street, Palo Alto, CA 94304 (United States)

2012-06-20

347

Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene.  

Science.gov (United States)

The peripheral myelin protein 22 gene (PMP22) encodes an intrinsic membrane protein of compact myelin. Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies. Charcot-Marie-Tooth disease type 1A is a hypertrophic de-remyelinating neuropathy manifesting with peroneal muscular atrophy and uniform, marked, slowing of nerve conduction velocities. Hereditary neuropathy with liability to pressure palsies is a recurrent focal neuropathy with sausage-like myelin thickening (tomacula) and non-uniform nerve conduction velocity changes. Missense or nonsense mutations also cause more severe Charcot-Marie-Tooth disease type 1A forms of infancy or hereditary neuropathy with liability to pressure palsies, but they are presumably very rare. We performed a mutational scanning of PMP22 in 229 index patients (46 familial, 183 isolated) referred for suspected inherited neuropathy. The series included 125 cases with hereditary neuropathy with liability to pressure palsies (mean age 42.5 years), 47 cases with Charcot-Marie-Tooth disease type 1A (motor nerve conduction velocities at median nerve below 38 m/s) (mean age 40.7 years) and 57 cases with Charcot-Marie-Tooth with unknown nerve conduction velocities (mean age 43 years). Preliminary molecular studies ruled out PMP22 duplication or deletion or mutations in a comprehensive panel of Charcot-Marie-Tooth genes. Mutational scanning of PMP22 was done by denaturing high performance liquid chromatography and automated nucleotide sequencing. To investigate the molecular basis of phenotype-to-genotype correlations, we performed a transcriptional analysis of PMP22 using reverse-transcriptase polymerase chain reaction and quantitative real-time polymerase chain reaction in two phenotypically divergent nerve biopsies. Ten patients harboured eight micromutations of PMP22 including four novel changes. In six familial and three sporadic cases, detected mutations caused premature or delayed stop codons and were associated with hereditary neuropathy with liability to pressure palsies; the related pathological pictures ranged from classical tomaculous neuropathy to a mild demyelinating neuropathy with atypical non-tomaculous myelin thickenings. In a single family a c.179-2A> G mutation affecting the splice acceptor site of intron 2 cosegregated with a Charcot-Marie-Tooth disease type 1A-like syndrome and a peculiar pathological picture of demyelinating neuropathy without Charcot-Marie-Tooth disease type 1A-like classical onion bulbs or tomacula. Transcriptional analysis of a novel c.174_178?+?7delAAACGGTGAGGC deletion involving exon 2 and intron 2 demonstrated an unstable mutant transcript leading to a p.Asn59GlyfsX12 change; the mutation represented a null allele and caused a typical tomaculous hereditary neuropathy with liability to pressure palsies. The Charcot-Marie-Tooth disease type 1-like c.179-2A >?G allele led to a stable transcript with an in-frame deletion of exon 3 (p.Glu60_Ala106del); the predicted shorter protein could exert variable molecular effects. In conclusion, micromutations of PMP22 cause a clinical and pathological continuum of demyelinating neuropathies that may include atypical phenotypes. PMID:21252112

Taioli, Federica; Cabrini, Ilaria; Cavallaro, Tiziana; Acler, Michele; Fabrizi, Gian Maria

2011-02-01

348

Radioimmunoassay of the myelin basic protein in biological fluids, conditions improving sensitivity and specificity  

International Nuclear Information System (INIS)

The radioimmunoassay (RIA) for myelin basic protein (MBP) in biological fluids was reassessed in order to improve its sensitivity and eliminate some interferences. By using the pre-incubation technique and the charcoal-dextram-horse serum mixture for the separation step, the detection limit could be lowered to 200 pg/ml for cerebrospinal fluids (CSF), amniotic fluids (AF) and nervous tissue extracts and 600 pg/ml for sera. The RIA could be used directly on CSF, AF and nervous tissue extracts. Sera, however, had to be heated in citrate buffer at 1000C in order to discard interfering material. The present method is 10 to 20 times more sensitive than others previously published. Moreover, it can be applied to amniotic fluid. The biological fluids had to be promptly frozen to avoid degradation of MBP

1980-01-01

349

Isospin Splittings of Doubly Heavy Baryons  

Energy Technology Data Exchange (ETDEWEB)

The SELEX Collaboration has reported a very large isospin splitting of doubly charmed baryons. We show that this effect would imply that the doubly charmed baryons are very compact. One intriguing possibility is that such baryons have a linear geometry Q-q-Q where the light quark q oscillates between the two heavy quarks Q, analogous to a linear molecule such as carbon dioxide. However, using conventional arguments, the size of a heavy-light hadron is expected to be around 0.5 fm, much larger than the size needed to explain the observed large isospin splitting. Assuming the distance between two heavy quarks is much smaller than that between the light quark and a heavy one, the doubly heavy baryons are related to the heavy mesons via heavy quark-diquark symmetry. Based on this symmetry, we predict the isospin splittings for doubly heavy baryons including {Xi}{sub cc}, {Xi}{sub bb} and {Xi}{sub bc}. The prediction for the {Xi}{sub cc} is much smaller than the SELEX value. On the other hand, the {Xi}{sub bb} baryons are predicted to have an isospin splitting as large as (6.3 {+-} 1.7) MeV. An experimental study of doubly bottomed baryons is therefore very important to better understand the structure of baryons with heavy quarks.

Brodsky, Stanley J.; /SLAC; Guo, Feng-Kun; /Bonn U., HISKP /Bonn U.; Hanhart, Christoph; /Julich, Forschungszentrum /JCHP, Julich /IAS, Julich; Meissner, Ulf-G.; /Julich, Forschungszentrum /JCHP, Julich /IAS, Julich /Bonn U., HISKP /Bonn U.

2011-08-18

350

Doublet-Triplet Splitting and Fat Branes  

CERN Document Server

We consider the doublet-triplet splitting problem in supersymmetric SU(5) grand unified theory in five dimensions where the fifth dimension is non-compact. We point out that an unnatural fine-tuning of parameters in order to obtain the light Higgs doublets is not required due to the exponential suppression of the overlap of the wave functions.

Maru, N

2001-01-01

351

Source splitting via the point source method  

International Nuclear Information System (INIS)

We introduce a new algorithm for source identification and field splitting based on the point source method (Potthast 1998 A point-source method for inverse acoustic and electromagnetic obstacle scattering problems IMA J. Appl. Math. 61 119–40, Potthast R 1996 A fast new method to solve inverse scattering problems Inverse Problems 12 731–42). The task is to separate the sound fields uj, j = 1, ..., n of n element of N sound sources supported in different bounded domains G1, ..., Gn in R3 from measurements of the field on some microphone array—mathematically speaking from the knowledge of the sum of the fields u = u1 + ... + un on some open subset ? of a plane. The main idea of the scheme is to calculate filter functions g1,…, gn, n element of N, to construct ul for l = 1, ..., n from u|? in the form ul (x) = ?? gl,x(y)u(y)ds(y), l=1,... n. (1) We will provide the complete mathematical theory for the field splitting via the point source method. In particular, we describe uniqueness, solvability of the problem and convergence and stability of the algorithm. In the second part we describe the practical realization of the splitting for real data measurements carried out at the Institute for Sound and Vibration Research at Southampton, UK. A practical demonstration of the original recording and the splitting results for real data is available online

2010-04-01

352

FSPLIT - Fortran Source File Splitting Program.  

