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1

Myelin Organization in the Nodal, Paranodal, and Juxtaparanodal Regions Revealed by Scanning X-Ray Microdiffraction  

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X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. ...

Inouye, Hideyo; Liu, Jiliang; Makowski, Lee; Palmisano, Marilena; Burghammer, Manfred; Riekel, Christian; Kirschner, Daniel A.

2014-01-01

2

Novel forms of neurofascin 155 in the central nervous system: alterations in paranodal disruption models and multiple sclerosis  

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Stability of the myelin-axon unit is achieved, at least in part, by specialized paranodal junctions comprised of the neuronal heterocomplex of contactin and contactin-associated protein and the myelin protein neurofascin 155. In multiple sclerosis, normal distribution of these proteins is altered, resulting in the loss of the insulating myelin and consequently causing axonal dysfunction. Previously, this laboratory reported that mice lacking the myelin-enriched lipid sulphatide are characteri...

Pomicter, Anthony D.; Shroff, Seema M.; Fuss, Babette; Sato-bigbee, Carmen; Brophy, Peter J.; Rasband, Matthew N.; Bhat, Manzoor A.; Dupree, Jeffrey L.

2010-01-01

3

Nfasc155H and MAG are specifically susceptible to detergent extraction in the absence of the myelin sphingolipid sulfatide.  

Science.gov (United States)

Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that deteriorate with age. Similar instability also occurs in mice that lack contactin, contactin-associated protein or neurofascin155 (Nfasc155), the proteins that cluster in the paranode and form the junctional complex that mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not been shown to be enriched in the paranode nor has a sulfatide paranodal binding partner been identified; thus, it remains unclear how the absence of sulfatide results in compromised paranode integrity. Using an in situ extraction procedure, it has been reported that the absence of the myelin sphingolipids, galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to detergent extraction. Here, employing a similar approach, we demonstrate that in the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is susceptible to detergent extraction. Furthermore, we use this in situ approach to show that stable association of myelin-associated glycoprotein (MAG) with the myelin membrane is sulfatide dependent while the membrane associations of myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide phosphodiesterase are sulfatide independent. These findings indicate that myelin proteins maintain their membrane associations by different mechanisms. Moreover, the myelin proteins that cluster in the paranode and require sulfatide mediate myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for maintaining Nfasc155 and MAG associations is intriguing since the fatty acid composition of sulfatide is altered and paranodal ultrastructure is compromised in multiple sclerosis. Thus, our findings present a potential link between sulfatide perturbation and myelin deterioration in multiple sclerosis. PMID:24081651

Pomicter, A D; Deloyht, J M; Hackett, A R; Purdie, N; Sato-Bigbee, C; Henderson, S C; Dupree, J L

2013-12-01

4

Nodes of Ranvier and Paranodes in Chronic Acquired Neuropathies  

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Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP) and chronic idiopathic axonal polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial per...

Cifuentes-diaz, Carmen; Dubourg, Odile; Irinopoulou, Theano; Vigny, Marc; Lachkar, Sylvie; Decker, Laurence; Charnay, Patrick; Denisenko, Natalia; Maisonobe, Thierry; Le?ger, Jean-marc; Viala, Karine; Hauw, Jean-jacques; Girault, Jean-antoine

2011-01-01

5

Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics.  

Science.gov (United States)

Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt-Lanterman incisures and the axo-glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics. PMID:25478838

Denninger, Andrew R; Demé, Bruno; Cristiglio, Viviana; LeDuc, Géraldine; Feller, W Bruce; Kirschner, Daniel A

2014-12-01

6

Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics  

Science.gov (United States)

Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics. PMID:25478838

Denninger, Andrew R.; Demé, Bruno; Cristiglio, Viviana; LeDuc, Géraldine; Feller, W. Bruce; Kirschner, Daniel A.

2014-01-01

7

The 4.1B cytoskeletal protein regulates the domain organization and sheath thickness of myelinated axons  

Science.gov (United States)

Myelinated axons are organized into specialized domains critical to their function in saltatory conduction, i.e. nodes, paranodes, juxtaparanodes, and internodes. Here, we describe the distribution and role of the 4.1B protein in this organization. 4.1B is expressed by neurons, and at lower levels by Schwann cells, which also robustly express 4.1G. Immunofluorescence and immuno-EM demonstrates 4.1B is expressed subjacent to the axon membrane in all domains except the nodes. Mice deficient in 4.1B have preserved paranodes, based on marker staining and EM in contrast to the juxtaparanodes, which are substantially affected in both the PNS and CNS. The juxtaparanodal defect is evident in developing and adult nerves and is neuron-autonomous based on myelinating cocultures in which wt Schwann cells were grown with 4.1B-deficient neurons. Despite the juxtaparanodal defect, nerve conduction velocity is unaffected. Preservation of paranodal markers in 4.1B deficient mice is associated with, but not dependent on an increase of 4.1R at the axonal paranodes. Loss of 4.1B in the axon is also associated with reduced levels of the internodal proteins, Necl-1 and Necl-2, and of alpha-2 spectrin. Mutant nerves are modestly hypermyelinated and have increased numbers of Schmidt-Lanterman incisures, increased expression of 4.1G, and express a residual, truncated isoform of 4.1B. These results demonstrate that 4.1B is a key cytoskeletal scaffold for axonal adhesion molecules expressed in the juxtaparanodal and internodal domains and, unexpectedly, that it regulates myelin sheath thickness. PMID:23109359

Einheber, Steven; Maurel, Patrice; Meng, Xiaosong; Rubin, Marina; Lam, Isabel; Mohandas, Narla; An, Xiuli; Shrager, Peter; Kissil, Joseph; Salzer, James L.

2012-01-01

8

?????????? ?????????????? ??? SPLIT-????????????? ??? ????????????? ?? ?????????????????? ??? ??????????  

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In this article it was used the method of the exergetic analysis of one-step freon cooling engines of the local autonomous air conditioners. It was defined the dependence of the exergetic output-input ratio for the “split” air conditioner of firm “Sanyo” with cooling capacity 2020 W from the adiabatic and the electromechanic output-input ratio for the compressor.

??????, ?. ??

2008-01-01

9

ATP-induced lipid membrane reordering in the myelinated nerve fiber identified using Raman spectroscopy  

International Nuclear Information System (INIS)

We demonstrate a successful application of Raman spectroscopy to the problem of lipid ordering with microscopic resolution in different regions of the myelinated nerve fiber. Simultaneous collection of Raman spectra of lipids and carotenoids has enabled us to characterize membrane fluidity and the degree of lipid ordering based on intensity ratios for the 1527/1160 and 2940/2885 cm?1 bands. We show that the intensity profiles of the major Raman bands vary significantly between the three major regions of myelinated nerve fiber: internode, paranode and the node of Ranvier. Mapping Raman peak intensities over these areas suggested that the carotenoid molecules are localized in the myelin membranes of nerve cells. Paranodal membranes were sensitive to extracellular ATP. ATP solutions (7 mM) influenced the 1527/1160 and 2940/2885 cm?1 intensity ratios. Changes in both carotenoid and lipid Raman spectra were in accord and indicated an increase in lipid ordering degree and decrease in membrane fluidity under ATP administration. The collected data provide evidence for the existence of a regulatory purinergic signaling pathway in the peripheral nervous system. (letter)

10

Neuregulin-1 and Myelination  

Science.gov (United States)

The trigger for the process of myelin formation during neural development has long been a mystery. Recent studies suggest that this trigger is the growth factor neuregulin-1, expressed on the surface of axons, which signals through ErbB2 and ErbB3 receptors expressed on the surface of myelin-forming glia.

Greg Lemke (The Salk Institute; REV)

2006-03-07

11

Theory of myelin coiling.  

Science.gov (United States)

A new model is proposed to explain coiling of myelins composed of fluid bilayers. This model allows the constituent bilayer cylinders of a myelin to be non-coaxial and the bilayer lateral tension to vary from bilayer to bilayer. The calculations show that a myelin would bend or coil to lower its free energy when the bilayer lateral tension is sufficiently large. From a mechanical point of view, the proposed coiling mechanism is analogous to the classical Euler buckling of a thin elastic rod under axial compression. The analysis of a simple two-bilayer case suggests that a bilayer lateral tension of about 1 dyne/cm can easily induce coiling of myelins of typical lipid bilayers. This model signifies the importance of bilayer lateral tension in determining the morphology of myelinic structures. PMID:16465468

Huang, J-R

2006-04-01

12

Theory of Myelin Coiling  

CERN Document Server

A new model is proposed to explain coiling of myelins composed of fluid bilayers. This model allows the constituent bilayer cylinders of a myelin to be non-coaxial and the bilayer lateral tension to vary from bilayer to bilayer. The calculations show that a myelin would bend or coil to lower its free energy when the bilayer lateral tension is sufficiently large. From a mechanical point of view, the proposed coiling mechanism is analogous to the classical Euler buckling of a thin elastic rod under axial compression. The analysis of a simple two-bilayer case suggests that a bilayer lateral tension of about 1 dyne/cm can easily induce coiling of myelins of typical lipid bilayers. This model signifies the importance of bilayer lateral tension in determining the morphology of myelinic structures.

Huang, J R

2005-01-01

13

Exogenous lipids in myelination and myelination.  

Science.gov (United States)

Myelinogenesis is a scheduled process that depends on both the intrinsic properties of the cell and extracellular signals. In rat brain, myelin development is an essentially postnatal event and environmental interferences could affect myelin synthesis. Nutrition plays an important role, since severe postnatal malnutrition and essential fatty acid (EFA) deficiency cause hypomyelination. Even though the dietary effects are more pronounced in the postnatal period, dietary lipids can affects myelin development also in the postweaning period. Rats fed with diets rich in polyunsaturated n3 fatty acids showed a decrease of the relative amount of myelin basic protein (MBP) and a CNPase activity indicating a delay in myelin deposition and/or an instability of its structure. Our recent studies have shown that dietary fatty acids can be positively involved in the control of central nervous system (CNS) myelinogenesis. Offspring of rats fed diets containing odd chain fatty acid during pregnancy and lactation show an early development of behavioral reflexes linked to myelination compared to controls fed a diet containing margarine. Subsequent studies have shown that the expression of myelin proteins is higher in test than in control animals, but the mechanism of the action of fatty acids is still unknown. Also human brain myelinogenesis can be affected by environmental factors. EFA deficiency has been well studied for the important role of C22:6 (a C18:3 metabolite) in the vision system development. The observation that dietary fatty acids can affect membrane composition has led to the use of modified diets in some CNS pathological conditions. For example, preterm infants characterized by low levels of C22:6 and fed with formulae diets enriched in this fatty acid, show a recovery of visual function. The administration of C22:6 has also been tested in patients affected by peroxisomal biogenesis disorders which are associated with very low levels of this fatty acid in the brain. During the treatment, C22:6 content increases in red blood cells, and probably in the brain membranes, as considerable neurologic and electrophysiological improvement suggest. A mixture of glyceryltrierucate and glyceryltrioleate has been tested in the demyelinating disease Adrenoleukodistrophy which is characterized by an abnormal accumulation of very long chain fatty acids (VLCFA) in tissues and fluids. The diet is able to lower VLCFA levels in plasma, but its efficacy for myelin damage is debated. Lastly, a diet which reduces the intake of saturated fatty acid and increases the quantity of polyunsaturates is suggested for multiple sclerosis patients since a decrease of linoleic acid in their plasma and erythrocytes has been observed. Such a diet seems able to reduce the severity of the attacks. PMID:9130819

Di Biase, A; Salvati, S

1997-01-01

14

Electron microscopy of trypsin-digested peripheral nerve myelin.  

Science.gov (United States)

Sciatic nerves from mice were removed and soaked in either PBS (phosphate buffered saline) or PBS plus I% trypsin (Sigma Type III) for various periods of time. Specimens were soaked at either room temperature or 37-degrees C at pH's ranging from 7.5 to 8.0. The epineural and perineural sheaths were split to allow the trypsin to penetrate the nerve. Tissue was prepared for electron microscopy by fixation in cacodylate buffered formaldehyde-glutaraldehyde solutions, post-fixed in OSO4 and embedded in Epon 812 or in glutaraldehyde-urea resin without osmication. After four h incubation at 37-degrees C or eight h at room temperature, the basement membranes of the Schwann cells became fragmented and detached and the myelin intraperiod band lost some density. After 18 h, myelin with swollen intraperiod bands displaying a loss of electron density and split main period bands was noted adjacent to normal myelin. Other areas had been transformed into vesicles indicating that the membranes of these vesicles appeared to have been derived from the detachment of both the intraperiod and main period bands within the myelin. Evidence is presented for the presence of trypsin digestable proteins in both the main period and intraperiod bands of peripheral nervouse system myelin. PMID:1113138

Peterson, R G

1975-02-01

15

Myelin imaging compound (MIC) enhanced magnetic resonance imaging of myelination.  

Science.gov (United States)

The vertebrate nervous system is characterized by myelination, a fundamental biological process that protects the axons and facilitates electric pulse transduction. Damage to myelin is considered a major effect of autoimmune diseases such as multiple sclerosis (MS). Currently, therapeutic interventions are focused on protecting myelin integrity and promoting myelin repair. These efforts need to be accompanied by an effective imaging tool that correlates the disease progression with the extent of myelination. To date, magnetic resonance imaging (MRI) is the primary imaging technique to detect brain lesions in MS. However, conventional MRI cannot differentiate demyelinated lesions from other inflammatory lesions and therefore cannot predict disease progression in MS. To address this problem, we have prepared a Gd-based contrast agent, termed MIC (myelin imaging compound), which binds to myelin with high specificity. In this work, we demonstrate that MIC exhibits a high kinetic stability toward transmetalation with promising relaxometric properties. MIC was used for in vivo imaging of myelination following intracerebroventricular infusion in the rat brain. MIC was found to distribute preferentially in highly myelinated regions and was able to detect regions of focally induced demyelination. PMID:22098543

Frullano, Luca; Zhu, Junqing; Wang, Changning; Wu, Chunying; Miller, Robert H; Wang, Yanming

2012-01-12

16

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.

2011-06-01

17

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

18

Myelin vacuolation, optic neuropathy and retinal degeneration after closantel overdosage in sheep and in a goat  

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Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4–70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and e...

Lugt, Jaco J.; Venter, I.

2007-01-01

19

In Situ Fluorescence Imaging of Myelination  

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We describe a novel fluorescent dye, 3-(4-aminophenyl)-2H-chromen-2-one (termed case myelin compound or CMC), that can be used for in situ fluorescent imaging of myelin in the vertebrate nervous system. When administered via intravenous injection into the tail vein, CMC selectively stained large bundles of myelinated fibers in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, CMC readily entered the brain and selectively localized in myelinated regions...

Wang, Changning; Popescu, Daniela C.; Wu, Chunying; Zhu, Junqing; Macklin, Wendy; Wang, Yanming

2010-01-01

20

Myelination in very low birth weight infants  

International Nuclear Information System (INIS)

The prognostic significance of cerebral myelination was evaluated with magnetic resonance imaging (MRI) in very low birth weight infants. Myelination was graded in two specified sites, optic radiation and corpus callosum, based on the stages of normal term babies and healthy premature infants. The subjects were 30 preterm infants weighing less than 1,500 gm at birth. MRI was performed at 4 to 7 months (corrected age). The normal myelination stage was seen in 18 cases, while a delayed stage was noticed in 12 cases. In the normal myelination group, only 1 case (6%) had handicaps. In the delayed myelination group, 8 cases (67%) had handicaps. Our results showed that delayed myelination was closely related to a poor prognosis. We believe that MRI would be a very good imaging modality for predicting the outcome of very low birth weight infants, particularly in terms of evaluation of myelination. (author)

 
 
 
 
21

Myelin synthesis in the peripheral nervous system.  

Science.gov (United States)

By imposing saltatory conduction on the nervous impulse, the principal role of the myelin sheath is to allow the faster propagation of action potentials along the axons which it surrounds. Peripheral nervous system (PNS) myelin is formed by the differentiation of the plasma membrane of Schwann cells. One of the biochemical characteristics that distinguishes myelin from other biological membranes is its high lipid-to-protein ratio. All the major lipid classes are represented in the myelin membrane, while several myelin-specific proteins have been identified. During development, the presence of axons is required for the initiation of myelination, but the nature of the axonal signal is still unknown. The only certainties are that this signal is synthesized by axons whose diameter is greater than 0.7 microm, and that the signal(s) include(s) a diffusible molecule. Morphological studies have provided us with information concerning the timing of myelination, the mechanism by which immature Schwann cells differentiate into a myelinating phenotype and lay down the myelin sheath around the axon, and the accumulation and the structure of the myelin membrane. The last 20 years have seen the identification and the cDNA and gene cloning of the major PNS myelin proteins, which signalled the beginning of the knock-out decade: transgenic null-mutant mice have been created for almost every protein gene. The study of these animals shows that the formation of myelin is considerably less sensitive to molecular alterations than the maintenance of myelin. During the same period, important data has been gathered concerning the synthesis and function of lipids in PNS myelin, although this field has received relatively little attention compared with that of their protein counterparts. PMID:10727776

Garbay, B; Heape, A M; Sargueil, F; Cassagne, C

2000-06-01

22

Schwann cell myelination requires Dynein function  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

Langworthy Melissa M

2012-11-01

23

MYELIN BASIC PROTEIN-MESSENGER RNA (MBP-MRNA) EXPRESSION DURING TRIETHYLTIN-INDUCED MYELIN EDEMA  

Science.gov (United States)

Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. ET has been reported to depress levels of myelin basic protein (MBP), a glycoprot...

24

Myelin vacuolation, optic neuropathy and retinal degeneration after closantel overdosage in sheep and in a goat.  

Science.gov (United States)

Toxicity of closantel, a halogenated salicylanilide anthelmintic, is described in 11 sheep and a goat, humanely killed 4-70 days after accidental overdosage. Status spongiosis of the cerebrum and cerebellum was present, its severity decreasing with time after treatment. Ultrastructurally, vacuoles in the cerebral white matter were seen to be intramyelinic due to splitting of myelin lamellae at the intraperiod lines, indicating myelin oedema. In the optic nerves, Wallerian degeneration and eventual fibrosis and atrophy of the nerves followed myelin vacuolation. Lesions in the optic nerves were particularly advanced in the intracanalicular portion, indicating a compressive neuropathy within the optic canal. Acute retinal lesions consisted of papilloedema, necrosis of the outer retinal layers (especially the photoreceptor layer), and retinal separation in tapetal and non-tapetal areas. In more chronic cases, the outer nuclear layer was diffusely attenuated and generally reduced to a single row of cells. PMID:17270202

van der Lugt, J J; Venter, I

2007-01-01

25

Myelin architecture: zippering membranes tightly together.  

Science.gov (United States)

Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular processes that extend from oligodendrocytes and wrap in a spiral fashion around an axon, resulting in the close apposition of adjacent myelin membrane bilayers. In this review, we discuss the physical principles underlying the zippering of the plasma membrane of oligodendrocytes at the cytoplasmic and extracellular leaflet. We propose that the interaction of the myelin basic protein with the cytoplasmic leaflet of the myelin bilayer triggers its polymerization into a fibrous network that drives membrane zippering and protein extrusion. In contrast, the adhesion of the extracellular surfaces of myelin requires the down-regulation of repulsive components of the glycocalyx, in order to uncover weak and unspecific attractive forces that bring the extracellular surfaces into close contact. Unveiling the mechanisms of myelin membrane assembly at the cytoplasmic and extracelluar sites may help to understand how the myelin bilayers are disrupted and destabilized in the different demyelinating diseases. PMID:24165921

Bakhti, Mostafa; Aggarwal, Shweta; Simons, Mikael

2014-04-01

26

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 nonenzyell 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

27

Axon-myelin transfer of phospholipids and phospholipid precursors. Labeling of myelin phosphoinositides through axonal transport.  

Science.gov (United States)

Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization process. The present study will examine the labeling of myelin phosphoinositides by this pathway. Both 32PO4 and [3H]inositol were injected monocularly into 7-9-wk-old rabbits and myelin was isolated 7 or 21 days later from pooled optic tracts and superior colliculi. In total lipids 32P counts of the isolated myelin samples showed significant contralateral/ipsilateral ratios as well as increasing magnitude of contralateral-ipsilateral differences during the time interval. Thin-layer chromatographic isolation of the myelin phosphoinositides revealed significant 32P-labeling of these species, with PIP and PIP2 showing time-related increases. This resembled the labeling pattern of the major phospholipids from rabbit optic system myelin in a previous study and suggested incorporation of axon-derived phosphate by myelin-associated enzymes. The 32P label in PI, on the other hand, remained constant between 7 and 21 days, suggesting transfer of intact lipid. This was supported by the labeling pattern with [3H]inositol, which also showed no increase over time for PI. These results suggest axon-myelin transfer of intact PI followed by myelin-localized incorporation of axon-derived phosphate groups into PIP and PIP2. The general topic of axon-myelin transfer of phospholipids and phospholipid precursors is reviewed. PMID:1282330

Ledeen, R W; Golly, F; Haley, J E

1992-01-01

28

MMP-28 as a regulator of myelination  

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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-2...

Dotzlaf Joseph E; Werner Sean R; Smith Rosamund C

2008-01-01

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ADAM17/TACE inhibits Schwann cell myelination  

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Abstract TACE, the tumor necrosis factor alpha-converting enzyme, is a proteolytic sheddase responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves NRG1 type III in the EGF domain, likely inactivating it, as assessed by deficient activation of PI-3 kinase pathway, thereby negatively regulating PNS myelination. Lentiviral mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hyperm...

La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, Maria Laura; Wrabetz, Lawrence; Blobel, Carl P.; Quattrini, Angelo; Salzer, James L.; Taveggia, Carla

2011-01-01

30

Exploring myelin dysfunction in multiple system atrophy.  

Science.gov (United States)

Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of ?-synuclein aggregates in the brain and therefore MSA is classified as an ?-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of ?-synuclein partly overlap with other ?-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for ?-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of ?-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis. PMID:25548533

Wong, Joanna H; Halliday, Glenda M; Kim, Woojin Scott

2014-12-01

31

Myelin as longitudinal conductor: a multi-layered model of the myelinated human motor nerve fibre.  

Science.gov (United States)

The myelin sheath is normally regarded as an electrical insulator. Low values of radial conductance and capacitance have been measured, and in electrical models of myelinated axons the contribution of longitudinal conduction within the sheath has been ignored. According to X-ray diffraction studies, however, myelin sheaths comprise alternate lipid and aqueous layers, and the latter may be expected to have a low resistivity. We propose a new model of myelinated axons in which the aqueous layers within the myelin provide appreciable longitudinal and radial conductance, the latter via a spiral pathway. We have investigated the likely contribution of these conductive paths within the myelin to the electrical properties of a human motor nerve fibre by computer simulation, representing the myelin sheath as a series of interconnecting parallel lamellae. With this new model, action potential conduction has been simulated along a 20-node cable, and the electrotonic responses to 100-ms depolarizing and hyperpolarizing current pulses have been simulated for a uniformly polarized fibre. We have found that the hypothesis of a longitudinally conducting myelin sheath improves our previous model in two ways: it is no longer necessary to make implausible assumptions about the resistivity or width of the periaxonal space to simulate realistic electrotonus, and the conduction velocity is appreciably faster (by 8.6%). PMID:11324341

Stephanova, D I

2001-04-01

32

Imaging of CNS myelin by positron-emission tomography  

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Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex v...

Stankoff, Bruno; Wang, Yanming; Bottlaender, Michel; Aigrot, Marie-stephane; Dolle, Frederic; Wu, Chunying; Feinstein, Douglas; Huang, Guo-feng; Semah, Frank; Mathis, Chester A.; Klunk, William; Gould, Robert M.; Lubetzki, Catherine; Zalc, Bernard

2006-01-01

33

Adult myelination: wrapping up neuronal plasticity  

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In this review, we outline the major neural plasticity mechanisms that have been identified in the adult central nervous system (CNS), and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to influence information processing and transfer in the mature CNS.

O’rourke, Megan; Gasperini, Robert; Young, Kaylene M.

2014-01-01

34

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.)

35

Autoantibodies against myelin antigens in patients with neuromyelitis optica  

Directory of Open Access Journals (Sweden)

Full Text Available In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO; titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.

Kota Moriguchi

2013-06-01

36

Myelination and isochronicity in neural networks  

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Full Text Available Our brain contains a multiplicity of neuronal networks. In many of these, information sent from presynaptic neurons travels through a variety of pathways of different distances, yet arrives at the postsynaptic cells at the same time. Such isochronicity is achieved either by changes in the conduction velocity of axons or by lengthening the axonal path to compensate for fast conduction. To regulate the conduction velocity, a change in the extent of myelination has recently been proposed in thalamocortical and other pathways. This is in addition to a change in the axonal diameter, a previously identified, more accepted mechanism. Thus, myelination is not a simple means of insulation or acceleration of impulse conduction, but it is rather an exquisite way of actively regulating the timing of communication among various neuronal connections with different length.

FumitakaKimura

2009-07-01

37

TACE (ADAM17) inhibits Schwann cell myelination  

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Tumor necrosis factor-?–converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TAC...

Marca, Rosa La; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M. Laura; Wrabetz, Lawrence; Blobel, Carl P.; Quattrini, Angelo; Salzer, James L.; Taveggia, Carla

2011-01-01

38

Myelination of the brain in MRI: a staging system  

International Nuclear Information System (INIS)

In a retrospective study 516 cranial MRI examinations of children aged 1 month to 14 years were reevaluated for myelination. An objective staging system for the assessment of the degree of myelination was designed, based on the characteristic patterns of myelin-typical signal which develop in the course of brain maturation. Thus myelination can be estimated using only routine MRI examinations; no additional measurements of signal intensities are necessary. In order to obtain detailed information, ten regions of the brain are ranked separately, with comparisons of the T1- and T2-weighted images for each region. The application of the staging system to the case material revealed typical age ranges for the stages, and retarded myelination in some children. In most cases the observed retardation affected several regions but never the whole brain. Such delays can only be detected by separate assessment of the degree of myelination in each region of the brain. (orig.)

39

Zebrafish as a model to investigate CNS myelination.  

Science.gov (United States)

Myelin plays a critical role in proper neuronal function by providing trophic and metabolic support to axons and facilitating energy-efficient saltatory conduction. Myelination is influenced by numerous molecules including growth factors, hormones, transmembrane receptors and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream signaling cascades controlling myelination have been identified in cell culture systems. However, in vitro systems are not able to faithfully replicate the complex in vivo signaling environment that occurs during development or following injury. Currently, it remains time-consuming and expensive to investigate myelination in vivo in rodents, the most widely used model for studying mammalian myelination. As such, there is a need for alternative in vivo myelination models, particularly ones that can test molecular mechanisms without removing oligodendrocyte lineage cells from their native signaling environment or disrupting intercellular interactions with other cell types present during myelination. Here, we review the ever-increasing role of zebrafish in studies uncovering novel mechanisms controlling vertebrate myelination. These innovative studies range from observations of the behavior of single cells during in vivo myelination as well as mutagenesis- and pharmacology-based screens in whole animals. Additionally, we discuss recent efforts to develop novel models of demyelination and oligodendrocyte cell death in adult zebrafish for the study of cellular behavior in real time during repair and regeneration of damaged nervous systems. GLIA 2015;63:177-193. PMID:25263121

Preston, Marnie A; Macklin, Wendy B

2015-02-01

40

Necl-4/SynCAM-4 Is Expressed in Myelinating Oligodendrocytes but Not Required for Axonal Myelination  

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The timing and progression of axonal myelination are precisely controlled by intercellular interactions between neurons and glia in development. Previous in vitro studies demonstrated that Nectin like 4 (Necl-4, also known as cell adhesion molecule Cadm-4 or SynCAM-4) plays an essential role in axonal myelination by Schwann cells in the peripheral nervous system (PNS). However, the role of Necl-4 protein in axonal myelination in the developing central nervous system (CNS) has remained unknown...

Zhu, Ying; Li, Hong; Li, Kehan; Zhao, Xiaofeng; An, Tai; Hu, Xuemei; Park, Jinsil; Huang, Hao; Bin, Yin; Qiang, Boqin; Yuan, Jiangang; Peng, Xiaozhong; Qiu, Mengsheng

2013-01-01

 
 
 
 
41

Myelination patterns in infants and children: MR imaging  

International Nuclear Information System (INIS)

A retrospective study was performed in 60 patients, aged 1 month to 4 years, to determine the normal progression of white matter myelination on MR imaging. All examinations were performed with a General Electric 1.5-T unit. Sagittal images (repetition time [TR]/echo time [TE] = 600/20 msec), axial multisection, multiecho images (TR/TE = 2,500/40-80), and axial images (TR/TE = 600/20) were obtained in each patient. Multiple sites in the brainstem, cerebellum, and cerebral hemispheres were examined in each case for the presence and degree of myelination. The results show that MR imaging is sensitive to the early changes of white matter myelination, and imaging patterns correlate with known patterns from pathologic studies. At the time of birth in a full-term infant the posterior limb of the internal capsule and corona radiata around the central sulcus show visible myelination. Myelination in the centrum semiovale then proceeds anteriorly and posteriorly. Both T1- and T2-weighted images showed these changes, which are best explained by a decrease in the water content of white matter as myelination progresses. Knowledge of these normal myelination patterns is essential in evaluating MR imaging studies in infants and children and in diagnosing delayed myelination

42

Ablation of the atrioventricular node executed after paranodal ablation of the atrioventricular node for the treatment of paroxysmal atrial-ventricular node of reentry tachycardia in conditions of artificial blood circulation  

Directory of Open Access Journals (Sweden)

Full Text Available In this clinical observation is shown the data of the patient who was previously undergone paranodal ablation of atrial-ventricular junction for the treatment of atrioventricular (AV nodal reentrant tachycardia. Radiofrequency ablation of right lower isthmus for treatment of the paroxysmal form of atrial flutter was made for the patient. Sick sinus node syndrome and paroxysmal form of atrial fibrillation were diagnosed. Then dual-chamber pacemaker was implanted. Antiarrhythmic therapy about the persistent form of atrial fibrillation had no effect. The decision for the implementation of radio frequency modification of atrioventricular connection using right ventriclar access failed because of the lack of verification of the His bundle's spike. Using retrograde access through the aorta we managed to create AV blockade of III degree. Taking into account the fact that in 1990-ies patients with atrioventricular nodal reentrant tachycardia were operated using paranodal ablation of the AV node using extracorporeal circulation, this case has a practical significance when endovascular catheter modification of AV nodal conduction in this category of patients is made.

Melikulov A.Kh.

2014-03-01

43

High-resolution fluorescence microscopy of myelin without exogenous probes.  

Science.gov (United States)

Myelin is a critical element of the central and peripheral nervous systems of all higher vertebrates. Any disturbance in the integrity of the myelin sheath interferes with the axon's ability to conduct action potentials. Thus, the study of myelin structure and biochemistry is critically important. Accurate and even staining of myelin is often difficult because of its lipid-rich nature and multiple tight membrane wraps, hindering penetration of immunoprobes. Here we show a method of visualizing myelin that is fast, inexpensive and reliable using the cross-linking fixative glutaraldehyde that produces strong, broad-spectrum auto-fluorescence in fixed tissue. Traditionally, effort is generally aimed at eliminating this auto-fluorescence. However, we show that this intrinsic signal, which is very photostable and particularly strong in glutaraldehyde-fixed myelin, can be exploited to visualize this structure to produce very detailed images of myelin morphology. We imaged fixed rodent tissues from the central and peripheral nervous systems using spectral confocal microscopy to acquire high-resolution 3-dimensional images spanning the visual range of wavelengths (400-750 nm). Mathematical post-processing allows accurate and unequivocal separation of broadband auto-fluorescence from exogenous fluorescent probes such as DAPI and fluorescently-tagged secondary antibodies. We additionally show the feasibility of immunohistochemistry with antigen retrieval, which allows co-localization of proteins of interest together with detailed myelin morphology. The lysolecithin model of de- and remyelination is shown as an example of a practical application of this technique, which can be routinely applied when high-resolution microscopy of central or peripheral myelinated tracts is required. PMID:24188810

Christensen, Pia Crone; Brideau, Craig; Poon, Kelvin W C; Döring, Axinia; Yong, V Wee; Stys, Peter K

2014-02-15

44

Myelin-associated inhibitors in axonal growth after CNS injury.  

Science.gov (United States)

There are multiple barriers to axonal growth after CNS injury. Myelin-associated inhibitors represent one group of barriers extrinsic to the injured neurons. Nogo, MAG and OMgp are three prototypical myelin inhibitors that signal through multiple neuronal receptors to exert growth inhibition. Targeting myelin inhibition alone modulates the compensatory sprouting of uninjured axons but the effect on the regeneration of injured axons is limited. Meanwhile, modulating sprouting, a naturally occurring repair mechanism, may be a more attainable therapeutic goal for promoting functional repair after CNS injury in the near term. PMID:24608164

Geoffroy, Cédric G; Zheng, Binhai

2014-08-01

45

Autophagy Is Involved in the Reduction of Myelinating Schwann Cell Cytoplasm during Myelin Maturation of the Peripheral Nerve  

Science.gov (United States)

Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination. PMID:25581066

Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Rha, Seo-Hee; Kim, Jong Kuk; Lee, Hye Jeong; Park, Hwan Tae

2015-01-01

46

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance  

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The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes pla...

Brazhe, A. R.; Maksimov, G. V.; Mosekilde, E.; Sosnovtseva, O. V.

2010-01-01

47

A Novel Fluorescent Probe That Is Brain Permeable and Selectively Binds to Myelin  

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Myelin is a multilayered glial cell membrane that forms segmented sheaths around large-caliber axons of both the central nervous system (CNS) and peripheral nervous system (PNS). Myelin covering insures rapid and efficient transmission of nerve impulses. Direct visual assessment of local changes of myelin content in vivo could greatly facilitate diagnosis and therapeutic treatments of myelin-related diseases. Current histologic probes for the visualization of myelin are based on antibodies or...