Science.gov (United States)

A program has been written which takes as input a file containing Fortran routines, and produces as output a file containing commands which describe how to split the input file into separate files each containing a separate routine. The program has been m...

M. R. Geary

1983-01-01

353

Czech, Slovak science ten years after split  

CERN Multimedia

Ten years after the split of Czechoslovakia Czech and Slovak science are facing the same difficulties: shortage of money for research, poor salaries, obsolete equipment and brain drain, especially of the young, according to a feature in the Daily Lidove Noviny (1 page).

2003-01-01

354

Domain Splitting for an Explicit Hyperbolic Solver.  

Science.gov (United States)

A method of splitting the solution domain to allow faster computations of practical hyperbolic problems is described. Results are presented which show the performance of the method in both one and two dimensions. An indication of the likely savings in com...

R. Loehner K. Morgan O. C. Zienkiewicz

1983-01-01

355

Splitting fields and general differential Galois theory  

CERN Multimedia

We present general Galois theory of nonlinear partial differential equations. For each system of differential equations we define its splitting field and differential Galois group. The main result is the theorem about Galois correspondence for normal extensions. An algebraic technique concerning constructed differential fields is presented.

Trushin, Dima

2009-01-01

356

On the tuning condition of split supersymmetry  

International Nuclear Information System (INIS)

Split supersymmetry does not attempt to solve the hierarchy problem, but it assumes a tuning condition for the electroweak scale. We clarify the meaning of this condition and show how it is related to the underlying parameters. Simple assumptions on the structure of the soft terms lead to predictions on tan? and on the physical Higgs mass

2005-10-27

357

Split liver transplantation: King's College Hospital experience.  

Science.gov (United States)

BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs.

Rela, M; Vougas, V; Muiesan, P; Vilca-Melendez, H; Smyrniotis, V; Gibbs, P; Karani, J; Williams, R; Heaton, N

1998-01-01

358

Time splitting integration methods in mesoscale models  

Science.gov (United States)

In numerical simulation models there arises the problem, that the time step is limited by the fastest process due to numerical stability constraints. In non-hydrostatic, compressible models the fast processes are the sound and sometimes gravity waves. For an efficient calculation one often uses time splitting schemes: the fast processes are calculated with a small time step more frequently and the slow processes with a large time step more seldom. This is especially advantageous because the sound process needs only little calculation expense. The additive splitting and different variants of the Klemp-Wilhelmson-splitting are discussed. Test simulations with the model KAMM2 (Karlsruher Atmospheric Mesoscale Model, Version 2) and von-Neumann-stability analyses of the linearised one-dimensional sound-advection-system and the two-dimensional sound-buoyancy-advection-system are presented. Especially for the sound-advection system, the Euler-forward scheme can be stabilized by use of a divergence filter, which stands in contrast to previous assumptions about principal instability of this scheme. Furthermore, there exists no stability constraint for the time splitting ratio.

Baldauf, M.

2003-04-01

359

Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses.  

Science.gov (United States)

Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of ?(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components. PMID:22408022

McCully, Belinda H; Brooks, Virginia L; Andresen, Michael C

2012-05-15

360

Myelinated afferent fibres innervating the primate skin and their response to noxious stimuli.  

Science.gov (United States)

1. The functional characteristics of cutaneous receptors in the squirrel monkey were determined by recording discharges of single myelinated afferent fibres in peripheral nerves with micro-electrodes or from fine filaments prepared by dissection. One hundred and sixty-nine fibres of the posterior femoral cutaneous nerve and 209 of the superficial radial nerve with conduction velocities between 4 and 88 m/sec were classified according to the nature of the most effective stimulus, discharge characteristics, adaptation rate and organization of the receptive field.2. Twenty per cent of the fibres innervating either hairy or glabrous skin required strong mechanical stimuli for activation; thresholds ranged from moderate to overtly damaging pressures. This class showed little or no sensitivity to thermal changes including noxious heat. Their receptive fields consisted of numerous, mechanically-excitable points or spots. All such fibres gave higher impulse frequencies to noxious than to innocuous mechanical stimuli and a large fraction were considered to be nociceptors because they responded only to noxious deformation. The conduction velocities of nociceptors were distributed between 5 and 28 m/sec.3. All but a few of the other fibres encountered responded vigorously to innocuous stimuli and were readily identified as corresponding to one of the receptor types known to exist in either the primate or the cat. These sensitive receptors were systematically tested by intense cutaneous stimuli; their response to injurious stimuli always could be mimicked by innocuous ones.4. Therefore, in the primate a particular class of slowly-conducting myelinated fibres is partially responsible for signalling mechanically-induced cutaneous damage. The probable relation between such afferent fibres and certain kinds of cutaneous pain is explored. PMID:4969883

Perl, E R

1968-08-01

 
 
 
 
361

Epitope diversity of N-glycans from bovine peripheral myelin glycoprotein P0 revealed by mass spectrometry and nano probe magic angle spinning 1H NMR spectroscopy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The carbohydrate structures present on the glycoproteins in the central and peripheral nerve systems are essential in many cell adhesion processes. The P0 glycoprotein, expressed by myelinating Schwann cells, plays an important role during the formation and maintenance of myelin, and it is the most abundant constituent of myelin. Using monoclonal antibodies, the homophilic binding of the P0 glycoprotein was shown to be mediated via the human natural keller cell (HNK)-1 epitope (3-O-SO3H-GlcUA...

Vliegenthart, J. F. G.; Gutie?rrez Gallego, R.; Jime?nez Blanco, J. L.; Thijssen-van Zuylen, C. W. E. M.; Gotfredsen, C. H.; Voshol, H.; Duus, J. Ø.; Schachner, M.

2001-01-01

362

Adolescent Tethered Cord Syndrome: Type II Split Cord Malformation with Dermoid Cyst at Split Site  

Directory of Open Access Journals (Sweden)

Full Text Available Presented here is a case of fourteen year old female with diagnosis of Tethered Cord Syndrome(TCS having type II Split Cord (Diplomyelia-D12 to L, vertebral level with dermoid cyst atthe split cord site (L,-L, vertebral level. She presented with acute onset paraplegia withsphincteric involvement. She was having asymptomatic patent ductus artJ!reosus. Afterinvestigations, she was operated upon and has shown significant neurological recovery.

Anil Sharma, Vijay Raina.

1999-01-01

363

Non-Mendelian transmission in a human developmental disorder: split hand/split foot.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The study of Mendelian disorders that do not meet some Mendelian expectations has led to an increased understanding of such previously obscure genetic phenomena as anticipation. Split hand/split foot (SHSF), a human developmental malformation, demonstrates such distinctive genetic features as reduced penetrance and variable expressivity. In this study, new pedigrees with defined ascertainment confirm the existence of non-Mendelian transmission characterized by the overtransmission of SHSF fro...

Jarvik, G. P.; Patton, M. A.; Homfray, T.; Evans, J. P.

1994-01-01

364

Evaluation of Glovebox Sectioning Using Weld Splitting Techniques.  

Science.gov (United States)

A weld splitting method is being evaluated for sectioning austenitic stainless steel components. Testing consists of sectioning simulated stainless steel gloveboxes into disposable pieces to determine the acceptability of using dissimilar metal weld split...

P. A. Titzler C. R. Allen

1986-01-01

365

Splitting Technique Initialization in Local PCA  

Directory of Open Access Journals (Sweden)

Full Text Available The local Principal Component Analysis (PCA reduces linearly redundant components that may present in higher dimensional space. It deploys an initial guess technique which can be utilized when the distribution of a given multivariate data is known to the user. The problem in initialization arises when the distribution is not known. This study explores a technique that can be easily integrated in the local PCA design and is efficient even when the given statistical distribution is unknown. The initialization using this proposed splitting technique not only splits and reproduces the mean vector but also the orientation of components in the subspace domain. This would ensure that all clusters are used in the design. The proposed integration with the reconstruction distance local PCA design enables easier data processing and more accurate representation of multivariate data. A comparative approach is undertaken to demonstrate the greater effectiveness of the proposed approach in terms of percentage error.

Alok Sharma

2006-01-01

366

Finite-bias Cooper pair splitting.  

Science.gov (United States)

In a device with a superconductor coupled to two parallel quantum dots (QDs) the electrical tunability of the QD levels can be used to exploit nonclassical current correlations due to the splitting of Cooper pairs. We experimentally investigate the effect of a finite potential difference across one quantum dot on the conductance through the other completely grounded QD in a Cooper pair splitter fabricated on an InAs nanowire. We demonstrate that the nonlocal electrical transport through the device can be tuned by electrical means and that the energy dependence of the effective density of states in the QDs is relevant for the rates of Cooper pair splitting (CPS) and elastic cotunneling. Such experimental tools are necessary to understand and develop CPS-based sources of entangled electrons in solid-state devices. PMID:22026885

Hofstetter, L; Csonka, S; Baumgartner, A; Fülöp, G; d'Hollosy, S; Nygård, J; Schönenberger, C

2011-09-23

367

Isospin breaking in octet baryon mass splittings  

Energy Technology Data Exchange (ETDEWEB)

Using an SU(3) flavour symmetry breaking expansion in the quark mass, we determine the QCD component of the nucleon, Sigma and Xi mass splittings of the baryon octet due to up-down (and strange) quark mass differences in terms of the kaon mass splitting. Provided the average quark mass is kept constant, the expansion coefficients in our procedure can be determined from computationally cheaper simulations with mass degenerate sea quarks and partially quenched valence quarks. Both the linear and quadratic terms in the SU(3) flavour symmetry breaking expansion are considered; it is found that the quadratic terms only change the result by a few percent, indicating that the expansion is highly convergent.

Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Najjar, J. [Regensburg Univ. (Germany). Institut fuer Theoretische Physik; Nakamura, Y. [RIKEN Advanced Institute for Computational Science, Kobe, Hyogo (Japan); Pleiter, D. [Forschungszentrum Juelich (Germany). Juelich Supercomputer Centre; Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Division; Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Zanotti, J.M. [Adelaide Univ., SA (Australia). CSSM, School of Chemistry and Physics

2012-06-15

368

Isospin breaking in octet baryon mass splittings  

CERN Document Server

Using an SU(3) flavour symmetry breaking expansion in the quark mass, we determine the QCD component of the nucleon, Sigma and Xi mass splittings of the baryon octet due to up-down (and strange) quark mass differences in terms of the kaon mass splitting. Provided the average quark mass is kept constant, the expansion coefficients in our procedure can be determined from computationally cheaper simulations with mass degenerate sea quarks and partially quenched valence quarks. Both the linear and quadratic terms in the SU(3) flavour symmetry breaking expansion are considered; it is found that the quadratic terms only change the result by a few percent, indicating that the expansion is highly convergent.

Horsley, R; Nakamura, Y; Pleiter, D; Rakow, P E L; Schierholz, G; Zanotti, J M

2012-01-01

369

Height in splittings of hyperbolic groups  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Suppose $H$ is a hyperbolic subgroup of a hyperbolic group $G$. Assume there exists $n > 0$ such that the intersection of $n$ essentially distinct conjugates of $H$ is always finite. Further assume $G$ splits over $H$ with hyperbolic vertex and edge groups and the two inclusions of $H$ are quasi-isometric embeddings. Then $H$ is quasiconvex in $G$. This answers a question of Swarup and provides a partial converse to the main theorem of \\cite{GMRS}.

Mitra, Mahan

2004-01-01

370

Fourier Collocation Splittings for Partial Differential Equations  

Science.gov (United States)

In this article we study computational issues related to a nonlinear Galerkin type splitting (NLG) of partial differential equations in the case of a Fourier collocation discretization. We present an extension of the method to two-dimensional problems and show that the sole separation of modes in NLG can bring precision and computational costs advantages to the standard collocation scheme. Numerical experiments with the Burgers and a reaction-diffusion equation for 1 and 2 dimensions are also shown.

Costa, Bruno; Dettori, Lucia

1998-05-01

371

Masses and Mass splittings of Charm mesons  

CERN Document Server

Open charm hadrons with strange quark have been discovered in recent years but non-strange part have been somewhat ignored. We aim to calculate ground and excited low lying states charm meson masses using mass formulae developed in heavy hadron chiral perturbation theory. Also various parameters in one loop mass formulae are analyzed graphically within their respective ranges. We here provide the more constrained fits for different parameters. Spin and mass splittings are also calculated

Upadhyay, A

2012-01-01

372

Molecular catalytic system for efficient water splitting  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The aim of this dissertation is to construct and explore artificial oxygen evolving complexes that are synthetically accessible, stable, functionally robust and efficient. To achieve this, a class of mono metal water splitting catalysts is introduced in this manuscript and exploitation of these complexes in homogeneous catalysis and in electrochemical studies with surface immobilized catalyst assemblies has been discussed. The catalysts are comprised of a single centre ruthenium or iridium me...

Joya, Khurram Saleem

2011-01-01

373

Split neutrinos - leptogenesis, dark matter and inflation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We propose a simple framework to split neutrinos with a slight departure from tribimaximal mixing - where two of the neutrinos are Majorana type which provide thermal leptogenesis. The Dirac neutrino with a tiny Yukawa coupling explains primordial inflation and the cosmic microwave background radiation, where the inflaton is the gauge invariant flat direction. The observed baryon asymmetry, and the scale of inflation are intimately tied to the observed reactor angle, which c...