Wu, Chunying; Tian, Donghua; Feng, Yue; Polak, Paul; Wei, Jingjun; Sharp, Adam; Stankoff, Bruno; Lubetzki, Catherine; Zalc, Bernard; Mufson, Elliott J.; Gould, Robert M.; Feinstein, Douglas L.; Wang, Yanming

2006-01-01

48

Dynamics of oligodendrocyte generation and myelination in the human brain.  

Science.gov (United States)

The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived (14)C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin modulation in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity. PMID:25417154

Yeung, Maggie S Y; Zdunek, Sofia; Bergmann, Olaf; Bernard, Samuel; Salehpour, Mehran; Alkass, Kanar; Perl, Shira; Tisdale, John; Possnert, Göran; Brundin, Lou; Druid, Henrik; Frisén, Jonas

2014-11-01

49

Extracellular currents and potentials of the active myelinated nerve fiber.  

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This paper is concerned with the accurate and rapid calculation of extracellular potentials and currents from an active myelinated nerve fiber in a volume conductor, under conditions of normal and abnormal conduction. The neuroelectric source for the problem is characterized mathematically by using a modified version of the distributed parameter model of L. Goldman and J. S. Albus (1968, Biophys. J., 8:596-607) for the myelinated nerve fiber. Solution of the partial differential equation asso...

Ganapathy, N.; Clark, J. W.

1987-01-01

50

Ceramide UDPgalactosyltransferase from myelinating rat brain: purification, cloning, and expression.  

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Cerebrosides and sulfatides are major glycosphingolipids of the lipid bilayer of the myelin sheath assembled by oligodendrocytes and Schwann cells during myelination. Cerebrosides are synthesized by ceramide UDPgalactosyltransferase [CGT; 2-hydroxyacylsphinogosine 1-beta-galactosyl-transferase; UDPgalactose:2-(2-hydroxyacyl)sphingosine 1-beta-D-galactosyltransferase; UDPgalactose:2-(2-hydroxyacyl)sphingosine 1-beta-D-galactosyltransferase, EC 2.4.1.45] with UDPgalactose and ceramide as substr...

Schulte, S.; Stoffel, W.

1993-01-01

51

PIKE is essential for oligodendroglia development and CNS myelination.  

Science.gov (United States)

Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE(-/-)) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE(-/-) OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE(-/-) mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE(-/-) brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation. PMID:24449917

Chan, Chi Bun; Liu, Xia; Zhao, Lixia; Liu, Guanglu; Lee, Chi Wai; Feng, Yue; Ye, Keiqang

2014-02-01

52

The Role of Collagens in Peripheral Nerve Myelination and Function.  

Science.gov (United States)

In the peripheral nervous system, myelin is formed by Schwann cells, which are surrounded by a basal lamina. Extracellular matrix (ECM) molecules in the basal lamina play an important role in regulating Schwann cell functions, including adhesion, survival, spreading, and myelination, as well as in supporting neurite outgrowth. Collagens are a major component of ECM molecules, which include 28 types that differ in structure and function. A growing body of evidence suggests that collagens are key components of peripheral nerves, where they not only provide a structural support but also affect cell behavior by triggering intracellular signals. In this review, we will summarize the main properties of collagen family, discuss the role of extensively studied collagen types (collagens IV, V, VI, and XV) in Schwann cell function and myelination, and provide a detailed overview of the recent advances with respect to these collagens in peripheral nerve function. PMID:25143238

Chen, Peiwen; Cescon, Matilde; Bonaldo, Paolo

2014-08-21

53

Rapid myelin water content mapping on clinical MR systems  

Energy Technology Data Exchange (ETDEWEB)

We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T{sub 1}, T{sup *}{sub 2} and total water content. Employing the multiexponential T{sup *}{sub 2} decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T{sup *}{sub 2} curve was compromised to 10 echo times with a T {sub Emax} of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T{sub 1}, T{sup *}{sub 2}, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

Tonkova, Vyara; Arhelger, Volker [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Schenk, Jochen [Radiologisches Institut, Koblenz (Germany); Neeb, Heiko [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Koblenz Univ. (Germany). Inst. for Medical Engineering and Information Processing - MTI Mittelrhein

2012-07-01

54

Rac1 controls Schwann cell myelination through cAMP and NF2/merlin  

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During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutatio...

Guo, Li; Moon, Chandra; Niehaus, Karen; Zheng, Yi; Ratner, Nancy

2012-01-01

55

Design, Synthesis and Evaluation of Coumarin-based Molecular Probes for Imaging of Myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelination represents one of the most fundamental biological processes in the vertebrate nervous system. Abnormalities and changes in myelination in the central nervous system (CNS) are seen in many neurodegenerative disorders such as multiple sclerosis (MS). A long-standing goal has been to directly detect and quantify myelin content in order to facilitate diagnosis and therapeutic treatments of myelin-related diseases. In the course of our studies, we have developed a series of small-molec...

Wang, Changning; Wu, Chunying; Zhu, Junqing; Miller, Robert H.; Wang, Yanming

2011-01-01

56

Endogenous phosphorylation of basic protein in myelin of varying degrees of compaction  

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Fractions containing myelin of varying degrees of compaction were prepared from human white matter. Protein kinase activity in these fractions was measured by using both endogenous and exogenous myelin basic protein (MBP) as substrates. In both cases, less compact myelin fractions possessed higher levels of protein kinase activity than the compact myelin fraction. In addition, the specific activity of phosphorylated basic protein was greater in the loosely compacted fractions than...

Schulz, Patricia; Cruz, Tony F.; Moscarello, Mario A.

1988-01-01

57

Making Myelin Basic Protein -from mRNA transport to localized translation  

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In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap neuronal axons with extensions of their plasma membrane to form the myelin sheath. Several proteins are characteristically found in myelin of which Myelin Basic Protein (MBP) is the second most abundant one after Proteolipid Protein (PLP). The lack of functional MBP in rodents results in a severe hypomyelinated phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA is transported from th...

RobinWhite

2013-01-01

58

Role and Specificity of LGI4-ADAM22 Interactions in Peripheral Nerve Myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the peripheral nervous system, large caliber axons are ensheathed and myelinated by Schwann cells. Myelin is crucial for a faster signal transduction along the nerve. Hence it is not surprising that defects in this myelination process cause serious neurological disease. Despite the medical importance of these cells, our understanding of the cellular and molecular mechanisms that control Schwann cell development and myelination is still incomplete. Continuous communication...

Kegel, L.

2013-01-01

59

Thermocouple split follower  

Science.gov (United States)

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

60

Bilateral hypermetropia, myelinated retinal nerve fibers, and amblyopia  

Directory of Open Access Journals (Sweden)

Full Text Available A 14-year-old hyperopic female with poor vision in both eyes was evaluated for ophthalmic and systemic diseases. The patient had bilateral retinal fiber myelination and greater vision loss in the more hyperopic eye. This was a rare case of reverse Straatsma syndrome, the clinical presentation which may be accompanied with significant vision loss.

Shenoy Radha

2011-01-01

 
 
 
 
61

Bilateral hypermetropia, myelinated retinal nerve fibers, and amblyopia.  

Science.gov (United States)

A 14-year-old hyperopic female with poor vision in both eyes was evaluated for ophthalmic and systemic diseases. The patient had bilateral retinal fiber myelination and greater vision loss in the more hyperopic eye. This was a rare case of reverse Straatsma syndrome, the clinical presentation which may be accompanied with significant vision loss. PMID:21572738

Shenoy, Radha; Bialasiewicz, Alexander A; Al Barwani, B

2011-01-01

62

Bilateral Hypermetropia, Myelinated Retinal Nerve Fibers, and Amblyopia  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A 14-year-old hyperopic female with poor vision in both eyes was evaluated for ophthalmic and systemic diseases. The patient had bilateral retinal fiber myelination and greater vision loss in the more hyperopic eye. This was a rare case of reverse Straatsma syndrome, the clinical presentation which may be accompanied with significant vision loss.

Shenoy Radha; Bialasiewicz Alexander; Al Barwani B

2011-01-01

63

Focal seizure-induced premature myelination: speculation from serial MRI  

Energy Technology Data Exchange (ETDEWEB)

Local changes in the white matter underlying a focus of cortical thickening were monitored using MRI in an epileptic 2-month-old boy. We hypothesise that these changes reflected seizure-induced premature myelination. (orig.) (orig.) With 2 figs., 10 refs.

Duprez, T.; Grandin, C. [Department of Medical Imaging, Universite Catholique de Louvain, Brussels (Belgium); Ghariani, S.; Gadisseux, J.F.; Evrard, P. [Department of Pediatric Neurology, Universite Catholique de Louvain, Brussels (Belgium); Smith, A.M. [MRI Laboratory, Universite Catholique de Louvain, Brussels (Belgium)

1998-09-01

64

Myelin basic protein is affected by reduced synthesis of myelin proteolipid protein in the jimpy mouse.  

Science.gov (United States)

Myelin basic proteins (MBPs) from 6-day-old, 10-day-old, 20-day-old and adult normal mouse brain were compared with those from 20-day-old jimpy (dysmyelinating mutant) mouse brain to determine the effect of reduced levels of proteolipid protein (PLP) on MBPs. Alkaline-urea-gel electrophoresis showed that 6-day-old and 10-day-old normal and jimpy MBPs lacked charge microheterogeneity, since C8 (the least cationic of the components; not be confused with complement component C8) was the only charge isomer present. In contrast, MBPs from 20-day-old and adult normal mouse brain displayed extensive charge microheterogeneity, having at least eight components. A 32 kDa MBP was the major isoform observed on immunoblots of acid-soluble protein from 6-day-old and 10-day-old normal and 20-day-old jimpy mouse brain. There were eight bands present in 20-day-old and adult normal mouse brain. Purified human MBP charge heteromers C1, C2, C3 and C4 reacted strongly with rat 14 kDa MBP antiserum, whereas the reaction with human C8 was weak. This suggested that MBPs from early-myelinating and jimpy mice did not react to MBP antisera because C8 was the major charge isomer in these animals. Purification of MBPs from normal and jimpy brain by alkaline-gel electrophoresis showed that both normal and jimpy MBPs have size heterogeneity when subjected to SDS/PAGE. However, the size isoforms in normal mouse brain (32, 21, 18.5, 17 and 14 kDa) differed from those in jimpy brain (32, 21, 20, 17, 15 and 14 kDa) in both size and relative amounts. Amino acid analyses of MBPs from jimpy brain showed an increase in glutamic acid, alanine and ornithine, and a decrease in histidine, arginine and proline. The changes in glutamic acid, ornithine and arginine are characteristic of the differences observed in human C8 when compared with C1. PMID:1693071

Fannon, A M; Moscarello, M A

1990-05-15

65

Detection of G proteins in purified bovine brain myelin.  

Science.gov (United States)

Following a previous report on detection of muscarinic receptors in myelin with the implied presence of G proteins, we now demonstrate by more direct means the presence of such proteins and their quantification. Using [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTP gamma S) as the binding ligand, purified myelin from bovine brain was found to contain approximately half the binding activity of whole white matter (138 +/- 9 vs. 271 +/- 18 pmol/mg of protein). Scatchard analysis of saturation binding data revealed two slopes, a result suggesting at least two binding populations. This binding was inhibited by GTP and its analog but not by 5'-adenylylimidodiphosphate [App(NH)p], GMP, or UTP. Following sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) of myelin proteins and blotting on nitrocellulose, [alpha-32P]GTP bound to three bands in the 21-27-kDa range in a manner inhibited by GTP and GTP gamma S but not App(NH)p. ADP-ribosylation of myelin with [32P]NAD+ and cholera toxin labeled a protein of 43 kDa, whereas reaction with pertussis toxin labeled two components of 40 kDa. Cholate extract of myelin subjected to chromatography on a column of phenyl-Sepharose gave at least three major peaks of [35S]GTP gamma S binding activity. SDS-PAGE and immunoblot analyses of peak I indicated the presence of Go alpha, Gi alpha, and Gs alpha. Further fractionation of peak II by diethyl-aminoethyl-Sephacel chromatography gave one [35S]GTP gamma S binding peak with the low-molecular-mass (21-27 kDa) proteins and a second showing two major protein bands of 36 and 40 kDa on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1904910

Larocca, J N; Golly, F; Ledeen, R W

1991-07-01

66

Reduced model and simulation of myelinated axon using eigenfunction expansion and singular perturbation.  

Science.gov (United States)

In a myelinated axon, there exist many nodes of Ranvier where myelin sheaths are absent and action potentials are actively regenerated. Hence, a myelinated axon is a nonuniform cable where myelinated parts and unmyelinated nodes of Ranvier are described by different cable equations. For the modelling of a myelinated axon, the compartment model based on finite volume or finite difference discretization was dominantly used. In this paper, we propose a hybrid approach where an eigenfunction expansion combined with singular perturbation is employed for myelinated parts, and demonstrate that the proposed scheme can achieve an order of magnitude accuracy improvement for low order models. Moreover, it is also shown that the proposed scheme converges faster to attain a given accuracy. Hence, for simulation of myelinated axons, the proposed scheme can be an attractive alternative to the compartment model, that leads to a low order model with much higher accuracy or that converges faster for a given accuracy. PMID:17182024

Woo, Bomje; Choi, Jinhoon

2007-08-01

67

Regulation of myelin genes implicated in psychiatric disorders by functional activity in axons.  

Science.gov (United States)

Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons. PMID:19521541

Lee, Philip R; Fields, R Douglas

2009-01-01

68

Regulation of myelin genes implicated in psychiatric disorders by functional activity in axons  

Directory of Open Access Journals (Sweden)

Full Text Available Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons.

DouglasFields

2009-06-01

69

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 CH4/H2O mixture by supplying heat and using a catalyst, into H2, CO and CO2. 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)

70

N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content  

International Nuclear Information System (INIS)

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase ?, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injurytablish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET2) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET2. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.

71

Coded Splitting Tree Protocols  

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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 p...

Sørensen, Jesper H.; Stefanovic?, Cedomir; Popovski, Petar

2013-01-01

72

Split-target neutronics  

International Nuclear Information System (INIS)

Monte Carlo simulations show that, for the LANSCE split-target of machineable tungsten, about 60% of the low-energy (20 MeV) particles are also forward directed. Consequently, the neutronic performance of the LANSCE Target-Moderator-Reflector-Shield (TMRS) system is not adversely impacted by employing a split-target. Implementing a split-target allows us to use flux-trap moderators around the void zone between the targets to simultaneously service twelve neutron flight paths. (author)

73

The heme precursor delta-aminolevulinate blocks peripheral myelin formation  

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Delta-aminolevulinic acid (?-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that ?-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to ?-A...

Felitsyn, Natalia; Mcleod, Colin; Shroads, Albert L.; Stacpoole, Peter W.; Notterpek, Lucia

2008-01-01

74

Myelin Basic Protein Autoantibodies, White Matter Disease and Stroke Outcome  

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Antibodies to brain antigens are present in stroke survivors. In this study, we assessed autoantibody responses to white matter antigens, their correlation to white matter disease and stroke outcome. Antibody titers (immunoglobulin G [igG]) to myelin basic protein (MBP), proteolipid protein (PLP) and tetanus toxoid (TT) were available at one or more time points for 112 subjects with ischemic stroke. In comparison to the control subjects (N=40), there was a global decrease in IgG titers to TT ...

Shibata, Dean; Cain, Kevin; Tanzi, Patricia; Zierath, Dannielle; Becker, Kyra

2012-01-01

75

Brain Axonal and Myelin Evaluation in Heart Failure  

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Although gray matter injury appears in heart failure (HF) patients, the presence, extent, and nature of axonal injury impacting on cardiovascular regulation and other functions is unclear. We performed diffusion tensor imaging (3.0-Tesla magnetic resonance imaging scanner) in 16 HF and 26 control subjects, and assessed whole-brain water diffusion parallel (axial diffusivity; axonal status) and perpendicular (radial diffusivity; myelin changes) to fibers. Regions with increased axial diffusivi...

Kumar, Rajesh; Woo, Mary A.; Macey, Paul M.; Fonarow, Gregg C.; Hamilton, Michele A.; Harper, Ronald M.

2011-01-01

76

Axonal regulation of Schwann cell ensheathment and myelination  

Science.gov (United States)

Axons in the vertebrate peripheral nervous system are intimately associated with Schwann cells. Axons regulate the Schwann cell phenotype, determining whether they myelinate individual axons or ensheathe multiple, small axons in Remak bundles. Our current understanding of the axonal signals that drive Schwann cells towards these distinct morphological and phenotypic fates will be briefly reviewed here. Elucidation of these signals, and the intracellular pathways they regulate, may lead to new, rational therapies for the treatment of inherited and acquired neuropathies. PMID:23279426

Salzer, James L.

2012-01-01

77

The Role of TSC in Oligodendrocyte Differentiation and Myelination  

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Tuberous Sclerosis Complex (TSC) is an autosomal dominant syndrome characterized by epilepsy, intellectual disability, and autism. Recent studies have suggested that white matter abnormalities, including hypomyelination, contribute to the cognitive deficits in TSC patients, but the mechanism has remained elusive. I used the neuron-specific Tsc1 knockout mice that display a marked decrease in myelin and show that oligodendrocytes are arrested at immature stages of development in vivo resulting...

Han, Juliette

2012-01-01

78

Strategies for myelin regeneration: lessons learned from development  

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Myelin regeneration is indispensably important for patients suffering from several central nervous system (CNS) disorders such as multiple sclerosis (MS) and spinal cord injury (SCI), because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certai...

Bhatt, Abhay; Fan, Lir-wan; Pang, Yi

2014-01-01

79

Brain axonal and myelin evaluation in heart failure.  

Science.gov (United States)

Although gray matter injury appears in heart failure (HF) patients, the presence, extent, and nature of axonal injury impacting on cardiovascular regulation and other functions is unclear. We performed diffusion tensor imaging (3.0-Tesla magnetic resonance imaging scanner) in 16 HF and 26 control subjects, and assessed whole-brain water diffusion parallel (axial diffusivity; axonal status) and perpendicular (radial diffusivity; myelin changes) to fibers. Regions with increased axial diffusivity only, indicating impaired axonal integrity, emerged in cardiovascular, hedonic, and pain regulatory areas, including basal forebrain, hypothalamic and limbic projections through the medial forebrain bundle and raphe magnus projections to the medulla and cerebellum. Other fiber paths between sites implicated in cognition, including limbic, basal-ganglia, thalamic, internal capsule, and corpus callosum were also altered. Sites with increased radial diffusivity only, indicating myelin breakdown, appeared in the corpus callosum, cingulate, and temporal, parietal, occipital, and frontal regions. Both higher axial and radial diffusivity, indicating loss of tissue integrity, appeared in parietal and occipital lobes, limbic regions, insula, internal capsule, cerebellum, and dorsolateral medulla. Axons and myelin are altered in HF, likely resulting from ischemic/hypoxic processes acting chronically and sub-acutely, respectively. The alterations would contribute to the multiple autonomic and neuropsychological symptoms found in HF. PMID:21612797

Kumar, Rajesh; Woo, Mary A; Macey, Paul M; Fonarow, Gregg C; Hamilton, Michele A; Harper, Ronald M

2011-08-15

80

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.)

 
 
 
 
81

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

82

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

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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

83

Myelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation  

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Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing degenerated myelin, are abundantly found in active multiple sclerosis lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence les...

Bogie, J. F. J.; Timmermans, S.; Huynh-thu, V.; Irrthum, A.; Smeets, H. J. M.; Gustafsson, J. A?; Steffensen, K. R.; Mulder, M.; Stinissen, P.; Hellings, N.; Hendriks, J. J. A.

2012-01-01

84

Regulation of Myelin Genes Implicated in Psychiatric Disorders by Functional Activity in Axons  

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Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between corti...

DouglasFields

2009-01-01

85

Guanine nucleotides stimulate hydrolysis of phosphatidyl inositol bis phosphate in human myelin membranes  

International Nuclear Information System (INIS)

Phosphodiesterase activity was stimulated in myelin membranes in the presence of guanine nucleotide analogues. This activity was reduced in myelin membranes which had been adenosine diphosphate ribosylated in the presence of cholera toxin which ADP-ribosylated three proteins of Mr 46,000, 43,000 and 18,500. Aluminum fluoride treatment of myelin had the same stimulatory effects on phosphodiesterase activity as did the guanine nucleotides

86

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance  

DEFF Research Database (Denmark)

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

Brazhe, A.R.; Maksimov, G.V.

2011-01-01

87

The QKI-PLP pathway controls SIRT2 abundance in CNS myelin  

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Sirtuin 2 (SIRT2), a NAD-dependent deacetylase expressed by oligodendrocytes (OLs), the myelin-producing cells of the central nervous system (CNS), is markedly up-regulated during active myelination (Li et al. 2007; Southwood et al. 2007; Werner et al. 2007). SIRT2 is a component of the myelin proteome and is severely reduced in the Plp1 knockout mouse brain, in which both PLP and DM20 are absent (Werner et al. 2007). The mechanisms that regulate SIRT2 expression in OLs and myelin remain to b...

Zhu, H.; Zhao, L.; Wang, E.; Dimova, N.; Liu, G.; Feng, Y.; Cambi, F.

2012-01-01

88

Two-photon fluorescent imaging of myelination in the spinal cord.  

Science.gov (United States)

Myelination is a fundamental biological process in the vertebrate nervous system. Damage to or malformation of myelin can lead to various neurological diseases; for example, demyelination in the spinal cord is a major cause of paralysis of patients suffering from multiple sclerosis and related diseases. The ability to directly track myelin levels in the spinal cord is needed in order to assess the efficacy of therapeutics in promoting myelin repair. To address this unmet need, 4-((E)-4-((E)-4-aminostyryl)-2,5-dimethoxystyryl)-N-methylaniline, known as Case Imaging Compound (CIC), has been developed as a myelin-targeted fluorescent imaging agent that selectively binds to myelin. CIC was synthesized via an improved route and evaluated as a fluorescent probe for two-photon fluorescent imaging of myelin in the spinal cord in both demyelinated and dysmyelinated models. In vitro and ex vivo tissue staining both suggest that CIC selectively binds to in animal models. Further evaluation in animal models indicated that CIC is sensitive to differences in myelin content in healthy versus pathological myelin. CIC could potentially be useful in the development and evaluation of novel therapies for multiple sclerosis and other demyelinating diseases. PMID:23136014

Condie, Allison G; Gerson, Stanton L; Miller, Robert H; Wang, Yanming

2012-12-01

89

Ultrastructural Changes in the Myelinated Nerve Fibers of the Sciatic Nerve in Galactose Intoxication in Rats  

Directory of Open Access Journals (Sweden)

Full Text Available The objectives were to study the ultrastructural changes in the myelinated nerve fibers in an animal model of galactosaemia. The study was done in the Anatomy Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia. Twenty-four adult male albino rats were used (6 control and 12 experimental animals. Galactosaemia was induced by adding 40% D-galactose to the rats' diet for 2 months. Sciatic nerves of the control and experimental animals were removed and processed for electron microscopic study. Four months following galactosaemia, the myelinated nerve fibers showed cytoplasmic vacuoles in Schwann cells, myelin degeneration, axonal retraction and destruction of the myelinated axons. 6 months after induction, some myelinated nerve fibers showed disruption of myelin sheaths with marked shrinkage of the axons. The endoneurial edema was prominent and some regenerating nerve fibers were reported. 8 months latter: the endoneurial and intra-axonal oedema accumulated more. Schwann cells showed cytoplasmic degenerated myelin, fat vacuoles and accumulation of fine glycogen granules in the axoplasm. It could be concluded that in galactose intoxication induced degenerative changes in the myelinated nerve fibers. It showed also decrease in diameters of the myelinated nerve fibers and axons.

Faris M. Altaf

2012-01-01

90

Microstructural Integrity of Early- vs. Late-Myelinating White Matter Tracts in Medial Temporal Lobe Epilepsy  

Science.gov (United States)

Purpose Patients with medial temporal lobe epilepsy (MTLE) exhibit structural brain damage involving gray (GM) and white matter (WM). The mechanisms underlying tissue loss in MTLE are unclear and may be associated with a combination of seizure excitotoxicity and WM vulnerability. The goal of this study was to investigate whether late-myelinating WM tracts are more vulnerable to injury in MTLE compared with early-myelinating tracts. Methods Diffusional kurtosis imaging scans were obtained from 25 patients with MTLE and from 36 matched healthy controls. Diffusion measures from regions of interest (ROIs) for both late- and early-myelinating WM tracts were analyzed. Regional Z-scores were computed with respect to normal controls to compare WM in early-myelinating tracts versus late-myelinating tracts. Key Findings We observed that late-myelinating tracts exhibited a larger decrease in mean, axial and radial kurtosis compared with early-myelinating tracts. We also observed that the change in radial kurtosis was more pronounced in late-myelinating tracts ipsilateral to the side of seizure onset. Significance These results suggest a developmentally based preferential susceptibility of late-myelinating WM tracts to damage in MTLE. Brain injury in epilepsy may be due to the pathological effects of seizures in combination with regional WM vulnerability. PMID:24032670

Lee, Chu-Yu; Tabesh, Ali; Benitez, Andreana; Helpern, Joseph A; Jensen, Jens H; Bonilha, Leonardo

2013-01-01

91

Bounding, splitting, and almost disjointness  

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We investigate some aspects of bounding, splitting, and almost disjointness. In particular, we investigate the relationship between the bounding number, the closed almost disjointness number, splitting number, and the existence of certain kinds of splitting families.

Brendle, Jo?rg; Raghavan, Dilip

2012-01-01

92

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 (P<0.001) along with 60-130% up-regulation in myelin-associated proteins and disorganized C fibers in the PNS. The hypermyelination of PNS in Col6a1(-/-) mice is supported by alterations of signaling pathways involved in myelination, including increase of P-FAK, P-AKT, P-ERK1, P-ERK2, and P-p38 (4.15, 1.67, 2.47, 3.34, and 2.60-fold, respectively) and reduction of vimentin (0.49-fold), P-JNK (0.74-fold), and P-c-Jun (0.50-fold). Pathologically, Col6a1(-/-) mice display an impairment of nerve conduction velocity and motor coordination (P<0.05), as well as a delayed response to acute pain stimuli (P<0.001), indicating that lack of collagen VI causes functional defects of peripheral nerves. Altogether, these results indicate that collagen VI is a critical 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

93

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

94

Splitting the voter criticality  

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Recently some two-dimensional models with double symmetric absorbing states were shown to share the same critical behaviour that was called the voter universality class. We show, that for an absorbing-states Potts model with finite but further than nearest neighbour range of interactions the critical point is splitted into two critical points: one of the Ising type, and the other of the directed percolation universality class. Similar splitting takes place in the three-dimen...

Droz, Michel; Ferreira, Antonio L.; Lipowski, Adam

2003-01-01

95

Aspects of Split Supersymmetry  

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We explore some fundamental differences in the phenomenology, cosmology and model building of Split Supersymmetry compared with traditional low-scale supersymmetry. We show how the mass spectrum of Split Supersymmetry naturally emerges from theories where the dominant source of supersymmetry breaking preserves an $R$ symmetry, characterize the class of theories where the unavoidable $R$-breaking by gravity can be neglected, and point out a new possibility, where supersymmetr...

Arkani-hamed, N.; Dimopoulos, S.; Giudice, G. F.; Romanino, A.

2004-01-01

96

Split Supersymmetry at Colliders  

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We consider the collider phenomenology of split-supersymmetry models. Despite the challenging nature of the signals in these models the long-lived gluino can be discovered with masses above 2 TeV at the LHC. At a future linear collider we will be able to observe the renormalization group effects from split supersymmetry on the chargino/neutralino mixing parameters, using measurements of the neutralino and chargino masses and cross sections. This indirect determination of cha...

Kilian, W.; Plehn, T.; Richardson, P.; Schmidt, E.

2004-01-01

97

Cleavage of Myelin Associated Glycoprotein by Matrix Metalloproteinases  

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Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases (MMPs) elevated with inflammatory and demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP-1, cleave recombinant human MAG. Cleavage by MMP-7 occurs at Leu 509, just distal to the transmembrane domain and, to a lesser extent, at Met 234. We also show that MMP-7 cleaves MAG expr...

Milward, Elizabeth; Kim, Kee Jun; Szklarczyk, Arek; Nguyen, Thien; Melli, Giorgia; Nayak, Mamatha; Deshpande, Deepa; Fitzsimmons, Chantel; Hoke, Ahmet; Kerr, Douglas; Griffin, John W.; Calabresi, Peter A.; Conant, Katherine

2007-01-01

98

Streamer Splitting in Sprites  

Science.gov (United States)

We report on observations of streamer tip splitting in sprites. High speed 10,000 frames per second with 50 micro second integration time observations of sprites were obtained on 23 June 2007 using a 300 mm lens on a Phantom 7 camera with a Video Scope HS 1845 HS image intensifier. Six sprites were observed showing clear streamer tip splitting. The locations of the parent lightning strikes were located using the National Lightning Detection Network, and the range to the 75 km altitude point above the parent lightning strike determined. The resulting resolution was approximately 30m per pixel. Streamer tip divisions were seen at altitudes from 60 to 76 km altitude, effectively across the entire vertical field of view. We observe streamers splitting into smaller and smaller streamer tips once the splitting starts. Typical distances between subsequent splitting of the same steamer tip are approximately 5 km, and the time needed to double the number of streamer tips due to splitting is approximately 100 to 200 micro seconds.

McHarg, M. G.; Stenbaek-Nielsen, H. C.; Kanmae, T.; Haaland, R. K.

2008-12-01

99

Myelin formation in rat dorsal root ganglion cultured in a serum-free medium.  

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Compact myelin formation was first observed in rat dorsal root ganglion culture using a serum-free alpha modified Eagle's Minimum Essential Medium (alpha MEM) supplemented with nerve growth factor. However, myelin formation did not occur when Earl's MEM was used instead of alpha MEM.

Ninomiya, T.; Takahashi, K.

1987-01-01

100

Depth-sensing nano-indentation on a myelinated axon at various stages  

International Nuclear Information System (INIS)

A nano-mechanical characterization of a multi-layered myelin sheath structure, which enfolds an axon and plays a critical role in the transmission of nerve impulses, is conducted. Schwann cells co-cultured in vitro with PC12 cells for various co-culture times are differentiated to form a myelinated axon, which is then observed using a transmission electron microscope. Three major myelination stages, with distinct structural characteristics and thicknesses around the axon, can be produced by varying the co-culture time. A dynamic contact module and continuous depth-sensing nano-indentation are used on the myelinated structure to obtain the load-on-sample versus measured displacement curve of a multi-layered myelin sheath, which is used to determine the work required for the nano-indentation tip to penetrate the myelin sheath. By analyzing the harmonic contact stiffness versus the measured displacement profile, the results can be used to estimate the three stages of the multi-layered structure on a myelinated axon. The method can also be used to evaluate the development stages of myelination or demyelination during nerve regeneration.

 
 
 
 
101

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

102

Syndrome of myelinated retinal nerve fibres, myopia, amblyopia and strabismus in a Nigerian  

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Myelinated retinal nerve fibres (MRNF) are rare congenital anomalies. They may present in a syndrome characterised by ipsilateral myelinated retinal nerve fibres, myopia and amblyopia. We report a case of this rare condition with unilateral extensive MRNF, axial myopia, amblyopia and strabismus in a Nigerian girl.

Osaguona, Vivian B.; Uhumwangho, Odarosa M.

2014-01-01

103

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

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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...

1987-01-01

104

Knockdown of Dock7 in vivo specifically affects myelination by Schwann cells and increases myelin thickness in sciatic nerves without affecting axon thickness  

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Full Text Available During development of the peripheral nervous system (PNS, Schwann cells (SCs wrap individual axons to form myelin sheaths, which act as surrounding insulators and markedly enhance the propagation of the action potential. In peripheral neuropathies such as Guillain-Barré syndrome (GBS and inherited demyelinating Charcot-Marie-Tooth (CMT disease and diabetic neuropathies, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought that development of a drug that promotes proper myelination with minimal side effects could provide an effective therapy for these diseases. As yet, however, little is known about therapeutic target molecules and genetically-modified mice for testing such approaches. We previously cloned the dock7 gene and characterized Dock7 as the regulator controlling SC myelination; however, an important issue, whether knockdown of Dock7 specifically affects myelination by SCs but not leaves neurons unaffected, has remained unclear. Here, we generate newly-produced transgenic mice harboring short-hairpin RNA (shRNA targeting Dock7. We also describe that Dock7 shRNA transgenic mice exhibit enhanced myelin thickness without affecting axon thickness in sciatic nerves of the PNS, as reduced thickness of the axon diameter is the primary indicator of denatured neurons. Similarly, purified in vitro SC-neuronal cocultures established from transgenic mice exhibit enhanced formation of myelin segments, suggesting that knockdown of Dock7 promotes myelination by SCs. Collectively, Dock7 knockdown specifically affects SC myelination in sciatic nerves, providing evidence that Dock7 may be a promising drug-target-specific molecules for developing a therapy for peripheral neuropathies that aims to enhance myeliantion.

Kazuaki Nakamura

2012-07-01

105

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.)

106

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

International Nuclear Information System (INIS)

Kinetics of phospholipid constituents transferred from the axon to the myelin sheath were studied in the oculomotor nerve (OMN) and the ciliary ganglion (CG) of chicken. Axons of the OMN were loaded with transported phospholipids after an intracerebral injection of [2-3H]glycerol or [3H]labeled choline. Quantitative electron microscope radioautography revealed that labeled lipids were transported in the axons mainly associated with the smooth endoplasmic reticulum. Simultaneously, the labeling of the myelin sheath was found in the Schmidt-Lanterman clefts and the inner myelin layers. The outer Schwann cell cytoplasm and the outer myelin layers contained some label with [methyl-3H]choline, but virtually none with [2-3H]glycerol. With time the radioactive lipids were redistributed throughout and along the whole myelin sheath. (Auth.)

107

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy  

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Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 gene region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.

Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R. [Univ. of California, San Francisco, CA (United States)] [and others

1994-09-01

108

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

109

Myelin-associated Glycoprotein gene and brain morphometry in schizophrenia  

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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

110

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

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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 pl...