Mazumdar, Anupam; Morisi, Stefano

2012-01-01

374

Thick Brane Split Caused by Spacetime Torsion  

CERN Multimedia

In this paper we apply the five-dimensional $f(T)$ gravity with $f(T)=T+k T^n$ to brane scenario to explore the solutions under a given warp factor, and we find that the analytic domain wall solution will be a double-kink solution when the geometric effect of spacetime torsion is strongly enhanced. We also investigate the localization of fermion fields on the split branes corresponding to the double-kink solution.

Yang, Jie; Zhong, Yuan; Li, Yang

2012-01-01

375

Advanced Split BIRCH Algorithm in Reconfigurable Network  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH) has a disadvantage that it reduced the accuracy of the arbitrary shape clustering algorithm clusters, to this end a split improved BIRCH algorithm (AS-Birch) was put forward. Through the analysis of the reconfigurable network and a detailed analysis of application scenarios and functional requirements of business clustering, according to the different characteristics of each clustering algorithm, we choose a hierarchical...

Li Wan; Jie Yang

2013-01-01

376

Source splitting via the point source method  

Science.gov (United States)

We introduce a new algorithm for source identification and field splitting based on the point source method (Potthast 1998 A point-source method for inverse acoustic and electromagnetic obstacle scattering problems IMA J. Appl. Math. 61 119-40, Potthast R 1996 A fast new method to solve inverse scattering problems Inverse Problems 12 731-42). The task is to separate the sound fields uj, j = 1, ..., n of n \\in \\mathbb {N} sound sources supported in different bounded domains G1, ..., Gn in \\mathbb {R}^3 from measurements of the field on some microphone array—mathematically speaking from the knowledge of the sum of the fields u = u1 + sdotsdotsdot + un on some open subset ? of a plane. The main idea of the scheme is to calculate filter functions g_1, \\ldots, g_n, n\\in \\mathbb {N} , to construct uell for ell = 1, ..., n from u|? in the form u_{\\ell }(x) = \\int _{\\Lambda } g_{\\ell,x}(y) u(y) {\\,\\rm d}s(y), \\qquad \\ell =1,\\ldots, n. We will provide the complete mathematical theory for the field splitting via the point source method. In particular, we describe uniqueness, solvability of the problem and convergence and stability of the algorithm. In the second part we describe the practical realization of the splitting for real data measurements carried out at the Institute for Sound and Vibration Research at Southampton, UK. A practical demonstration of the original recording and the splitting results for real data is available online.

Potthast, Roland; Fazi, Filippo M.; Nelson, Philip A.

2010-04-01

377

Habitat split leads to biodiversity decline  

Science.gov (United States)

Amphibians such as frogs are at risk, especially those that have to travel from their homes in forest habitats to aquatic areas to breed and back; and with this added risk, the diversity, or variety, of species declines, according to a new report. Traveling to the water to breed, then returning to the forest is called habitat split, and researchers say that it is usually caused by human activity.

American Association for the Advancement of Science (AAAS;)

2007-12-13

378

Cohomology of Courant algebroids with split base  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We study the (standard) cohomology $H^\\bullet_{st}(E)$ of a Courant algebroid $E$. We prove that if $E$ is transitive, the standard cohomology coincides with the naive cohomology $H_{naive}^\\bullet(E)$ as conjectured by Stienon and Xu. For a general Courant algebroid we define a spectral sequence converging to its standard cohomology. If $E$ is with split base, we prove that there exists a natural transgression homomorphism $T_3$ (with image in $H^3_{naive}(E)$) which, toget...

Ginot, Gregory; Grutzmann, Melchior

2008-01-01

379

A thermodynamically compatible splitting procedure in hyperelasticity  

Science.gov (United States)

A material is hyperelastic if the stress tensor is obtained by variation of the stored energy function. The corresponding 3D mathematical model of hyperelasticity written in the Eulerian coordinates represents a system of 14 conservative partial differential equations submitted to stationary differential constraints. A classical approach for numerical solving of such a 3D system is a geometrical splitting: the 3D system is split into three 1D systems along each spatial direction and solved then by using a Godunov type scheme. Each 1D system has 7 independent eigenfields corresponding to contact discontinuity, longitudinal waves and shear waves. The construction of the corresponding Riemann solvers is not an easy task even in the case of isotropic solids. Indeed, for a given specific energy it is extremely difficult, if not impossible, to check its rank-one convexity which is a necessary and sufficient condition for hyperbolicity of the governing equations. In this paper, we consider a particular case where the specific energy is a sum of two terms. The first term is the hydrodynamic energy depending only on the density and the entropy, and the second term is the shear energy which is unaffected by the volume change. In this case a very simple criterion of hyperbolicity can be formulated. We propose then a new splitting procedure which allows us to find a numerical solution of each 1D system by solving successively three 1D sub-systems. Each sub-system is hyperbolic, if the full system is hyperbolic. Moreover, each sub-system has only three waves instead of seven, and the velocities of these waves are given in explicit form. The last property allows us to construct reliable Riemann solvers. Numerical 1D tests confirm the advantage of the new approach. A multi-dimensional extension of the splitting procedure is also proposed.

Favrie, N.; Gavrilyuk, S.; Ndanou, S.

2014-08-01

380

LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin  

Science.gov (United States)

Summary In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) as a high-affinity, endocytic receptor for MAG. In contrast with previously identified MAG receptors, binding of MAG to LRP1 occurs independently of terminal sialic acids. In primary neurons, functional inactivation of LRP1 with receptor-associated protein, depletion by RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth. Similar results are observed when LRP1 is antagonized in PC12 and N2a cells. By contrast, inhibiting LRP1 does not attenuate inhibition of neurite outgrowth caused by chondroitin sulfate proteoglycans. Mechanistic studies in N2a cells showed that LRP1 and p75NTR associate in a MAG-dependent manner and that MAG-mediated activation of RhoA may involve both LRP1 and p75NTR. LRP1 derivatives that include the complement-like repeat clusters CII and CIV bind MAG and other MAIs. When CII and CIV were expressed as Fc-fusion proteins, these proteins, purified full-length LRP1 and shed LRP1 all attenuated the inhibition of neurite outgrowth caused by MAG and CNS myelin in primary neurons. Collectively, our studies identify LRP1 as a novel MAG receptor that functions in neurite outgrowth inhibition.

Stiles, Travis L.; Dickendesher, Travis L.; Gaultier, Alban; Fernandez-Castaneda, Anthony; Mantuano, Elisabetta; Giger, Roman J.; Gonias, Steven L.