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

2012-01-01

111

Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair.  

Science.gov (United States)

Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4(+) T cells by a foreign antigen in the peripheral blood. The activated CD4(+) T cells liberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Inside the CNS, CD4(+) T cells become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the immune response. The CD4(+) T cells continue to liberate inflammatory cytokines, such as tumor necrosis factor ? (TNF?), which activates macrophages and antibodies responsible for the phagocytosis of myelin. Acute CNS lesions can be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins, such as nerve growth factor (NGF) for myelin repair. NGF promotes axonal regeneration, survival, protection and differentiation of oligodendrocytes (OGs) and facilitates migration and proliferation of oligodendrocyte precursors (OPs) to the sites of myelin damage. NGF also directly regulates key structural proteins that comprise myelin. Interestingly, NGF also induces the production of brain-derived neurotrophic factor (BDNF), another integral neurotrophin involved in myelination. The intricate signaling between neurotrophins and cytokines that governs myelin repair supports the role of NGF as a leading therapeutic candidate in white matter disorders, such as MS. PMID:23844684

Acosta, C M R; Cortes, C; MacPhee, H; Namaka, M P

2013-12-01

112

Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome  

Science.gov (United States)

Background Restless legs syndrome (RLS) is a neurological disorder characterized by a strong urge to move the legs and has been linked in many studies with abnormally low brain iron. Iron deficiency is associated with hypomyelination in brains of animals. Therefore we hypothesized that a myelin deficit should be present in the brains of patients with RLS. Methods We performed western blot analysis on myelin isolated from RLS (n=11) and control (n=11) brain tissue obtained at autopsy for the expression of the integral myelin proteins, myelin basic protein (MBP), and proteolipid protein (PLP) and the oligodendrocyte specific enzyme 3’5’-cyclic nucleotide phosphohydrolase (CNPase). To expand the postmortem findings to in vivo, we analyzed the brains of RLS patients (n=23) and controls (n=23) using Voxel-based morphometry (VBM). Results The expression of MBP, PLP and CNPase in the myelin from RLS was decreased by approximately 25% (p<0.05) compared to controls. The amounts of transferrin (Tf) and H-ferritin (H-Frt) in the myelin fraction were also significantly decreased in RLS compared to controls. The imaging analysis revealed significant small decreases in white matter volume in RLS patients compared to controls in the corpus callosum, anterior cingulum and precentral gyrus. Conclusion A decrease in myelin similar to that reported in animal models of iron deficiency was found in the brains of individuals with RLS. The evidence for less myelin and loss of myelin integrity in RLS brains, coupled with decreased ferritin and transferrin in the myelin fractions, is a compelling argument for brain iron insufficiency in RLS. These data also indicate the need to look beyond the sensorimotor symptoms that typically define the syndrome and its assumed relationship to the dopaminergic system. Understanding the full range of RLS pathology may help us better understand the complex, intermittent nature and diversity of the clinical features of RLS and expand our consideration of treatment options for RLS. PMID:21570342

Connor, James R.; Ponnuru, Padmavathi; Lee, Byeong-Yeul; Podskalny, Gerald D.; Alam, Shoaib; Allen, Richard P.; Earley, Christopher J.; Yang, Qing X.

2011-01-01

113

Distances of Heegaard splittings  

CERN Document Server

The distance of a Heegaard splitting is the length of the shortest path between the two handlebodies, thought of as subsets of the curve complex associated to the splitting surface S. Let h be a pseudo-Anosov map on S, and consider the distances of splittings with gluing maps h^n. If h satisfies a certain non-degeneracy condition, J. Hempel [Topology, 2001] has shown that this set of distances is unbounded. We quantify Hempel's result by showing that the distance grows linearly with n. This answers a question of A. Casson. In addition we prove the converse of Hempel's theorem. Our method is to study the dynamics of h acting on the curve complex. We rely heavily on the result, due to H. Masur and Y. Minsky [Invent. Math., 1999], that the curve complex is Gromov hyperbolic.

Abrams, A; Schleimer, Saul

2003-01-01

114

Distances of Heegaard splittings  

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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

115

Boring split links  

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Boring is an operation which converts a knot or two-component link in a 3--manifold into another knot or two-component link. It generalizes rational tangle replacement and can be described as a type of 2--handle attachment. Sutured manifold theory is used to study the existence of essential spheres and planar surfaces in the exteriors of knots and links obtained by boring a split link. It is shown, for example, that if the boring operation is complicated enough, a split link...

Taylor, Scott A.

2007-01-01

116

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

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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

117

Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination.  

Science.gov (United States)

Neuregulin 1 type III is processed following regulated intramembrane proteolysis, which allows communication from the plasma membrane to the nucleus. We found that the intracellular domain of neuregulin 1 type III upregulated the prostaglandin D2 synthase (L-pgds, also known as Ptgds) gene, which, together with the G protein-coupled receptor Gpr44, forms a previously unknown pathway in PNS myelination. Neuronal L-PGDS is secreted and produces the PGD2 prostanoid, a ligand of Gpr44. We found that mice lacking L-PGDS were hypomyelinated. Consistent with this, specific inhibition of L-PGDS activity impaired in vitro myelination and caused myelin damage. Furthermore, in vivo ablation and in vitro knockdown of glial Gpr44 impaired myelination. Finally, we identified Nfatc4, a key transcription factor for myelination, as one of the downstream effectors of PGD2 activity in Schwann cells. Thus, L-PGDS and Gpr44 are previously unknown components of an axo-glial interaction that controls PNS myelination and possibly myelin maintenance. PMID:25362470

Trimarco, Amelia; Forese, Maria Grazia; Alfieri, Valentina; Lucente, Alessandra; Brambilla, Paola; Dina, Giorgia; Pieragostino, Damiana; Sacchetta, Paolo; Urade, Yoshihiro; Boizet-Bonhoure, Brigitte; Martinelli Boneschi, Filippo; Quattrini, Angelo; Taveggia, Carla

2014-12-01

118

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

119

Association between brain metastasis from lung cancer and the serum level of myelin basic protein  

Science.gov (United States)

The aim of the present study was to determine the association between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. A total of 68 lung cancer patients, treated in the Department of Respiratory Medicine of the People’s Hospital of Rizhao (Rizhao, China), were divided into two groups, those with brain metastasis (32 cases) and those without brain metastasis (36 cases). The expression levels of myelin basic protein were measured for all the patients. The results indicated that the expression levels of myelin basic protein in the brain metastasis group were significantly higher when compared with those in the group without metastasis (Pbrain metastasis and the expression levels of myelin basic protein (P>0.05). Furthermore, no statistically significant difference was found in the average level of myelin basic protein between the two subgroups of patients with brain tumor diameters of >1.5 cm and 0.05). Therefore, the results demonstrated a statistically significant correlation between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. Myelin basic protein may thus prove useful in the early diagnosis of brain metastases in lung cancer patients.

LIU, WEI; ZHAO, JING; WEI, YUJUAN

2015-01-01

120

Myelin localization of peptidylarginine deiminases 2 and 4: comparison of PAD2 and PAD4 activities.  

Science.gov (United States)

An understanding of the structure and composition of the myelin sheath is essential to understand the pathogenesis of demyelinating diseases such as multiple sclerosis (MS). The presence of citrulline in myelin proteins in particular myelin basic protein (MBP) causes an important change in myelin structure, which destabilizes myelin. The peptidylarginine deiminases (PADs) are responsible for converting arginine in proteins to citrulline. Two of these, PAD2 and PAD4, were localized to the myelin sheath by immunogold electron microscopy. Deimination of MBP by the recombinant forms of these enzymes showed that it was extensive, that is, PAD2 deiminated 18 of 19 arginyl residues in MBP, whereas PAD4 deiminated 14 of 19 residues. In the absence of PAD2 (the PAD2-knockout mouse) PAD4 remained active with limited deimination of arginyl residues. In myelin isolated from patients with MS, the amounts of both PAD2 and PAD4 enzymes were increased compared with that in normals, and the citrullinated proteins were also increased. These data support the view that an increase in citrullinated proteins resulting from increased PAD2 and 4 is an important change in the pathogenesis of MS. PMID:18227806

Wood, Dorothy D; Ackerley, Cameron A; Brand, Ben van den; Zhang, Li; Raijmakers, Reinout; Mastronardi, Fabrizio G; Moscarello, Mario A

2008-04-01

 
 
 
 
121

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

122

Label-free imaging of Schwann cell myelination by third harmonic generation microscopy.  

Science.gov (United States)

Understanding the dynamic axon-glial cell interaction underlying myelination is hampered by the lack of suitable imaging techniques. Here we demonstrate third harmonic generation microscopy (THGM) for label-free imaging of myelinating Schwann cells in live culture and ex vivo and in vivo tissue. A 3D structure was acquired for a variety of compact and noncompact myelin domains, including juxtaparanodes, Schmidt-Lanterman incisures, and Cajal bands. Other subcellular features of Schwann cells that escape traditional optical microscopies were also visualized. We tested THGM for morphometry of compact myelin. Unlike current methods based on electron microscopy, g-ratio could be determined along an extended length of myelinated fiber in the physiological condition. The precision of THGM-based g-ratio estimation was corroborated in mouse models of hypomyelination. Finally, we demonstrated the feasibility of THGM to monitor morphological changes of myelin during postnatal development and degeneration. The outstanding capabilities of THGM may be useful for elucidation of the mechanism of myelin formation and pathogenesis. PMID:25453108

Lim, Hyungsik; Sharoukhov, Denis; Kassim, Imran; Zhang, Yanqing; Salzer, James L; Melendez-Vasquez, Carmen V

2014-12-16

123

TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.  

Science.gov (United States)

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-? converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGF? and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. PMID:25186737

Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

2014-09-01

124

Functionally distinct PI 3-kinase pathways regulate myelination in the peripheral nervous system.  

Science.gov (United States)

The PI 3-kinase (PI 3-K) signaling pathway is essential for Schwann cell myelination. Here we have characterized PI 3-K effectors activated during myelination by probing myelinating cultures and developing nerves with an antibody that recognizes phosphorylated substrates for this pathway. We identified a discrete number of phospho-proteins including the S6 ribosomal protein (S6rp), which is down-regulated at the onset of myelination, and N-myc downstream-regulated gene-1 (NDRG1), which is up-regulated strikingly with myelination. We show that type III Neuregulin1 on the axon is the primary activator of S6rp, an effector of mTORC1. In contrast, laminin-2 in the extracellular matrix (ECM), signaling through the ?6?4 integrin and Sgk1 (serum and glucocorticoid-induced kinase 1), drives phosphorylation of NDRG1 in the Cajal bands of the abaxonal compartment. Unexpectedly, mice deficient in ?6?4 integrin signaling or Sgk1 exhibit hypermyelination during development. These results identify functionally and spatially distinct PI 3-K pathways: an early, pro-myelinating pathway driven by axonal Neuregulin1 and a later-acting, laminin-integrin-dependent pathway that negatively regulates myelination. PMID:24687281

Heller, Bradley A; Ghidinelli, Monica; Voelkl, Jakob; Einheber, Steven; Smith, Ryan; Grund, Ethan; Morahan, Grant; Chandler, David; Kalaydjieva, Luba; Giancotti, Filippo; King, Rosalind H; Fejes-Toth, Aniko Naray; Fejes-Toth, Gerard; Feltri, Maria Laura; Lang, Florian; Salzer, James L

2014-03-31

125

In vivo labeling of peroxisomes by photoconvertible mEos2 in myelinating glia of mice.  

Science.gov (United States)

Mutations of several genes encoding peroxisomal proteins have been associated with human diseases. Some of these display specific white matter abnormalities in the brain, although the affected proteins are ubiquitously expressed. To better understand the etiology of peroxisomal myelin diseases, we aimed to label these organelles in vivo and in a cell type specific fashion. We had previously shown that in oligodendrocytes and Schwann cells numerous peroxisomes reside in the cytoplasmic channels of "non-compacted" myelin. These organelles are smaller and biochemically distinct from non-myelin peroxisomes. Targeting peroxisomal functions in various cell types of the brain has demonstrated that oligodendroglial peroxisomes are specifically important for long-term integrity of the CNS. To visualize myelin peroxisomes in intact cells and tissues by live imaging, we have generated a novel line of transgenic mice for the expression of fluorescently tagged peroxisomes specifically in myelinating glia. This was achieved by modifying the gene for a photoconvertible mEos2 with a peroxisomal targeting signal type 1 (PTS1) and generating a fusion gene with the myelin-specific Cnp1 promoter. In the brain of resulting transgenic mice, peroxisomes are selectively labeled in oligodendrocytes. In this novel genetic tool, photoconversion of single peroxisomes from green to red fluorescence can be used to monitor the fate of single organelles and to determine the dynamics of PTS1-mediated protein import in the context of myelin diseases that affect peroxisomal functions. PMID:24262602

Richert, Sarah; Kleinecke, Sandra; Günther, Jenniffer; Schaumburg, Florian; Edgar, Julia; Nienhaus, Gerd Ulrich; Nave, Klaus-Armin; Kassmann, Celia M

2014-03-01

126

Soluble Neuregulin and Schwann Cell Myelination: a Therapeutic Potential for Improving Remyelination of Adult Axons  

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Full Text Available Myelination in the peripheral nervous system (PNS is induced by close contact signaling between axons and Schwann cells. Previous studies have identified membrane-bound neuregulin-1 (Nrg1 type III, expressed on the axons, as the key instructive signal that regulates Schwann cell myelination. In our recent study, we show that recombinant soluble Nrg1 elicits a similar pro-myelinating effect on Schwann cells, albeit in a dosage-dependent manner: Nrg1 promotes myelination at low concentrations but inhibits it at high concentrations. The inhibitory effect of Nrg1 is mediated through its activation of the Ras/Raf/Erk pathway in Schwann cells, and inhibition of the pathway using a pharmacologic inhibitor restores myelination. We also show that soluble Nrg1 enhances myelination on axons that do not express sufficient amount of Nrg1 type III needed for robust myelination. These findings are significant as they suggest that combined therapies aimed at enhancing Nrg1 signaling and blocking the Ras/Raf/Erk activation may be an effective strategy for improving remyelination on adult axons, which, as shown in our recent data, express low levels of Nrg1 type III. In this report we provide an overview of our recent findings and discuss the therapeutic potential of soluble Nrg1.

Haesun A. Kim

2010-01-01

127

Making myelin basic protein -from mRNA transport to localized translation.  

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In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap neuronal axons with extensions of their plasma membrane to form the myelin sheath. Several proteins are characteristically found in myelin of which myelin basic protein (MBP) is the second most abundant one after proteolipid protein. The lack of functional MBP in rodents results in a severe hypomyelinated phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA is transported from the nucleus to the plasma membrane and is translated locally at the axon-glial contact site. Axonal properties such as diameter or electrical activity influence the degree of myelination. As oligodendrocytes can myelinate many axonal segments with varying properties, localized MBP translation represents an important part of a rapid and axon-tailored synthesis machinery. MBP's ability to compact cellular membranes may be problematic for the integrity of intracellular membranous organelles and can also explain why MBP is transported in oligodendrocytes in the form of an mRNA rather than as a protein. Here we review the recent findings regarding intracellular transport and signaling mechanisms leading to localized translation of Mbp mRNA in oligodendrocytes. More detailed insights into the MBP synthesis pathway are important for a better understanding of the myelination process and may foster the development of remyelination therapies for demyelinating diseases. PMID:24098271

Müller, Christina; Bauer, Nina M; Schäfer, Isabelle; White, Robin

2013-01-01

128

Developmental changes in myelin-induced proliferation of cultured Schwann cells  

International Nuclear Information System (INIS)

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 [3H]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 [14C]thymidine followed by a pulse of [3H]thymidine 24 h later, every Schwann cell labeled with [3H]thymidine was also labeled with [14C]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

129

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

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Full Text Available 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 A 66-year-old Japanese man, having experienced sternocostoclavicular pain for ten years, was admitted to our hospital because of gait disturbance and numbness of the limbs. Our patient had normal cranial nerve function and normal limb muscle strength. His vibratory and position sense was severely impaired and his touch, temperature and pinprick sensations were mildly disturbed in a glove and stocking distribution. A myelin-associated glycoprotein western blot analysis showed the presence of a 91 to 94kDa band using purified human myelin-associated glycoprotein antigen. His skin lesions were moderately pruritic and Auspitz’s sign was positive. Our patient also showed osteitis of his clavicle and manubrium. We diagnosed our patient with myelin-associated glycoprotein-related neuropathy associated with psoriatic arthritis. Five days after intravenous immunoglobulin therapy, his deep sensory impairment began to improve and his sternocostoclavicular pain diminished dramatically. Conclusions Because myelin-associated glycoprotein-related neuropathy and psoriatic arthritis are both considered autoimmune diseases, we conclude that intravenous immunoglobulin therapy is very effective for patients with an association of these diseases.

Murata Ken-ya

2013-01-01

130

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

131

Plasmonic solar water splitting  

International Nuclear Information System (INIS)

The study of the optoelectronic effects of plasmonic metal nanoparticles on semiconductors has led to compelling evidence for plasmon-enhanced water splitting. We review the relevant physics, device geometries, and research progress in this area. We focus on localized surface plasmons and their effects on semiconductors, particularly in terms of energy transfer, scattering, and hot electron transfer.

132

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

133

Central nervous system myelin proteins and glycoproteins in vertebrates: a phylogenetic study.  

Science.gov (United States)

CNS myelin was isolated by a conventional method from a wide range of vertebrate classes and analyzed by SDS-PAGE for proteins (Coomassie blue) and glycoproteins (concanavalin A (Con-A)-peroxidase). Mammalian, avian and reptilian myelin shared similar protein patterns (basic protein, BP; intermediate protein, DM-20; proteolipid protein, PLP; Wolfgram protein, W). Amphibians lacked DM-20 but were characterized by specific activities of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) higher than those of the other classes examined. The Con A-binding profiles were similar in the high molecular weight (HMW) regions of the classes listed above, while the typical myelin proteins in the low molecular weight (LMW) regions were devoid of Con A-binding properties. In teleost myelin a putative BP band ran well ahead of rat small basic protein (SBP), whereas the region corresponding to rat PLP was covered by several closely spaced bands, most of which bound Con A. In elasmobranch myelin, apart from bands corresponding to BP, Con A-binding glycoproteins were detected migrating in the region of rat DM-20 and PLP as well as with mammalian PNS P0 protein. Cyclostomates yielded only very small amounts of material in the myelin preparation and displayed undifferentiated Coomassie blue- and Con A-binding in the HMW region, while typical LMW myelin proteins were absent. These results demonstrate that CNS myelin from bony and cartilaginous fishes is characterized by containing several major Con A-binding proteins of low molecular weight. This is in striking contrast to myelin from phylogenetically higher classes. PMID:6271345

Franz, T; Waehneldt, T V; Neuhoff, V; Wächtler, K

1981-12-01

134

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

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Full Text Available 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 cells (DCs in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood. Methods Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified. Results We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1, but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype. Conclusions These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris.

Martin Roland

2011-09-01

135

NF-?B signaling regulates myelination in the CNS  

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Full Text Available Besides myelination of neuronal axons by oligodendrocytes to facilitate propagation of action potentials, oligodendrocytes also support axon survival and function. A key transcription factor involved in these processes is nuclear factor-?B (NF-?B, a hetero- or homodimer of the Rel family of proteins, including p65, c-Rel, RelB, p50, and p52. Under unstimulated conditions, NF-?B remains inactive in the cytoplasm through interaction with NF-?B inhibitors (I?Bs. Upon activation of NF-?B the cytoplasmic I?Bs gets degradated, allowing the translocation of NF-?B into the nucleus where the dimer binds to the ?B consensus DNA sequence and regulates gene transcription. In this review we describe how oligodendrocytes are, directly or indirectly via neighboring cells, regulated by NF-?B signaling with consequences for innate and adaptive immunity and for regulation of cell apoptosis and survival.

Thomas Blank

2014-05-01

136

Myelin loss associated with neuroinflammation in hypertensive rats  

Science.gov (United States)

Background and purpose Small vessel disease is the major cause of white matter injury in patients with vascular cognitive impairment. Matrix metalloproteinase (MMP)-mediated inflammation may be involved in the white matter damage with oligodendrocyte (Ol) death. Therefore, we used spontaneously hypertensive stroke-prone rats (SHR-SP) to study the role of neuroinflammation in white matter damage. Methods Permanent unilateral carotid artery occlusion (UCAO) was performed at 12-weeks of age in SHR-SP. Following surgery, rats were placed on a Japanese permissive diet (JPD) and received 1 % NaCl in drinking water. MRI, histology, biochemistry, and ELISA characterized white matter lesions and cognitive impairment was tested by Morris water maze (MWM). Results white matter damage was observed 4-5 weeks following UCAO/JPD. Immunoblotting showed marked reduction in myelin basic protein (MBP) and up regulation of immature Ols. Mature Ols underwent caspase-3-mediated apoptosis. MWM showed cognitive impairment. Abnormally appearing vessels were observed and surrounded by inflammatory-like cells. IgG extravasation and hemorrhage, indicating blood-brain barrier (BBB) disruption, was closely associated with MMP-9 expression. Lesions in white matter showed reactive astrocytosis and activated microglia that expressed tumor necrosis factor-? (TNF-?). MMP-3 and MMP-9 were significantly increased and MMP-2 reduced in astrocytes and Ol. Conclusion We found apoptosis of mature Ols with an increase in immature Ols. Increased MMP-3, MMP-9 and TNF-? were associated with myelin breakdown and BBB disruption. Neuroinflammation is an important factor in white matter damage and Ol death, and studies using this new model can be done to assess agents to block inflammation. PMID:22363061

Jalal, Fakhreya Yousuf; Yang, Yi; Thompson, Jeffrey; Lopez, Anita Claudine; Rosenberg, Gary A.

2013-01-01

137

Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope  

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The degradation of myelin in the CNS is the hallmark of multiple sclerosis. Reduction in the net positive charge of myelin basic protein (MBP), through deimination, correlates strongly with disease severity and may mediate myelin instability and loss of compaction. Using Cys scanning, spin labeling, EPR spectroscopy, and site-specific proteolysis, we show that in the membrane-bound state the primary immunodominant epitope, V83-T92, of the less cationic recombinant murine MBP C8 mimic (rmC8) f...

Musse, Abdiwahab A.; Boggs, Joan M.; Harauz, George

2006-01-01

138

PMP22 expression in dermal nerve myelin from patients with CMT1A  

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Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a 1.4 Mb duplication on chromosome 17p11.2, which contains the peripheral myelin protein-22 (PMP22) gene. Increased levels of PMP22 in compact myelin of peripheral nerves have been demonstrated and presumed to cause the phenotype of CMT1A. The objective of the present study was to determine whether an extra copy of the PMP22 gene in CMT1A disrupts the normally coordinated expression of PMP22 protein in peripheral nerve myelin and to eva...

Katona, Istvan; Wu, Xingyao; Feely, Shawna M. E.; Sottile, Stephanie; Siskind, Carly E.; Miller, Lindsey J.; Shy, Michael E.; Li, Jun

2009-01-01

139

Surface bundles versus Heegaard splittings  

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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, David; Schleimer, Saul

2002-01-01

140

Nature's recipe for splitting inteins.  

Science.gov (United States)

Protein splicing in trans by split inteins has increasingly become a powerful protein-engineering tool for protein ligation, both in vivo and in vitro. Over 100 naturally occurring and artificially engineered split inteins have been reported for protein ligation using protein trans-splicing. Here, we review the current status of the reported split inteins in order to delineate an empirical or rational strategy for constructing new split inteins suitable for various applications in biotechnology and chemical biology. PMID:25096198

Aranko, A Sesilja; Wlodawer, Alexander; Iwaï, Hideo

2014-08-01

 
 
 
 
141

Splitting the Cartesian point  

International Nuclear Information System (INIS)

It is argued that the point structure of space and time must be constructed from the primitive extensional character of space and time. A procedure for doing this is laid down and applied to one-dimensional and two-dimensional systems of abstract extensions. Topological and metrical properties of the constructed point systems, which differ nontrivially from the usual R and R2 models, are examined. Briefly, constructed points are associated with directions and the Cartesian point is split. In one-dimension each point splits into a point pair compatible with the linear ordering. An application to one-dimensional particle motion is given, with the result that natural topological assumptions force the number of left point, right point transitions to remain locally finite in a continuous motion. In general, Cartesian points are seen to correspond to certain filters on a suitable Boolean algebra. Constructed points correspond to ultrafilters. Thus, point construction gives a natural refinement of the Cartesian systems

142

Split ergativity in Nêlêmwa  

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Nêlêmwa (New Caledonia) is a split ergative language. Pronouns are accusative, while nominal arguments are marked as ergative-absolutive. The two ergative markers signal the distinction between animate and inanimate agents. With active intransitive verbs (motion, position, affect, perception, cognition, discourse, Aktionsart), there is a choice of absolutive or ergative constructions, according to the position of the oblique NP. If in the canonical position of the patient (VPA), the oblique...

Bril, Isabelle

1997-01-01

143

Splitting Extended Supersymmetry  

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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 induc...

Antoniadis, Ignatios; Benakli, Karim; Delgado, Antonio; Quiros, Mariano; Tuckmantel, Marc

2005-01-01

144

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2  

Science.gov (United States)

Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

Laulumaa, Saara; Kursula, Petri; Natali, Francesca

2015-01-01

145

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2  

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Full Text Available Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

Laulumaa Saara

2015-01-01

146

The structural and functional role of myelin fast-migrating cerebrosides : pathological importance in multiple sclerosis  

DEFF Research Database (Denmark)

A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds - FMC-1 and FMC-2 - of this series have been characterized as the 3-SAG containing nonhydroxy and hydroxy fatty acyl, respectively. The next two - FMC-3 and FMC-4 - add 6-O-acetyl-galactose and the most complex glycosphingolipids, FMC-5, -6 and -7, are 2,3,4,6-tetra-O-acetyl-3-SAG. These hydrophobic myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases including multiple sclerosis.

Podbielska, Maria; Levery, Steven B

2011-01-01

147

Morphometric analysis of axons myelinated during adult life in the mouse superior cervical ganglion.  

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In experimental studies addressing the regulation of myelin formation and maintenance by Schwann cells, the sympathetic nervous system of young adult rodents has served a key role as an essentially nonmyelinated yet modifiable control tissue. Nevertheless there is clear evidence of substantial myelination in the superior cervical ganglion (SCG) of normal mice and rats of more advanced age. Against this background, interpretation of experimental outcomes in particular sympathetic tissues will ...

Little, G. J.; Heath, J. W.

1994-01-01

148

The central role of Fyn kinase in axon-glial signalling and translation of myelin proteins  

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During central nervous system myelination, oligodendrocytes extend membrane processes towards an axonal contact site which is followed by ensheathment resulting in a compacted multilamellar myelin sheath. The formation of this axon-glial unit facilitates rapid saltatory propagation of action potentials along the axon and requires the synthesis and transport of copious amounts of lipids and proteins to the axon-glial contact site. Fyn is a member of the Src family of non receptor tyrosine kina...

White, Robin

2007-01-01

149

A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.  

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Transcription of the myelin basic protein (MBP) gene is regulated in a cell-type-specific and developmental stage-specific manner during myelin formation in the murine central nervous system. The 5'-flanking region of the MBP gene contains several regulatory elements that differentially contribute to the cell-type-specific transcription of MBP in cells derived from the central nervous system. The proximal element, termed MB1, which is located between nucleotides -14 and -50 with respect to th...

Haas, S.; Gordon, J.; Khalili, K.

1993-01-01

150

Treatment with Thyroxine Restores Myelination and Clinical Recovery after Intraventricular Hemorrhage  

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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 decrea...

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.; Ballabh, Praveen

2013-01-01

151

Neurotrophic Modulation of Myelinated Cutaneous Innervation and Mechanical Sensory Loss in Diabetic Mice  

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Human diabetic patients often lose touch and vibratory sensations, but to date, most studies on diabetes-induced sensory nerve degeneration have focused on epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous myelinated fibers in relation to the behavioral responses to tactile stimuli from diabetic mice. Weekly behavioral testing began prior to STZ administration and continued until 8 weeks, at which time myelinated fiber innervation was examined in the footpad by immuno...

Christianson, Julie A.; Ryals, Janelle M.; Johnson, Megan S.; Dobrowsky, Rick T.; Wright, Douglas E.

2007-01-01

152

Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10  

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Sox10 is a high-mobility-group transcriptional regulator in early neural crest. Without Sox10, no glia develop throughout the peripheral nervous system. Here we show that Sox10 is restricted in the central nervous system to myelin-forming oligodendroglia. In Sox10-deficient mice progenitors develop, but terminal differentiation is disrupted. No myelin was generated upon transplantation of Sox10-deficient neural stem cells into wild-type hosts showing the permanent, cell-autonomous nature of t...

Stolt, C. Claus; Rehberg, Stephan; Ader, Marius; Lommes, Petra; Riethmacher, Dieter; Schachner, Melitta; Bartsch, Udo; Wegner, Michael

2002-01-01

153

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

Science.gov (United States)

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 adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups. PMID:19100839

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

2009-03-01

154

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

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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

155

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria  

DEFF Research Database (Denmark)

ABSTRACT: 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 (n = 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

156

White matter tract integrity metrics reflect the vulnerability of late-myelinating tracts in Alzheimer's disease?  

Science.gov (United States)

Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD. PMID:24319654

Benitez, Andreana; Fieremans, Els; Jensen, Jens H.; Falangola, Maria F.; Tabesh, Ali; Ferris, Steven H.; Helpern, Joseph A.

2013-01-01

157

White matter tract integrity metrics reflect the vulnerability of late-myelinating tracts in Alzheimer's disease.  

Science.gov (United States)

Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD. PMID:24319654

Benitez, Andreana; Fieremans, Els; Jensen, Jens H; Falangola, Maria F; Tabesh, Ali; Ferris, Steven H; Helpern, Joseph A

2014-01-01

158

Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent.  

Science.gov (United States)

The Schwann cell (SC)-axon interface represents a membrane specialization that integrates axonal signals to coordinate cytoskeletal dynamics resulting in myelination. Here we show that LKB1/Par-4 is asymmetrically localized to the SC-axon interface and co-localizes with the polarity protein Par-3. Using purified SCs and myelinating cocultures, we demonstrate that localization is dependent on the phosphorylation of LKB1 at serine-431. SC-specific deletion of LKB1 significantly attenuates developmental myelination, delaying the initiation and altering the myelin extent into adulthood, resulting in a 30% reduction in the conduction velocity along the adult sciatic nerves. Phosphorylation of LKB1 by protein kinase A is essential to establish the asymmetric localization of LKB1 and Par-3 and rescues the delay in myelination observed in the SC-specific knockout of LKB1. Our findings suggest that SC polarity may coordinate multiple signalling complexes that couple SC-axon contact to the redistribution of specific membrane components necessary to initiate and control myelin extent. PMID:25255972

Shen, Yun-An A; Chen, Yan; Dao, Dang Q; Mayoral, Sonia R; Wu, Laiman; Meijer, Dies; Ullian, Erik M; Chan, Jonah R; Lu, Q Richard

2014-01-01

159

Changes in tissue directionality reflect differences in myelin content after demyelination in mice spinal cords.  

Science.gov (United States)

Changes in myelin integrity are key manifestations of many neurological diseases including multiple sclerosis but precise measurement of myelin in vivo is challenging. The goal of this study was to evaluate myelin content in histological images obtained from a lysolecithin mouse model of demyelination, using a new quantitative method named structure tensor analysis. Injury was targeted at the dorsal column of mice spinal cords. We obtained 16 histological images stained with luxol fast blue for myelin from 9 mice: 9 images from lesion epicenter and 7 from a distant area 500-?m away from the epicenter. In each image, we categorized 3 tissue types: healthy, completely demyelinated, and partially demyelinated. Structure tensor analysis was applied to quantify the coherency (anisotropy), energy (trace of dominant directions), and angular entropy (degree of disorder) of each tissue. We found that completely demyelinated lesions had significantly lower coherency and energy but higher angular entropy than partially demyelinated and healthy tissues at both the epicenter and distant areas of the injury. In addition, the coherency of healthy tissue was greater than partially demyelinated tissue at each site. Within tissue category, we did not find differences in any measure between spinal cord locations. Our findings suggest that greater myelin integrity is associated with better tissue anisotropy, independent of injury location. Structure tensor analysis may serve as a new tool for quantitative measurement of myelin content in white matter, and this may help understand disease mechanisms and development in MS and other demyelinating disorders. PMID:25281497

Ansari, Mohammad K; Yong, Heather Y F; Metz, Luanne; Yong, V Wee; Zhang, Yunyan

2014-11-01

160

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

International Nuclear Information System (INIS)

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

 
 
 
 
161

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

162

Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?  

Directory of Open Access Journals (Sweden)

Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

William L. Maxwell

2013-09-01

163

Inhibitors of myelination: ECM changes, CSPGs and PTPs.  

Science.gov (United States)

After inflammation-induced demyelination, such as in the disease multiple sclerosis, endogenous remyelination often fails. However, in animal models of demyelination induced with toxins, remyelination can be quite robust. A significant difference between inflammation-induced and toxin-induced demyelination is the response of local cells within the lesion, including astrocytes, oligodendrocytes, microglia/macrophages, and NG2+ cells, which respond to inflammatory stimuli with increased extracellular matrix (ECM) protein and chondroitin sulfate proteoglycan (CSPG) production and deposition. Here, we summarize current knowledge of ECM changes in demyelinating lesions, as well as oligodendrocyte responses to aberrant ECM proteins and CSPGs after various types of demyelinating insults. The discovery that CSPGs act through the receptor protein tyrosine phosphatase sigma (PTP?) and the Rho-ROCK pathway to inhibit oligodendrocyte process extension and myelination, but not oligodendrocyte differentiation (Pendleton et al., Experimental Neurology (2013) vol. 247, pp. 113-121), highlights the need to better understand the ECM changes that accompany demyelination and their influence on oligodendrocytes and effective remyelination. PMID:24200549

Harlow, Danielle E; Macklin, Wendy B

2014-01-01

164

Fatty acid synthase expression during peripheral nervous system myelination.  

Science.gov (United States)

The expression of fatty acid synthase (FAS) in rat and mouse sciatic nerves during postnatal development was investigated. FAS activity was not sensitive to the nutritional status of the animals. During development, the specific activity of FAS was low in rat and mouse nerves immediately after birth. Then, there was a steady increase in the activity (8- to 10-fold) which reached a maximal level around postnatal day 11, plateaued till day 32, and decreased to reach 30% of the maximum at day 80. A similar developmental profile was obtained when the amount of FAS protein was quantified, thus suggesting that the variations in activity observed during sciatic nerve development are mainly due to variations in FAS protein content. Northern blot analysis showed that the mRNA levels for FAS parallels those of the ceramide galactosyl transferase (CGT) during mouse sciatic nerve development and in a rat demyelination-nerve regeneration model. In addition, we measured FAS expression in the sciatic nerves of the trembler mutant, which is a mouse model of PNS dysmyelination. In 20-day-old trembler nerves, FAS specific activity, protein amount and mRNA levels represented only 25% of the normal values. Altogether, our data indicate that FAS expression is linked to the PNS myelination process, and that the main regulation occurs at the level of the gene expression. PMID:12007831

Salles, Jérôme; Sargueil, Françoise; Knoll-Gellida, Anja; Witters, Lee A; Shy, Michael; Jiang, Huiyuan; Cassagne, Claude; Garbay, Bertrand

2002-05-30

165

Solid-State NMR Spectroscopy of Membrane-Associated Myelin Basic Protein—Conformation and Dynamics of an Immunodominant Epitope  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin basic protein (MBP) maintains the tight multilamellar compaction of the myelin sheath in the central nervous system through peripheral binding of adjacent lipid bilayers of oligodendrocytes. Myelin instability in multiple sclerosis (MS) is associated with the loss of positive charge in MBP as a result of posttranslational enzymatic deimination. A highly-conserved central membrane-binding fragment (murine N81-PVVHFFKNIVTPRTPPP-S99, identical to human N83-S101) represents a primary immun...

Ahmed, Mumdooh A. M.; Bamm, Vladimir V.; Harauz, George; Ladizhansky, Vladimir

2010-01-01

166

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 ...

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

167

Age-Related Slowing in Cognitive Processing Speed is Associated with Myelin Integrity in a Very Healthy Elderly Sample  

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Performance on measures of cognitive processing speed (CPS) slows with age, but the biological basis associated with this cognitive phenomenon remains incompletely understood. We assessed the hypothesis that the age-related slowing in CPS is associated with myelin breakdown in late-myelinating regions in a very healthy elderly population. An in vivo MRI biomarker of myelin integrity was obtained from the prefrontal lobe white matter and the genu of the corpus callosum for 152 healthy elderly ...

Lu, Po H.; Lee, Grace J.; Raven, Erika P.; Tingus, Kathleen; Khoo, Theresa; Thompson, Paul M.; Bartzokis, George

2011-01-01

168

A central role for Necl4 (SynCAM4) in Schwann cell–axon interaction and myelination  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelination in the peripheral nervous system requires close contact between Schwann cells and the axon, but the underlying molecular basis remains largely unknown. Here we show that cell adhesion molecules (CAMs) of the Nectin–like (Necl, also known as SynCAM or Cadm) family mediate Schwann cell–axon interaction during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells and is located along the internodes in direct apposition to Necl1, which is localized on axons. N...

Spiegel, Ivo; Adamsky, Konstantin; Eshed, Yael; Milo, Ron; Sarig–nadir, Offra; Horresh, Ido; Scherer, Steven S.; Rasband, Matthew N.; Peles, Elior

2007-01-01

169

Crystal structure of the extracellular domain of human myelin protein zero  

Energy Technology Data Exchange (ETDEWEB)

Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125 different mutations in the MPZ gene leading to peripheral neuropathy in patients have been reported worldwide (http://www.molgen. ua.ac.be/CMTMutations). All identified mutations resulting in a change or deletion of amino acid residues in MPZ give rise to neuropathy with the exception of R215L, which instead causes a benign polymorphism. Furthermore, more detailed analysis has classified the MPZ mutations into two major groups. In the first group, the mutations disrupt the intracellular processing of MPZ and are primarily associated with early onset neuropathy. It has been proposed that the mutated MPZ is trapped inside the cell rather than being transported to the plasma membrane. However, other evidence suggests that the mutated MPZ protein is expressed on the plasma membrane, but dominant-negatively disrupts the structure of myelin. In the second group, the MPZ mutations are associated with late onset neuropathy as these mutations cause only mild demyelination. The underlying mechanism is elusive with the hypothesis being that the second group of mutations cause minor abnormalities in the myelin sheath that over time may lead to aberrant Schwann cell-axon interactions and subsequently to axonal degeneration. The crystal structure of the extracellular domain of human MPZ (hP0ex) fused with maltose binding protein (MBP) is reported at 2.1 {angstrom} resolution. While the crystal structure of rat MPZ extracellular domain (rP0ex) is available, the crystal structure of the human counterpart is useful for the analysis of the two homologs as well as a comparison between the two species. The hP0ex molecule reveals subtle structural variations between two homologs allowing comparison of the human myelin protein zero to that of the rat protein. The alignment of these homologs is shown in Figure 1(a).

Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

2012-03-27

170

Correspondences between retinotopic areas and myelin maps in human visual cortex.  

Science.gov (United States)

We generated probabilistic area maps and maximum probability maps (MPMs) for a set of 18 retinotopic areas previously mapped in individual subjects (Georgieva et al., 2009 and Kolster et al., 2010) using four different inter-subject registration methods. The best results were obtained using a recently developed multimodal surface matching method. The best set of MPMs had relatively smooth borders between visual areas and group average area sizes that matched the typical size in individual subjects. Comparisons between retinotopic areas and maps of estimated cortical myelin content revealed the following correspondences: (i) areas V1, V2, and V3 are heavily myelinated; (ii) the MT cluster is heavily myelinated, with a peak near the MT/pMSTv border; (iii) a dorsal myelin density peak corresponds to area V3D; (iv) the phPIT cluster is lightly myelinated; and (v) myelin density differs across the four areas of the V3A complex. Comparison of the retinotopic MPM with cytoarchitectonic areas, including those previously mapped to the fs_LR cortical surface atlas, revealed a correspondence between areas V1-3 and hOc1-3, respectively, but little correspondence beyond V3. These results indicate that architectonic and retinotopic areal boundaries are in agreement in some regions, and that retinotopy provides a finer-grained parcellation in other regions. The atlas datasets from this analysis are freely available as a resource for other studies that will benefit from retinotopic and myelin density map landmarks in human visual cortex. PMID:24971513

Abdollahi, Rouhollah O; Kolster, Hauke; Glasser, Matthew F; Robinson, Emma C; Coalson, Timothy S; Dierker, Donna; Jenkinson, Mark; Van Essen, David C; Orban, Guy A

2014-10-01

171

Production and use of lentivirus to selectively transduce primary oligodendrocyte precursor cells for in vitro myelination assays.  

Science.gov (United States)

Myelination is a complex process that involves both neurons and the myelin forming glial cells, oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). We use an in vitro myelination assay, an established model for studying CNS myelination in vitro. To do this, oligodendrocyte precursor cells (OPCs) are added to the purified primary rodent dorsal root ganglion (DRG) neurons to form myelinating co-cultures. In order to specifically interrogate the roles that particular proteins expressed by oligodendrocytes exert upon myelination we have developed protocols that selectively transduce OPCs using the lentivirus overexpressing wild type, constitutively active or dominant negative proteins before being seeded onto the DRG neurons. This allows us to specifically interrogate the roles of these oligodendroglial proteins in regulating myelination. The protocols can also be applied in the study of other cell types, thus providing an approach that allows selective manipulation of proteins expressed by a desired cell type, such as oligodendrocytes for the targeted study of signaling and compensation mechanisms. In conclusion, combining the in vitro myelination assay with lentiviral infected OPCs provides a strategic tool for the analysis of molecular mechanisms involved in myelination. PMID:25650722

Peckham, Haley M; Ferner, Anita H; Giuffrida, Lauren; Murray, Simon S; Xiao, Junhua

2015-01-01

172

Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K  

DEFF Research Database (Denmark)

Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation of protein synthesis represents one mechanism used to control the different requirements for myelin sheath at each axo–glia interaction. Prior work has established that ?1-integrins are involved in the axoglial interactions that initiate myelination. Here, we show that integrin activation regulates translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3?UTR. During oligodendrocyte differentiation and myelination ?6?1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin sheath. Furthermore, knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Together, these results identify a novel pathway by which axoglial adhesion molecules coordinate MBP synthesis with myelin sheath formation

Laursen, Lisbeth Schmidt; Chan, Colin W

2011-01-01

173

Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime  

Science.gov (United States)

Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

Knoll, W.; Peters, J.; Kursula, P.; Gerelli, Y.; Natali, F.

2014-11-01

174

Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy  

Science.gov (United States)

The myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. Electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. However, microscopic observation of myelin in living organisms remains a challenge. Using a newly developed stimulated Raman scattering microscopy approach, we report noninvasive, label-free, real-time in vivo imaging of myelination by a single-Schwann cell, maturation of a single node of Ranvier, and myelin degradation in the transparent body of the Xenopus laevis tadpole.

Hu, Chun-Rui; Zhang, Delong; Slipchenko, Mikhail N.; Cheng, Ji-Xin; Hu, Bing

2014-08-01

175

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

176

Baryogenesis through split Higgsogenesis  

CERN Document Server

We study the cosmological evolution of asymmetries in the two-Higgs doublet extension of the Standard Model, prior to the electroweak phase transition. If Higgs flavour-exchanging interactions are sufficiently slow, then a relative asymmetry among the Higgs doublets corresponds to an effectively conserved quantum number. Since the magnitude of the Higgs couplings depends on the choice of basis in the Higgs doublet space, we attempt to formulate basis-independent out-of-equilibrium conditions. We show that an initial asymmetry between the Higgs scalars, which could be generated by CP violation in the Higgs sector, will be transformed into a baryon asymmetry by the sphalerons, without the need of $B-L$ violation. This novel mechanism of baryogenesis through (split) Higgsogenesis is exemplified with simple scenarios based on the out-of-equilibrium decay of heavy singlet scalar fields into the Higgs doublets.

Davidson, Sacha; Serodio, H; Silva, Joao P

2013-01-01

177

Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope.  

Science.gov (United States)

The degradation of myelin in the CNS is the hallmark of multiple sclerosis. Reduction in the net positive charge of myelin basic protein (MBP), through deimination, correlates strongly with disease severity and may mediate myelin instability and loss of compaction. Using Cys scanning, spin labeling, EPR spectroscopy, and site-specific proteolysis, we show that in the membrane-bound state the primary immunodominant epitope, V83-T92, of the less cationic recombinant murine MBP C8 mimic (rmC8) forms a more highly surface-exposed and shorter amphipathic alpha-helix than in the unmodified form, recombinant murine MBP C1 mimic (rmC1), analogous to the most cationic and abundant isomer of MBP in normal myelin. Moreover, cathepsin D digested lipid-associated rmC8 3-fold faster than rmC1, and cleavage at F86-F87 occurred more readily in rmC8 than rmC1. These findings suggest a mechanism for initial loss of myelin stability and the autoimmune pathogenesis of multiple sclerosis. PMID:16537438

Musse, Abdiwahab A; Boggs, Joan M; Harauz, George

2006-03-21

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

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)

180

Myelin contributes to the parallel orientation of axonal growth on white matter in vitro  

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Full Text Available Abstract Background Brain and spinal cord white matter can support extensive axonal growth. This growth is generally constrained to an orientation that is parallel to the longitudinal axis of the fiber tract. This constraint is presumably due to permissive and non-permissive substrates that are interleaved with each other and oriented in parallel within the tract. Results Embryonic chick sympathetic neurons were cultured on cryostat sections of rat brain and the orientation of neurite growth on white matter was assessed. To determine if haptotaxis is sufficient to guide parallel neurite growth, neurons were cultured under conditions designed to interfere with interactions between growing neurites and factors that act as biochemical contact guidance cues but not interactions with haptotactic cues. Under these conditions, neurites extending on white matter were not exclusively oriented in parallel to the fiber tract, suggesting that biochemical cues are involved. To assess the role of myelin in guiding parallel neurite growth, neurons were cultured on myelin-deficient corpus callosum. These neurons also extended neurites that were not constrained to a parallel orientation. Moreover, preincubation with NGF and treatment with cAMP analogs, manipulations that attenuate overall myelin-mediated inhibition of neurite growth, also led to a reduced parallel orientation of neurite growth. Conclusions The present studies suggest that some of the relevant factors that constrain axonal growth on white matter are not haptotactic in nature and appear to be partly mediated by factors that are associated with myelin and may involve myelin-associated "inhibitors".

Crutcher Keith A

2001-05-01

 
 
 
 
181

Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor.  

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Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects. PMID:23821361

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-01-01

182

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

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Full Text Available 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 accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h gene. Results Fa2h-/-/Cgt-/- double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to Cgt-/- mice the amount of GlcCer in CNS myelin was strongly reduced in Fa2h-/-/Cgt-/- mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in Fa2h-/-/Cgt-/- mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in Fa2h-/-/Cgt-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h-/-/Cgt-/- mice did not differ significantly from that of Cgt-/- mice, and there was no obvious phenotypic difference between Fa2h-/-/Cgt-/- and Cgt-/- mice Conclusions These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in Cgt-/- mice does not functionally compensate the loss of HFA-GalCer.

Gieselmann Volkmar

2011-03-01

183

TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes oligodendrocyte myelination.  

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Brain-derived neurotrophic factor (BDNF) plays critical roles in the development and maintenance of the central (CNS) and peripheral nervous systems (PNS). BDNF exerts its biological effects via tropomyosin-related kinase B (TrkB) and the p75 neurotrophin receptor (p75(NTR)). We have recently identified that BDNF promotes CNS myelination via oligodendroglial TrkB receptors. In order to selectively target TrkB to promote CNS myelination, we have used a putative TrkB agonist, a small multicyclic peptide (tricyclic dimeric peptide 6, TDP6) previously described by us that structurally mimics a region of BDNF that binds TrkB. We confirmed that TDP6 acts as a TrkB agonist as it provoked autophosphorylation of TrkB and its downstream signalling effector extracellular related-kinase 1 and 2 (Erk1/2) in primary oligodendrocytes. Using an in vitro myelination assay, we show that TDP6 significantly promotes myelination by oligodendrocytes in vitro, as evidenced by enhanced myelin protein expression and an increased number of myelinated axonal segments. In contrast, a second, structurally distinct BDNF mimetic (cyclo-dPAKKR) that targets p75(NTR) had no effect upon oligodendrocyte myelination in vitro, despite the fact that cyclo-dPAKKR is a very effective promoter of peripheral (Schwann cell) myelination. The selectivity of TDP6 was further verified by using TrkB-deficient oligodendrocytes, in which TDP6 failed to promote myelination, indicating that the pro-myelinating effect of TDP6 is oligodendroglial TrkB-dependent. Together, our results demonstrate that TDP6 is a novel BDNF mimetic that promotes oligodendrocyte myelination in vitro via targeting TrkB. PMID:25461619

Wong, Agnes W; Giuffrida, Lauren; Wood, Rhiannon; Peckham, Haley; Gonsalvez, David; Murray, Simon S; Hughes, Richard A; Xiao, Junhua

2014-10-16

184

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

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The simultaneous incorporation of (/sup 3/H)fucose and (1-/sup 14/C)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.

Peterson, R.G.; Baughman, S.; Scheidler, D.M.

1981-02-01

185

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

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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

186

Structure and expression of a novel compact myelin protein - small VCP-interacting protein (SVIP).  

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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. PMID:24055875

Wu, Jiawen; Peng, Dungeng; Voehler, Markus; Sanders, Charles R; Li, Jun

2013-10-11

187

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria  

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Full Text Available Abstract 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 (n?=?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

2012-06-01

188

Systemic injections of lipopolysaccharide accelerates myelin phagocytosis during Wallerian degeneration in the injured mouse spinal cord.  

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The phagocytic cell response within the injured spinal cord is inefficient, allowing myelin debris to remain for prolonged periods of time within white matter tracts distal to the injury. Several proteins associated with this degenerating myelin are inhibitory to axon growth and therefore prevent severed axons from regenerating. Inflammatory agents such as lipopolysaccharide (LPS) can stimulate both the migration and phagocytic activity of macrophages. Using in situ hybridization, we found that the expression of the LPS membrane receptor, CD14, was enhanced in the mouse dorsal column following a dorsal hemisection. Double labeling studies showed that microglia and macrophages are the two major cell types expressing CD14 mRNA following spinal cord injury (SCI). We therefore tested whether systemic injections of LPS would increase the number and phagocytic activity of macrophages/microglia in the ascending sensory tract (AST) of the mouse dorsal column following a dorsal hemisection. Mice were treated daily via intraperitoneal injections of either LPS or phosphate-buffered saline (PBS). At 7 days post-SCI, greater numbers of activated mononuclear phagocytes were present in the AST undergoing Wallerian degeneration (WD) in LPS-treated animals compared with controls. Animals treated with LPS also exhibited greater Oil Red O staining, which is specific for degenerating myelin and macrophages phagocytosing myelin debris. Myelin clearance was confirmed at 7 days using Luxol Fast Blue staining and on toluidine blue-stained semi-thin sections. These results indicate that it is possible to manipulate the innate immune response to accelerate myelin clearance during WD in the injured mouse spinal cord. PMID:16206158

Vallières, Nicolas; Berard, Jennifer L; David, Samuel; Lacroix, Steve

2006-01-01

189

Normal myelination of the child brain on MRI - a meta-analysis  

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Purpose: To establish age limits for the assessment of normal myelination of the brain on T1-weighted (T1w) and T2-weighted (T2w) images. Method: Comparison of previous publications (Barkovich et al. 1988, Grodd 1993, Hayakawa et al. 1990, Hittmair et al. 1994, Martin et al. 1988/1990/1991, Nakagawa et al. 1998, Staudt et al. 1993/1994, Stricker et al. 1990). Results: Despite technical and methodological differences, these studies principally agreed on the timing of myelination for most regions of the brain. Thus, a common timetable could be established: At 1 month, myelin is visible on both T1w and T2w in the medulla oblongata, tegmentum pontis, cerebellar peduncles and vermis, quadrigeminal plate, decussation of superior cerebellar peduncles, thalamus, posterior limb of internal capsule, optic radiation, corona radiata. Thereafter, the myelin-typical signal in the different regions of the brain should be present at the following ages (M=months): Anterior limb of internal capsule (2 M: T1w; 7 M: T2w), splenium of corpus callosum (4 M: T1w; 6 M: T2w), genu of corpus callosum (6 M: T1w; 8 M: T2w), centrum semiovale (2 M: T1w; 7 M: T2w). Branching of myelin into the gyri of the telencephalon (=arborization) appears at the latest at: occipital lobe (5 M: T1w; 12 M: T2w) and frontal lobe (7 M: T2w) and frontal lobe (7 M: T1w; 14 M: T2w). Conclusion: These extracted age limits can be used for a more reliable assessment of myelination than the time-tables from a single study. (orig.)

190

Sonic hedgehog and neurotrophin-3 increase oligodendrocyte numbers and myelination after spinal cord injury.  

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Spinal cord injury (SCI) results in loss of sensory and motor function below the level of injury and has limited available therapies. Multiple channel bridges have been investigated as a means to create a permissive environment for regeneration, with channels supporting axonal growth through the injury. Bridges support robust axon growth and myelination. Here, we investigated the cell types that myelinate axons in the bridges and whether over-expression of trophic factors can enhance myelination. Lentivirus encoding for neurotrophin-3 (NT3), sonic hedgehog (SHH) and the combination of these factors was delivered from bridges implanted into a lateral hemisection defect at T9/T10 in mice, and the response of endogenous progenitor cells within the spinal cord was investigated. Relative to control, the localized, sustained expression of these factors significantly increased growth of regenerating axons into the bridge and enhanced axon myelination 8 weeks after injury. SHH decreased the number of Sox2(+) cells and increased the number of Olig2(+) cells, whereas NT3 alone or in combination with SHH enhanced the numbers of GFAP(+) and Olig2(+) cells relative to control. For delivery of lentivirus encoding for either factor, we identified cells at various stages of differentiation along the oligodendrocyte lineage (e.g., O4(+), GalC(+)). Expression of NT3 enhanced myelination primarily by infiltrating Schwann cells, whereas SHH over-expression substantially increased myelination by oligodendrocytes. These studies further establish biomaterial-mediated gene delivery as a promising tool to direct activation and differentiation of endogenous progenitor cells for applications in regenerative medicine. PMID:24873988

Thomas, Aline M; Seidlits, Stephanie K; Goodman, Ashley G; Kukushliev, Todor V; Hassani, Donna M; Cummings, Brian J; Anderson, Aileen J; Shea, Lonnie D

2014-07-24

191

Myelin-associated glycoprotein (MAG) protects neurons from acute toxicity using a ganglioside-dependent mechanism.  

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Myelin-associated glycoprotein (MAG), a protein expressed on the innermost wrap of myelin, contributes to long-term axon stability as evidenced by progressive axon degeneration in Mag-null mice. Recently, MAG was also found to protect axons from acute toxic insults. In the current study, rat dorsal root ganglion neurons were cultured on control substrata and substrata adsorbed with myelin proteins. Neurons on myelin-adsorbed surfaces were resistant to acute degeneration of neurites induced by vincristine, a cancer chemotherapeutic agent with neuropathic side effects. Myelin-mediated protection was reversed by anti-MAG antibody and was absent when cells were cultured on extracts from Mag-null mouse myelin, confirming the protective role of MAG. Gangliosides (sialylated glycosphingolipids) are one functional class of axonal receptors for MAG. In the current studies, a direct role for gangliosides in mediating the acute protective effects of MAG was established. Treatment of neurons with sialidase, an enzyme that cleaves the terminal sialic acids required for MAG binding, reversed MAG's protective effect, as did treatment with (1R,2R)-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol, an inhibitor of glycosphingolipid biosynthesis. In contrast, treatment with phosphatidylinositol-specific phospholipase C, an enzyme that cleaves Nogo receptors (NgR, another class of MAG receptor), or with a peptide inhibitor of an NgR-associated signaling molecule p75(NTR), failed to diminish MAG-mediated protection. Inhibiting the Rho-associated protein kinase ROCK reversed protection. We conclude that MAG protects neurites from acute toxic insult via a ganglioside-mediated signaling pathway that involves activation of RhoA. Understanding MAG-mediated protection may provide opportunities to reduce axonal damage and loss. PMID:20436925

Mehta, Niraj R; Nguyen, Thien; Bullen, John W; Griffin, John W; Schnaar, Ronald L

2010-03-17

192

Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure  

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Abstract Background The myelin sheath is a multilamellar membrane structure wrapped around the axon, enabling the saltatory conduction of nerve impulses in vertebrates. Myelin basic protein, one of the most abundant myelin-specific proteins, is an intrinsically disordered protein that has been shown to bind calmodulin. In this study, we focus on a 19-mer synthetic peptide from the predicted calmodulin-binding segment near the C-terminus of human myelin basic protein. R...

Hayashi Nobuhiro; Petoukhov Maxim V; Majava Viivi; Pirilä Päivi; Svergun Dmitri I; Kursula Petri

2008-01-01

193

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome  

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Abstract Background The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the myelin protein zero (MPZ) gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P0) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P0ex) is known, while...

Sand Jette C; Braathen Geir J; Russell Michael B

2010-01-01

194

Protein profile of the myelin membrane of the fruit bat Rousettus aegyptiacus.  

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Integral membrane protein composition of the myelin membrane from normal and vitamin B12-deficient fruit bats has been compared with that of the rat. Purified myelin from the fruit bat shows only one basic protein which co-migrates with the large basic protein of the rat, and thus presents a pattern similar to that of the guinea pig. No gross differences were seen in the protein patterns from normal and vitamin B12-deficient animals. Bats between 4-10 days and 10-20 days post partum were also investigated. PMID:6661904

Cantrill, R C; Oldfield, M; van der Westhuyzen, J; McLoughlin, J

1983-01-01

195

Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves  

International Nuclear Information System (INIS)

Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths. (orig.)

196

Leydig cells express the myelin proteolipid protein gene and incorporate a new alternatively spliced exon  

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Although the myelin proteolipid protein gene (Plp1) is highly expressed in the central nervous system encoding the most abundant myelin protein in oligodendrocytes, it is also expressed in other tissues, including testis. Transgenic studies with mice that harbor Plp1-lacZ fusion genes suggest that Leydig cells are the source of Plp1 gene expression in testis. However, virtually nothing is known about Plp1 gene regulation in Leydig cells, which is the focus of this study. The first intron cont...

Li, Shenyang; Greuel, Brian T.; Meng, Fanxue; Pereira, Glauber B.; Pitts, Adria; Dobretsova, Anna; Wight, Patricia A.

2009-01-01

197

Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves  

Energy Technology Data Exchange (ETDEWEB)

Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths. (orig.)

Vargas, V.; Vargas, R.; Marquez, G.; Vonasek, E.; Mateu, L. [Dept. de Biologia Estructural, Caracas (Venezuela); Luzzati, V. [Centre de Genetique Moleculaire, CNRS, Gif-sur-Yvette (France); Borges, J. [Servicio de Neurologia, Universidad Central de Venezuela, Caracas (Venezuela)

2000-07-01

198

Cytoplasmic Domain of Zebrafish Myelin Protein Zero: Adhesive Role Depends on ?-Conformation  

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Solution spectroscopy studies on the cytoplasmic domain of human myelin protein zero (P0) (hP0-cyt) suggest that H-bonding between ?-strands from apposed molecules is likely responsible for the tight cytoplasmic apposition in compact myelin. As a follow-up to these findings, in the current study we used circular dichroism and x-ray diffraction to analyze the same type of model membranes previously used for hP0-cyt to investigate the molecular mechanism underlying the zebrafish cytoplasmic ap...

Luo, Xiaoyang; Inouye, Hideyo; Gross, Abby A. R.; Hidalgo, Marla M.; Sharma, Deepak; Lee, Daniel; Avila, Robin L.; Salmona, Mario; Kirschner, Daniel A.

2007-01-01

199

Split SUSY Radiates Flavor  

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Radiative flavor models where the hierarchies of Standard Model (SM) fermion masses and mixings are explained via loop corrections are elegant ways to solve the SM flavor puzzle. Here we build such a model in the context of Mini-Split Supersymmetry (SUSY) where both flavor and SUSY breaking occur at a scale of 1000 TeV. This model is consistent with the observed Higgs mass, unification, and WIMP dark matter. The high scale allows large flavor mixing among the sfermions, which provides part of the mechanism for radiative flavor generation. In the deep UV, all flavors are treated democratically, but at the SUSY breaking scale, the third, second, and first generation Yukawa couplings are generated at tree level, one loop, and two loops, respectively. Save for one, all the dimensionless parameters in the theory are O(1), with the exception being a modest and technically natural tuning that explains both the smallness of the bottom Yukawa coupling and the largeness of the Cabibbo angle.

Baumgart, Matthew; Zorawski, Thomas

2014-01-01

200

Split supersymmetry radiates flavor  

Science.gov (United States)

Radiative flavor models where the hierarchies of Standard Model (SM) fermion masses and mixings are explained via loop corrections are elegant ways to solve the SM flavor puzzle. Here we build such a model in the context of mini-split supersymmetry (SUSY) where both flavor and SUSY breaking occur at a scale of 1000 TeV. This model is consistent with the observed Higgs mass, unification, and dark matter as a weakly interacting massive particle. The high scale allows large flavor mixing among the sfermions, which provides part of the mechanism for radiative flavor generation. In the deep UV, all flavors are treated democratically, but at the SUSY-breaking scale, the third, second, and first generation Yukawa couplings are generated at tree level, one loop, and two loops, respectively. Save for one, all the dimensionless parameters in the theory are O(1), with the exception being a modest and technically natural tuning that explains both the smallness of the bottom Yukawa coupling and the largeness of the Cabibbo angle.

Baumgart, Matthew; Stolarski, Daniel; Zorawski, Thomas

2014-09-01

 
 
 
 
201

Photosynthetic water splitting  

Energy Technology Data Exchange (ETDEWEB)

This paper presents recent progress in the field of photosynthetic water splitting for both on vitro and in vivo systems. It is demonstrated that platinized chloroplasts are a novel photocatalytic material that is capable of the sustained simultaneous photoevolution of hydrogen and oxygen when irradiated with visible light. By using the technique of single-turnover saturating flashes of light an upper limit can be set on the number of platinum atoms that are neccesary for the formation of a catalytically active cluster. The results of these experiments indicate that the onset of catalytic hydrogen evolution during the creation of platinum metal catalyst can be observed with 50 atoms or less, and that a stable metal catalyst is created at about 500 atoms or less. Absolute thermodynamic efficiencies of conversion of light energy into chemical free-energy of molecular hydrogen by intact microalgae have been measured with an original physical measuring technique using a tin-oxide semiconducting gas sensor. Thin films of microalgae comprising 5--20 celluar monolayers have been entrapped on filter paper, thereby constraining them in a well-defined circular geometry. Based on absolute light absorption of visible polychromatic illumination in the low-intensity region of the light saturation curve, conversion efficiencies of 6 to 24% have been obtained. These values are the highest ever measured for hydrogen evolution by green algae. 35 refs., 5 figs., 1 tab.

Greenbaum, E.

1988-01-01

202

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

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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).

Nona, S.N.; Stafford, C.A.; Cronly-Dillon, J.R. (Manchester Univ. (United Kingdom). Inst. of Science and Technology); Duncan, A. (Guy' s Hospital, London (United Kingdom). Dept. of Anatomy); Scholes, J. (University Coll., London (United Kingdom))

1994-07-01

203

Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin.  

Science.gov (United States)

Wrapping and compaction of myelin sheaths around axons require specific membrane and membrane-associated proteins. Transmembrane proteins like proteolipid protein (PLP), the peripheral myelin protein 22 (PMP-22) and P0 as well as myelin basic protein (MBP) are crucial for this process. We have isolated a rat cDNA, initially denominated NS 3, that is mainly expressed in the myelinating cells of the nervous system, the oligodendrocytes and Schwann cells. The cDNA encodes a highly hydrophobic protein of 16.8 kDa with four putative transmembrane domains. The putative NS 3 protein lacks a N-terminal hydrophobic leader sequence and has no consensus sequence for N-linked glycosylation. In contrast to PLP and PMP-22, the first and third putative transmembrane domain of the NS 3 protein contain charged amino acids, a feature which resembles the structure of gap junction proteins. Sequence analysis showed that NS 3 is the rat homolog of a human gene called MAL that was cloned from, and is expressed in various T-cell lines. Therefore, we call this gene rMAL (rat MAL). In the nervous system, the expression of rMAL, mRNA begins after birth and is highest during myelination. In situ hybridization shows that rMAL mRNA is exclusively expressed in white and gray matter oligodendrocytes in the CNS and in myelinating Schwann cells in peripheral nerves. Immunohistochemistry using a peptide-specific antibody localized the rMAL protein in the myelinated areas of the CNS and PNS. Furthermore, we demonstrate by immunoblot analysis that rMAL is a component of myelin. Its structure and distribution suggest that the rMAL protein might play an important role in compact myelin. We propose that the name rMAL protein refers to rat Myelin And Lymphocyte protein. PMID:7643216

Schaeren-Wiemers, N; Valenzuela, D M; Frank, M; Schwab, M E

1995-08-01

204

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

205

Split-illumination electron holography  

International Nuclear Information System (INIS)

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.

206

Neutrino masses in split supersymmetry  

International Nuclear Information System (INIS)

We investigate the possibility of generating neutrino masses in the context of split supersymmetric scenarios where all sfermions are very heavy. All relevant contributions coming from the R-parity violating terms to the neutrino mass matrix up to one-loop level are computed showing the importance of the Higgs bosons one-loop corrections. We conclude that it is not possible to generate all neutrino masses and mixings in split SUSY with bilinear R-parity violating interactions. In the case of partial split SUSY, the one-loop Higgs bosons contributions are enough to generate the neutrino masses and mixings in agreement with the experiment. In the context of minimal SUSY SU(5), we find new contributions that help us to generate neutrino masses in the case of split SUSY.

207

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.)

208

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

209

Role of myelin plasticity in oscillations and synchrony of neuronal activity.  

Science.gov (United States)

Conduction time is typically ignored in computational models of neural network function. Here we consider the effects of conduction delays on the synchrony of neuronal activity and neural oscillators, and evaluate the consequences of allowing conduction velocity (CV) to be regulated adaptively. We propose that CV variation, mediated by myelin, could provide an important mechanism of activity-dependent nervous system plasticity. Even small changes in CV, resulting from small changes in myelin thickness or nodal structure, could have profound effects on neuronal network function in terms of spike-time arrival, oscillation frequency, oscillator coupling, and propagation of brain waves. For example, a conduction delay of 5ms could change interactions of two coupled oscillators at the upper end of the gamma frequency range (?100Hz) from constructive to destructive interference; delays smaller than 1ms could change the phase by 30°, significantly affecting signal amplitude. Myelin plasticity, as another form of activity-dependent plasticity, is relevant not only to nervous system development but also to complex information processing tasks that involve coupling and synchrony among different brain rhythms. We use coupled oscillator models with time delays to explore the importance of adaptive time delays and adaptive synaptic strengths. The impairment of activity-dependent myelination and the loss of adaptive time delays may contribute to disorders where hyper- and hypo-synchrony of neuronal firing leads to dysfunction (e.g., dyslexia, schizophrenia, epilepsy). PMID:24291730

Pajevic, S; Basser, P J; Fields, R D

2014-09-12

210

Adapting brain metabolism to myelination and long-range signal transduction.  