2013-01-01

 
 
 
 
381

Sunspot splitting triggering an eruptive flare  

CERN Multimedia

We investigate how the splitting of the leading sunspot and associated flux emergence and cancellation in active region NOAA 11515 caused an eruptive M5.6 flare on 2012 July 2. Our study employs multi-wavelength observations from HMI, AIA and ChroTel. Emerging flux formed a neutral line ahead of the leading sunspot and new satellite spots. The sunspot splitting caused a long-lasting flow toward this neutral line, where a filament formed. Further flux emergence, partly of mixed-polarity, as well as episodes of flux cancellation occurred repeatedly at the neutral line. Following a nearby C-class precursor flare with signs of interaction with the filament, the filament erupted nearly simultaneously with the onset of the M5.6 flare and evolved into a coronal mass ejection. The sunspot stretched without forming a light bridge, splitting unusually fast (within about a day, complete approximately 6 hours after the eruption) in two nearly equal parts. The front part separated strongly from the active region to approa...

Louis, Rohan E; Kliem, Bernhard; Balthasar, Horst; Denker, Carsten

2013-01-01

382

Universal exchange-driven phonon splitting  

Science.gov (United States)

We report on a linear dependence of the phonon splitting on the non-dominant exchange coupling Jnd in the antiferromagnetic monoxides MnO, Fe0.92O, CoO and NiO, and in the highly frustrated antiferromagnetic spinels CdCr2O4, MgCr2O4 and ZnCr2O4. For the monoxides our results directly confirm the theoretical prediction of a predominantly exchange induced splitting of the zone-centre optical phonon [1,2]. We find the linear relation ??= ?JndS^2 with slope ? = 3.7. This relation also holds for a very different class of systems, namely the highly frustrated chromium spinels. Our finding suggests a universal dependence of the exchange-induced phonon splitting at the antiferromagnetic transition on the non-dominant exchange coupling [3].[4pt] [1] S. Massidda et al., Phys. Rev. Lett. 82, 430 (1999).[0pt] [2] W. Luo et al., Solid State Commun. 142, 504 (2007).[0pt] [3] Ch. Kant et al., arxiv:1109.4809.

Deisenhofer, Joachim; Kant, Christian; Schmidt, Michael; Wang, Zhe; Mayr, Franz; Tsurkan, Vladimir; Loidl, Alois

2012-02-01

383

Communication: Selection rules for tunneling splitting of vibrationally excited levels.  

Science.gov (United States)

Five symmetry-based selection rules are formulated that relate the tunneling splitting of a vibrationally excited level to that of the ground level in molecules with a symmetric double-minimum potential. The rules, which explain why excited levels frequently have smaller splittings than zero-point levels, are used to interpret the observed and calculated splittings in malonaldehyde. PMID:23862915

Siebrand, Willem; Smedarchina, Zorka; Fernández-Ramos, Antonio

2013-07-14

384

T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Objectives: It has been suggested that autoimmunity to peripheral myelin proteins is involved in the pathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We aimed to compare reactivity of peripheral blood mononuclear cells (PBMC) to antigens of peripheral myelin proteins in patients with GBS and patients with CIDP with that of healthy controls and patients with other non-immune mediated neuropathies (ON).

Csurhes, P.; Sullivan, A.; Green, K.; Pender, M.; Mccombe, P.

2005-01-01

385

Disruption of Fibroblast Growth Factor Receptor Signaling In Non-Myelinating Schwann Cells Causes Sensory Axonal Neuropathy and Impairment of Thermal Pain Sensitivity  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Axon-glial interactions are critical for normal functioning of peripheral nerves, and their disruption leads to peripheral neuropathies. Fibroblast growth factors (FGF) are key players in peripheral nerve regeneration after injury. We investigated the role of FGF receptor (Fgfr) signaling in Schwann cells and the consequent regulation of normal Schwann cell-axon interactions. Fgfr1 and Fgfr2 were conditionally inactivated, either singly or in combination, in myelinating and non-myelinating Sc...

Furusho, M.; Dupree, J. L.; Bryant, M.; Bansal, R.

2009-01-01

386

Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.  

Science.gov (United States)

The nosology of the inborn errors of myelin metabolism has been stymied by the lack of molecular genetic analysis. Historically, Pelizaeus-Merzbacher disease has encompassed a host of neurologic disorders that present with a deficit of myelin, the membrane elaborated by glial cells that encircles and successively enwraps axons. We describe here a Pelizaeus-Merzbacher pedigree of the classical type, with X-linked inheritance, a typical clinical progression, and a pathologic loss of myelinating cells and myelin in the central nervous system. To discriminate variants of Pelizaeus-Merzbacher disease, a set of oligonucleotide primers was constructed to polymerase-chain-reaction (PCR) amplify and sequence the gene encoding proteolipid protein (PLP), a structural protein that comprises half of the protein of the myelin sheath. The PLP gene in one of two affected males and the carrier mother of this family exhibited a single base difference in the more than 2 kb of the PLP gene sequenced, a C----T transition that would create a serine substitution for proline at the carboxy end of the protein. Our results delineate the clinical features of Pelizaeus-Merzbacher disease, define the possible molecular pathology of this dysmyelinating disorder, and address the molecular classification of inborn errors of myelin metabolism. Patients with the classical form (type I) and the more severely affected, connatal variant of Pelizaeus-Merzbacher disease (type II) would be predicted to display mutation at the PLP locus. The other variants (types III-VI), which have sometimes been categorized as Pelizaeus-Merzbacher disease, may represent mutations in genes encoding other structural myelin proteins or proteins critical to myelination. PMID:2773936

Gencic, S; Abuelo, D; Ambler, M; Hudson, L D

1989-09-01

387

Schwann-cell differentiation in clonal cultures of the neural crest, as evidenced by the anti-Schwann cell myelin protein monoclonal antibody.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the vertebrate embryo, Schwann cells lining the peripheral nerves originate from the neural crest (NC), a structure that also gives rise to ganglion satellite cells, most of the neurons of the peripheral nervous system, melanocytes, and part of the cranial mesenchyme. We have studied the emergence of the Schwann cell lineage in vitro in clonal cultures of quail mesencephalic NC cells by using the Schwann cell myelin protein antigen as an early and specific marker for myelinating and nonmye...

1990-01-01

388

Heterogeneity of T-cell receptor alpha-chain complementarity-determining region 3 in myelin basic protein-specific T cells increases with severity of multiple sclerosis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The pathogenesis of multiple sclerosis (MS) is thought to involve a T-cell-mediated autoimmune process. Experimental allergic encephalomyelitis (EAE), an animal model resembling MS, can be induced by immunization with myelin antigens such as myelin basic protein. The T-cell antigen receptor (TCR) usage in EAE is highly restricted in some strains of animals and experimental treatments targeting the TCR have been successful in EAE. Examination of the TCR beta-chain variable-region (V beta) usag...

Utz, U.; Brooks, J. A.; Mcfarland, H. F.; Martin, R.; Biddison, W. E.

1994-01-01

389

Charcot-Marie-Tooth 1B caused by expansion of a familial myelin protein zero (MPZ) gene duplication.  

Science.gov (United States)

Charcot-Marie-Tooth (CMT) disease is a group of hereditary disorders affecting the motor and sensory nerves of the peripheral nervous system. CMT patterns of inheritance include dominant, recessive, and X-linked disorders. Charcot-Marie-Tooth disease, type 1B (CMT1B, OMIM 118200) is an autosomal dominant neuropathy caused by mutations in myelin protein zero (MPZ, OMIM 159440), a structural protein of peripheral myelin. Most causative MPZ mutations are missense sequence variants; however, recent clinical reports have described cases of CMT1B caused by increased dosage of the MPZ gene, with over-expression of the MPZ protein suspected to be causative of the disorder. We report an unusual case of early onset de novo CMT1B, caused by amplification of a familial, apparently benign, MPZ duplication. PMID:23811036

Speevak, Marsha D; Farrell, Sandra A

2013-10-01

390

Results of Split Liver Transplantation in Children  

Science.gov (United States)

Objective To analyze the outcome of 80 consecutive pediatric split liver transplants performed at the authors’ center between 1994 and 2000. Summary Background Data Split liver transplantation has become an accepted method of increasing the number of available grafts for pediatric liver transplant recipients. Methods The age of the patients at the time of transplantation ranged from 5 days to 16 years (median 3 years). Sixteen transplants were performed for acute liver failure and 64 for chronic liver failure. The ex situ splitting technique was used for all but four grafts. Fourteen livers were split for two pediatric recipients. Posttransplant follow-up ranged from 6 to 84 months (median 42 months). Results Overall patient survival at 6 months follow-up was 96.2%. Graft survival at six months was 93.7%. The Kaplan-Meier patient survival rates at 1 and 3 years were 93.5% and 88.1%, and the graft survival rates were 89.7% and 86.1%, respectively. Four patients required retransplantation. In the acute group (n = 16), the patient survival rates were 93.7% at 1 year and 76.4% at 3 years; there were three deaths due to posttransplant lymphoproliferative disease (PTLD), sepsis, and chronic rejection. In the chronic group (n = 64), the 1- and 3-year patient survival rates were 93.6% and 90.9%, respectively. There were six deaths in this group. Four patients died in the first year after the transplant due to intracranial bleeding, cerebral tumor recurrence, PTLD, and chronic rejection. There were two deaths at 3 years, one due to progressive renal failure secondary to cyclosporin toxicity and the other due to sepsis, portal hypertension, and recurrent bleeding. Vascular complications occurred in six (7.5%) patients and biliary complications in seven (8.7%). Conclusions These results, which represent the experience of a single institution over the last 6 years, indicate that ex situ split liver transplantation can be performed in children with good overall outcome and acceptable morbidity.

Deshpande, Rahul R.; Bowles, Matthew J.; Vilca-Melendez, Hector; Srinivasan, Parthi; Girlanda, Raffaele; Dhawan, Anil; Mieli-Vergani, Giorgina; Muiesan, Paolo; Heaton, Nigel D.; Rela, Mohamed

2002-01-01

391

TGF? Signaling Regulates the Timing of CNS Myelination by Modulating Oligodendrocyte Progenitor Cell Cycle Exit through SMAD3/4/FoxO1/Sp1.  

Science.gov (United States)

Research on myelination has focused on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. Here, we show that transforming growth factor ? (TGF?) signaling is crucial for allowing oligodendrocyte progenitor (OP) cell cycle withdrawal, and therefore, for oligodendrogenesis and postnatal CNS myelination. Enhanced oligodendrogenesis and subcortical white matter (SCWM) myelination was detected after TGF? gain of function, while TGF? receptor II (TGF?-RII) deletion in OPs prevents their development into mature myelinating OLs, leading to SCWM hypomyelination in mice. TGF? signaling modulates OP cell cycle withdrawal and differentiation through the transcriptional modulation of c-myc and p21 gene expression, mediated by the interaction of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the first to demonstrate an autonomous and crucial role of TGF? signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases. PMID:24899714

Palazuelos, Javier; Klingener, Michael; Aguirre, Adan

2014-06-01

392

Shortened internodal length of dermal myelinated nerve fibres in Charcot–Marie-Tooth disease type 1A  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Charcot–Marie-Tooth disease type 1A is the most common inherited neuropathy and is caused by duplication of chromosome 17p11.2 containing the peripheral myelin protein-22 gene. This disease is characterized by uniform slowing of conduction velocities and secondary axonal loss, which are in contrast with non-uniform slowing of conduction velocities in acquired demyelinating disorders, such as chronic inflammatory demyelinating polyradiculoneuropathy. Mechanisms responsible for the slowed con...

Saporta, Mario A.; Katona, Istvan; Lewis, Richard A.; Masse, Stacey; Shy, Michael E.; Li, Jun

2009-01-01

393

Protein-tyrosine Phosphatase ? Acts as an Upstream Regulator of Fyn Signaling to Promote Oligodendrocyte Differentiation and Myelination*  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The tyrosine kinase Fyn plays a key role in oligodendrocyte differentiation and myelination in the central nervous system, but the molecules responsible for regulating Fyn activation in these processes remain poorly defined. Here we show that receptor-like protein-tyrosine phosphatase ? (PTP?) is an important positive regulator of Fyn activation and signaling that is required for the differentiation of oligodendrocyte progenitor cells (OPCs). PTP? is expressed in OPCs and is up-regulated d...

Wang, Pei-shan; Wang, Jing; Xiao, Zhi-cheng; Pallen, Catherine J.

2009-01-01

394

Schwann cells but not olfactory ensheathing cells inhibit CNS myelination via the secretion of connective tissue growth factor.  

Science.gov (United States)

Cell transplantation is a promising strategy to promote CNS repair and has been studied for several decades with a focus on glial cells. Promising candidates include Schwann cells (SCs) and olfactory ensheathing cells (OECs). Both cell types are thought to be neural crest derived and share many properties in common, although OECs appear to be a better candidate for transplantation by evoking less astrogliosis. Using CNS mixed myelinating rat cultures plated on to a monolayer of astrocytes, we demonstrated that SCs, but not OECs, secrete a heat labile factor(s) that inhibits oligodendrocyte myelination. Comparative qRT-PCR and ELISA showed that SCs expressed higher levels of mRNA and protein for connective tissue growth factor (CTGF) than OECs. Anti-CTGF reversed the SCM-mediated effects on myelination. Both SCM and CTGF inhibited the differentiation of purified rat oligodendrocyte precursor cells (OPCs). Furthermore, pretreatment of astrocyte monolayers with SCM inhibited CNS myelination and led to transcriptional changes in the astrocyte, corresponding to upregulation of bone morphogenic protein 4 mRNA and CTGF mRNA (inhibitors of OPC differentiation) and the downregulation of insulin-like growth factor 2 mRNA (promoter of OPC differentiation). CTGF pretreatment of astrocytes increased their expression of CTGF, suggesting that this inhibitory factor can be positively regulated in astrocytes. These data provide evidence for the advantages of using OECs, and not mature SCs, for transplant-mediated repair and provide more evidence that they are a distinct and unique glial cell type. PMID:24259589

Lamond, Rebecca; Barnett, Susan C

2013-11-20

395

Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers  

International Nuclear Information System (INIS)

Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

2014-04-01

396

Myelin basic protein in the CSF of patients with multiple sclerosis, optic neuritis and various neurological diseases.  