Science.gov (United States)

In the mammalian brain, the subcortical white matter comprises long-range axonal projections and their associated glial cells. Here, astrocytes and oligodendrocytes serve specific functions during development and throughout adult life, when they meet the metabolic needs of long fiber tracts. Within a short period of time, oligodendrocytes generate large amount of lipids, such as cholesterol, and membrane proteins for building the myelin sheaths. After myelination has been completed, a remaining function of glial metabolism is the energetic support of axonal transport and impulse propagation. Astrocytes can support axonal energy metabolism under low glucose conditions by the degradation of stored glycogen. Recently it has been recognized that the ability of glycolytic oligodendrocytes to deliver pyruvate and lactate is critical for axonal functions in vivo. In this review, we discuss the specific demands of oligodendrocytes during myelination and potential routes of metabolites between glial cells and myelinated axons. As examples, four specific metabolites are highlighted (cholesterol, glycogen, lactate, and N-acetyl-aspartate) that contribute to the specific functions of white matter glia. Regulatory processes are discussed that could be involved in coordinating metabolic adaptations and in providing feedback information about metabolic states. PMID:25130164

Hirrlinger, Johannes; Nave, Klaus-Armin

2014-11-01

211

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

212

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: [1-14C]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 transaxona along the axons, could undergo transaxonal transfer into myelin

213

Cation-binding sites in trigeminal ganglia and maxillary nerve: unusual reactivity of perikarya, stem axons and satellite cells.  

Science.gov (United States)

We have used the cupric/ferrocyanide reaction to study cation-binding in trigeminal ganglia and maxillary nerve of adult rats. Unmyelinated axons did not react, whereas myelinated axons were stained at nodal, paranodal or cleft sites. At 'nodal' sites, metallic deposits were found in the axoplasm, along the axolemma, and at the extracellular interfaces of the paranodal myelin. At 'paranodal' sites, particles were concentrated in the paranodal axoplasm and in the intracellular spaces of the myelin loops. Most maxillary axons examined at successive sites had all nodal or all paranodal staining, but 13 of 51 had a mixture. In trigeminal ganglia there was no staining of perineurial sheath, endoneurial cells or mast cells. Satellite cells and their basal laminae were prominently stained, with those around small neurons more reactive than those of large neurons. Patches of neuronal membrane on cell bodies were stained, more often for small than large neurons. The axon hillock and proximal stem axon were not stained in some cases, but approximately half the neurons had staining of perikaryal cytoplasm at the axon hillock or a dense asymmetric band in the proximal stem axon. Strong intraaxonal staining was found at the junction between unmyelinated proximal and myelinated distal stem axon. In distal stem axons, staining was found at the first myelin segment and at each successively thicker myelin segment; staining was mostly weak and paranodal, with intensity proportional to myelin thickness. The T-junction between stem and main myelinated axon had nodal or paranodal patterns; unmyelinated T-junctions were not stained. The varied cation-binding patterns in trigeminal ganglia show unusual properties of satellite cells and important differences between stem and main axons. The results that the cell membrane of axon hillock and proximal stem regions of many sensory large and small neurons may have numerous sodium channels and could affect signal propagation. PMID:2451989

Byers, M R; Costello, R J

1988-03-01

214

Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves  

International Nuclear Information System (INIS)

To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerveed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

215

The SNARE protein SNAP-29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia.  

Science.gov (United States)

During myelin formation, vast amounts of specialized membrane proteins and lipids are trafficked toward the growing sheath in cell surface-directed transport vesicles. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment proteins (SNAPs) are important components of molecular complexes required for membrane fusion. We have analyzed the expression profile and molecular interactions of SNAP-29 in the nervous system. In addition to its known enrichment in neuronal synapses, SNAP-29 is abundant in oligodendrocytes during myelination and in noncompact myelin of the peripheral nervous system. By yeast two-hybrid screen and coimmunoprecipitation, we found that the GTPases Rab3A, Rab24, and septin 4 bind to the N-terminal domain of SNAP-29. The interaction with Rab24 or septin 4 was GTP independent. In contrast, interaction between SNAP-29 and Rab3A was GTP dependent, and colocalization was extensive both in synapses and in myelinating glia. In HEK293 cells, cytoplasmic SNAP-29 pools were redistributed upon coexpression with Rab3A, and surface-directed trafficking of myelin proteolipid protein was enhanced by overexpression of SNAP-29 and Rab3A. Interestingly, the abundance of SNAP-29 in sciatic nerves was increased during remyelination and in a rat model of Charcot-Marie-Tooth disease, two pathological situations with increased myelin membrane biogenesis. We suggest that Rab3A may regulate SNAP-29-mediated membrane fusion during myelination. PMID:19170188

Schardt, Anke; Brinkmann, Bastian G; Mitkovski, Miso; Sereda, Michael W; Werner, Hauke B; Nave, Klaus-Armin

2009-11-15

216

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. PMID:24174657

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; Ballabh, Praveen

2013-10-30

217

Whole brain myelin mapping using T1- and T2-weighted MR imaging data  

Directory of Open Access Journals (Sweden)

Full Text Available Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio, fractional anisotropy and fluid-attenuated inversion recovery. With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease.

Dante Mantini

2014-09-01

218

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

219

Spontaneous optic nerve compression in the osteopetrotic (op/op) mouse: a novel model of myelination failure  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We report a focal disturbance in myelination of the optic nerve in the osteopetrotic (op/op) mouse, which results from a spontaneous compression of the nerve due to stenosis of the optic canal. The growth of the op/op optic nerve was significantly affected, being maximally suppressed at postnatal day (P)-30 (33% of age matched control). Myelination of the nerve in the optic canal was significantly delayed at P15 and myelin was almost completely absent at P30. The size of nerves...

Kondo, Yoichi; Ramaker, Jenna M.; Radcliff, Abigail B.; Baldassari, Simona; Mayer, Joshua A.; Ver Hoeve, James N.; Zhang, Chuan-li; Chiu, Shing-yan; Colello, Raymond J.; Duncan, Ian D.

2013-01-01

220

Folding and function of the myelin proteins from primary sequence data.  

Science.gov (United States)

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides. PMID:1710279

Inouye, H; Kirschner, D A

1991-01-01

 
 
 
 
221

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

222

Testing Split Supersymmetry with Inflation  

CERN Document Server

Split supersymmetry (SUSY) -- in which SUSY is relevant to our universe but largely inaccessible at current accelerators -- has become increasingly plausible given the absence of new physics at the LHC, the success of gauge coupling unification, and the observed Higgs mass. Indirect probes of split SUSY such as electric dipole moments (EDMs) and flavor violation offer hope for further evidence but are ultimately limited in their reach. Inflation offers an alternate window into SUSY through the direct production of superpartners during inflation. These particles are capable of leaving imprints in future cosmological probes of primordial non-gaussianity. Given the recent observations of BICEP2, the scale of inflation is likely high enough to probe the full range of split SUSY scenarios and therefore offers a unique advantage over low energy probes. The key observable for future experiments is equilateral non-gaussianity, which will be probed by both cosmic microwave background (CMB) and large scale structure (L...

Craig, Nathaniel

2014-01-01

223

The space of Heegaard Splittings  

CERN Document Server

For a Heegaard surface F in a closed orientable 3-manifold M, H(M,F) = Diff(M)/Diff(M,F) is the space of Heegaard surfaces equivalent to the Heegaard splitting (M,F). Its path components are the isotopy classes of Heegaard splittings equivalent to (M,F). We describe H(M,F) in terms of Diff(M) and the Goeritz group of (M,F). In particular, for hyperbolic M each path component is a classifying space for the Goeritz group, and when the (Hempel) distance of (M,F) is greater than 3, each path component of H(M,F) is contractible. For splittings of genus 0 or 1, we determine the complete homotopy type (modulo the Smale Conjecture for M in the cases when it is not known).

Johnson, Jesse

2010-01-01

224

Mass splitting induced by gravitation  

International Nuclear Information System (INIS)

The exact combination of internal and geometrical symmetries and the associated mass splitting problem is discussed. A 10-parameter geometrical symmetry is defined in a curved space-time in such a way that it is a combination of de Sitter groups. In the flat limit it reproduces the Poincare-group and its Lie algebra has a nilpotent action on the combined symmetry only in that limit. An explicit mass splitting expression is derived and an estimation of the order of magnitude for spin-zero mesons is made. (author)

225

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

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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

226

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

Science.gov (United States)

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 batches of HPS were unable to promote myelin formation in the absence of EE, as assessed by quantitative evaluation of cultures stained with Sudan black; such HPS also failed to promote basal lamina assembly, as assessed by immunofluorescence using antibodies against laminin, type IV collagen, and heparan sulfate proteoglycan. The addition of EE or L-ascorbic acid with such HPS led to the formation of large quantities of myelin and to the assembly of basal laminae. Pretreatment of EE with ascorbic acid oxidase abolished the EE activity, whereas trypsin did not. Other batches of HPS were found to promote both basal lamina and myelin formation in the absence of either EE or ascorbic acid. Ascorbic acid oxidase treatment or dialysis of these batches of HPS abolished their ability to promote Schwann cell differentiation, whereas the subsequent addition of ascorbic acid restored that ability. Ascorbic acid in the absence of serum was relatively ineffective in promoting either basal lamina or myelin formation. Fetal bovine serum was as effective as HPS in allowing ascorbic acid (and several analogs but not other reducing agents) to manifest its ability to promote Schwann cell differentiation. We suggest that ascorbic acid promotes Schwann cell myelin formation by enabling the Schwann cell to assemble a basal lamina, which is required for complete differentiation. PMID:3624305

Eldridge, C F; Bunge, M B; Bunge, R P; Wood, P M

1987-08-01

227

AGE CHANGES IN MYELINATED NERVE FIBERS OF THE CINGULATE BUNDLE AND CORPUS CALLOSUM IN THE RHESUS MONKEY  

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Aging is accompanied by deficits in cognitive function, which may be related to the vulnerability of myelinated nerve fibers to the normal process of aging. Loss of nerve fibers, together with age-related alterations in myelin sheath structure, may result in the inefficient and poorly coordinated conduction of neuronal signals. Until now, the ultrastructural analysis of cerebral white matter fiber tracts associated with frontal lobe areas critical in cognitive processing has been limited. In ...

Bowley, Michael P.; Cabral, Howard; Rosene, Douglas L.; Peters, Alan

2010-01-01

228

Connexin29 and Connexin32 at Oligodendrocyte and Astrocyte Gap Junctions and in Myelin of the Mouse Central Nervous System  

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The cellular localization, relation to other glial connexins (Cx30, Cx32, and Cx43), and developmental expression of Cx29 were investigated in the mouse central nervous system (CNS) with an anti-Cx29 antibody. Cx29 was enriched in subcellular fractions of myelin, and immunofluorescence for Cx29 was localized to oligodendrocytes and myelinated fibers throughout the brain and spinal cord. Oligodendrocyte somata displayed minute Cx29-immunopositive puncta around their periphery and intracellular...

Nagy, James I.; Ionescu, Andrei V.; Lynn, Bruce D.; Rash, John E.

2003-01-01

229

Promoting Myelination in an In Vitro Mouse Model of the Peripheral Nerve System: The Effect of Wine Ingredients  

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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 Schwa...

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

230

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex.  

Science.gov (United States)

Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA1-6). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2(+) precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases. PMID:25226845

García-Díaz, Beatriz; Riquelme, Raquel; Varela-Nieto, Isabel; Jiménez, Antonio Jesús; de Diego, Isabel; Gómez-Conde, Ana Lsabel; Matas-Rico, Elisa; Aguirre, José Angel; Chun, Jerold; Pedraza, Carmen; Santín, Luis Javier; Fernández, Oscar; Rodríguez de Fonseca, Fernando; Estivill-Torrús, Guillermo

2014-09-17

231

Immunoscintigraphy of experimental transplantable tumours using monoclonal antibody against myelin basic protein  

Energy Technology Data Exchange (ETDEWEB)

Monoclonal antibody was prepared against myelin basic protein a so called pancarcinoma antigen. After labelling with {sup 131}I the monoclonal antibody was injected into Lewis-lung cancer mice and rats with Walker breast cancer. Two, 24, 48, 72 and 96 hours after the labelled monoclonal antibody injection, radioimmunoimaging studies were carried out. After each gamma-camera study, organ distribution of the labelled monoclonal antibody was determined with radiobioassay technique which showed signficantly higher activity in the tumour tissue than in healthy ones. Significant sample radioactivity could be recovered in the tumour masses 48 hours after injection, which persisted even after 96 hours. The later finding might enable diagnosing types of malignancy with isotope-labelled monoclonal antibody against myelin basic protein. (orig.).

Koevesi, G.; Mohari, K.; Kocsar, L.; Fekete, B.; Szilvasi, I.; Szabo, G. (Semmelweis Univ. of Medicine, Budapest (Hungary). Dept. of Maxillofacial Surgery National Frederic Joliot Curie Radiology Radiohygiene Inst., Budapest (Hungary) Biological Centre of Hungary, Szeged (Hungary) Central State Hospital, Budapest (Hungary) Postgraduate Univ. of Medicine, Budapest (Hungary). 3. Physiological Clinic)

1991-07-01

232

Structure and chromosomal localization of the gene encoding the human myelin protein zero (MPZ)  

Energy Technology Data Exchange (ETDEWEB)

The authors describe the cloning, characterization, and chromosomal mapping of the human myelin protein zero (MPZ) gene (a structural protein of myelin and an adhesive glycoprotein of the immunoglobulin superfamily). The gene is about 7 kb long and consists of six exons corresponding of the functional domains. All exon-intron junction sequences conform to the GT/AG rule. The 5[prime]-flanking region of the gene has a TA-rich element (TATA-like box), two CAAT boxes, and a single defined transcription initiation site detected by the primer extension method. The gene for human MPZ was assigned to chromosome 1q22-q23 by spot blot hybridization of flow-sorted human chromosomes and fluorescence in situ hybridization. The localization of the MPZ gene coincides with the locus for Charcot-Marie-Tooth disease type 1B, determined by linkage analysis. 20 refs., 3 figs., 1 tab.

Hayasaka, Kiyoshi; Himoro, Masato; Takada, Goro (Akita Univ. School of Medicine, Akita (Japan)); Wang, Yimin; Takata, Mizuho; Minoshima, Shinsei; Shimizu, Nobuyoshi; Miura, Masayuki; Uyemura, Keiichi (Keio Univ. School of Medicine, Tokyo (Japan))

1993-09-01

233

Phosphoinositide breakdown in isolated myelin is stimulated by GTP analogues and calcium.  

Science.gov (United States)

Purified myelin from rat brainstem, prelabeled in vivo by intracerebral injection of [3H]myoinositol, showed enhanced breakdown of phosphoinositides on treatment with 5'-guanylylimidodiphosphate [Gpp-(NH)p] and Ca2+. Concentration variation of the former in the presence of Ca2+ showed a dose-dependent release of inositol 1,4-bisphosphate (IP2) and inositol 1,4,5-trisphosphate (IP3), while inositol 1-phosphate (IP) release was erratic. Concentration-dependent release of IP2 and IP3 was also observed with Ca2+ as the variable in the presence of Gpp(NH)p. Carbachol, when present, did not enhance the stimulatory effect of Gpp(NH)p alone. Addition of diphosphoglycerate during incubation enhanced IP3 at the expense of IP2, suggesting the presence of IP3 phosphatase in myelin. PMID:1965838

Golly, F; Larocca, J N; Ledeen, R W

1990-11-01

234

An elevated level of circulating galanin promotes developmental expression of myelin basic protein in the mouse brain.  

Science.gov (United States)

Myelinogenesis is a scheduled process that is regulated by the intrinsic properties of the cell and extracellular signals. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system. Chronic increase in circulating GAL levels protects the demyelination processes. Furthermore, GAL is synthesized in myelin-producing glial cells, such as oligodendrocytes and its expression level is at its highest between postnatal days 10 and 40. In the present study, we use our GAL transgenic mouse model to examine the effects of GAL on postnatal myelinogenesis in the CNS. Although we observed no difference in the proliferation of oligodendrocyte precursor cells, we found that GAL has a strong pro-myelinating effect. The transgenic mice at postnatal day 10 appeared to undergo myelinogenesis at an accelerated rate, as demonstrated by the increase in myelin basic protein (MBP) synthesis. The immunohistochemical results are consistent with our preliminary findings that suggest that GAL is a regulator of myelination and may be one of the myelination promoters. This finding is especially important for studies focusing on endogenous molecules for treating myelin-related diseases, such as multiple sclerosis and other leukodystrophies. PMID:25450959

Lyubetska, H; Zhang, L; Kong, J; Vrontakis, M

2015-01-22

235

The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination.  

Science.gov (United States)

The basic helix-loop-helix transcription factor Olig1 promotes oligodendrocyte maturation and is required for myelin repair. We characterized an Olig1-regulated G protein-coupled receptor, GPR17, whose function is to oppose the action of Olig1. Gpr17 was restricted to oligodendrocyte lineage cells, but was downregulated during the peak period of myelination and in adulthood. Transgenic mice with sustained Gpr17 expression in oligodendrocytes exhibited stereotypic features of myelinating disorders in the CNS. Gpr17 overexpression inhibited oligodendrocyte differentiation and maturation both in vivo and in vitro. Conversely, Gpr17 knockout mice showed early onset of oligodendrocyte myelination. The opposing action of Gpr17 on oligodendrocyte maturation reflects, at least partially, upregulation and nuclear translocation of the potent oligodendrocyte differentiation inhibitors ID2/4. Collectively, these findings suggest that GPR17 orchestrates the transition between immature and myelinating oligodendrocytes via an ID protein-mediated negative regulation and may serve as a potential therapeutic target for CNS myelin repair. PMID:19838178

Chen, Ying; Wu, Heng; Wang, Shuzong; Koito, Hisami; Li, Jianrong; Ye, Feng; Hoang, Jenny; Escobar, Sabine S; Gow, Alexander; Arnett, Heather A; Trapp, Bruce D; Karandikar, Nitin J; Hsieh, Jenny; Lu, Q Richard

2009-11-01

236

QUANTITATIVE MR IMAGING OF TWO-POOL MAGNETIZATION TRANSFER MODEL PARAMETERS IN MYELIN MUTANT SHAKING PUP  

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Magnetization transfer (MT) imaging quantitatively assesses cerebral white matter disease through its sensitivity to macromolecule-bound protons including those associated with myelin proteins and lipid bilayers. However, traditional MT contrast measured by the MT ratio (MTR) lacks pathologic specificity as demyelination, axon loss, inflammation and edema all impact MTR, directly and/or indirectly through multiple covariances among imaging parameters (particularly MTR with T1) and tissue feat...

Samsonov, Alexey; Alexander, Andrew L.; Mossahebi, Pouria; Wu, Yu-chien; Duncan, Ian D.; Field, Aaron S.

2012-01-01

237

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

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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 molecul...

Lin, Shu-ting; Fu, Ying-hui

2009-01-01

238

Emerging functions of myelin associated proteins during development neuronal plasticity and and neurpdegeneration.  

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Adult mammalian central nervous system (CNS) axons have a limited regrowth capacity following injury. Myelin-associated inhibitors (MAIs) limit axonal outgrowth and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo-A, MAG and OMgp, share two common neuronal receptors: NgR1, together with its co-receptors (p75(NTR), TROY and Lingo-1), and the recently described paired immunoglobulin-like receptor B (PirB). These proteins impair neuronal regeneratio...

Llorens, Franc; Gil, V.; Ri?o Ferna?ndez, Jose? Antonio Del

2011-01-01

239

Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice  

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Experimental allergic encephalomyelitis (EAE) is an autoimmune demyelinating disease of the central nervous system (CNS) that occurs after immunization of animals with myelin basic protein (MBP). The disease is a prototype model for the study of antigen-specific T helper cell-mediated autoimmune disease. In SJL/J mice, EAE is mediated by T helper cells directed against a 40-amino acid COOH-terminal peptic fragment of mouse small MBP. To identify the minimal T cell epitopes of MBP responsible ...

1988-01-01

240

Myelin repair is accelerated by inactivating CXCR2 on non-hematopoietic cells  

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Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and remyelination in MS ultimately fails. Although strategies to promote myelin repair are eagerly sought, mechanisms underlying remyelination in vivo have been elusive. CXCR2 is expressed on neutrophils and oligodendrocyte lineage cells in the central nervous system (CNS). CXCR2 positive neutrophils facilitate inflammatory demyelination in demyelination models such as experimental autoimmune ...

Liu, Liping; Darnall, Lindsey; Hu, Taofang; Choi, Karen; Ransohoff, Richard M.

2010-01-01

 
 
 
 
241

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis  

International Nuclear Information System (INIS)

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

242

An autometallographic technique for myelin staining in formaldehyde-fixed tissue  

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A new autometallographic (AMG) technique for staining myelin in formaldehyde- or paraformaldehyde- (PFA) fixed tissue is presented. The tissue sections were exposed to AMG development without prior treatment with silver salts. The method was examined on PFA-fixed tissue from mouse, rat, pig, and formaldehyde-fixed human autopsy material. Samples from brain, spinal cord, cranial, and spinal nerves were either cut on a vibratome, frozen and cryostat sectioned...

Larsen, M.; Bjarkam, C. R.; Stoltenberg, M.; Sorensen, J. C.; Danscher, G.

2003-01-01

243

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

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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

244

Adhesion and hemifusion of cytoplasmic myelin lipid membranes are highly dependent on the lipid composition  

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We report the effects of calcium ions on the adhesion and hemifusion mechanisms of model supported myelin lipid bilayer membranes of differing lipid composition. As in our previous studies [1, 2], the lipid compositions used mimic “healthy” and “diseased-like” (experimental autoimmune encephalomyelitis, EAE) membranes. Our results show that the interaction forces as a function of membrane separation distance are well described by a generic model that also (and in particular) includes ...

Banquy, Xavier; Kristiansen, Kai; Lee, Dong Woog; Israelachvili, Jacob N.

2012-01-01

245

Age-dependent B cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis  

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Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface antigens in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed diff...

Mclaughlin, Katherine A.; Chitnis, Tanuja; Newcombe, Jia; Franz, Bettina; Kennedy, Julia; Mcardel, Shannon; Kuhle, Jens; Kappos, Ludwig; Rostasy, Kevin; Pohl, Daniela; Gagne, Donald; Ness, Jayne M.; Tenembaum, Silvia; O Connor, Kevin C.; Viglietta, Vissia

2009-01-01

246

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

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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

247

Charmed hadrons and mass splitting  

International Nuclear Information System (INIS)

Mass splitting of charmed baryons are derived by weight diagrams, using the modified version of the parallelogram law of Feldman and Mathews. The quantum numbers of the family of 3+/2 baryons and 1+/2 baryons are listed. The sum rules are obtained directly from weight diagrams. The results are consistent with those obtained by others. (A.K.)

248

Split-field magnet (SFM)  

CERN Multimedia

The split-field magnet (SFM) completely assembled and undergoing power tests in its assembly hall. On the gallery at the far right is one of the large compensator magnets which restore ISR beams to their orbits after deviation by the SFM's field.

1972-01-01

249

Splitting solitons on a torus  

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New CP1-soliton behaviour on a flat torus is reported. Defined by the Weierstrass elliptic function and numerically-evolved from rest, each soliton splits up in two lumps which eventually reunite, divide and get back together again, etc.. This result invites speculation on the question of fractional topological charge.

Cova, R. J.

1997-01-01

250

Myelin-like structures seen intracellularly in renal tubule cells subjected to ischemia.  

Directory of Open Access Journals (Sweden)

Full Text Available Renal cortex was studied during experimentally induced ischemia. A transient increase in anerobic glycolysis occurred with concomitant swelling of both the Golgi apparatus and mitochondria. These intracytoplasmic organelles underwent marked changes in their intracellular positions. Infolding of cytoplasmic membrane at the basal side of proximal tubule cells increased in complexity and proceeded to enclose various intracytoplasmic microorganelles such as mitochondria and the Golgi apparatus. Piling up in layers was particularly marked around mitochondria. This piling up appeared as myelin-like structures on the free surface of, and within, proximal tubule cells, and followed disruption of the brush border at the free surface. Histological examination of thin sections showed that the fused portions of this brush border were actually brush border cytoplasmic membrane piled up in layers giving the appearance of myelin-like structures. After two hours of ischemia, parts of the membrane of these myelin-like structures were disrupted. Large vacuoles developed and these were thought to be related to the large vacuoles seen during cell degeneration.

Yamada,Teruo

1980-02-01

251

Vitamin D3 potentiates myelination and recovery after facial nerve injury.  

Science.gov (United States)

Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves. PMID:25261104

Montava, Marion; Garcia, Stéphane; Mancini, Julien; Jammes, Yves; Courageot, Joël; Lavieille, Jean-Pierre; Feron, François

2014-09-27

252

Adhesive properties and inflammatory potential of citrullinated myelin basic protein peptide 45-89.  

Science.gov (United States)

Deimination of arginyl residue of myelin basic protein (MBP) reduces cationicity of MBP and impedes the normal myelin membrane assembly. Less ordered structure of MBP is more susceptible to proteolytic attack that may lead to the release of highly immunogenic deiminated peptides into extracellular milieu. We have studied the association of peptides 45-89 derived from citrullinated MBP (C8 isomer) and phosphorylated MBP (C3 isomer) with the myelin lipids in a model membrane system using optical waveguide lightmode spectrometry. The analysis of association/dissociation kinetics to planar lipids under controlled hydrodynamic conditions has shown that MBP 45-89 peptide from citrullinated C8 isomer is less effectively adsorbed on the lipid membrane, than peptide from phosphorylated C3 isomer and packing densities for phosphorylated 45-89 MBP peptide is higher than for citrullinated forms. On the other hand, our results shown that continuous (24 h) exposure of mixed oligodendrocyte/microglial cells to peptides 45-89 from MBP-C8 induces apoptosis via mitochondrial pathway. In addition, peptides 45-89 stimulated the secretion of nitric oxide from microglial cells via induction of iNOS and decreased the level of the inhibitory protein IkB, indicating involvement of the transcription factor NF-kB in these processes. Our results suggest that some citrullinated peptides, initially released from oligodendrocytes, might activate microglia, which produces reactive nitrogen species and generates in turn fatal feedbacks that kill oligodendrocytes. PMID:22678722

Shanshiashvili, Lali V; Kalandadze, Irina V; Ramsden, Jeremy J; Mikeladze, David G

2012-09-01

253

SOX10 Transactivates S100B to Suppress Schwann Cell Proliferation and to Promote Myelination  

Science.gov (United States)

Schwann cells are an important cell source for regenerative therapy for neural disorders. We investigated the role of the transcription factor sex determining region Y (SRY)-box 10 (SOX10) in the proliferation and myelination of Schwann cells. SOX10 is predominantly expressed in rat sciatic nerve-derived Schwann cells and is induced shortly after birth. Among transcription factors known to be important for the differentiation of Schwann cells, SOX10 potently transactivates the S100B promoter. In cultures of Schwann cells, overexpressing SOX10 dramatically induces S100B expression, while knocking down SOX10 with shRNA suppresses S100B expression. Here, we identify three core response elements of SOX10 in the S100B promoter and intron 1 with a putative SOX motif. Knockdown of either SOX10 or S100B enhances the proliferation of Schwann cells. In addition, using dissociated cultures of dorsal root ganglia, we demonstrate that suppressing S100B with shRNA impairs myelination of Schwann cells. These results suggest that the SOX10-S100B signaling axis critically regulates Schwann cell proliferation and myelination, and therefore is a putative therapeutic target for neuronal disorders. PMID:25536222

Fujiwara, Sayaka; Hoshikawa, Shinya; Ueno, Takaaki; Hirata, Makoto; Saito, Taku; Ikeda, Toshiyuki; Kawaguchi, Hiroshi; Nakamura, Kozo; Tanaka, Sakae; Ogata, Toru

2014-01-01

254

Ciliary neurotrophic factor role in myelin oligodendrocyte glycoprotein expression in Cuprizone-induced multiple sclerosis mice.  

Science.gov (United States)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of MS. Ciliary neurotrophic factor (CNTF) has been shown to enhance the generation, maturation, and survival of oligodendrocytes in culture medium. The aim of this study was to demonstrate the role of CNTF on MOG expression in the cerebral cortex of Cuprizone-induced MS mice. The mice were treated by Cuprizone for five weeks in order to induce MS. The mice were then divided into 3 groups. The first group was injected subcutaneously (SC) by CNTF in the amount of 250 ?g/kg BW per day. The second group (SHAM) was injected SC by normal saline and the third group was left without injection as the control group. After four weeks the mice were killed and the cerebral cortex was harvested and the expression of MOG was studied by Western blotting. The data from this study show that the MOG expression was significantly increased in the CNTF-injected group as compared to the other groups. It is concluded that CNTF increases the MOG expression and may be important in the pathophysiology of MS. It is also concluded that CNTF may play a role in the process of remyelination by inducing the MOG expression. PMID:23443463

Salehi, Zivar; Hadiyan, Sara Pishgah; Navidi, Reza

2013-05-01

255

Many length scales surface fractality in monomolecular films of whole myelin lipids and proteins.  

Science.gov (United States)

Monomolecular films prepared with all the lipid and protein components of myelin were spread at the air/aqueous buffer interface from isolated bovine spinal cord myelin fully dissolved in chloroform:methanol (2:1) or by surface free energy shock of myelin membrane microvesicles. These monolayers show indistinguishable surface behavior, with similar compositional phase coexistence through all the compression isotherm on several subphase conditions. The domains were observed through epifluorescence and Brewster angle microscopy on the air/water interface and on Langmuir-Blodgett films. Their thickness was measured ellipsometrically. Under molecular packing conditions resembling those found in the natural membrane, the morphology and size of the domains are highly self-similar, displaying no characteristic length scale. These properties are the hallmark of fractal objects. The fractality extends at least three orders of magnitudes, from the micrometer to the millimeter range, the fractal dimension being about 1.7. A possible implication of fractality in membrane structure and/or function is demonstrated through the high fluctuation of the propagation of signals through constrained diffusion in corrals formed by domains in the plane of the monolayer, which restricts the diffusion of a fluorescent probe over many length scale domains. PMID:15681232

Oliveira, Rafael G; Tanaka, Motomu; Maggio, Bruno

2005-02-01

256

Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients  

Energy Technology Data Exchange (ETDEWEB)

The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. (Univ. of California, San Francisco, CA (United States)); Brooks, D.G.; Ravetch, J.V. (Sloan-Kettering Institute, New York, NY (United States)); Trofatter, J.A. (Massachusetts General Hospital, Boston, MA (United States))

1993-11-15

257

Molecular species of choline and ethanolamine glycerophospholipids in rat brain myelin during development.  

Science.gov (United States)

The composition of the molecular species of various phospholipid subclasses was examined in myelin isolated from brain of 15-, 21- and 90-day-old rats. The molecular species of diacylglycerophosphocholine (PtdCho), diacylglycerophosphoethanolamine (PtdEtn) and plasmenyl-ethanolamine (PlsEtn) were quantified by high-performance liquid chromatography (HPLC) after phospholipase C treatment and dinitrobenzoyl derivatization. In rat brain myelin, each phospholipid subclass showed a specific pattern of molecular species that changed during development. PtdCho contained large amounts of saturated/monounsaturated and disaturated species and low amounts of saturated/polyunsaturated species. During brain development, the levels of saturated/monounsaturated molecular species increased whereas those of the disaturated and saturated/polyunsaturated species decreased. PtdEtn were characterized by their low levels of disaturated species and a high content of saturated/monounsaturated and saturated/polyunsaturated species, of which those containing fatty acids of the n-3 series decreased, whereas those containing fatty acids of the n-6 series did not change during brain development. The levels of saturated/monounsaturated species increased in PtdEtn. No disaturated molecular species could be detected in PlsEtn. This alkenylacyl subclass contained large amounts of saturated/polyunsaturated, saturated/monounsaturated and dimonounsaturated molecular species. During development, the levels of saturated/polyunsaturated molecular species decreased while those of the two others increased. The data indicated that myelin sheaths undergo phospholipid changes during brain development and maturation. PMID:8139401

Leray, C; Sarliève, L L; Dreyfus, H; Massarelli, R; Binaglia, L; Freysz, L

1994-01-01

258

In vitro study of the direct effect of extracellular hemoglobin on myelin components.  

Science.gov (United States)

There is a relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of dilated veins in MS plaques. The sources of this iron can be varied, but capillary and venous hemorrhages leading to blood extravasation have been recorded, and could result in the release of hemoglobin extracellularly. Extracellular hemoglobin oxidizes quickly and is known to become a reactive molecule that triggers low-density lipoprotein oxidation and plays a pivotal role in atherogenesis. In MS, it could lead to local oxidative stress, inflammation, and tissue damage. Here, we investigated whether extracellular hemoglobin and its breakdown products can cause direct oxidative damage to myelin components in a peroxidative environment such as occurs in inflamed tissue. Oxidation of lipids was assessed by the formation of fluorescent peroxidized lipid-protein covalent adducts, by the increase in conjugated diene and malondialdehyde. Oxidation of proteins was analyzed by the change in protein mass. The results suggest that the globin radical could be a trigger of myelin basic protein oxidative cross-linking, and that heme transferred to the lipids is involved in lipid peroxidation. This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease. PMID:25463632

Bamm, Vladimir V; Lanthier, Danielle K; Stephenson, Erin L; Smith, Graham S T; Harauz, George

2015-01-01

259

Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination.  

Science.gov (United States)

The cellular interactions that drive the formation and maintenance of the insulating myelin sheath around axons are only partially understood. Leucine-rich glioma-inactivated (LGI) proteins play important roles in nervous system development and mutations in their genes have been associated with epilepsy and amyelination. Their function involves interactions with ADAM22 and ADAM23 cell surface receptors, possibly in apposing membranes, thus attenuating cellular interactions. LGI4-ADAM22 interactions are required for axonal sorting and myelination in the developing peripheral nervous system (PNS). Functional analysis revealed that, despite their high homology and affinity for ADAM22, LGI proteins are functionally distinct. To dissect the key residues in LGI proteins required for coordinating axonal sorting and myelination in the developing PNS, we adopted a phylogenetic and computational approach and demonstrate that the mechanism of action of LGI4 depends on a cluster of three amino acids on the outer surface of the LGI4 protein, thus providing a structural basis for the mechanistic differences in LGI protein function in nervous system development and evolution. PMID:24715463

Kegel, Linde; Jaegle, Martine; Driegen, Siska; Aunin, Eerik; Leslie, Kris; Fukata, Yuko; Watanabe, Masahiko; Fukata, Masaki; Meijer, Dies

2014-04-01

260

Acetyl-CoA carboxylase and SREBP expression during peripheral nervous system myelination.  

Science.gov (United States)

The expression of acetyl-CoA carboxylase (ACC) in mouse peripheral nervous system (PNS) was investigated. Both ACC 265 and ACC 280 isoforms were expressed in the sciatic nerve, although ACC 265 was predominant. ACC 265 transcripts originating from promoters P1 and P2 could be detected in the developing nerve, as well as the two splice products, which are characterized by the presence or the absence of a 24-base sequence before the codon serine-1200. The mRNA levels for ACC 265 parallel those of other lipogenic genes whose expression is linked to the myelination process. In addition, ACC 265 mRNA and protein levels in the nerves of the trembler mutant, which is a mouse model of PNS dysmyelination, represented around 30% of the normal values. The expression of the sterol regulatory element-binding proteins (SREBPs) was also studied. SREBP 1 mRNAs were expressed at a constant level during nerve development, and their quantities were normal in trembler. On the contrary, SREBP 2 mRNA quantities varied during the myelination period similarly to the lipogenic gene mRNAs, and the levels measured in trembler represented only 10% of the normal values. Taken together, these results suggest that the coordinate expression of several lipogenic genes, which occurs during PNS myelination, could possibly be regulated by SREBP 2. PMID:12668174

Salles, Jérôme; Sargueil, Françoise; Knoll-Gellida, Anja; Witters, Lee A; Cassagne, Claude; Garbay, Bertrand

2003-04-01

 
 
 
 
261

The Effects of Threonine Phosphorylation on the Stability and Dynamics of the Central Molecular Switch Region of 18.5-kDa Myelin Basic Protein  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The classic isoforms of myelin basic protein (MBP) are essential for the formation and maintenance of myelin in the central nervous system of higher vertebrates. The protein is involved in all facets of the development, compaction, and stabilization of the multilamellar myelin sheath, and also interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa isoform of MBP is an intrinsically-disordered protein that is a candidate auto-antigen in the human demyelinating disease mul...

Vassall, Kenrick A.; Bessonov, Kyrylo; Avila, Miguel; Polverini, Eugenia; Harauz, George

2013-01-01

262

ABSENCE OF OLIGODENDROGLIAL GLUCOSYLCERAMIDE SYNTHESIS DOES NOT RESULT IN CNS MYELIN ABNORMALITIES OR ALTER THE DYSMYELINATING PHENOTYPE OF CGT-DEFICIENT MICE  

Digital Repository Infrastructure Vision for European Research (DRIVER)

To examine the function of glycosphingolipids (GSLs) in oligodendrocytes, the myelinating cells of the central nervous system (CNS), mice were generated that lack oligodendroglial expression of UDP-glucose ceramide glucosyltransferase (encoded by Ugcg). These mice (Ugcgflox/flox;Cnp/Cre) did not show any apparent clinical phenotype, their total brain and myelin extracts had normal GSL content, including ganglioside composition, and myelin abnormalities were not detected in their CNS. These da...

Saadat, Laleh; Dupree, Jeffrey L.; Kilkus, John; Han, Xianlin; Traka, Maria; Proia, Richard L.; Dawson, Glyn; Popko, Brian

2010-01-01

263

Spontaneous optic nerve compression in the osteopetrotic (op/op) mouse: a novel model of myelination failure.  

Science.gov (United States)

We report a focal disturbance in myelination of the optic nerve in the osteopetrotic (op/op) mouse, which results from a spontaneous compression of the nerve resulting from stenosis of the optic canal. The growth of the op/op optic nerve was significantly affected, being maximally suppressed at postnatal day 30 (P30; 33% of age matched control). Myelination of the nerve in the optic canal was significantly delayed at P15, and myelin was almost completely absent at P30. The size of nerves and myelination were conserved both in the intracranial and intraorbital segments at P30, suggesting that the axons in the compressed site are spared in all animals at P30. Interestingly, we observed recovery both in the nerve size and the density of myelinated axons at 7 months in almost half of the optic nerves examined, although some nerves lost axons and became atrophic. In vivo and ex vivo electrophysiological examinations of P30 op/op mice showed that nerve conduction was significantly delayed but not blocked with partial recovery in some mice by 7 months. Transcardial perfusion of FITC-labeled albumin suggested that local ischemia was at least in part the cause of this myelination failure. These results suggest that the primary abnormality is dysmyelination of the optic nerve in early development. This noninvasive model system will be a valuable tool to study the effects of nerve compression on the function and survival of oligodendrocyte progenitor cells/oligodendrocytes and axons and to explore the mechanism of redistribution of oligodendrocyte progenitor cells with compensatory myelination. PMID:23426679

Kondo, Yoichi; Ramaker, Jenna M; Radcliff, Abigail B; Baldassari, Simona; Mayer, Joshua A; Ver Hoeve, James N; Zhang, Chuan-Li; Chiu, Shing-Yan; Colello, Raymond J; Duncan, Ian D

2013-02-20

264

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

265

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

266

Splitting Methods in Image Processing  

Digital Repository Infrastructure Vision for European Research (DRIVER)

It is often necessary to restore digital images which are affected by noise (denoising), blur (deblurring), or missing data (inpainting). We focus here on variational methods, i.e., the restored image is the minimizer of an energy functional. The first part of this thesis deals with the algorithmic framework of how to compute such a minimizer. It turns out that operator splitting methods are very useful in image processing to derive fast algorithms. The idea is that, in general, the functiona...

Setzer, Simon

2009-01-01

267

Low frequency split cycle cryocooler  

Science.gov (United States)

A split cycle Stirling cryocooler with two different drive motors and operating at a low drive frequency can have high thermodynamic efficiency. The temperature of the cold end of the cryocooler varies with drive frequency, voltage of the input electrical power and initial charge pressure values. The cryocooler operating at 8 Hz can provide 7 watts of refrigeration at 77 K for 230 watts of electrical input power.

Bian, S. X.; Zhang, Y. D.; Wan, W. W.; Wang, L.; Hu, Q. C.

1985-05-01

268

Splitting Supersymmetry in String Theory  

CERN Document Server

We point out that type I string theory in the presence of internal magnetic fields provides a concrete realization of split supersymmetry. To lowest order, gauginos are massless while squarks and sleptons are superheavy. We build such realistic U(3)xU(2)xU(1) models on stacks of magnetized D9-branes. Though not unified into a simple group, these theories preserve the successful supersymmetric relation of gauge couplings, as they start out with equal SU(3) and SU(2) couplings and the correct initial sin^2\\theta_W at the compactification scale of M_{GUT}\\simeq 2x10^{16} GeV, and they have the minimal low-energy particle content of split supersymmetry. We also propose a mechanism in which the gauginos and higgsinos are further protected by a discrete R-symmetry against gravitational corrections, as the gravitino gets an invariant Dirac mass by pairing with a member of a Kaluza-Klein tower of spin-3/2 particles. In addition to the models proposed here, split supersymmetry offers novel strategies for realistic mod...

Antoniadis, Ignatios

2005-01-01

269

Phase separation of myelin sheath in Triton X-114 solution: predominant localization of the 21.5-kDa isoform of myelin basic protein in the lipid raft-associated domain.  

Science.gov (United States)

Myelin basic protein (MBP) isoforms in the myelin sheath are known to have distinct intracellular expression patterns, which are profoundly related to functional specificity. Determining the differential localization of MBP isoforms is therefore important for understanding their pathophysiological roles. In this study, we have developed a new method for phase separation of myelin. The non-ionic detergent Triton X-114 is used to solubilize myelin sheath which then undergoes phase separation to yield four fractions. The lipid raft-associated proteins and lipids in each fraction were analysed by immunoblotting and lipid analysis, respectively. The present method gives two lipid raft-enriched fractions, one of them was found to contain only lipid raft-associated galactocerebroside and cholesterol as the major lipids. The 21.5-kDa MBP isoforms (21.5 MBP), both unphosphorylated and phosphorylated, were exclusively contained in this fraction. Phosphorylated 21.5 MBP (21.5 pMBP) has been shown to specifically disappear from demyelinated loci. The present analytical method clearly indicated that disappearance of 21.5 pMBP corresponded to demyelination and its reappearance corresponded to prevention of demyelination. Demyelination was also associated with aging and was prevented by the myelin-protecting herbal medicine, Chinpi, a type of dried citrus peel. PMID:24459152

Uruse, Michihiro; Yamamoto, Masahiro; Sugawa, Makoto; Matsuura, Keiko; Sato, Yurie; Seiwa, Chika; Watanabe, Kenji; Aiso, Sadakazu; Asou, Hiroaki

2014-04-01

270

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

International Nuclear Information System (INIS)

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. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. • The retina exhibits diminished neurotrophin levels and cellular differentiation. • The toxic effect is apoptotic

271

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

Energy Technology Data Exchange (ETDEWEB)

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. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. • The retina exhibits diminished neurotrophin levels and cellular differentiation. • The toxic effect is apoptotic.

Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

2013-12-01

272

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

273

Isolation of myelin basic protein-specific T cells predominantly from the memory T-cell compartment in multiple sclerosis.  

Science.gov (United States)

Myelin antigen-reactive T cells have been implicated in the pathogenesis of multiple sclerosis (MS). Myelin-reactive T cells can be isolated from control subjects as well as individuals who have MS. Experimental models of MS indicate that recently stimulated, myelin-reactive T cells have greater encephalitogenic potential than resting T cells. Activation induces changes in T-cell surface antigens that may distinguish previously stimulated, memory T cells from naive T cells. Therefore, we examined 108 myelin basic protein (MBP)-reactive T-cell lines from 7 MS and 8 control subjects to determine whether MBP-reactive T cells originated in the memory T-cell subset or in the naive subset. Isotypes of CD45 were used that designate memory or naive T cells. In subjects having MS, 84% of the MBP-reactive T cells resided in the memory T-cell subset. However, in control subjects, only 13% of MBP-specific T cells originated from the memory T-cell subset. This result suggests that a substantial proportion of MBP-reactive T cells from some individuals with MS have been previously activated in vivo. This difference provides additional support for the hypothesis that myelin antigen-specific T cells are involved in the pathogenesis of MS. PMID:9894874

Burns, J; Bartholomew, B; Lobo, S

1999-01-01

274

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

Science.gov (United States)

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 dramatically after the onset of myelination. BDNF expression is controlled in part by transcriptional regulation and the increased expression of the truncated TrkB receptor on SCs. To investigate the possible mechanism of BDNF transport and release, multicompartment Campenot chambers were used. DRG neurons transported and secreted endogenous BDNF along the surface of axons in anterograde fashion. In an attempt to enhance myelination by SCs, DRG neurons were transduced with an adenovirus to overexpress BDNF. BDNF was transported and secreted along the axons and enhanced myelination when compared with control cocultures. Together, the events surrounding the expression, localization, and mechanism of BDNF action in DRG neurons may hint at potential therapeutic implications to efficiently promote remyelination. PMID:17626221

Ng, Benjamin K; Chen, Lian; Mandemakers, Wilhelm; Cosgaya, José M; Chan, Jonah R

2007-07-11

275

Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

Han Ruolan

2008-04-01

276

Human mesenchymal stem cells isolated from olfactory biopsies but not bone enhance CNS myelination in vitro.  

Science.gov (United States)

Spinal cord injury (SCI) is a devastating condition with limited capacity for repair. Cell transplantation is a potential strategy to promote SCI repair with cells from the olfactory system being promising candidates. Although transplants of human olfactory mucosa (OM) are already ongoing in clinical trials, the repair potential of this tissue remains unclear. Previously, we identified mesenchymal-like stem cells that reside in the lamina propria (LP-MSCs) of rat and human OM. Little is known about these cells or their interactions with glia such as olfactory ensheathing cells (OECs), which would be co-transplanted with MSCs from the OM, or endogenous CNS glia such as oligodendrocytes. We have characterized, purified, and assessed the repair potential of human LP-MSCs by investigating their effect on glial cell biology with specific emphasis on CNS myelination in vitro. Purified LP-MSCs expressed typical bone marrow MSC (BM-MSC) markers, formed spheres, were clonogenic and differentiated into bone and fat. LP-MSC conditioned medium (CM) promoted oligodendrocyte precursor cell (OPC) and OEC proliferation and induced a highly branched morphology. LP-MSC-CM treatment caused OEC process extension. Both LP and BM-MSCs promoted OPC proliferation and differentiation, but only myelinating cultures treated with CM from LP and not BM-MSCs had a significant increase in myelination. Comparison with fibroblasts and contaminating OM fibroblast like-cells showed the promyelination effect was LP-MSC specific. Thus LP-MSCs harvested from human OM biopsies may be an important candidate for cell transplantation by contributing to the repair of SCI. PMID:23281012

Lindsay, Susan L; Johnstone, Steven A; Mountford, Joanne C; Sheikh, Saghir; Allan, David B; Clark, Louise; Barnett, Susan C

2013-03-01

277

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

Science.gov (United States)

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, 2',3'-dihydrophylloquinone (dK), for 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 (MK-4) in the brain. The efficiency of dietary dK conversion to MK-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to that in the hippocampus. There were significant positive correlations between sulfatides and MK-4 in the hippocampus (phylloquinone-supplemented diet, 12 and 24 months; dK-supplemented diet, 12 months) and cortex (phylloquinone-supplemented diet, 12 and 24 months). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dK to convert to brain MK-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure and behavior functions. PMID:20092997

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

2010-11-01

278

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

Science.gov (United States)

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 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 in the brain. The efficiency of dietary dihydrophylloquinone conversion to menaquinone-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to those in the hippocampus. There were significant positive correlations between sulfatides and menaquinone-4 in the hippocampus (phylloquinone-supplemented diet -12mo and 24mo; dihydrophylloquinone -supplemented diet - 12mo) and cortex (phylloquinone-supplemented diet -12mo and 24 mo). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dihydrophylloquinone to convert to brain menaquinone-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure, and behavior functions. PMID:20092997

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

2009-01-01

279

Nuclear proteins in mouse brain cells bind specifically to the myelin basic protein regulatory region.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Expression of myelin basic protein (MBP) in mice is regulated in a cell- and stage-specific manner during brain development. The MBP control region contains multiple cis-acting elements, shown by in vivo and in vitro assays, which are responsible for its unique pattern of transcription. Using synthetic DNA fragments spanning the MBP control region, we have analyzed nuclear proteins obtained from newborn (2-3 d), young adult (18-30 d), and adult (60 d) animals; these nuclear proteins form DNA-...

Lashgari, M. S.; Devine-beach, K.; Haas, S.; Khalili, K.

1990-01-01

280

Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Clustering of Kv1 channels at the juxtaparanodal region (JXP) in myelinated axons depends on their association with the Caspr2/TAG-1 adhesion complex. The interaction between these channels and Caspr2 was suggested to depend on PDZ scaffolding proteins. Here we show that at a subset of the JXP, PSD-93 colocalizes with Caspr2, K+ channels and its related protein PSD-95. The localization of PSD-93 and PSD-95 depends on the presence of Caspr2, as both scaffolding proteins failed to accumulate at...

Horresh, Ido; Poliak, Sebastian; Grant, Seth; Bredt, David; Rasband, Matthew N.; Peles, Elior

2008-01-01

 
 
 
 
281

Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively...

Su, Y.; Brooks, D. G.; Li, L.; Lepercq, J.; Trofatter, J. A.; Ravetch, J. V.; Lebo, R. V.

1993-01-01

282

Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease  

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Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear. We hypothesize that one function of ASPA is to provide acetate for the increased lipid synthesis that occurs during postnatal CNS myelination. The gene...

Madhavarao, Chikkathur N.; Arun, Peethambaran; Moffett, John R.; Szucs, Sylvia; Surendran, Sankar; Matalon, Reuben; Garbern, James; Hristova, Diana; Johnson, Anne; Jiang, Wei; Namboodiri, M. A. Aryan

2005-01-01

283

Phosphate groups modifying myelin basic proteins are metabolically labile; methyl groups are stable  

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Young and adult rats received intracranial injections of [33P]orthophosphoric acid. The time course of the appearance and decay of the radioactive label on basic proteins in isolated myelin was followed for 1 mo. Incorporation was maximal by 1 h, followed by a decay phase with a half-life of approximately 2 wk. However, radioactivity in the acid-soluble precursor pool (which always constituted at least half of the total radioactivity) decayed with a similar half-life, suggesting that the true...

1983-01-01

284

Antigen-Specific Therapy Promotes Repair of Myelin and Axonal Damage in Established EAE  

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Inflammation results in CNS damage in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how much repair of injured myelin and axons can occur following highly selective anti-inflammatory therapy in EAE and MS. In this study, SJL/J mice with established EAE were treated successfully with an antigen-specific recombinant T cell receptor ligand (RTL), RTL401, a mouse I-As/PLP-139–151 construct, after the peak of EAE. To define th...

Wang, Chunhe; Gold, Bruce G.; Kaler, Laurie J.; Yu, Xiaolin; Afentoulis, Michael E.; Burrows, Gregory G.; Vandenbark, Arthur A.; Bourdette, Dennis N.; Offner, Halina

2006-01-01

285

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.

2006-01-01

286

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

287

Curing CNS autoimmune disease with myelin-reactive Foxp3+ Treg.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The potential use of CD4(+)Foxp3(+) Treg as a cellular therapy for autoimmune disease is of great interest. For clinical translation, the key objective is to reverse established disease. Here we demonstrate that myelin basic protein (MBP)-reactive CD4(+)CD25(+) Treg from TCR Tg mice, but not polyclonal (non-MBP-reactive) Treg, can transfer efficient protection against MBP-induced EAE when used either directly from donor mice, or after in vitro expansion. MBP-reactive Treg transfer also showed...

La, Stephens; Kh, Malpass; Sm, Anderton

2009-01-01

288

TRANSDUCED SCHWANN CELLS PROMOTE AXON GROWTH AND MYELINATION AFTER SPINAL CORD INJURY  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We sought to directly compare growth and myelination of local and supraspinal axons by implanting into the injured spinal cord Schwann cells (SCs) transduced ex vivo with adenoviral (AdV) or lentiviral (LV) vectors encoding a bifunctional neurotrophin molecule (D15A). D15A mimics actions of both neurotrophin-3 and brain-derived neurotrophic factor. Transduced SCs were injected into the injury center one week after a moderate thoracic (T8) adult rat spinal cord contusion. D15A expression and b...

Golden, Kevin L.; Pearse, Damien D.; Blits, Bas; Garg, Maneesh S.; Oudega, Martin; Wood, Patrick M.; Bunge, Mary Bartlett

2007-01-01

289

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

290

Split quaternion nonlinear adaptive filtering.  

Science.gov (United States)

A split quaternion learning algorithm for the training of nonlinear finite impulse response adaptive filters for the processing of three- and four-dimensional signals is proposed. The derivation takes into account the non-commutativity of the quaternion product, an aspect neglected in the derivation of the existing learning algorithms. It is shown that the additional information taken into account by a rigorous treatment of quaternion algebra provides improved performance on hypercomplex processes. A rigorous analysis of the convergence of the proposed algorithms is also provided. Simulations on both benchmark and real-world signals support the approach. PMID:19926443

Ujang, Bukhari Che; Took, Clive Cheong; Mandic, Danilo P

2010-04-01

291

Nanofibers support oligodendrocyte precursor cell growth and function as a neuron-free model for myelination study.  

Science.gov (United States)

Nanofiber-based scaffolds may simultaneously provide immediate contact guidance for neural regeneration and act as a vehicle for therapeutic cell delivery to enhance axonal myelination. Additionally, nanofibers can serve as a neuron-free model to study myelination of oligodendrocytes. In this study, we fabricated nanofibers using a polycaprolactone and gelatin copolymer. The ratio of the gelatin component in the fibers was confirmed by energy dispersive X-ray spectroscopy. The addition of gelatin to the polycaprolactone (PCL) for nanofiber fabrication decreased the contact angle of the electrospun fibers. We showed that both polycaprolactone nanofibers as well as polycaprolactone and gelatin copolymer nanofibers can support oligodendrocyte precursor cell (OPC) growth and differentiation. OPCs maintained their phenotype and viability on nanofibers and were induced to differentiate into oligodendrocytes. The differentiated oligodendrocytes extend their processes along the nanofibers and ensheathed the nanofibers. Oligodendrocytes formed significantly more myelinated segments on the PCL and gelatin copolymer nanofibers than those on PCL nanofibers alone. PMID:24304204

Li, Yongchao; Ceylan, Muhammet; Shrestha, Bikesh; Wang, Haibo; Lu, Q Richard; Asmatulu, Ramazan; Yao, Li

2014-01-13

292

Rapid Simultaneous Mapping of Total and Myelin Water Content, T1 and T2* in Multiple Sclerosis  

CERN Document Server

Quantitative magnetic resonance imaging might provide a more specific insight into disease process, progression and therapeutic response of multiple sclerosis. We present an extension of a previously published approach for the simultaneous mapping of brain T1, T2* and total water content. In addition to those three parameters, the method presented in the current work allows for the measurement of myelin bound water content, a surrogate marker of tissue myelination. Myelin water was measured based on its distinct relaxation with reduced T2*, resulting in a multiexponential decay signal. However, only 10 points could be acquired on the relaxation curve within a maximum echo time of <40ms as the quantitative protocol has been adapted previously for fast acquisitions with whole brain coverage. The sparse sampling required an adaption of the optimisation approach with additional constraints necessary in order to obtain reliable results. Therefore, the corresponding pool fractions were determined using linear op...

Arhelger, Volker; Gliedstein, Detlef; Lafontaine, Marie-Sofie; Tonkova, Vyara; Holz, Dietrich; Böer, Andreas; Schenk, Jochen; Neeb, Heiko; (,; Koblenz, University of Applied Sciences; Koblenz, Radiologisches Institut Hohenzollernstrasse; Engineering, Institute for Medical; Koblenz, Information Processing; Boeer, Neurologie Dr; Koblenz,

2010-01-01

293

Neurological disturbances, premature lethality, and central myelination deficiency in transgenic mice overexpressing the homeo domain transcription factor Oct-6  

DEFF Research Database (Denmark)

Pit, Oct, Unc (POU) homeo domain transcription factors have been implicated in various developmental processes, including cell division, differentiation, specification, and survival of specific cell types. Although expression of the transcription factor Oct-6 in oligodendroglia is confined to the promyelin stage and is downregulated at the myelin stage of development, the effect of Oct-6 overexpression on oligodendrocyte development has not been established. Here we show that transgenic animals overexpressing Oct-6 at late oligodendrocyte development develop a severe neurologic syndrome characterized by action tremors, recurrent seizures, and premature death. Axons in the central nervous system of Oct-6 transgenics were hypomyelinated, hypermyelinated, or dysmyelinated, and ultrastructural analyses suggested that myelin formation was premature. The vulnerability of developing oligodendroglia to Oct-6 deregulation provides evidence that the POU factor may play a direct role in myelin disease pathogenesis in the mammalian CNS.

Jensen, N A; Pedersen, Karen-Marie

1998-01-01

294

Cell-cell interactions during the migration of myelin-forming cells transplanted in the demyelinated spinal cord.  

Science.gov (United States)

In the present paper, Dil-labeled myelin-forming cells were traced after their transplantation at a distance from a lysolecithin induced lesion in the adult wild-type and shiverer mouse spinal cord. Optical and ultrastructural observations indicate that after their transplantation, Dil-labeled Schwann cells and oligodendrocyte progenitors were found at the level of the graft as well as at the level of the lesion thus confirming that myelin-forming cells were able to migrate in the adult lesioned CNS (Gout et al., Neurosci Lett 87:195-199, 1988). Between the graft and the lesion, labeled Schwann cells and oligodendrocyte progenitors were absent in the gray matter, but were found as previously described, in specific locations (Baron-Van Evercooren et al., J Neurosci Res 35:428-438, 1993; Vignais et al., J Dev Neurosci 11:603-612, 1993). Both cell types were found along blood vessel walls and more precisely in the Virchow-Robin perivascular spaces. They were identified in the meninges among meningeal cells, collagen fibers, or occasionally in direct contact with the basement membrane forming the glia limitans. In addition to these findings, three major observations were made. In the ependymal region, myelin-forming cells were localized between or at the basal pole of ependymocytes. While Dil-labeled oligodendrocyte progenitors were noted to migrate along the outer surface of myelin sheats in CNS wild-type and shiverer white matter, Schwann cells were excluded from this structure in the wild-type mouse spinal cord. Moreover, in the shiverer mouse, migrating Schwann cells did not seem to interact directly with myelin sheats nor with mature oligodendrocytes. Finally, both cell types were seen to invade extensively the spinal peripheral roots. Our ultrastructural observations clearly suggest that multiple cell-cell and cell-substrate interactions rule the migration of myelin-forming cells in the adult CNS infering that multiple mechanisms are involved in this process. PMID:8929902

Baron-Van Evercooren, A; Avellana-Adalid, V; Ben Younes-Chennoufi, A; Gansmuller, A; Nait-Oumesmar, B; Vignais, L

1996-02-01

295

Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system.  

Science.gov (United States)

Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/?-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and ?-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair. PMID:22365546

Weng, Qinjie; Chen, Ying; Wang, Haibo; Xu, Xiaomei; Yang, Bo; He, Qiaojun; Shou, Weinian; Chen, Yan; Higashi, Yujiro; van den Berghe, Veronique; Seuntjens, Eve; Kernie, Steven G; Bukshpun, Polina; Sherr, Elliott H; Huylebroeck, Danny; Lu, Q Richard

2012-02-23

296

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyel...

Baer, Alexandra S.; Syed, Yasir A.; Kang, Sung Ung; Mitteregger, Dieter; Vig, Raluca; Ffrench-constant, Charles; Franklin, Robin J. M.; Altmann, Friedrich; Lubec, Gert; Kotter, Mark R.

2009-01-01

297

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Although there are indications of growth in the size and myelination of the rat corpus callosum during adulthood, it is not known how long this growth continues. In addition, the potential for age-related changes in these measures to affect the sex differences seen in adulthood has not been examined. Here the size of callosal subregions and area occupied by myelin were examined in the genu and splenium of male and female rats in adulthood, middle-age, and old age. Our findings revealed increa...

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

2007-01-01

298

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

299

Accelerated myelination in early Sturge-Weber syndrome: MRI-SPECT correlations  

International Nuclear Information System (INIS)

The prognosis of Sturge-Weber syndrome (SWS) is partly related to early occurrence of seizures but the diagnosis of this phakomatosis may be difficult during the 1st year of life. We have performed a retrospective study of seven patients with confirmed SWS (age 7 days to 3 months). None of the patients was asymptomatic at the time of the study. They all underwent MRI (T1 and T2 sequences) and single photon emission computed tomography (SPECT) at the same time. Regional cerebral blood flow was measured using xenon-133. In all cases, myelination appeared to be accelerated in the areas underlying the leptomeningeal angioma on both MRI sequences. In five cases, SPECT showed hyperperfusion in the damaged hemisphere. In one case, the SPECT was symmetrical and in another it showed hypoperfusion in the damaged hemisphere which was already atrophied. These data suggest that the accelerated myelination is not related to ischemia but to transient hyperperfusion. This MRI pattern can be helpful for the early diagnosis of SWS, which is of utmost importance for preventive antiepileptic treatment. (orig.). With 3 figs., 1 tab

300

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

 
 
 
 
301

Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: English Abstract in english Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in th [...] e CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs) and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insufficient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs) represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and differentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in different MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment.

Francisco J, Rivera; Ludwig, Aigner.

302

Modelling the effects of electric fields on nerve fibres: influence of the myelin sheath.  

Science.gov (United States)

The excitation and conduction properties of computer-based cable models of mammalian motor nerve fibres, incorporating three different myelin representations, are compared. The three myelin representations are a perfectly insulating single cable (model A), a finite impedance single cable (model B) and a finite impedance double cable (model C). Extracellular stimulation of the three models is used to study their strength-duration and current-distance (I-X) relationships, conduction velocity (CV) and action potential shape. All three models have a chronaxie time that is within the experimental range. Models B and C have increased threshold currents compared with model A, but each model has slope to the I-X relationship that matches experimental results. Model B has a CV that matches experimental data, whereas the CV of models A and C are above and below the experimental range, respectively. Model C is able to produce a depolarising afterpotential (DAP), whereas models A and B exhibit hyperpolarising afterpotentials. Models A and B are determined to be the preferred models when low-frequency stimulation (< approximately 25 Hz) is used, owing to their efficiency and accurate excitation and conduction properties. For high frequency stimulation (approximately 25 Hz and greater), model C, with its ability to produce a DAP, is necessary accurately to simulate excitation behaviour. PMID:10984943

Richardson, A G; McIntyre, C C; Grill, W M

2000-07-01

303

Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis  

Directory of Open Access Journals (Sweden)

Full Text Available Multiple sclerosis (MS is a demyelinating immune-mediated disease of the central nervous system (CNS. It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in the CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insufficient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and differentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in different MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment.

Francisco J Rivera

2012-01-01

304

Sensitization of cerebrospinal fluid and peripheral blood lymphocytes to myelin basic protein in multiple sclerosis.  

Science.gov (United States)

Cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocyte sensitization to rabbit myelin basic protein (MBP) in 44 multiple sclerosis (MS) patients, 21 patients with other neurological diseases (OND) and 14 persons with neurosis was studied with the antigen-active rosette forming cells (Ag-ARFC) assay. The frequency of sensitization of CSF lymphocytes to MBP in groups of MS patients in the relapse stage and the chronic progressive stage was higher than in the group of MS patients in the stable stage and the OND patients. None of the healthy subjects showed a positive reaction with MBP. In BP there were no differences in the incidence of sensitization to MBP between patients in various stages of the disease, but it was higher than in the group of patients with OND and neuroses. In the patients who had suffered from MS for less than 4 years, sensitization to MBP was more common in CSF lymphocytes than in BP lymphocytes. The results suggest that primary sensitization to MBP occurs in CSF, and is probably secondary to myelin damage. However at present it is difficult to determine the extent to which sensitization of CSF and PB lymphocytes to MBP play a role in further demyelination processes. PMID:6180592

Cz?onkowska, A; Pó?torak, M; Cendrowski, W; Korlak, J

1982-07-01

305

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.)

306

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

307

Controllable valley splitting in silicon quantum devices  

CERN Document Server

Silicon has many attractive properties for quantum computing, and the quantum dot architecture is appealing because of its controllability and scalability. However, the multiple valleys in the silicon conduction band are potentially a serious source of decoherence for spin-based silicon quantum dot qubits. Only when these valleys are split by a large energy does one obtain well-defined and long-lived spin states appropriate for quantum computing. Here we show that the small valley splittings observed in previous experiments on Si/SiGe heterostructures result from atomic steps at the quantum well interface. Lateral confinement in a quantum point contact, which confines the electron wavefunctions to just a few steps, enhances the valley splitting substantially, up to 1.5 meV. With electronic confinement, the valley splitting is larger than the spin splitting, enabling clean spin qubits. Combined with magnetic confinement, the valley splitting can be controlled over a wide range.

Goswami, S; Friesen, M; McGuire, L M; Truitt, J L; Tahan, C; Klein, L J; Chu, J O; Mooney, P M; Van der Weide, D W; Joynt, R; Coppersmith, S N; Eriksson, M A; Goswami, Srijit; Friesen, Mark; Tahan, Charles; Joynt, Robert; Eriksson, Mark A.

2006-01-01

308

Quasiperiodic Tip Splitting in Directional Solidification  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 s...

Utter, B.; Ragnarsson, R.; Bodenschatz, E.

2001-01-01

309

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

310

Stock splits on the Athens Stock exchange  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This study is based on a sample of stock splits initiated by Greek firms between January 1st 1999 and April 30th 2006. We investigate the price reaction to Greek stock splits by applying the “market model methodology” as described in Brown and Warner (1985). Moreover, a cross- sectional analysis is presented so as to identify the factors that can explain any abnormal stock returns around split announcement. The rest of this study is organized as follows. Section 2 describes...

???????, ?????????

2007-01-01

311

Split fracture in molybdenum, nickel and titanium  

International Nuclear Information System (INIS)

Some results are presented on the study splitting of molybdenum, nickel and titanium. Loading levels for typical loading time (1.3... 1.5 mks) are determined. They correspond to initiation of split microdamages in materials. A degree of split damage in specimens is established for higher loading level. Results of metallographic observations as well as the results of microhardness measurements are presented. The results obtained are copmared with those obtained previously

312

System of split variational inequality problems  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In this paper, we introduce a system of split variational inequality problems in real Hilbert spaces. Using projection method, we propose an iterative algorithm for the system of split variational inequality problems. Further, we prove that the sequence generated by the iterative algorithm converges strongly to a solution of the system of split variational inequality problems. Furthermore, we discuss some consequences of the main result. The iterative algorithms and results ...