Science.gov (United States)

We tested 104 patients for myelin basic protein (MBP) content in the CSF. Of these subjects 14 were selected as control group, 36 were affected by multiple sclerosis (MS), 14 by optic neuritis (ON) and 42 presented other not primarily demyelinating neurological diseases (ND ND). CSF MBP level was significantly higher in the MS group than in the other groups of patients, while no statistical difference was found between the MS patients with acute exacerbation and those in remission. PMID:2433886

Pavarotti, V; Merelli, E; De Palma, M; Bettelli, G; Faglioni, P

1986-01-01

397

Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Peripheral sensory nerve abnormalities were investigated in long-term streptozotocin diabetic rats using quantitative analysis. To determine whether the characteristic structural changes occur with a proximodistal gradient, three levels of the sensory peripheral nervous system were investigated: the postganglionic segment of the dorsal root, the midportion of the sciatic nerve, and the distal sural nerve. Reduction of myelinated fiber size due to reduced axonal caliber was the most characteri...

Yagihashi, S.; Kamijo, M.; Watanabe, K.

1990-01-01

398

Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease, lesions are predominantly found in the optic nerves and spinal cord but not the brain. The immunological bases of the different forms of MS are unknown. We previously generated myelin oligodendrocyte glycoprotein–specific (MOG-specific) TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that a large proportion of t...

Bettelli, Estelle; Baeten, Dominique; Ja?ger, Anneli; Sobel, Raymond A.; Kuchroo, Vijay K.

2006-01-01

399

Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers  

Energy Technology Data Exchange (ETDEWEB)

Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

2014-04-15

400

Serum and cerebrospinal fluid antibodies against myelin basic protein and their IgG subclass distribution in multiple sclerosis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

IgG class antibodies reactive with myelin basic protein (MBP) were determined by enzyme-linked immunosorbent assay (ELISA) in serum and cerebrospinal fluid (CSF) of 37 patients with multiple sclerosis and a control group of 32 patients with tension headache or psychoneurosis. Using standardised amounts of IgG from CSF and serum in ELISA, significantly higher mean antibody levels were found in CSF as well as in serum from the patients with multiple sclerosis. Ten (27%) of the multiple sclerosi...

1986-01-01

 
 
 
 
401

Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients.  

Science.gov (United States)

Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers. PMID:15082135

Dougherty, Patrick M; Cata, Juan P; Cordella, Joseph V; Burton, Allen; Weng, Han-Rong

2004-05-01

402

Rapid voltage-dependent dissociation of scorpion alpha-toxins coupled to Na channel inactivation in amphibian myelinated nerves  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The voltage-dependent action of several scorpion alpha-toxins on Na channels was studied in toad myelinated nerve under voltage clamp. These toxins slow the declining phase of macroscopic Na current, apparently by inhibiting an irreversible channel inactivation step and thus permitting channels to reopen from a closed state in depolarized membranes. In this article, we describe the rapid reversal of alpha- toxin action by membrane depolarizations more positive than +20 mV, an effect not achie...

1986-01-01

403

Early postnatal repeated maternal deprivation causes a transient increase in OMpg and BDNF in rat cerebellum suggesting precocious myelination.  

Science.gov (United States)

Repetitive maternal deprivation (MD) of neonatal rats during early life is known as one of the strongest stressors to pre-weaned animals. There is increasing evidence that the cerebellum is involved in cognition and emotion. In the present study, we examined how neurotrophic factors and myelin-associated molecules and their receptors (NGF, BDNF, OMgp, TrkA, TrkB, p75 NTR, and NgR) in the cerebellum are affected by early postnatal maternal separation. Rat pups were separated from their mothers for 3h/day during postnatal days (PND) 10-15. At PND 16 and 30, the levels of mRNA and protein in the cerebellum were determined using real-time PCR and Western blot analysis. Cerebellar mRNA and protein levels of BDNF, TrkB, and OMgp were significantly increased in MD rats at PND 16. However, by PND 30 these variables normalized to control levels. In contrast, the levels of mRNA and protein for NGF, TrkA, p75 NTR, and NgR were unchanged at both ages examined. Transient enhancement of neurotrophic system and myelin-associated molecule expression may cause interference of normal development of the cerebellum such as precocious myelination, which may lead to functional and cognitive deficits later in life. PMID:24157309

Miki, Takanori; Yokoyama, Toshifumi; Kusaka, Takashi; Suzuki, Shingo; Ohta, Ken-ichi; Warita, Katsuhiko; Wang, Zhi-Yu; Ueki, Masaaki; Sumitani, Kazunori; Bellinger, Frederick P; Tamai, Motoki; Liu, Jun-Qian; Yakura, Tomiko; Takeuchi, Yoshiki

2014-01-15

404

Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration.  

Science.gov (United States)

Remyelination is an important aspect of nerve regeneration after nerve injury, but the underlying mechanisms are not fully understood. Here, we show that meltrin-beta (ADAM19), a member of the ADAM (a disintegrin and metalloprotease) family, plays crucial roles in nerve regeneration after a crush injury to the sciatic nerves. The expression of meltrin-beta was up-regulated in neurons after the crush injury. Morphometrical analysis revealed a delay in remyelination in meltrin-beta-deficient nerves, whereas no significant defects were observed in their axon elongation. The activation of Krox-20, an indispensable transcription factor for myelination, was delayed in meltrin-beta-deficient nerves and was accompanied by the retarded expression of myelin-related proteins. Expression of Krox-20 in Schwann cells was mediated by Akt. Phosphorylation of Akt but not that of Erks was reduced in regenerating nerves of meltrin-beta-deficient mice. The cell membrane fraction prepared from meltrin-beta-deficient nerves showed a defective activation of Akt in the membrane-loaded Schwann cells. Meltrin-beta-deficient mice exhibited delayed sciatic functional recovery after the nerve crush. Altogether, these results reveal a role of meltrin-beta in Schwann cell differentiation and re-myelination in nerve regeneration. Moreover, this study suggests that meltrin-beta functions as a modulator of juxtacrine signaling from axons that activate the Akt pathway and the Krox-20 expression, which is the prerequisite for Schwann cell differentiation. PMID:19049978

Wakatsuki, Shuji; Yumoto, Norihiro; Komatsu, Koji; Araki, Toshiyuki; Sehara-Fujisawa, Atsuko

2009-01-30

405

Cdc42 regulates Schwann cell radial sorting and myelin sheath folding through NF2/merlin-dependent and independent signaling.  