Kazmi, Kaleem Raza

2014-01-01

313

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

314

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 CH4/H2O mixture is split into H2, CO and CO2 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 9500C and 39 bar, and gives up heat to the splitting tubes projecting down from above; it is taken away at 8000C and is taken to the steam raising unit and the blower after it. The helium is returned from the blower at 3000C 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 CH4/H2O mixture enters the space above the support plate at 5000C and 44 bar, where it is distributed to the individual splitting tubes. It flows down in these, where it is split into H2, CO and CO2 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 6800C. (RB)

315

Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The myelin sheath is a multilamellar membrane structure wrapped around the axon, enabling the saltatory conduction of nerve impulses in vertebrates. Myelin basic protein, one of the most abundant myelin-specific proteins, is an intrinsically disordered protein that has been shown to bind calmodulin. In this study, we focus on a 19-mer synthetic peptide from the predicted calmodulin-binding segment near the C-terminus of human myelin basic protein. Results The interaction of native human myelin basic protein with calmodulin was confirmed by affinity chromatography. The binding of the myelin basic protein peptide to calmodulin was tested with isothermal titration calorimetry (ITC in different temperatures, and Kd was observed to be in the low ?M range, as previously observed for full-length myelin basic protein. Surface plasmon resonance showed that the peptide bound to calmodulin, and binding was accompanied by a conformational change; furthermore, gel filtration chromatography indicated a decrease in the hydrodynamic radius of calmodulin in the presence of the peptide. NMR spectroscopy was used to map the binding area to reside mainly within the hydrophobic pocket of the C-terminal lobe of calmodulin. The solution structure obtained by small-angle X-ray scattering indicates binding of the myelin basic protein peptide into the interlobal groove of calmodulin, while calmodulin remains in an extended conformation. Conclusion Taken together, our results give a detailed structural insight into the interaction of calmodulin with a C-terminal segment of a major myelin protein, the myelin basic protein. The used 19-mer peptide interacts mainly with the C-terminal lobe of calmodulin, and a conformational change accompanies binding, suggesting a novel mode of calmodulin-target protein interaction. Calmodulin does not collapse and wrap around the peptide tightly; instead, it remains in an extended conformation in the solution structure. The observed affinity can be physiologically relevant, given the high abundance of both binding partners in the nervous system.

Hayashi Nobuhiro

2008-02-01

316

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

317

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

318

Salt splitting with ceramic membranes  

Energy Technology Data Exchange (ETDEWEB)

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.

Kurath, D. [Pacific Northwest National Lab., Richland, WA (United States)

1996-10-01

319

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

320

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 reductf 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

 
 
 
 
321

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 Natura...

Kameswara Rao, T.; Prasa, Dr T. V.

2014-01-01

322

Quintessence and phantom emerging from the split-complex field, split-quaternion field and split-complex DBI field  

CERN Document Server

Motivated by the mathematic theory of split-complex numbers (or hyperbolic numbers, also perplex numbers) and the split-quaternion numbers (or coquaternion numbers), we define the notion of split-complex scalar field and the split-quaternion scalar field. Then we explore the cosmic evolution of these scalar fields in the background of spatially flat Friedmann-Robertson-Walker Universe. We find that both the quintessence field and the phantom field could naturally emerge in these scalar fields. Introducing the metric of field space, these theories fall into a subclass of the multi-field theories which have been extensively studied in inflationary cosmology. Using the brane world model, the split-complex Dirac-Born-Infeld Lagrangian is constructed and analyzed.

Gao, Changjun; Shen, You-Gen

2015-01-01

323

Topology of Wolfgram proteins and 2', 3'-cyclic nucleotide 3'-phosphodiesterase in CNS myelin: studies with proteases.  

Science.gov (United States)

The topological disposition of Wolfgram proteins (WP) and their relationship with 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in human, rat, sheep, bovine, guinea pig and chicken CNS myelin was investigated. Controlled digestion of myelin with trypsin gave a 35KDa protein band (WP-t) when electrophoresed on dodecyl sulfate-polyacrylamide gel in all species. Western blot analysis showed that the WP-t was derived from WP. WP-t was also formed when rat myelin was treated with other proteases such as kallikrein, thermolysin and leucine aminopeptidase. Staining for CNPase activity on nitrocellulose blots showed that WP-t is enzymatically active. Much of the CNPase activity remained with the membrane fraction even after treatment with high concentrations of trypsin when WP were completely hydrolysed and no protein bands with M.W > 14KDa were detected on the gels. Therefore protein fragments of WP with M.W 35KDa fragment is embedded in the lipid bilayer and the remaining fragment exposed at the intraperiod line in the myelin structure which may play a role in the initiation of myelinogenesis. PMID:7824062

Vemuri, G S; Rao, K V; Sastry, P S

1994-09-01

324

A simple protocol for paraffin-embedded myelin sheath staining with osmium tetroxide for light microscope observation.  

Science.gov (United States)

Experimental investigation of peripheral nerve fiber regeneration is attracting more and more attention among both basic and clinical researchers. Assessment of myelinated nerve fiber morphology is a pillar of peripheral nerve regeneration research. The gold standard for light microscopic imaging of myelinated nerve fibers is toluidine blue staining of resin-embedded semithin sections. However, many researchers are unaware that the dark staining of myelin sheaths typically produced by this procedure is due to osmium tetroxide postfixation and not due to toluidine blue. In this article, we describe a simple pre-embedding protocol for staining myelin sheaths in paraffin-embedded nerve specimens using osmium tetroxide. The method involves immersing the specimen in 2% osmium tetroxide for 2 h after paraformaldehyde fixation, followed by routine dehydration and paraffin embedding. Sections can then be observed directly under the microscope or counterstained using routine histological methods. Particularly good results were obtained with Masson's trichrome counterstain, which permits the imaging of connective structures in nerves that are not detectable in toluidine blue-stained resin sections. Finally, we describe a simple protocol for osmium etching of sections, which makes further immunohistochemical analysis possible on the same specimens. Taken together, our results suggest that the protocol described in this article is a valid alternative to the conventional resin embedding-based protocol: it is much cheaper, can be adopted by any histological laboratory, and allows immunohistochemical analysis to be conducted. PMID:18320578

Di Scipio, Federica; Raimondo, Stefania; Tos, Pierluigi; Geuna, Stefano

2008-07-01

325

Four-month enriched environment prevents myelinated fiber loss in the white matter during normal aging of male rats.  

Science.gov (United States)

White matter degenerates with normal aging and accordingly results in declines in multiple brain functions. Previous neuroimaging studies have implied that the white matter is plastic by experiences and contributory to the experience-dependent recovery of brain functions. However, it is not clear how and how far enriched environment (EE) plays a role in the white matter remodeling. Male rats exhibit earlier and severer age-related damages in the white matter and its myelinated fibers than female rats; therefore, in this current study, 24 middle-aged (14-month-old) and 24 old-aged (24-month-old) male SD rats were randomly assigned to an EE or standard environment (SE) for 4 months prior to Morris water maze tests. Five rats from each group were then randomly sampled for stereological assessment of the white matter. Results revealed that EE could somewhat induce improvement of spatial learning and significantly increase the white matter volume, the myelinated fiber volume and the myelinated fiber length during normal aging. The EE-induced improvement of spatial learning ability was significantly correlated with the EE-induced increase of the white matter and its myelinated fibers. We suggested that exposure to an EE could delay the progress of age-related changes in the white matter and the effect could extend to old age. PMID:24553809

Yang, Shu; Lu, Wei; Zhou, De-Shan; Tang, Yong

2014-02-20

326

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

327

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

328

Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity.  

Science.gov (United States)

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 Ig-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, we examine whether Nogo and OMgp influence functional synaptic plasticity, the efficacy by which synaptic transmission occurs. In acute hippocampal slices of adult mice, Nogo-66 and OMgp suppress NMDA receptor-dependent long-term potentiation (LTP) when locally applied to Schaffer collateral-CA1 synapses. Neither Nogo-66 nor OMgp influences basal synaptic transmission or paired-pulse facilitation, a form of short-term synaptic plasticity. PirB(-/-) and NgR1(-/-) single mutants and NgR1(-/-);PirB(-/-) double mutants show normal LTP, indistinguishable from wild-type controls. In juvenile mice, LTD in NgR1(-/-), but not PirB(-/-), slices is absent. Mechanistic studies revealed that Nogo-66 and OMgp suppress LTP in an NgR1-dependent manner. OMgp inhibits LTP in part through PirB but independently of p75. This suggests that NgR1 and PirB participate in ligand-dependent inhibition of synaptic plasticity. Loss of NgR1 leads to increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), signaling intermediates known to regulate neuronal growth and synaptic function. In primary cortical neurons, BDNF elicited phosphorylation of AKT and p70S6 kinase is attenuated in the presence of myelin inhibitors. Collectively, we provide evidence that mechanisms of neuronal growth inhibition and inhibition of synaptic strength are related. Thus, myelin inhibitors and their receptors may coordinate structural and functional neuronal plasticity in CNS health and disease. PMID:20844138

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

2010-09-15

329

Distinguishing division algebras by finite splitting fields  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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; Mckinnie, Kelly

2010-01-01

330

Split mesencephalon: diplomyelia of the basicranium.  

Science.gov (United States)

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

331

Antenna splitting functions for massive particles  

International Nuclear Information System (INIS)

An antenna shower is a parton shower in which the basic move is a color-coherent 2?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.

332

rMAL is a glycosphingolipid-associated protein of myelin and apical membranes of epithelial cells in kidney and stomach.  

Science.gov (United States)

rMAL, the rat myelin and lymphocyte protein, is a small hydrophobic protein of 17 kDa with four putative transmembrane domains and is expressed in oligodendrocytes and Schwann cells, the myelinating cells of the nervous system. In addition, transcript expression has been found in kidney, spleen, and intestine. Confocal microscopy and immunoelectron microscopy with an affinity-purified antibody localized rMAL to compact myelin in a pattern similar to the structural myelin proteins: myelin basic protein and proteolipid protein. In kidney and stomach epithelia, rMAL is located almost exclusively on the apical (luminal) membranes of the cells lining distal tubuli in kidney and the glandular part of the stomach. Biochemical analysis of plasma membranes isolated from spinal cord and kidney demonstrated that rMAL is a proteolipid that is present in detergent insoluble complexes typical for proteins associated with glycosphingolipids. Lipid and protein analysis showed a co-enrichment of glycosphingolipids and rMAL protein within these complexes, indicating a close association of rMAL to glycosphingolipids in myelin and in kidney in vivo. We conclude that specific rMAL-glycosphingolipid interactions may lead to the formation and maintenance of stable protein-lipid microdomains in myelin and apical epithelial membranes. They may contribute to specific properties of these highly specialized plasma membranes. PMID:9634556

Frank, M; van der Haar, M E; Schaeren-Wiemers, N; Schwab, M E

1998-07-01

333

Implications of olfactory lamina propria transplantation on hyperreflexia and myelinated fiber regeneration in rats with complete spinal cord transection.  

Science.gov (United States)

Transplantation with olfactory ensheathing cells (OECs) has been adopted after several models of spinal cord injury (SCI) with the purpose of creating a favorable environment for the re-growth of injured axons. However, a consensus on the efficacy of this cellular transplantation has yet to be reached. In order to explore alternative parameters that could demonstrate the possible restorative properties of such grafts, the present study investigated the effects of olfactory lamina propria (OLP) transplantation on hyperreflexia and myelinated fiber regeneration in adult rats with complete spinal cord transection. The efficacy of OLP (graft containing OECs) and respiratory lamina propria (RLP, graft without OECs) was tested at different post-injury times (acutely, 2- and 4-week delayed), to establish the optimum period for transplantation. In the therapeutic windows used, OLP and RLP grafts produced no considerable improvements in withdrawal reflex responses or on the low-frequency dependent depression of H-reflex. Both lamina propria grafts produced comparable results for the myelinated fiber density and for the estimated total number of myelinated fibers at the lesion site, indicating that the delayed transplantation approach does not seem to limit the regenerative effects. However, animals transplanted with OLP 2 or 4 weeks after injury exhibit smaller myelin sheath thickness and myelinated fiber area and diameter at the lesion site compared to their respective RLP groups. Despite the ongoing clinical use of OECs, it is important to emphasize the need for more experimental studies to clarify the exact nature of the repair capacity of these grafts in the treatment of SCI. PMID:23179588

Centenaro, Lígia Aline; da Cunha Jaeger, Mariane; Ilha, Jocemar; de Souza, Marcelo Alves; Balbinot, Luciane Fachin; do Nascimento, Patrícia Severo; Marcuzzo, Simone; Achaval, Matilde

2013-02-01

334

Encephalitogenic T cell clones specific for myelin basic protein. An unusual bias in antigen recognition  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Class II-restricted T cell clones specific for myelin basic protein (MBP) have been generated from PL/J and (PL/J X SJL/J)F1 [((PLSJ)F1] mice following sensitization to rat MBP. Of 17 T cell clones generated from (PLSJ)F1 mice, 5 are I-Au(A alpha uA beta u) restricted, one is restricted to I-As(A alpha sA beta s), 10 are restricted to hybrid I- A(u X s)F1 (A alpha sA beta u) determinants, and one clone is restricted to hybrid I-E(u X s) (E alpha uE beta s) molecules. Thus, of 16 I-A-restricte...

1985-01-01

335

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

336

GAPO syndrome: four new patients with congenital glaucoma and myelinated retinal nerve fiber layer.  

Science.gov (United States)

This article reports on the ophthalmological features of four Turkish children with GAPO syndrome, a very rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P) (failure of tooth eruption), and optic atrophy (O). The children were from two unrelated families born to consanguineous parents. They had the characteristic facial appearance of alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, midfacial hypoplasia, hypertelorism, and thickened eyelids and lips. Two children had severe end-stage glaucoma in both eyes and unilateral corneal opacity, whereas other two children had myelinated retinal nerve fiber layer; one with bilateral optic atrophy and the other one with persistent pupillary membrane in the left eye. PMID:23494824

Bozkurt, Banu; Yildirim, Mahmut Selman; Okka, Mehmet; Bitirgen, Gülfidan

2013-04-01

337

Equivalent aqueous phase modulation of domain segregation in myelin monolayers and bilayer vesicles  

International Nuclear Information System (INIS)

Full text: Purified myelin can be spread as monomolecular films at the air/aqueous interface. These films were visualized by fluorescence and Brewster angle microscopy, showing phase coexistence at low and medium surface pressures (2) in Ringers and physiological solution leads to phase domain microheterogeneity over the whole compression isotherm. These results show that surface heterogeneity is favored by the ionic milieu. The modulation of the phase-mixing behavior in monolayers is paralleled by the behavior of multilamellar vesicles as determined by small-angle and wide-angle x-ray scattering. The correspondence of the behavior of monolayers and multilayers is achieved only at high surface pressures near the equilibrium adsorption surface pressure; at lower surface pressures, the correspondence breaks down. The equilibrium surface tension on all sub phases corresponds to that of the air/alkane interface (27 mN/m), independently on the surface tension of the clean sub phase. (author)

338

From the ganglioside GQ1balpha to glycomimetic antagonists of the myelin-associated glycoprotein (MAG).  

Science.gov (United States)

The tetrasaccharide 4, a substructure of ganglioside GQ1balpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 4, antagonists with modifications of the core disaccharide Galbeta(1-3)GalNAc, as well as the terminal alpha(2-3)- and the internal alpha(2-6)-linked neuraminic acid were synthesized and tested in target-based binding assays. Compared to the reference tetrasaccharide 4, the most potent antagonist 17 exhibits a 360-fold improved affinity. Furthermore, pharmacokinetic parameters such as stability in the cerebrospinal fluid, logD and permeation through the BBB indicate the drug-like properties of antagonist 17. PMID:21137678

Ernst, Beat; Schwardt, Oliver; Mesch, Stefanie; Wittwer, Matthias; Rossato, Gianluca; Vedani, Angelo

2010-01-01

339

Characterization of myelin basic protein charge isomers from adult mouse brain.  

Science.gov (United States)

ADULT mouse MBP charge isomers (C1 or component 1, C2 or component 2, etc.) were purified from an acid soluble brain protein fraction by cation exchange chromatography. They were characterized by their elution profiles, their migration rates in alkaline-urea gels and by SDS-PAGE. Mouse C1 and C2 were both 14 kD in size, while C3, C4 and C5 consisted of the 18.5, 17 and 14 kD isoforms. Comparison of mouse and human MBP charge isomers showed that they were similar in that they both showed extensive charge heterogeneity, but different in that mouse MBP charge isomers were more cationic than their human counterparts. Finally, a possible explanation for the presence of the 14 kD MBP isoform in mouse myelin was suggested. PMID:1722721

Fannon, A M; Moscarello, M A

1991-03-01

340

Instability of Myelin Tubes under Dehydration deswelling of layered cylindrical structures  

CERN Document Server

We report experimental observations of an undulational instability of myelin figures. Motivated by this, we examine theoretically the deformation and possible instability of concentric, cylindrical, multi-lamellar membrane structures. Under conditions of osmotic stress (swelling or dehydration), we find a stable, deformed state in which the layer deformation is given by \\delta R ~ r^{\\sqrt{B_A/(hB)}}, where B_A is the area compression modulus, B is the inter-layer compression modulus, and h is the repeat distance of layers. Also, above a finite threshold of dehydration (or osmotic stress), we find that the system becomes unstable to undulations, first with a characteristic wavelength of order \\sqrt{xi d_0}, where xi is the standard smectic penetration depth and d_0 is the thickness of dehydrated region.

Chen, C M; Olmsted, P D; MacKintosh, F C

2001-01-01

 
 
 
 
341

Internodal sodium channels ensure active processes under myelin manifesting in depolarizing afterpotentials.  

Science.gov (United States)

The current opinion about processes in myelinated axon is that action potential saltatorially propagates between nodes of Ranvier and passively charges internodal axolemma thus causing depolarizing afterpotentials (DAP). Demyelination blocks the conduction that gives additional argument in favor of hypothesis that internode is not able to be activated by the existing internodal sodium channels. The results of our modeling study shows that, when periaxonal space is sufficiently narrow, saltatorial action potential is able to activate internodes. Low density of internodal sodium channels is sufficient to generate active internodal waves that slowly propagate from nodes towards corresponding midinternodes where they collide. The periaxonal width that stops internodal wave propagation (about 400 nm) is significantly larger than the highest value of the physiological range for this parameter (30 nm). Internodal activation is directly manifested as transmembrane internodal potential or as a full-sized action potential in periaxonal space where it can hardly be detected, and only as a small deflection in intracellular space. However, changes in the periaxonal potential cause transmyelin currents that lead to significant DAP. The shape and amplitude of DAP depends on myelin parameters and densities of internodal channels. Several technical parameters affect the results of calculations. Internodal spatial segmentation has to be sufficiently fine (at most 20 microm) for the model to be able to simulate internodal activation. We employ 338 internodal segments as compared with up to 21 used in previous models. Ionic accumulation together with related diffusive and electrical processes alter the calculated DAP amplitude. Inclusion of these processes in calculations demands such increase in the total number of segments that the numerical methods used up to now become unapplicable. To overcome the problem, an iterative implicit approach is proposed. It reduces a matrix of general type in multi-cable models to tridiagonal one and accelerates calculations considerably. PMID:15935164

Dimitrov, Alexander G

2005-08-21

342

Changes of myelin in the rat brain after whole-brain irradiation  

International Nuclear Information System (INIS)

The whole brain of SD rats was irradiated by the single dose of 2, 10, or 30Gy. The enzyme-linked immunosorbent assay was used for the content measurement of myelin basic protein (MBP) in telencephalon tissue at 1 week, 1 month, 3 months and 6 months after irradiation. Both the Luxol fast blue staining with image analysis and the electron microscope were used to investigate the histomorphologic and ultrastructural characteristics of demyelination. The MBP content of telencephalon tissue in control rats were 78-82 ?g/mL, there were no difference in all the 2Gy irradiated, 1 week and 1 month after 10 to 30Gy irradiated groups. But at 3 and 6 months after 10Gy and 30Gy irradiated rats, there MBP content were in 50-62 ?g/mL level, which were a significant decrease compared with the control groups (p<0.01). Typical demyelination in corpus callosum of rats was observed in 30Gy irradiation after 6 months, but no evidence of demyelination was seen in all the other rats. The ultra-structural changes of myelin and oligodendrocytes were detected in 10Gy and 30Gy exposure after 1 to 6 months observed by electron microscope. All the demyelination changes were seen correlated with the dosage and duration after irradiation. These findings indicate that the radiation-related molecular and pathological characteristic changes of demyelination can be assessed in 3 to 6 months after single 10Gy to 30Gy whole-brain irradiation in SD rats. (authors))

343

Split supersymmetry in unified models  

International Nuclear Information System (INIS)

In the context of split supersymmetry, the gaugino mass spectrum seems to be very important to satisfy the dark matter content of the universe and the gauge coupling unification. In this Letter, we have considered various sources of gaugino masses in the context of unified models. We show that the gaugino mass spectrum varies in different unification pictures. In the context of SU(5), we have found that the bino/wino mass ratio can be close to one at the weak scale which is helpful to satisfy the WMAP data. The gluino/wino mass ratio is also different from the usual scenario of unified gaugino masses. The gaugino masses can be around one TeV and mSUSY is chosen so that the gluino mass does not create any cosmological problem. In the context of the Pati-Salam model, we show that the gluino mass can be made very heavy even after maintaining the unification of the gauge couplings

344

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

345

PirB, a second receptor for the myelin inhibitors of axonal regeneration Nogo66, MAG, and OMgp: implications for regeneration in vivo.  

Science.gov (United States)

Inhibitors of axonal regeneration in myelin are believed to be major contributors to the lack of regeneration in the adult CNS. Three of the four known myelin inhibitors, although very different structurally, interact with the same receptor, NgR. However, the absence of NgR has no effect on inhibition of neurite outgrowth in culture, and there is no improvement in CST regeneration in vivo. In a recent issue of Science, a second receptor for these myelin inhibitors was described, PirB, a receptor first described in the immune system. Will PirB be the answer to CST regeneration in vivo? PMID:19081369

Filbin, Marie T

2008-12-10

346

Signature splitting in magnetic rotational bands  

International Nuclear Information System (INIS)

Nearly-spherical nuclei in three mass regions have recently been observed to exhibit rotational-like features. We have identified almost 80 such bands; largest number (43) lie in the lead region. Most of these bands are assigned oblate multi-quasiparticle configurations. Their interpretation in terms of magnetic rotation does not allow for signature splitting in these bands. We have however found signature splitting as well as signature inversion in many bands. We apply the two-quasiparticle plus rotor model to understand the occurrence of signature splitting vis-a-vis the role of shears mechanism in these bands. (author)

347

Zeeman splitting in ballistic hole quantum wires  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We have studied the Zeeman splitting in ballistic hole quantum wires formed in a (311)A quantum well by surface gate confinement. Transport measurements clearly show lifting of the spin degeneracy and crossings of the subbands when an in-plane magnetic field B is applied parallel to the wire. When B is oriented perpendicular to the wire, no spin-splitting is discernible up to B = 8.8 T. The observed large Zeeman splitting anisotropy in our hole quantum wires demonstrates the...

Danneau, R.; Klochan, O.; Clarke, W. R.; Ho, L. H.; Micolich, A. P.; Simmons, M. Y.; Hamilton, A. R.; Pepper, M.; Ritchie, D. A.; Zulicke, U.

2006-01-01

348

The Penrose Transform in the Split Signature  

CERN Document Server

A version of the Penrose transform is introduced in the split signature. It relates the cohomological data with supports on the open subsets of the complex 3-projective space and kernel of differential operators on the (real) Grassmannian of 2-planes in the Euclidean 4-space. As an example we derive a cohomological interpretation of the so-called X-ray transform. Furthermore, a cohomological realization of the so-called "minimal" representation of SL(4,R) is given. We also present the split Penrose transform in split instanton backgrounds.

Aryapoor, Masood

2008-01-01

349

Semi-strong split domination in graphs  

Directory of Open Access Journals (Sweden)

Full Text Available Given a graph $G = (V,E$, a dominating set $D subseteq V$ is called a semi-strong split dominating set of $G$ if $|V setminus D| geq 1$ and the maximum degree of the subgraph induced by $V setminus D$ is 1. The minimum cardinality of a semi-strong split dominating set (SSSDS of G is the semi-strong split domination number of G, denoted $gamma_{sss}(G$. In this work, we introduce the concept and prove several results regarding it.

Anwar Alwardi

2014-06-01

350

Split-coil-system SULTAN  

International Nuclear Information System (INIS)

The high field superconductor test facility SULTAN started operation successfully in May 1992. Originally designed for testing full scale conductors for the large magnets of the next generation fusion reactors, the SULTAN facility installed at PSI (Switzerland) was designed as a common venture of three European Laboratories: ENEA (Italy), ECN (Netherlands) and PSI, and built by ENEA and PSI in the framework of the Euratom Fusion Technology Program. Presently the largest facility in the world, with its superconducting split coil system generating 11 Tesla in a 0.6 m bore, it is ready now for testing superconductor samples with currents up to 50 kA at variable cooling conditions. Similar tests can be arranged also for other applications. SULTAN is offered by the European Community as a contribution to the worldwide cooperation for the next step of fusion reactor development ITER. First measurements on conductor developed by CEA (Cadarache) are now in progress. Others like those of ENEA and CERN will follow. For 1993, a test of an Italian 12 TZ model coil for fusion application is planned. SULTAN is a worldwide unique facility marking the competitive presence of Swiss technology in the field of applied superconductivity research. Based on development and design of PSI, the high field Nb3Sn superconductors and coils were fabricated at the works of Kabelwerke Brugg and ABB, numerous Swiss companies contributed to the success of this international effort. Financicess of this international effort. Financing of the Swiss contribution of SULTAN was made available by NEFF, BEW, BBW, PSI and EURATOM. (author) figs., tabs., 20 refs

351

Structural basis of photosynthetic water-splitting  

International Nuclear Information System (INIS)

Photosynthetic water-splitting takes place in photosystem II (PSII), a membrane protein complex consisting of 20 subunits with an overall molecular mass of 350 kDa. The light-induced water-splitting reaction catalyzed by PSII not only converts light energy into biologically useful chemical energy, but also provides us with oxygen indispensible for sustaining oxygenic life on the earth. We have solved the structure of PSII at a 1.9 Å resolution, from which, the detailed structure of the Mn4CaO5-cluster, the catalytic center for water-splitting, became clear. Based on the structure of PSII at the atomic resolution, possible mechanism of light-induced water-splitting was discussed

352

Small-molecule-dependent split aptamer ligation.  

Science.gov (United States)

Here we describe the first use of small-molecule binding to direct a chemical reaction between two nucleic acid strands. The reported reaction is a ligation between two fragments of a DNA split aptamer using strain-promoted azide-alkyne cycloaddition. Utilizing the split aptamer for cocaine, we demonstrate small-molecule-dependent ligation that is dose-dependent over a wide range of cocaine concentrations and is compatible with complex biological fluids such as human blood serum. Moreover, studies of split aptamer ligation at varying salt concentrations and using structurally similar analogues of cocaine have revealed new insight into the assembly and small-molecule binding properties of the cocaine split aptamer. The ability to translate the presence of a small-molecule target into the output of DNA ligation is anticipated to enable the development of new, broadly applicable small-molecule detection assays. PMID:21761903

Sharma, Ashwani K; Heemstra, Jennifer M

2011-08-17

353

Heegaard splittings with large subsurface distances  

CERN Document Server

We show that sub-surfaces of a Heegaard surface for which the relative Hempel distance of the splitting is sufficiently high have to appear in any Heegaard surface of genus bounded by half that distance.

Johnson, Jesse; Moriah, Yoav

2010-01-01

354

Forced splitting of fractions in CE.  

Science.gov (United States)

In order to increase the electrophoretic separation between fractions of analytes on a microfluidic chip, without the need for a longer separation channel, we propose and demonstrate a preparative electrokinetic procedure by which overlapping or closely spaced fractions are automatically split. The method involves an extra T-junction at the end of a separation channel and detector-triggered reconfiguration of voltages at channel outlets. Forced splitting of a separated four-component mixture is demonstrated, and possible sources of errors leading to contamination of split fractions are also discussed in detail and illustrated both by computational fluid dynamics and experiments. The splitting method can be applied in preparative CE-on-a-chip systems, for which it greatly simplifies downstream fraction manipulation and helps in reducing cross-contamination between collected fractions. PMID:19130596

Zalewski, Dawid R; Schlautmann, Stefan; Gardeniers, Han J G E

2008-12-01

355

Structural basis of photosynthetic water-splitting  

Energy Technology Data Exchange (ETDEWEB)

Photosynthetic water-splitting takes place in photosystem II (PSII), a membrane protein complex consisting of 20 subunits with an overall molecular mass of 350 kDa. The light-induced water-splitting reaction catalyzed by PSII not only converts light energy into biologically useful chemical energy, but also provides us with oxygen indispensible for sustaining oxygenic life on the earth. We have solved the structure of PSII at a 1.9 Å resolution, from which, the detailed structure of the Mn{sub 4}CaO{sub 5}-cluster, the catalytic center for water-splitting, became clear. Based on the structure of PSII at the atomic resolution, possible mechanism of light-induced water-splitting was discussed.

Shen, Jian-Ren [Graduate School of Natural Science and Technology/Faculty of Science, Okayama University, Okayama (Japan); Umena, Yasufumi [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka, Japan and PRESTO, JST (Japan); Kawakami, Keisuke [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka (Japan); Kamiya, Nobuo [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka, Japan and Department of Chemistry, Graduate School of Science, Osaka City University, Osaka (Japan)

2013-12-10

356

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)

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. PMID:23132925

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

2013-01-01

357

Heegaard splittings and the pants complex  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We define integral measures of complexity for Heegaard splittings based on the graph dual to the curve complex and on the pants complex defined by Hatcher and Thurston. As the Heegaard splitting is stabilized, the sequence of complexities turns out to converge to a non-trivial limit depending only on the manifold. We then use a similar method to compare different manifolds, defining a distance which converges under stabilization to an integer related to Dehn surgeries betwee...

Johnson, Jesse

2005-01-01

358

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

359

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.

2006-09-01

360

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

 
 
 
 
361

Ray splitting in paraxial optical cavities  

CERN Document Server

We present a numerical investigation of the ray dynamics in a paraxial optical cavity when a ray splitting mechanism is present. The cavity is a conventional two-mirror stable resonator and the ray splitting is achieved by inserting an optical beam splitter perpendicular to the cavity axis. We show that depending on the position of the beam splitter the optical resonator can become unstable and the ray dynamics displays a positive Lyapunov exponent.

Puentes, G; Woerdman, J P

2003-01-01

362

Determination of structure coefficients from splitting matrices  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The splitting matrix for a set of coupled multiplets is a linear combination of structure coefficients, first-order Coriolis terms and terms for ellipticity and centrifugal force. These latter terms are calculated for a good 1-D earth model and removed. The first-order Coriolis terms are then uniquely determined. They are linear functionals of the density of the 1-D model. The remaining splitting matrix is an orthogonal transformation of the structure coefficients. The inverse orthogonal tran...

Gilbert, F.; Woodhouse, Jh

2000-01-01

363

On Clifford Subalgebras, Spacetime Splittings and Applications  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Z2-gradings of Clifford algebras are reviewed and we shall be concerned with an alpha-grading based on the structure of inner automorphisms, which is closely related to the spacetime splitting, if we consider the standard conjugation map automorphism by an arbitrary, but fixed, splitting vector. After briefly sketching the orthogonal and parallel components of products of differential forms, where we introduce the parallel [orthogonal] part as the space [time] component, w...

Da Rocha, Roldao; Vaz Jr, Jayme

2006-01-01

364

Backbone Dynamics of the 18.5 kDa Isoform of Myelin Basic Protein Reveals Transient ?-Helices and a Calmodulin-Binding Site  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The 18.5 kDa isoform of myelin basic protein (MBP) is the predominant form in adult human central nervous system myelin. It is an intrinsically disordered protein that functions both in membrane adhesion, and as a linker connecting the oligodendrocyte membrane to the underlying cytoskeleton; its specific interactions with calmodulin and SH3-domain containing proteins suggest further multifunctionality in signaling. Here, we have used multidimensional heteronuclear nuclear magnetic resonance s...

Libich, David S.; Harauz, George

2008-01-01

365

Structure determination of Myelin Oligodendrocyte Glycoprotein and of its complex with (8-18C5)-Fab and structure determination of 12-Oxophytodienoic Acid Reductases 1 and 3  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Die gelöste Struktur des Komplexes zwischen dem Multiple Sklerose (MS) Autoantigen Myelin Oligodendrocyte Glycoprotein (MOG) und dem Antigen-bindenden Fragment des Maus-Antikörpers 8-18C5, der im Tiermodell von MS die extensive Zerstörung des Myelins bewirkt, gibt erstmalig detaillierte Einblicke in das Epitop eines klassischen Autoantigens. Durch Mutation der zentralen Epitop-Aminosäuren konnte zudem gezeigt werden, dass es sich bei dem 8-18C5-Epitop um ein – zumindest in der Maus – ...

Breithaupt, Constanze

2006-01-01

366

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

367

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 cancellor frequency distributions of cancellation and emergence based on this idea.

368

Phosphatidylinositol 4,5-bisphosphate-dependent interaction of myelin basic protein with the plasma membrane in oligodendroglial cells and its rapid perturbation by elevated calcium.  

Science.gov (United States)

Myelin basic protein (MBP) is an essential structural component of CNS myelin. The electrostatic association of this positively charged protein with myelin-forming membranes is a crucial step in myelination, but the mechanism that regulates myelin membrane targeting is not known. Here, we demonstrate that phosphatidylinositol 4,5-bisphosphate (PIP2) is important for the stable association of MBP with cellular membranes. In oligodendrocytes, overexpression of synaptojanin 1-derived phosphoinositide 5-phosphatase, which selectively hydrolyzes membrane PIP2, causes the detachment of MBP from the plasma membrane. In addition, constitutively active Arf6/Q67L induces the formation of PIP2-enriched endosomal vacuoles, leading to the redistribution of MBP to intracellular vesicles. Fluorescence resonance energy transfer imaging revealed an interaction of the PIP2 sensing probe PH-PLCdelta1 with wild-type MBP, but not with a mutant MBP isoform that fails to associate with the plasma membrane. Moreover, increasing intracellular Ca(2+), followed by phospholipase C-mediated PIP2 hydrolysis, as well as reduction of the membrane charge by ATP depletion, resulted in the dissociation of MBP from the glial plasma membrane. When the corpus callosum of mice was analyzed in acute brain slices by electron microscopy, the reduction of membrane surface charge led to the loss of myelin compaction and rapid vesiculation. Together, these results establish that PIP2 is an essential determinant for stable membrane binding of MBP and provide a novel link between glial phosphoinositol metabolism and MBP function in development and disease. PMID:19369548

Nawaz, Schanila; Kippert, Angelika; Saab, Aiman S; Werner, Hauke B; Lang, Thorsten; Nave, Klaus-Armin; Simons, Mikael

2009-04-15

369

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

370

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

371

Neurological disturbances, premature lethality, and central myelination deficiency in transgenic mice overexpressing the homeo domain transcription factor Oct-6.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Pit, Oct, Unc (POU) homeo domain transcription factors have been implicated in various developmental processes, including cell division, differentiation, specification, and survival of specific cell types. Although expression of the transcription factor Oct-6 in oligodendroglia is confined to the promyelin stage and is downregulated at the myelin stage of development, the effect of Oct-6 overexpression on oligodendrocyte development has not been established. Here we show that transgenic anima...