Science.gov (United States)

The Rho family GTPase Cdc42 has been implicated in developmental Schwann cell (SC) proliferation, providing sufficient SCs for radial sorting of axons preceding SC differentiation in the peripheral nervous system. We generated Cdc42 conditional knockout (Cdc42-CKO) mice and confirmed aberrant axon sorting in Cdc42-CKO nerves. In adult Cdc42-CKO nerves, blood vessels were enlarged, and mature Remak bundles containing small axons were absent. Abnormal infoldings and outfoldings of myelin sheaths developed in Cdc42-CKO nerves, mimicking pathological features of Charcot-Marie-Tooth (CMT) disease. The NF2/merlin tumor suppressor has been implicated up- and down-stream of Cdc42. In Cdc42-CKO;NF2-del double mutant mice, radial sorting defects seen in Cdc42-CKO nerves were rescued, while changes in myelin sheaths in Cdc42-CKO nerves were not. Phosphorylation of Focal adhesion kinase (FAK) and P-GSK3?, as well as expression of ?-catenin were decreased in Cdc42-CKO nerves, and these changes were rescued by NF2/merlin mutation in Cdc42-CKO;NF2-del double mutant mice. Thus, Cdc42 regulates SC radial sorting in vivo through NF2/merlin dependent signaling pathways, while Cdc42 modulation of myelin sheath folding is NF2/merlin independent. PMID:24014231

Guo, Li; Moon, Chandra; Zheng, Yi; Ratner, Nancy

2013-11-01

406

One-sided and two-sided Heegaard splittings  

CERN Document Server

We define a notion of Hempel distance for one-sided Heegaard splittings and show that the existence of alternate surfaces restricts distance for one-sided splittings in a manner similar to Hartshorn's and Scharlemann-Tomova's results for two-sided splittings. We also show that every geometrically compressible one-sided Heegaard surface in a non-Haken 3-manifold is stabilized, and show that the mapping class group of the two-sided Heegaard splitting induced by a high distance one-sided splitting is isomorphic to the fundamental group of the one-sided surface.

Johnson, Jesse

2011-01-01

407

The isomorphism problem for almost split Kac-Moody groups  

CERN Document Server

We consider the isomorphism problem for almost split Kac--Moody groups, which have been constructed by R\\'emy via Galois descent from split Kac-Moody groups as defined by Tits. We show that under certain technical assumptions, any isomorphism between two such groups must preserve the canonical subgroup structure, i.e. the twin root datum associated to these groups, which generalizes results of Caprace in the split case. An important technical tool we use is the existence of maximal split subgroups inside almost split Kac-Moody groups, which generalizes the corresponding result of Borel-Tits for reductive algebraic groups.

Hainke, Guntram

2011-01-01

408

Splitting in dual-phase 590 high strength steel plates  

Energy Technology Data Exchange (ETDEWEB)

The influence of splitting on Charpy impact energy was investigated by analyzing the primary fracture (from the Charpy V-notch) and splitting (secondary fracture) surfaces at different test temperatures quantitatively. The morphology of splitting at the primary fracture surface of Charpy impact specimens made of dual-phase (DP) 590 hot-rolled steel in TL direction at +60 deg. C and -30 deg. C were surveyed by scanning electron microscope (SEM). The broken Charpy impact specimens in both TL and LT directions at different test temperatures were studied by examining sliced images obtained from micro-radiography imaging system. Three-dimension (3D) and plane sliced images of specimens were analyzed using GEHC microview software. Results show that fracture appearance inside the splitting is cleavage. The length and depth of the splitting increased with decreasing test temperature. Splitting width decreased first then the trend becomes irregular when test temperature falls due to variation of steel ductility and reaction between splitting and the primary crack. The surface areas of splitting and primary crack changed with test temperature as well. Splitting area increased with decreasing test temperature, while the surface area of the primary crack decreased as the test temperature was lowered. Influence of splitting on the impact energy in upper shelf of DP590 hot-rolled steel is small. In the ductile-to-brittle transition temperature (DBTT) range, splitting tends to increase the Charpy impact energy and consequently reduced the DBTT of DP590 hot-rolled steel.

Yang Min [School of Materials Science and Engineering, Shandong University, Jinan, Shandong 250061 (China); Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Chao, Yuh J. [Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States)], E-mail: chao@sc.edu; Li Xiaodong [Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Immel, David [Savannah River National Laboratory, Aiken, SC (United States); Tan Jinzhu [College of Mechanical and Power Engineering, Nanjing University of Technology, Nanjing, Jiangsu 210009 (China); Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States)

2008-12-15

409

Splitting in dual-phase 590 high strength steel plates  

International Nuclear Information System (INIS)

The influence of splitting on Charpy impact energy was investigated by analyzing the primary fracture (from the Charpy V-notch) and splitting (secondary fracture) surfaces at different test temperatures quantitatively. The morphology of splitting at the primary fracture surface of Charpy impact specimens made of dual-phase (DP) 590 hot-rolled steel in TL direction at +60 deg. C and -30 deg. C were surveyed by scanning electron microscope (SEM). The broken Charpy impact specimens in both TL and LT directions at different test temperatures were studied by examining sliced images obtained from micro-radiography imaging system. Three-dimension (3D) and plane sliced images of specimens were analyzed using GEHC microview software. Results show that fracture appearance inside the splitting is cleavage. The length and depth of the splitting increased with decreasing test temperature. Splitting width decreased first then the trend becomes irregular when test temperature falls due to variation of steel ductility and reaction between splitting and the primary crack. The surface areas of splitting and primary crack changed with test temperature as well. Splitting area increased with decreasing test temperature, while the surface area of the primary crack decreased as the test temperature was lowered. Influence of splitting on the impact energy in upper shelf of DP590 hot-rolled steel is small. In the ductile-to-brittle transition temperature (DBTT) range, splitting tends to increase the Charpy impact energy and consequently reduced the DBTT of DP590 hot-rolled steel

2008-12-15

410

Precision of a splitting device for water samples  

Science.gov (United States)

Two identical cone splitters, devices designed to split water and its suspended solids into equal aliquots for semi-volatile organic chemical and trace element analyses, were evaluated for their precision. The water-splitting evaluations consisted of experiments to test the effect of water volume, the effect of combining outlet ports, and the effect of different techniques of water introduction. The solids-splitting evaluations consisted of experi- ments to test the effect of particle size (nine different particle diameters ranging from very coarse sand to clay) and suspended-solids concentration. In general, water was equally split with a precision of less than 5 percent relative standard deviation. The accuracy of splitting the solids was a function of particle size. Clay, silt, and fine and medium sand were split with a precision relative standard deviation of less than 7 percent, and coarse sand was split with a relative standard deviation between 12 and 45 percent.

Capel, Paul D.; Nacionales, Fernando C.; Larson, Steven J.

1995-01-01

411