Jensen, N. A.; Pedersen, K. M.; Celis, J. E.; West, M. J.

1998-01-01

372

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.)

373

Direkter ex vivo Nachweis Myelin Bacis Protein (MBP)-spezifischer T-Helferzellen bei Multiple Sklerose Patienten  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In der Pathogenese der Multiplen Sklerose (MS) wird autoantigenspezifischen proinflammatorischen T-Helferzellen eine entscheidende Rolle zugeschrieben. Das am meisten untersuchte Autoantigen ist das Myelin Basic Protein (MBP). Bisher waren zum Nachweis autoantigenspezifischer T-Zellen deren Kultur über Tage bis Monate unumgänglich. In dieser Arbeit wurden Methoden zum direkten ex vivo-Nachweis autoreaktiver T-Helferzellen etabliert, die die reaktive Sekretion der proinflammatorischen Zytoki...

Holzknecht, Barbara Juliane

2003-01-01

374

Q-space and Conventional Diffusion Imaging of Axon and Myelin Damage in the Rat Spinal Cord after Axotomy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Parallel and perpendicular diffusion properties of water in the rat spinal cord were investigated 3 and 30 days after dorsal root axotomy, a specific insult resulting in early axonal degeneration followed by later myelin damage in the dorsal column white matter (WM). Results from q-space analysis (i.e. the diffusion probability density function, PDF) obtained with strong diffusion weighting were compared to conventional anisotropy and diffusivity measurements at low b-values, as well as to hi...

Farrell, Jonathan A. D.; Zhang, Jiangyang; Jones, Melina V.; Deboy, Cynthia A.; Hoffman, Paul N.; Landman, Bennett A.; Smith, Seth A.; Reich, Daniel S.; Calabresi, Peter A.; Zijl, Peter C. M.

2010-01-01

375

Beneficial effects of Rituximab in patients with anti-MAG (myelin-associated glycoprotein) neuropathy: case reports.  

Science.gov (United States)

Anti-myelin-associated glycoprotein (MAG) neuropathy is a primary demyelinating sensorimotor polyneuropathy that can be very debilitating and is known to be resistant to treatment. There are only a few conflicting reports on the effect of Rituximab in anti-MAG neuropathy. We present three patients who improved remarkably with Rituximab infusions. Until the safety and efficacy of this drug are determined in larger controlled studies, use of Rituximab should be limited to patients with significant neurologic deficits. PMID:23944288

Souayah, Nizar; Noopur, Raje; Tick-Chong, Peter Siao

2013-10-01

376

Copper Accumulation and Lipid Oxidation Precede Inflammation and Myelin Lesions in N,N-Diethyldithiocarbamate Peripheral Myelinopathy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Dithiocarbamates have a wide spectrum of applications in industry, agriculture and medicine with new applications being actively investigated. One adverse effect of dithiocarbamates is the neurotoxicity observed in humans and experimental animals. Results from previous studies have suggested that dithiocarbamates elevate copper and promote lipid oxidation within myelin membranes. In the current study, copper levels, lipid oxidation, protein oxidative damage and markers of inflammation were mo...

Viquez, Olga M.; Valentine, Holly L.; Amarnath, Kalyani; Milatovic, Dejan; Valentine, William M.

2008-01-01

377

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment ...

Vyas, Alka A.; Patel, Himatkumar V.; Fromholt, Susan E.; Heffer-lauc, Marija; Vyas, Kavita A.; Dang, Jiyoung; Schachner, Melitta; Schnaar, Ronald L.

2002-01-01

378

Soluble Adenylyl Cyclase Is Necessary and Sufficient to Overcome the Block of Axonal Growth by Myelin-Associated Factors  

Science.gov (United States)

Neurons in the CNS do not regenerate following injury; regeneration is blocked by inhibitory proteins in myelin, such as myelin-associated glycoprotein (MAG). Elevating neuronal levels of the second messenger cAMP overcomes this blocked axonal outgrowth. One way to elevate cAMP is pretreating neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF). However, pleiotropic effects and poor bioavailability make exogenous administration of neurotrophins in vivo problematic; therefore, alternative targets must be considered. In neurons, two families of adenylyl cyclases synthesize cAMP, transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). Here, we demonstrate that sAC is the essential source of cAMP for BDNF to overcome MAG-dependent inhibition of neurite outgrowth. Elevating sAC in rat and mouse neurons is sufficient to induce neurite outgrowth on myelin in vitro and promotes regeneration in vivo. These results suggest that stimulators of sAC might represent a novel therapeutic strategy to promote axonal growth and regeneration. PMID:25009261

Martinez, Jennifer; Stessin, Alexander M.; Campana, Aline; Hou, Jianwei; Nikulina, Elena; Buck, Jochen; Filbin, Marie T.

2014-01-01

379

PTPBR7 Binding Proteins in Myelinating Neurons of the Mouse Brain  

Directory of Open Access Journals (Sweden)

Full Text Available Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane protein that is localized on the surface of neuronal cells. Its protein phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice display motor coordination defects. Extracellular molecules that may influence PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7 extracellular domain binds to highly myelinated regions in mouse brain, in particular the white matter tracks in cerebellum. PTPBR7 deficiency does not alter this binding pattern, as witnessed by RAP in situ staining of Ptprr-/- mouse brain sections. Additional in situ and in vitro experiments also suggest that sugar moieties of heparan sulphate and chondroitin sulphate glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding proteins were affinity-purified exploiting the PTPBR7 extracellular domain and identified by mass spectrometric means. Results support the suggested link between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an additional role in the process of cell-cell adhesion.

Irene M. Chesini, Griet Debyser, Huib Croes, Gerdy B. ten Dam, Bart Devreese, Andrew W. Stoker, Wiljan J.A.J. Hendriks

2011-01-01

380

Myelin basic protein-responsive blood T lymphocytes in patients with multiple sclerosis.  

Science.gov (United States)

Previous studies from our laboratory showed the development of circulating T lymphocytes sensitized to myelin basic protein (MBP) in guinea pigs challenged with MBP. Also, lymphocytes sensitized to MBP were found in patients with multiple sclerosis (MS). In this report, we describe the kinetics of MBP-sensitized lymphocytes in a longitudinal study (140-316 days) of seven MS patients using the MBP-stimulated active rosette-forming T cell assay (MBP-ARFC). Expressed as the ratio of MBP-ARFC over ARFC (early and 37 degrees C stable rosette-forming T lymphocytes without added antigen), the results show a considerable degree of variation in the levels of MBP-ARFC. Although the levels of ARFC during the study period were relatively unchanged for each patient, increases in the MBP-ARFC/ARFC ratios were associated with the development of neurological symptoms of disease. The results of this study demonstrate the development of T-cell-mediated immunity to MBP in patients with MS. Detection of MBP-sensitive cells was possible during the course of the disease. The level of sensitivity was influenced by the clinical status, degree of neurological deficit, and particular treatment course. PMID:2580989

Hashim, G A; Brewen, M

1985-01-01

 
 
 
 
381

Equivalent aqueous phase modulation of domain segregation in myelin monolayers and bilayer vesicles  

Energy Technology Data Exchange (ETDEWEB)

Full text: Purified myelin can be spread as monomolecular films at the air/aqueous interface. These films were visualized by fluorescence and Brewster angle microscopy, showing phase coexistence at low and medium surface pressures (<20-30 mN/m). Beyond this threshold, the film becomes homogeneous or not, depending on the aqueous sub phase composition. Pure water as well as sucrose, glycerol, dimethylsulfoxide, and dimethylformamide solutions (20% in water) produced monolayers that become homogeneous at high surface pressures; on the other hand, the presence of salts (NaCl, CaCl{sub 2}) in Ringers and physiological solution leads to phase domain microheterogeneity over the whole compression isotherm. These results show that surface heterogeneity is favored by the ionic milieu. The modulation of the phase-mixing behavior in monolayers is paralleled by the behavior of multilamellar vesicles as determined by small-angle and wide-angle x-ray scattering. The correspondence of the behavior of monolayers and multilayers is achieved only at high surface pressures near the equilibrium adsorption surface pressure; at lower surface pressures, the correspondence breaks down. The equilibrium surface tension on all sub phases corresponds to that of the air/alkane interface (27 mN/m), independently on the surface tension of the clean sub phase. (author)

Oliveira, R.G. [Universidad Nacional de Cordoba, Cordoba, CO (Argentina)

2012-07-01

382

Characterization of fatty acid binding by the P2 myelin protein  

International Nuclear Information System (INIS)

In recent years, significant sequence homology has been found between the P2 protein of peripheral myelin and intracellular retinoid- and fatty acid-binding proteins. They have found that salt extracts of bovine intradural nerve roots contain the P2 basic protein in association with free fatty acid. Preliminary results from quantitative analyses showed a ratio of 0.4-1.1 fatty acid (mainly oleate and palmitate) per P2 molecule. P2/ligand interactions were partially characterized using (3H)-oleate in gel permeation assays and binding studies using lipidex to separated bound and free fatty acid. Methyloleate was found to displace (3H)-oleate from P2, indicating that ligand binding interactions are predominantly hydrophobic in nature. On the other hand, myristic acid and retinol did not inhibit the binding of oleate to the protein, results consistent with a decided affinity for long chain fatty acids but not for the retinoids. The binding between P2 and oleic acid showed an apparent Kd in the micromolar range, a value comparable to those found for other fatty acid-binding proteins. From these results they conclude that P2 shares not only structural homology with certain fatty acid binding proteins but also an ability to bind long chain fatty acids. Although the significance of these similarities is not yet clear, they may, by analogy, expect P2 to have a role in PNS lipid metabolism

383

Using high-resolution quantitative mapping of R1 as an index of cortical myelination.  

Science.gov (United States)

A fundamental tenet of neuroscience is that cortical functional differentiation is related to the cross-areal differences in cyto-, receptor-, and myeloarchitectonics that are observed in ex-vivo preparations. An ongoing challenge is to create noninvasive magnetic resonance (MR) imaging techniques that offer sufficient resolution, tissue contrast, accuracy and precision to allow for characterization of cortical architecture over an entire living human brain. One exciting development is the advent of fast, high-resolution quantitative mapping of basic MR parameters that reflect cortical myeloarchitecture. Here, we outline some of the theoretical and technical advances underlying this technique, particularly in terms of measuring and correcting for transmit and receive radio frequency field inhomogeneities. We also discuss new directions in analytic techniques, including higher resolution reconstructions of the cortical surface. We then discuss two recent applications of this technique. The first compares individual and group myelin maps to functional retinotopic maps in the same individuals, demonstrating a close relationship between functionally and myeloarchitectonically defined areal boundaries (as well as revealing an interesting disparity in a highly studied visual area). The second combines tonotopic and myeloarchitectonic mapping to localize primary auditory areas in individual healthy adults, using a similar strategy as combined electrophysiological and post-mortem myeloarchitectonic studies in non-human primates. PMID:23756203

Lutti, Antoine; Dick, Frederic; Sereno, Martin I; Weiskopf, Nikolaus

2014-06-01

384

Diffusion-weighted MRI of myelination in the rat brain following treatment with gonadal hormones  

International Nuclear Information System (INIS)

Previous studies have demonstrated the ability of high-resolution diffusion-weighted MRI to show maturation of white-matter structures in the developing rat brain. The purpose of this study was to investigate the influence of gonadal steroid hormones on the rate of this development. Starting from their second postnatal day, 16 rat-pups of either sex were repeatedly treated with subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17 dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and hemisphere commissures was assessed. Diffusion-weighted images were processed to produce ''anisotropy index maps'', previously shown to be sensitive to white-matter maturation. Compared with untreated rat-pups, estrogen-treated animals showed accelerated, and testosterone-treated animals delayed maturation on anisotropy index maps and histological sections. In all animals, maturational changes appeared earlie on anisotropy index maps than on other MRI sequences or on myelin-sensitive stained sections. Diffusion-weighted imaging, and the construction of spatial maps sensitive to diffusion anisotropy, seem to be the most sensitive approach for the detection of maturational white-matter changes, and thus may hold potential for early diagnosis of temporary delay or permanent disturbances of white-matter development. (orig.). With 6 figs., 1 tabith 6 figs., 1 tab

385

Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid.  

Science.gov (United States)

Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl-sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty-acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid. The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated glycolipids was examined in central nervous system (CNS) infectious disease, noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid binding in MS and other neurological disease groups revealed that the greatest anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some MS patients had increased reactivity with the hydrophobic FMCs and with glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked. PMID:20154333

Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B; Tourtellotte, Wallace W; Annuk, Heidi; Moran, Anthony P; Hogan, Edward L

2010-06-01

386

Wave Splitting in Direct and Inverse Scattering Problems  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The focus of this thesis is on the use of wave splitting in electromagnetic direct and inverse scattering problems. Wave splitting offers a decomposition of wave fields into appropriate input and output wave constituents. Several different wave splittings are studied including one-dimensional, multi-dimensional energy-flux, and multi-dimensional locally exact wave splittings. The Bremmer series is naturally connected to wave splitting as a method to decompose a complex scattering problem into...

Gustafsson, Mats

2000-01-01

387

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 H0 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

388

Reflection hologram solar spectrum-splitting filters  

Science.gov (United States)

In this paper we investigate the use of holographic filters in solar spectrum splitting applications. Photovoltaic (PV) systems utilizing spectrum splitting have higher theoretical conversion efficiency than single bandgap cell modules. Dichroic band-rejection filters have been used for spectrum splitting applications with some success however these filters are limited to spectral control at fixed reflection angles. Reflection holographic filters are fabricated by recording interference pattern of two coherent beams at arbitrary construction angles. This feature can be used to control the angles over which spectral selectivity is obtained. In addition focusing wavefronts can also be used to increase functionality in the filter. Holograms fabricated in dichromated gelatin (DCG) have the benefit of light weight, low scattering and absorption losses. In addition, reflection holograms recorded in the Lippmann configuration have been shown to produce strong chirping as a result of wet processing. Chirping broadens the filter rejection bandwidth both spectrally and angularly. It can be tuned to achieve spectral bandwidth suitable for spectrum splitting applications. We explore different DCG film fabrication and processing parameters to improve the optical performance of the filter. The diffraction efficiency bandwidth and scattering losses are optimized by changing the exposure energy, isopropanol dehydration bath temperature and hardening bath duration. A holographic spectrum-splitting PV module is proposed with Gallium Arsenide (GaAs) and silicon (Si) PV cells with efficiency of 25.1% and 19.7% respectively. The calculated conversion efficiency with a prototype hologram is 27.94% which is 93.94% compared to the ideal spectrum-splitting efficiency of 29.74%.

Zhang, Deming; Gordon, Michael; Russo, Juan M.; Vorndran, Shelby; Escarra, Matthew; Atwater, Harry; Kostuk, Raymond K.

2012-10-01

389

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

390

Trees of cylinders and canonical splittings  

CERN Document Server

Let T be a tree with an action of a finitely generated group G. Given a suitable equivalence relation on the set of edge stabilizers of T (such as commensurability, co-elementarity in a relatively hyperbolic group, or commutation in a commutative transitive group), we define a tree of cylinders T_c. This tree only depends on the deformation space of T; in particular, it is invariant under automorphisms of G if T is a JSJ splitting. We thus obtain Out(G)-invariant cyclic or abelian JSJ splittings. Furthermore, T_c has very strong compatibility properties (two trees are compatible if they have a common refinement).

Guirardel, Vincent

2008-01-01

391

Electromagnetic Splittings and Light Quark Masses  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A method for computing electromagnetic properties of hadrons in lattice QCD is described. The electromagnetic field is introduced dynamically, using a noncompact formulation. Employing enhanced electric charges, the dependence of the pseudoscalar meson mass on the (anti)quark charges and masses can be accurately calculated. At $\\beta=5.7$ with Wilson action, the $\\pi^+-\\pi^0$ splitting is found to be $4.9(3)$ MeV. Using the measured $K^0-K^+$ splitting, we also find $m_u/m_d...

Duncan, A.; Eichten, E.; Thacker, H.

1996-01-01

392

Medium-induced splitting kernels from SCETG  

International Nuclear Information System (INIS)

Using the framework of soft-collinear effective theory with Glauber gluons (SCETG), we evaluate medium-induced splitting kernels. Because of the power counting of the effective theory, our results are valid for arbitrary, not necessarily small values of the energy fraction x taken by the emitted parton. In this framework we prove the factorization from the hard process and gauge invariance of the splitting kernels, we also show how nuclear recoil and the phase space cuts can be implemented into the phenomenology

393

High Distance Heegaard Splittings via Dehn Twists  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In 2001, J. Hempel proved the existence of Heegaard splittings of arbitrarily high distance by using a high power of a pseudo-Anosov map as the gluing map between two handlebodies. We show that lower bounds on distance can also be obtained when using a high power of a suitably chosen Dehn twist. In certain cases, we can then determine the exact distance of the resulting splitting. These results can be seen as a natural extension of work by A. Casson and C. Gordon in 1987 reg...

Yoshizawa, Michael

2012-01-01

394

On the Birman invariants of Heegaard splittings  

Digital Repository Infrastructure Vision for European Research (DRIVER)

J. Birman had observed that the homological information about a given Heegaard splitting of genus g is contained in a double coset in the group of symplectic 2g×2g integer matrices with respect to a suitable subgroup, and found a determinant invariant of this double coset. We obtain complete invariants of these double cosets by characterizing it in terms of the linking form of the manifold lifted to a handlebody of the Heegaard splitting and then finding complete invariants of this lifted form.

Montesinos Amilibia, Jose? Mari?a; Safont Edo, Carmen

1988-01-01

395

Symplectic Heegaard splittings and linked abelian groups  

CERN Document Server

Let $f$ be the gluing map of a Heegaard splitting of a 3-manifold $W$. The goal of this paper is to determine the information about $W$ contained in the image of $f$ under the symplectic representation of the mapping class group. We prove three main results. First, we show that the first homology group of the three manifold together with Seifert's linking form provides a complete set of stable invariants. Second, we give a complete, computable set of invariants for these linking forms. Third, we show that a slight augmentation of Birman's determinantal invariant for a Heegaard splitting gives a complete set of unstable invariants.

Birman, Joan S; Putman, Andrew

2007-01-01

396

Photon splitting in an ultrastrong magnetic field  

International Nuclear Information System (INIS)

We analyze the splitting of a photon with energy ? below the e+e- pair-production threshold in an ultrastrong magnetic field. We use the amplitudes found by employing the operator diagrammatic technique. In a field considerably above the critical values the process amplitudes become independent of the field strength. A study of the polarization operator of a photon in an external field of arbitrary strength in the energy range considered in the present investigation shows that there is only one set of polarizations of the initial and final photons for which the splitting amplitude is nonzero

397

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

398

Effect of palytoxin on membrane and potential and current of frog myelinated fibers.  

Science.gov (United States)

Palytoxin is a highly toxic compound isolated form several zoanthid Palythoa species. The effects of palytoxin on the nodal membrane of frog myelinated fiber have been studied under current clamp and under voltage clamp conditions. Under current clamp conditions, palytoxin (0.1 microng/ml, 3 x 10(-8)M) induces a depolarization which is not reversed by washing. The resting potential reaches a value of -35 mV after 10 minutes. During the same period, the evoked action potential shows a gradual decline and finally disapears after about 30 minutes. The membrane depolarization is suppressed by removal of Na ions from the external medium, but only slightly diminished when tetrodotoxin (10(-6)M) is subsequently added to the external medium. When the potential of the nodal membrane is maintained at -70 mV, palytoxin (0.1 microng/ml) causes the appearance of an inward current that increases in magnitude during 30 minutes before attaining a steady-state value. The kinetics of development of that current is modified in the presence of tetrodotoxin or saxitoxin. Voltage clamp analysis shows that palytoxin causes an increase of the resting sodium permeability that is accompanied by a shift of the voltage dependence of the transient sodium permeability in the direction of membrane hyperpolarization. The shift in the voltage dependence of the transient permeability is accompanied by a decrease of the peak transient permeability. A similar shift in the potential dependence of the sodium inactivation is observed. During and after the application of palytoxin, the internal sodium concentration increases. The steady-state (potassium) conductance is also decreased at the same time as the leak current is increasing. PMID:15101

Dubois, J M; Cohen, J B

1977-04-01

399

Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system.  

Science.gov (United States)

Breakdown in immunological self tolerance, leading to autoimmune diseases such as multiple sclerosis, might arise from immune recognition of self proteins that have undergone heightened posttranslational modification under pathophysiological conditions. A posttranslational modification of particular interest is the deimination of Arg to citrulline, catalyzed by peptidylarginyl deiminase (PAD) enzymes. As a CD4(+) T cell-driven model of multiple sclerosis, we used experimental autoimmune encephalomyelitis (EAE) induced with the immunodominant 35-55 peptide of myelin oligodendrocyte glycoprotein (pMOG) in C57BL/6 mice to test whether citrullination of a T cell epitope can contribute to disease etiopathology. Immunization with an altered peptide ligand (APL) of pMOG with an Arg-->citrulline conversion at a TCR contact (residue 41) led to the activation of two populations of APL-responsive T cells that either did, or did not cross-react with the native pMOG peptide. This APL could induce EAE. However, this reflected the activation of T cells that cross-reacted with the native pMOG epitope, because prior tolerization of these T cells using pMOG prevented APL-induced EAE. Using a passive transfer model, we found that T cells that responded specifically to the citrullinated form of pMOG were neither necessary, nor sufficient to initiate the EAE lesion. Nevertheless, these cells could provoke exacerbation of pathology if transferred into mice with ongoing EAE. The PAD2 and PAD4 enzymes were markedly upregulated in the inflamed CNS. Therefore, once inflammation is established, citrullination of target autoantigens can allow an expanded repertoire of T cells to contribute to CNS pathology. PMID:20164413

Carrillo-Vico, Antonio; Leech, Melanie D; Anderton, Stephen M

2010-03-15

400

Single-channel analysis of a delayed rectifier K+ channel in Xenopus myelinated nerve.  

Science.gov (United States)

Single-channel properties of a delayed rectifier voltage-gated K+ channel (I-type) were investigated in peripheral myelinated axons from Xenopus laevis. Channels activated between -60 and -40 mV with a potential of half-maximal activation, E50, at -47.5 mV. Averaged single-channel currents activated with a time delay at all membrane potentials tested. Time to half-maximal activation decreased from 80 to 1.6 msec between -60 and +40 mV. The channel inactivated monoexponentially with a time constant of 10.9 sec at -40 mV. The time constant of deactivation was 126 msec at -80 mV and 16.9 msec at -110 mV. In symmetrical 105 mM K+, the single-channel conductance (gamma) was 22 and 13 pS at negative and positive membrane potentials, respectively, at 13-15 degrees C. In Na+ -rich solution with 2.5 mM extracellular K+ gamma was 7 pS and the reversal potential was negative to -80 mV, indicating a high selectivity for K+ over Na+. gamma depended on extracellular K+ concentration (KD = 19.6 mM) and temperature (Q10 = 1.45). External tetraethylammonium (TEA) reduced the apparent single-channel amplitude at all potentials tested with a half-maximal inhibiting concentration (IC50) of 0.6 mM. Open probability of the channel, but not single-channel current amplitude was decreased by extracellular dendrotoxin (DTX, IC50 = 6.8 nM). mast cell degranulating peptide (MCDP, IC50 = 41.9 microM). In Ringer solution the membrane potential of macroscopic I-channel patches was about -65 mV and depolarized under TEA and DTX. It is concluded that besides their activation during action potentials, I-channels may also stabilize the resting membrane potential. PMID:8801354

Koh, D S; Vogel, W

1996-02-01

 
 
 
 
401

Improved lung preservation relates to an increase in tubular myelin-associated surfactant protein A  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Declining levels of surfactant protein A (SP-A after lung transplantation are suggested to indicate progression of ischemia/reperfusion (IR injury. We hypothesized that the previously described preservation-dependent improvement of alveolar surfactant integrity after IR was associated with alterations in intraalveolar SP-A levels. Methods Using immuno electron microscopy and design-based stereology, amount and distribution of SP-A, and of intracellular surfactant phospholipids (lamellar bodies as well as infiltration by polymorphonuclear leukocytes (PMNs and alveolar macrophages were evaluated in rat lungs after IR and preservation with EuroCollins or Celsior. Results After IR, labelling of tubular myelin for intraalveolar SP-A was significantly increased. In lungs preserved with EuroCollins, the total amount of intracellular surfactant phospholipid was reduced, and infiltration by PMNs and alveolar macrophages was significantly increased. With Celsior no changes in infiltration or intracellular surfactant phospholipid amount occurred. Here, an increase in the number of lamellar bodies per cell was associated with a shift towards smaller lamellar bodies. This accounts for preservation-dependent changes in the balance between surfactant phospholipid secretion and synthesis as well as in inflammatory cell infiltration. Conclusion We suggest that enhanced release of surfactant phospholipids and SP-A represents an early protective response that compensates in part for the inactivation of intraalveolar surfactant in the early phase of IR injury. This beneficial effect can be supported by adequate lung preservation, as e.g. with Celsior, maintaining surfactant integrity and reducing inflammation, either directly (via antioxidants or indirectly (via improved surfactant integrity.

Ochs Matthias

2005-06-01

402

Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease  

Energy Technology Data Exchange (ETDEWEB)

Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses is to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.

Su, Y.; Zhang, H.; Madrid, R. [Univ. of California, San Francisco, CA (United States)] [and others

1994-09-01

403

Different cellular and molecular mechanisms for early and late-onset myelin protein zero mutations.  

Science.gov (United States)

Mutations in the gene MPZ, encoding myelin protein zero (MPZ), cause inherited neuropathies collectively called Charcot-Marie-Tooth type 1B (CMT1B). Based on the age of onset, clinical and pathological features, most MPZ mutations are separable into two groups: one causing a severe, early-onset, demyelinating neuropathy and a second, causing a late-onset neuropathy with prominent axonal loss. To investigate potential pathomechanisms underlying the two phenotypes, we transiently transfected HeLa cells with two late-onset (T95M, H10P) and two early-onset (H52R, S22_W28 deletion) mutations and analyzed their effects on intracellular protein trafficking, glycosylation, cell viability and intercellular adhesion. We found that the two late-onset mutations were both transported to the cell membrane and moderately reduced MPZ-mediated intercellular adhesion. The two early-onset mutations caused two distinct abnormalities. H52R was correctly glycosylated and trafficked to the plasma membrane, but strongly affected intercellular adhesion. When co-expressed with wild-type MPZ (wtMPZ), a functional dominant negative effect was observed. Alternatively, S22_W28 deletion was retained within the cytoplasm and reduced both adhesion caused by wtMPZ and cellular viability. Since the same trafficking patterns were observed in transfected murine Schwann cells, they are not an artifact of heterologous cell expression. Our results suggest that at least some late-onset mutations cause a partial loss of function in the transfected cells, whereas multiple abnormal gain of function pathways can result in early-onset neuropathy. Further characterization of these pathways will lead to a better understanding of the pathogenesis of CMT1B and a rational basis for treating these debilitating inherited neuropathies. PMID:18337304

Grandis, Marina; Vigo, Tiziana; Passalacqua, Mario; Jain, Manisha; Scazzola, Sara; La Padula, Veronica; Brucal, Michelle; Benvenuto, Federica; Nobbio, Lucilla; Cadoni, Angela; Mancardi, Gian Luigi; Kamholz, John; Shy, Michael E; Schenone, Angelo

2008-07-01

404

Modulation of adult hippocampal neurogenesis during myelin-directed autoimmune neuroinflammation.  

Science.gov (United States)

In chronic autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) clinical signs of cognitive dysfunction have been associated with structural changes in the hippocampus. Moreover, experimental studies indicate that inflammatory responses within the CNS modulate the homeostasis of newborn cells in the adult dentate gyrus (DG). However, it remained open whether such changes happen regardless of the primary immunological target or whether a CNS antigen-directed T lymphocyte-mediated autoimmune response may exert a specific impact. We therefore induced experimental autoimmune encephalomyelitis (EAE), a common model of MS serving as a paradigm for a CNS-specific immune response, by immunizing C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG) p35-55. In EAE animals, we found enhanced de novo generation and survival of doublecortin (DCX)-positive immature neurons when compared with controls immunized with CNS-irrelevant antigen (ovalbumine). However, despite activation of neurogenesis, we observed a reduced capacity of these cells to generate mature neurons. Moreover, the high number of newly born cells retained the expression of the glial marker GFAP. These effects were associated with downregulation of pro-neurogenic factors Neurogenin1 and Neurogenin2 and dysregulation of Notch, ?-catenin, Sonic Hedgehog (Shh) signaling as suggested by altered gene expression of effector molecules. Thus, a CNS antigen-specific immune response leads to an aberrant differentiation of neural precursors associated with dysbalance of signaling pathways relevant for adult hippocampal neurogenesis. These results may further extend our understanding of disturbed regeneration in the course of chronic inflammatory CNS diseases such as MS. PMID:20967885

Huehnchen, Petra; Prozorovski, Timour; Klaissle, Philipp; Lesemann, Anne; Ingwersen, Jens; Wolf, Susanne A; Kupsch, Andreas; Aktas, Orhan; Steiner, Barbara

2011-01-01

405

Tracing Myelin Protein Zero (P0 in vivo by construction of P0-GFP fusion proteins  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Mutations in P0, the major protein of the myelin sheath in peripheral nerves, cause the inherited peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B, Dejerine-Sottas syndrome (DSS and congenital hypomyelination (CH. We reported earlier a de novo insertional mutation c.662_663GC (Ala221fs in a DSS patient. The c.662_663GC insertion results in a frame shift mutation Ala221fs altering the C-terminal amino acid sequence. The adhesion-relevant intracellular RSTK domain is replaced by a sequence similar to Na+/K+ ATPase. To further clarify the molecular disease mechanisms in this sporadic patient we constructed wild type P0 and the c.662_663GC mutant expression cassettes by site-specific mutagenesis and transfected the constructs into insect cells (S2, High5. To trace the effects in live cells, green fluorescent protein (GFP has been added to the carboxyterminus of the wild type and mutated P0 protein. Results In contrast to the membrane-localized wild type P0-GFP the Ala221fs P0-GFP protein was detectable almost only in the cytoplasm of the cells, and a complete loss of adhesion function was observed. Conclusions The present study provides evidence that GFP is a versatile tool to trace in vivo effects of P0 and its mutations. Not only a loss of adhesion function as a result of the loss of the RSTK domain, but also altered intracellular trafficking indicated by a loss of membrane insertion are possible consequences of the Ala221fs mutation.

Van Broeckhoven Christine

2002-11-01

406

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The Charcot-Marie-Tooth (CMT phenotype caused by mutation in the myelin protein zero (MPZ gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P0 mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P0ex is known, while the transmembrane and intracellular structure is unknown. Findings One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome. Conclusions The phenotypic variation caused by different missense mutations in the MPZ gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.

Sand Jette C

2010-04-01

407

Splitting time for irrational triangle billiards  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We find an upper estimate for a splitting time of a thin parallel beam for irrational triangle billiards in terms of some number-theoretic function of angles. We provide an upper estimate on this function for some class of angles.

Scheglov, Dmitri

2011-01-01

408

Splitting of the ruby fluorescence under stress  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A splitting of the R1 ruby fluorescence is observed when a pressure P is applied on the crystal along special directions. It is linear as a function of P2, in agreement with the theory. It comes from the lifting of the degeneracy of Cr3+ ions located in two different sublattices.

Monteil, A.; Duval, E.; Attar, A.; Viliani, G.; Lacroix, R.

1984-01-01

409

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

410

Chiral symmetry and hyperfine qq splittings  

Energy Technology Data Exchange (ETDEWEB)

We review theoretical calculations for the pseudoscalar-vector meson hyperfine splitting with no open flavor and also report a many body field theoretical effort to assess the impact of chiral symmetry in the choice of effective potentials for relativistic quark models. Our calculations predict the missing {eta}{sub b} meson to have mass near 9400 MeV. (orig.)

Llanes-Estrada, Felipe J. [Depto. de Fisica Teorica I, Univ. Complutense, Madrid (Spain); Cotanch, Stephen R. [Department of Physics, North Carolina State University, Raleigh, NC (United States); Szczepaniak, Adam P. [Department of Physics and Nuclear Theory Center, Indiana University Bloomington, IN (United States); Swanson, Eric S. [Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA (United States); Jefferson Lab., Newport News, VA (United States)

2004-07-01

411

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

412

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

413

Polynomial splittings of Casson-Gordon invariants  

Science.gov (United States)

We prove that the Casson-Gordon invariants of the connected sum of two knots split when the Alexander polynomials of the knots are coprime. As one application, for any knot K, all but finitely many algebraically slice twisted doubles of K are linearly independent in the knot concordance group.

Kim, Se-Goo

2005-01-01

414

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

415

Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene.  

Science.gov (United States)

Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21 days in all mice. Shortly after reinnervation the conduction of P0+/- regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1 month, regenerated P0+/- axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating myelinated fibers became similar to regenerated WT. Our data suggest that in the presence of heterozygously P0 deficient Schwann cells, regenerating motor axons retain their ability to reinnervate their targets and remyelinate, though their functional recovery is delayed. PMID:23564290

Rosberg, Mette Romer; Alvarez, Susana; Krarup, Christian; Moldovan, Mihai

2013-06-01